Technology EPIDEMIOLOGICAL , CLINICAL AND LABORATORY FEATURES OF ROTAVIRUS GASTROENTERITIS AMONG HOSPITALIZED CHILDREN LESS THAN FIVE YEARS OLD IN SELECTED HOSPITALS IN JORDAN , 2007-2008

Background: Acute gastroenteritis continues to be a significant cause of morbidity and mortality worldwide. Rotavirus causes more than 130 million episodes of severe diarrhea in children less than five years throughout the world and is considered as main problem in many countries. Few data are available about gastroenteritis attributable to rotavirus in Jordan. Objectives: The primary purpose of this study is to determine epidemiological, clinical and laboratory characteristics of hospitalized cases attributable to rotavirus gastroenteritis in children less than five years old in selected hospitals during the period May 2007-April 2008 to provide Ministry of Health with evidence upon which to base its futuristic decision in regard to development of more suitable preventive measures. This study will improve the existing diarrhea surveillance system in MoH, facilitate and support the decision of introducing rotavirus vaccine in national immunization programme. Methods: Descriptive Cross-sectional study was performed on the hospitalized children less than five years old with acute gastroenteritis in three selected hospitals in three governorates (north, middle and south regions) with population about 45.3% of Jordan population for the period May 2007 to April 2008. Standard case definition was adopted. Analysis was performed using SPSS and Epi Info statistical packages. Results: 377 cases were enrolled with 171 positive for rotavirus. Results showed that Incidence rate of rotavirus disease is 5.2/ 10000 children less than five years old per year; male: female ratio is 1.8:1 with largest proportion of cases among children 6-11 months old. Southern region has the highest incidence rate. Vomiting is an outstanding symptom for rotavirus cases (P< 0.01) in addition to diarrhea and fever which require admission to hospital for fluid replacement. Majority of rotavirus cases were with some dehydration (30%). Mean stay duration is 3 days. Predominant genotypes are G1P8.G2P4 and G9P untypeable. Conclusions: Although mortality of gastroenteritis is no longer a problem in Jordan due to accessibility to health services, morbidity is still high and rotavirus is a relevant cause for gastroenteritis in children less than five years old; which require hospitalization most of the time (45.4% of admitted gastroenteritis).


INTRODUCTION
cute gastroenteritis continues to be a significant cause of morbidity and mortality worldwide. [1]Despite improved treatment of gastroenteritis, the disease has not been controlled; this raises questions regarding the need for national intervention programmes based on reliable epidemiological data.A major concern is raised based on international literature and experience regarding rotavirus gastroenteritis.Each year, rotavirus causes approximately 111 million episodes of gastroenteritis requiring only home care, 25 million clinic visits, 2 million hospitalizations, and 352,000-592,000 deaths (median, 440,000 deaths) in children <5 years of age.By age 5, nearly every child will have an episode of rotavirus gastroenteritis, 1 in 5 will visit a clinic, 1 in 60 will be hospitalized, and approximately 1 in 293 will die.Children in the poorest countries account for 82% of rotavirus deaths. [2]Approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life, resulting in a direct medical cost of millions US dollars.

A
The surveillance system for diarrheal diseases is clinical and laboratory based surveillance for bacterial and parasite agents.There is no such system available for viral causes of diarrhea.Diarrhea diseases (watery and bloody) are a compulsory notifiable disease.It is passive surveillance system based on weekly and monthly reporting system from all reporting sites using special reporting form.According to the Ministry of Health (MoH) annual epidemiological report, total admissions of diarrhea cases in MoH hospitals in one year is 7722 and the average hospitalization days is 4 days, the cost per day is estimated to be $ 150.The annual cost would be about $ 5 million, which constitutes an economic burden for health services besides its emotional stress for parents and community.Additionally, the rapid progress towards the development of rotavirus vaccines has prompted a reassessment of the disease burden of rotavirus gastroenteritis in developed and developing countries and the possible impact of these vaccines in reducing gastroenteritis morbidity and mortality among infants and young children.

The current study is carried out with the following rationale in mind:
• Few data and limited information in addition to lack of awareness of importance of gastroenteritis attributable to rotavirus in Jordan.
• To improve the existing diarrhea disease surveillance system by providing information regarding characteristics of gastroenteritis attributable to rotavirus in children less than five years old in Jordan.
• To define strategies for management and prevention and clarify the benefits of potential preventive measures for gastroenteritis attributable to rotavirus (vaccine).
The present study aimed to determine epidemiological, clinical and laboratory characteristics of hospitalized cases attributable to rotavirus gastroenteritis in children less than five years old in selected hospitals during the period May 2007-April 2008 to provide MoH with evidence upon which to base its futuristic decision in regard to development of more suitable preventive measures.Specifically, the study was planned to attain the following objectives:

PATIENTS AND METHODS
This study is a Descriptive Cross sectional hospital-based study.

Data Sources and Characteristics:
Population in Jordan in the year 2007 is 5744473, of which 732604(12.7%)were under the age of five years.
The study is carried out at three governorates, which are representative of different geographical areas of Jordan (Irbid in the north, Amman in the middle and Karak in the south).The three governorates cover 45.3% of Jordan population.Amman has 31.0%,Irbid 11.0% and Karak city 3.3% of Jordan population.

Rotavirus Screening:
A sufficient amount of bulk stool, approximately 5 ml, was obtained from each suspected case during the acute illness, on the day of presentation to hospital.Attempts were made to obtain a stool specimen from all possible cases within 48 hours of hospital admission so as to avoid the detection of nosocomial infection.
Stool samples were collected and divided into aliquots to be tested by hospital laboratory on weekly basis for group A rotavirus by an enzyme-linked immunosorbent assay (Rota DakoCytomation Ltd, United Kingdom) to detect VP6 antigen.All positive stool samples for rotavirus were subject for quality control while only 25% of negative samples were sent to central laboratory for the same purpose every two weeks and were retested by expert personnel.The positive samples were stored for strain characterization and genotyped at NAMRU-3 as referral laboratory.

Statistical analysis:
To ensure standardization of data entry an electronic investigation form was developed for data entry and code checking using Epi Info for windows programme and SPSS software.Data were analyzed using Epi Info programme and SPSS software.

Study Limitations:
-Advantages of this study: In middle region the prevalent genotype is G1, G9 with P4, P8.
In northern region the prevalent genotype is G1, G9 with P8 P untypeable.
The prevalent combined genotype is G1P8, followed by G2P4 and G9PUT.

[ 3 ]o
In Jordan there are many health care providers including: Public sector: • Ministry of health: (which cover 80% of health services) • Royal medical services • University hospitals.o Private sector.o UNRWA.

[5] Sample Size All
children under 5 years of age (less than 60 months of age) presenting to the three selected hospitals with acute gastroenteritis and requiring hospitalization for treatment of gastroenteritis and fit the adopted case definition, between May 2007 and April 2008, were included in the study.Informed consent was obtained from the parents of all children enrolled in the hospitalbased study.The study was approved by National Rotavirus Surveillance Committee in Ministry of Health.World Health Organization provided the financial and logistic support.Inclusion criteria: 1. Child less five years of age (< 60 months).Exclusion Criteria: 1. Child with bloody diarrhoea.2. Patients acquired gastroenteritis during their hospitalization for treatment of other diseases (hospital acquired gastroenteritis).Confirmed case: A suspected case in whose stool the presence of rotavirus is demonstrated by means of an enzyme immunoassay EIA.No probable case definition was adopted in this study.Data Collection Methods: 1. Questionnaire: For this study special questionnaire was designed based on data obtained through rotavirus surveillance system.The questionnaire includes: Patient information: ID, name, age (by months), sex and address.Clinical information: duration of symptoms, symptoms (fever, diarrhea, No. of episodes of diarrhea, vomiting, No. of episodes of vomiting), dehydration status, treatment, duration of hospitalization, outcome.Laboratory information: EIA rotavirus identification in stool, genotype G and P.

Table 7 . Percent of major G-P rotavirus strain combinations in hospitals
explained by population under study, which represent children treated at hospitals, who are the most severely ill: on Vesikari Scale (>10 score), while vomiting was a dominant symptom for children with rotavirus gastroenteritis, so for further understanding of the spectrum of disease and clinical symptoms a combined community and hospital based studies which investigate both mild and severe disease could be carried out.In similar studies children infected with rotavirus gastroenteritis were more likely to have watery stools, severe vomiting and less severe dehydration. [12,13]ificant finding in this study was the high percentage of G1P8, G2P4 and G9 with untypeable P type, accounting for 19.7%, 17.4% and 15.9% respectively of rotavirus gastroenteritis.A recent review of global rotavirus genotypes states that G1P8 accounts for 70% of rotavirus infections in North America, Australia and Europe, whereas it represents about 30% of infections in South America and Asia and about 23% in Africa.[14]RotavirusserotypeG9 is recognized as the most widespread of the emerging genotypes, representing 4.1% of global rotavirus infections and accounting for up to 70% of rotavirus infections in recent reports.[13]InJordan the most prevalent genotype in Southern region is G2P4; in Northern and Middle regions is G1P8.Mean stay duration of rotavirus positive cases is 3 days.The mean length of stay in similar studies was 4.0 days.[16]CONCLUSIONSIncidence rate of Rotavirus gastroenteritis in children less than five years old is 5.2 per 10000 children per year.It comprises a relevant cause of severe gastroenteritis and requires admission to hospitals most of the time, with average duration of stay of 3 days.Vomiting is a dominant symptom for rotavirus cases.