Foodborne disease is a global public health problem. Non-typhoidal Salmonella (NTS) remains one of the most commonly reported bacterial causes of foodborne infections diseases [1]. It is well-recognized that salmonellosis can be acquired by consumption of contaminated water, meat, eggs, or milk, or by contact with infected food animals and patients [2]. Manifestations of NTS included diarrheal and septicemia. Estimates suggest that globally 93.8 million people are infected by NTS, with 155,000 deaths each year [3]. In the United States, NTSis estimated to cause 1,027,561 illnesses, 19,336 hospitalizations and 378 deaths annually [4]. It has also been shown that children aged <5 years are a susceptible population to Salmonella infection [5]. However, similar data with respect to NTS infections is lacking in China [6]. NTS is typically self-limiting; antimicrobials are generally reserved for invasive infections [7]. Fluoroquinolones are among the antimicrobials commonly used to treat invasive salmonellosis among adults while cephalosporins are often employed for children [8,9]. However, several studies have shown a decreased susceptibility to ciprofloxacin as well as cephalosporins in Salmonella [9-12]. Furthermore, fluoroquinolone treatment failure in Salmonella infection has been reported in some countries [13-15]. Antimicrobial -resistant Salmonella has become a global concern [16,17].

Currently, the national notifiable infectious diseases reporting system required diarrhea case reporting based on symptoms only. Laboratory-based surveillance is not commonly conducted at this time in China [18]. However, laboratory-based surveillance can provide information that permits identification of risk factors and control of infectious diseases, and implementation of NTS surveillance will allow for investigation of characteristics of Salmonella infections. Guangdong Province is a subtropical area in south China, with a season of high temperatures and humidity from March to October. Since 2009, laboratory-based surveillance for NTS has been established by the Guangdong Center for Disease Control and Prevention (GDCDC) [19]. In this report,epidemiological characteristics,including seasonal tendency, age distribution associated with serotype diversity, and antimicrobial resistance of NTS infections in Guangdong province are presented.

In this study, we report epidemiologic characteristics of NTS infections in Guangdong Province from 2009 to 2012. An increase in the NTS isolation rate was observed beginning at 3.4% in 2009, 3.5% in 2010, 4.4% in 2011 and 5.1% in 2012. Since the surveillance was conducted, several training courses were designed by GDCDC for clinicians and lab staff to improve the capacity of detecting and reporting food-borne disease cases in Guangdong Province [23].

Our study showed that children aged <5 years were the group most affected by NTS in Guangdong Province. In a previous study, children <5 years were shown to be at risk for NTS infections [24]. In the United States, the NTS isolation rate was highest in patients aged < 1 year [25]. In our study, children aged <5 years accounted for 73% of the overall NTS infections. Even in general hospitals, children <5 years accounted for 65% of the infections. This rateis were higher than that in a previous national report, which NTS isolated from eight provinces were associated with diarrhea in 34% of patients < 5 years in China [6]. In other countries, a high prevalence of NTS infection in children < 5 years has also been reported [26,27]. Future epidemiological investigations about risk factors should be conducted to determine why children <5 years, especially infants (<1 year) in Guangdong have become the majority of infections for disease control and prevention.

Salmonella serotype 4,5,12:i:- is considered a monophasic variant of serotype Typhimurium with similar antigenic and genotypic characteristics. In our study, the percentage of S. serotype 4,5,12:i:- increased from 3.6% in 2009 to 20% in 2011 and down to 15% in 2012, becoming one of the most common Salmonella serotypes in Guangdong. In Europe,S. serotype 4,5,12:i:-showed a marked increase in foodborne infections with an association in pig meat [28]. This serotype has also been recognized as an emerging cause of infection in other countries in the world [29].

Increasing antimicrobial resistance was observed in this study, especially to the conventional first-line agents, such as β-lactam antibiotics and quinolones. Regionally, NTS isolates recovered in Malaysia also showed high resistance rates to tetracycline (70%), sulfonamides (57%), and streptomycin (53%) but lower rates to ampicillin (30%),nalidicix acid (28%) and chloramphenicol (21%) than in China [30]. Resistance rates in the United States to ampicillin, chloramphenicol, and nalidixicacid were even lower, 20%, 11%, and 2.7%, respectively [31]. Drug resistance in China is likely multifaceted, with resistant isolates selected after environmental, clinical and veterinary antibiotic exposures. Further investigations exploring the emergence of resistant NTS isolates are required to control this public health problem.

Extended-spectrum cephalosporins and fluoroquinolones have been recommended for treatment of diarrhea resulting from a NTS infection [32,33], although a recent review suggests that there is little added benefit for treatment in an otherwise healthy individual [33]. It is noted that the prevalence of cephalosporins resistance was higher in children aged <5 years than in patients aged ≥5 years. Also the majority of isolates resistant to all three cephalosporins were from children aged <5 years, suggesting more attention should be given to the severe resistance of Salmonella infections in young children. High resistance will increase the diarrhea burden among children [34]. In the United States, 4.1% of the isolates displayed decreased susceptibility to either ceftriaxone or ceftiofur in 2005 and 2006, while it was only 1% in 1996-1998 [9]. An increase in the number of isolates displaying decreased susceptibility may have an impact on clinical treatment and may lead to treatment failure as cephalosporins are the primary choice for children.

Reduced susceptibility to ciprofloxacin is a current trend in NTS isolates globally. The MIC of NTS isolates from Asian countries rose from 0.125 to 1 μg/ml during 2003 to 2005 [12]. Nalidixic acid susceptibility testing has been recommended by CLSI before using ciprofloxacin for treatment, as isolates resistant to nalidixic acid are probably resistant to ciprofloxacin [35].

This study had some limitations. First, selection of the sentinel hospitals was based on convenience but not the catchment size of the local population. Ten of the 28 hospitals involved were located in the capital city, Guangzhou, while only two or three hospitals included from the other cities in Guangdong. Future expansion of NTS surveillance in Guangdong should incorporate hospitals based on the coverage of the population in each catchment area. Second, only a minority of all patients with diarrhea have stool specimens collected for culture, as stool culture is not required in China for diarrheal patients. Finally, the Salmonella isolation rate was not very high, possibly because of previous antibiotic use or laboratory testing sensitivity. In the future, increasing the rate of specimen collection, the rate of isolation, the number of facilities in surveillance, and improving the representativeness of the surveillance system will help to improve our understanding of foodborne disease incidence and increase sensitivity for outbreak detection in Guangdong China.

In conclusion, S. Typhimurium represented the most common serotype followed by serotype 4,5,12:i:- in Guangdong Province in China. Children aged <5 years were the group most affected by Salmonella in Guangdong Province. A high prevalence of antimicrobial resistance, including resistance to ciprofloxacin and cephalosporins, was observed among the isolates, especially from children aged <5 years. Improved characterization of Salmonella infections would facilitate risk assessment of Salmonella infections. Moreover, making the antimicrobial susceptibility testing of Salmonella isolates by clinical laboratories routinely would allow clinicians to choose appropriate antimicrobials for treatment of infectious diarrhea. However, additional data and more refined methods can improve future surveillance. The invasive Salmonella isolates should also be included to the antibiotic resistance surveillance for clinical care or public health.

Written informed consent was obtained from the patient’s guardian/parent/next of kin for the publication of this report and any accompanying images.