| Paratyphoid fever A (PA) has been endemic since 1999, and remains a serious public-health problem in Yuxi city. The incidence of PA was high, >100 cases per 100000 population per year, in Hongta area of Yuxi, and higher than the average rate in China (1 case per 100000 population per year). Salmonella enterica serotype paratyphi A (SPA) was responsible for a growing proportion of typhoid and paratyphoid fever, accounting for 99.4% (4543:4569) of Salmonella bloodstream isolates among patients with typhoid and paratyphoid fever. The PA activities suggest that SPA could increase in importance and represents a challenge to human in the future. Continuing pathogenic monitoring was performed with a number of sporadic patients with suspected PA in Yuxi City from 1999 to 2009, and the dynamic variations of SPA isolates per month and year were analyzed. To obtain the yields of detection of SPA from the blood of patients with suspected PA. To understand the antimicrobial susceptibility, phagocyte types and pulsed field gel electrophoresis (PFGE) patterns of SPA isolates, and confirm the links between them. Reveal and determine the genetic diversity, epidemic clones, risk factors for spread, transmission routes and clonal expansion of SPA isolates. It is useful to determine whether the epidemic PA found throughout Yuxi from 1999 to 2009 was due mainly to multiple SPA clones or a single one, and understand the mode of spread and ecological and epidemical determinants of transmission of SPA, in order to implement crative strategies for the prevention and control of PA. With the BacT/ALERT 3D system, the broth blood cultures of suspected paratyphoid fever A patients were performed. Antimicrobial susceptibility testing was performed with SPA isolates by the controlled Kirby-Bauer disc diffusion technique on Muller-Hinton agar plates. The SPA isolates with nalidixic acid resistance for mutations in gyrA, gyrB, parC and parE genes within the quinolone-resistant determination region were examined. The nalidixic acid-resistant (NAR) and nalidixic acid-susceptible (NAS) isolates of SPA were randomly selected to determine the minimum inhibitory concentrations (MICs) for nalidixic acid, etc. Subtyping of the isolates of SPA was performed using phage of Salmonella. The isolates were typed by PFGE analysis following digestion of chromosomal DNA with restriction endonucleases SpeI and XbaI. PFGE patterns were analyzed by cluster analysis. The risk factors on transmission of SPA were determined by case-control study and cohort study. Salmonella, indicator bacteria of pollution were examined with the samples of sewage, well water and raw vegetables associated with transmission of SPA. The relationships among epidemic PA and ecological determinants and epidemiological factors were investigated and studied.Continued pathogenic monitor was performed with 15500 sporadic patients with suspected PA from 1999 to 2009. A total of 4543 SPA isolates were recovered. The ratios of culture-proven PA to typhoid fever cases were 6:4, 77:3, 1262:3, 493:4, 258:6, 751:1, 412:1, 712:2, 420:3, and 152:0 per year from 1999 to 2008, respectively. The incidence of urban people was obviously more than rural people. Seasonal variation was single peak in summer and autumn (from April to October). The case group aged from 15 to 45 years accounted for more than 77% of total reported cases. Reveal the ecological laws governing the upsurges of the numbers of SPA isolates from April to October every year and at 1 to 2 years intervals. The incidences of resistance to nalidixic acid of the isolates in 1999 and 2000 were 12.5% (1/8) and 82.2%(60/73), respectively. More than 97.0% of the isolates obtained from 2001 to 2008 were resistant to nalidixic acid, and the incidence of resistance to nalidixic acid of the isolates increased from 95.0%(880/926) in 2001 to 100%(407/407) in 2005. The incidences of resistance to nalidixic acid of 2006, 2007 and 2008 were 99.3%(678/683), 99.5%(400/402) and 100%(182/182), respectively. All NAR isolates studied had a reduced susceptibility to fluoroquinolone, the MICs were higher than that for NAS isolates. The NAS isolates predominated in 1999 but was replaced by NAR isolates after 2000. Amplification by PCR and sequencing of the genes with subsets of 15 NAR strains revealed that the mechanisms of nalidixic acid resistance had resulted from single point mutations in the gyrA gene leading to the Ser83Phe substitution. SpeI and XbaI digestion of 194 isolates give 10 and 7 different PFGE patterns with predominance of the SpeI01 and SpeI02 (or the XbaI01) epidemic patterns, respectively. SpeI01 and SpeI02 consisted of 46.40%(90/194) and 43.30%(84/194) of isolates, respectively, or XbaI01 consisted of 93.81%(182/194) of isolates. There only 1 phagocyte type among 121 isolates. No links were observed between the nalidixic acid-resistant phenotype, phagocyte types and PFGE patterns. PA cases was associated with consumption of food from restaurants, especially with consumption of raw vegetables(OR, >3.2; 95% CI, 1.60-12.1). Fecal contaminations of well water, river water, and vegetables were all verified, all (25/25) well and river water and 60 (84.5%) raw vegetable samples from restaurants contained fecal coliforms. The rates of regions exposed risk factors were higher and more widespread than the rates of regions non-exposed risk factors. The relationships among PA and ecological determinants, epidemiological factors, biological mechanisms and ecological dynamics of SPA clonal expansion were clear-cut.The incidence of resistance to nalidixic acid of the isolates increased during the study period and the rates may predominantly reflect clonal expansion after infrequent mutation or selection events. Creative prevention strategies are becoming more important in the face of increasing NA resistance. A limited number of clones are responsible for the epidemic PA. PFGE patterns SpeI01 and SpeI02 (or XbaI01), the main clones of the epidemics, are highly prevalent in Yuxi. PA was associated with fecal contaminations of well water, river water, and vegetable, as well as geographical regions. The PA was caused by eating raw vegetables washing with surface water which was polluted with PA patients and carriers. The distinct rates appear to be driven by a combination of different ecological and epidemiological determinants. The control of environment pollution is a radical strategy. Not only is PA a serious public-health problem, but also urbanization and ecological dynamics problems. Elucidate the underlying biological and ecological mechanisms on transmission chains, transmission nets, transmission modes, clonal expansion, transmission dynamics of PA; improve understanding of how paratyphoid fever A (re)emerge, and increase capacity to forecast outbreaks; development of paratyphoid fever A transmission theory, and ultimately the development of strategies to prevent or control PA. For containment of PA some creative strategies to prevent or control PA may be needed, because rural-urban migration could have resulted in inadequacy of sanitation and other basic infrastructure issues associated with population growth.
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