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G-2436

Etiology, molecular and epidemiological characteristics of enteric pathogens in Georgia.

Project Status: 3 Approved without Funding
Duration in months: 24 months

Objective

Diarrheal disease in one of the most spread disease and is the second leading cause of death in children under five years old. It is both preventable and treatable, but these advantages are not used adequately. Each year diarrhea kills more than half million children aged under five in the world. A significant proportion of diarrheal disease can be prevented through safe drinking-water and adequate sanitation and hygiene. Three main types of diarrhea are identified: First is acute watery diarrhea, that lasts several hours or days. Second is acute bloody diarrhea, also called dysentery and third, persistent or chronic diarrhea, lasts 14 days or longer. Shiga toxin-producing Escherichia coli (STEC) can cause illness ranging from mild diarrhea, to bloody diarrhea, to the hemolytic uremic syndrome (HUS), a life-threatening condition and manifests with a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.
Bloody diarrhea is often caused by different strains of Shigella, Salmonella and pathogenic E. coli including STEC, EHEC or others. A special study conducted in US determines various species of enteropathogens as an etiological factor of bloody diarrhea, from them Shigella (15.3%), Campylobacter (6.2%), Salmonella (5.8%), STEC (2.6%), and other enteric pathogens (1.6%). In Germany, STEC/VTEC and HUS have been statutorily notifiable since 2001 according to the Protection against Infection Act. HUS and STEC infections are under epidemiological surveillance in the EU. In 2012, the European Commission updated the European case definition for STEC, requiring laboratory confirmation of Stx or stx gene(s), except when STEC O157 is directly isolated.
Georgia is a small Eastern European country situated on the black sea coast, bordering Russia and Turkey. The population of Georgia is 3.7 million inhabitants. Based on annual diseases surveillance report of National Center for Diseases, Control and Prevention in Georgia (NCDC) country characterizes with high incidence of food poisoning and diarrheal diseases 921.6 per 100,000 populations. The national communicable disease surveillance system of Georgia monitors diarrheal diseases. More than three epidemiologically-linked cases of diarrheal diseases trigger an epidemiological investigation, including collecting data about risk factors and laboratory testing results. During the last years, the incidence of diarrhea was significantly increased in Georgia. The prevalence of hemorrhagic colitis was increased 3-4 times, but there is no surveillance system to register bloody diarrhea or HUS cases in the country. The first outbreak of bloody diarrhea and HUS was officially registered and investigated in Georgia in 2009. The investigation of this outbreak was supported by US CDC and SC/FELTP. During the study cases of E. Coli O104:H4, O103 and other STECs were identified first time in Georgia. The majority of cases of this outbreak were detected in Tbilisi and Shida Kartli region. Based on literature review and studies conducted in this field form 2009 till 2016, various types of E. coli and enteric pathogens are causing diarrheal diseases in Georgia and children under 15 years are most affected population.
The adequate methodology to detect STEC is limitedly available only in one reference laboratory at NCDC of Georgia.
Use of antibiotic to treat diarrheal diseases is very common in Georgia. Base on retrospective data analysis more than 80% of patients with any diarrhea are treated with antibiotics. Very often patients start self treatment with different antibiotics before visiting to doctor and only if this treatment is not effective they admit to clinics. Irrational use of antibiotics to treat diarrheal diseases, especially for diarrhea caused by viruses, fungi's or STEC may cause antibiotic resistance and/or bring patients to possible complications such as dysbacteriosis and activation fungal infection. Use antibiotics to treat diarrheal disease caused by pathogenic E. coli (STEC) increases risk of developing HUS.
Analysis of national surveillance data of diarrheal diseases demonstrates that detection rate of enteric pathogens is very low and cases of diarrheal diseases are reported without identification of enteric pathogens in majority of cases. The capacity to detect viruses causing diarrhea is not well developed and the same time country has very limited ability to detect diarrheas associated with Campilobacter species. Studies conducting in Georgia revealed that the prevalence and molecular epidemiology of diarrhea caused by pathogenic E. Coli strains are still in demand to investigate. There are many different strains of E. Coli causing diarrheal diseases and have complications with HUS.
Presented circumstances are strong evidence to conduct study able to discover enteric pathogens causing diarrheal diseases in Georgia. Study results will serve to provide understandable representation of enteric pathogens circulating in the country and will support to produce evidence based recommendations for implementation better treatment and prevention measures.
The main goal of proposed study is to determine etiology, molecular and epidemiological characteristics and antibiotic resistance of enteric pathogens causing diarrheal disease in Georgia. Specific objectives and tasks include:
Objective 1: Determine the etiology of diarrheal diseases in patients with community-acquired diarrhea.
Task 1: Identify and collect stool samples of case patients with diarrheal disease.
Task 2: Culture stool samples in the bacteriology laboratory and do serology testing.
Task 3: Conduct antibiotic resistance testing.
Objective 2: Determine the characteristics of pathogenic E. coli strains (STEC/EHEC others) causing diarrhea in Georgia.
Task 4: Conduct Multiplex PCR testing to identify shiga toxin genes of pathogenic E. coli.
Task 5: Conduct Pulls Field Gel Electrophoresis (PFGE) testing.
Task 6: Collect demographic and epidemiologic data of patients with pathogenic E. coli.
The major innovations will be introduced in the proposed study, including: 1) Determining the etiology of diarrheal diseases; 2) Identify and study pathogenic E. coli strains; 3) Evaluation molecular epidemiology of diarrheal cases.

Participating Institutions

LEADING

Georgian AIDS and Clinical Immunology Research Center

COLLABORATOR

Robert Koch-Institut

PARTICIPATING

National Center for Disease Control and Public Health (NCDC)