Cronobacter Support
06-23-2009, 10:24 AM
2. EPIDEMIOLOGY AND PUBLIC HEALTH ASPECTS
2.1 ORGANISMS OF CONCERN
2.1.1 Enterobacter sakazakii
Enterobacter sakazakii is a gram-negative, non-spore-forming bacterium belonging to the Enterobacteriaceae family. On occasion, it has been associated with sporadic cases or small outbreaks of sepsis, meningitis, cerebritis and necrotizing enterocolitis. While E. sakazakii has caused disease in all age groups, the focus of this meeting was on cases that are reported in infants under 28 days old. Although incomplete, the published data on these infants indicate that approximately half of them had a birth weight of less than 2 000 g, and two-thirds were premature, being born at less than 37 weeks gestation. It is also likely that immunocompromised or medically debilitated infants are more susceptible to infections with E. sakazakii. The pattern of disease in term infants is less clear, with some having a major congenital abnormality (e.g. neural tube defects and Trisomy 21 [Down syndrome]), while others have no reported evidence of a compromised host defence, yet have been afflicted with E. sakazakii sepsis or meningitis (Lai, 2001). E. sakazakii bacteraemia has also been identified among older infants and infants at home (CDC, unpublished data). In addition, asymptomatic infants have been identified with E. sakazakii in their stools or urine (Biering et al., 1989; CDC, 2002; Block et al., 2002) and stool carriage has been demonstrated for up to 18 weeks (Block et al., 2002).
Mortality rates from E. sakazakii infection have been reported to be as high as 50 percent or more, but this figure has declined to under 20 percent in recent years. Significant morbidity in the form of neurological deficits can result from infection, especially among those with bacterial meningitis and cerebritis. While the disease is usually responsive to antibiotic therapy, a number of authors have reported increasing antibiotic resistance to drugs commonly used for initial treatment of suspected Enterobacter infection. Reports have also been made of β-lactamases and cephalosporinases from E. sakazakii (Pitout et al., 1997). Long-term neurologic sequelae are well recognized (Lai, 2001; Clark et al., 1990).
While the reservoir for E. sakazakii is unknown in many cases, a growing number of reports have established powdered infant formula as the source and vehicle of infection (Biering et al., 1989; Simmons et al., 1989; Van Acker et al., 2001; CDC, 2002). In several investigations of outbreaks of E. sakazakii infection that occurred among neonates in neonatal intensive care units, investigators were able to show both statistical and microbiological association between infection and powdered infant formula consumption (Simmons et al., 1989; Van Acker et al., 2001; CDC, 2002). These investigations included cohort studies which implicated infant formula consumed by the infected infants. In addition, there was no evidence of infant-to-infant or environmental transmission; all cases had consumed the implicated formula (Simmons et al., 1989; Van Acker et al., 2001; CDC, 2002). The formula consumed by infected infants in each of these outbreaks yielded E. sakazakii; in two outbreaks, formula from previously unopened cans from the same manufacturing batch also yielded E. sakazakii. A combination of typing methods (plasmid analysis, antibiograms, chromosomal restriction fragment analysis, ribotyping, multilocus enzyme electrophoresis) were used to evaluate the isolates from each outbreak as to their relatedness. Though the typing methods differed, the isolates among cases and those obtained from the implicated formula shared the same typing pattern in each of these investigations.
In addition, the stomach of newborns, especially of premature babies, is less acidic than that of adults: a possible important factor contributing to the survival of an infection with E. sakazakii in infants. The frequency of intrinsic E. sakazakii contamination in powdered infant formula is of concern, even though intrinsic concentration levels of E. sakazakii appear to be typically very low.
In a study of the prevalence of E. sakazakii contamination in 141 powdered infant formulas, 20 were found culture-positive, yet all met the microbiological specifications for coliform counts in powdered infant formula (<3 cfu/g) of the current Codex code (Van Acker et al., 2001; Muytjens, Roelofs-Willemse, and Jasper, 1988). Such formula has been linked to outbreaks (Van Acker et al., 2001). Furthermore, outbreaks have occurred in which the investigators have failed to identify lapses in formula preparation procedures (Van Acker et al., 2001; CDC, 2002). Thus, it seems that neither high levels of contamination nor lapses in preparation hygiene are necessary to cause infection from E. sakazakii in powdered infant formula. While it can be assumed that lapses in preparation hygiene or extended holding at non-refrigerated temperatures could lead to increases in the levels of contamination at the time of consumption, it is not possible to assess the contribution that these factors have on the cases of infection that have been associated with powdered infant formula that contained low levels of E. sakazakii. Thus it must be currently assumed that low levels of E. sakazakii in infant formula (<3 cfu/100 g) can lead to infections.
Formula preparation equipment contaminated by E. sakazakii has been demonstrated to have caused two outbreaks (Noriega et al., 1990; Block et al., 2002), but the original source of E. sakazakii was not determined in either case. Environmental swabbing of formula preparation areas in the course of outbreak investigations has not demonstrated E. sakazakii in the general environment. E. sakazakii has been identified in the environments of milk powder production facilities and other food production facilities, as well as in households (Kandhai, Reij, and Gorris, 2004). Not all infants with E. sakazakii infection have been exposed to powdered infant formula, and E. sakazakii infections can also occur in adults (Lai, 2001). Thus, although an environmental source of E. sakazakii infection other than infant formula has not been strictly identified, other sources undoubtedly exist. The relative contribution of powdered infant formula sources and other sources to the burden of E. sakazakii disease is unknown.
There is very little known about virulence factors and pathogenicity of E. sakazakii. The work done by Pagotto et al. (2003) was the first describing putative virulence factors for E. sakazakii. Enterotoxin-like compounds were produced by some strains. Using tissue cultures, some strains produced a cytotoxic effect. Two strains (out of 18 isolates) were capable of causing death in suckling mice by the peroral route. Therefore, there appear to be differences in virulence among E. sakazakii strains, and some strains may be non-pathogenic. Brain abscesses due to E. sakazakii and the related bacterium (Citrobacter koseri) are morphologically similar and may be due to similar virulence mechanisms (Kline, 1988).
Posted from ftp.fao.org/docrep/fao/007/y5502e/y5502e00.pdf
2.1 ORGANISMS OF CONCERN
2.1.1 Enterobacter sakazakii
Enterobacter sakazakii is a gram-negative, non-spore-forming bacterium belonging to the Enterobacteriaceae family. On occasion, it has been associated with sporadic cases or small outbreaks of sepsis, meningitis, cerebritis and necrotizing enterocolitis. While E. sakazakii has caused disease in all age groups, the focus of this meeting was on cases that are reported in infants under 28 days old. Although incomplete, the published data on these infants indicate that approximately half of them had a birth weight of less than 2 000 g, and two-thirds were premature, being born at less than 37 weeks gestation. It is also likely that immunocompromised or medically debilitated infants are more susceptible to infections with E. sakazakii. The pattern of disease in term infants is less clear, with some having a major congenital abnormality (e.g. neural tube defects and Trisomy 21 [Down syndrome]), while others have no reported evidence of a compromised host defence, yet have been afflicted with E. sakazakii sepsis or meningitis (Lai, 2001). E. sakazakii bacteraemia has also been identified among older infants and infants at home (CDC, unpublished data). In addition, asymptomatic infants have been identified with E. sakazakii in their stools or urine (Biering et al., 1989; CDC, 2002; Block et al., 2002) and stool carriage has been demonstrated for up to 18 weeks (Block et al., 2002).
Mortality rates from E. sakazakii infection have been reported to be as high as 50 percent or more, but this figure has declined to under 20 percent in recent years. Significant morbidity in the form of neurological deficits can result from infection, especially among those with bacterial meningitis and cerebritis. While the disease is usually responsive to antibiotic therapy, a number of authors have reported increasing antibiotic resistance to drugs commonly used for initial treatment of suspected Enterobacter infection. Reports have also been made of β-lactamases and cephalosporinases from E. sakazakii (Pitout et al., 1997). Long-term neurologic sequelae are well recognized (Lai, 2001; Clark et al., 1990).
While the reservoir for E. sakazakii is unknown in many cases, a growing number of reports have established powdered infant formula as the source and vehicle of infection (Biering et al., 1989; Simmons et al., 1989; Van Acker et al., 2001; CDC, 2002). In several investigations of outbreaks of E. sakazakii infection that occurred among neonates in neonatal intensive care units, investigators were able to show both statistical and microbiological association between infection and powdered infant formula consumption (Simmons et al., 1989; Van Acker et al., 2001; CDC, 2002). These investigations included cohort studies which implicated infant formula consumed by the infected infants. In addition, there was no evidence of infant-to-infant or environmental transmission; all cases had consumed the implicated formula (Simmons et al., 1989; Van Acker et al., 2001; CDC, 2002). The formula consumed by infected infants in each of these outbreaks yielded E. sakazakii; in two outbreaks, formula from previously unopened cans from the same manufacturing batch also yielded E. sakazakii. A combination of typing methods (plasmid analysis, antibiograms, chromosomal restriction fragment analysis, ribotyping, multilocus enzyme electrophoresis) were used to evaluate the isolates from each outbreak as to their relatedness. Though the typing methods differed, the isolates among cases and those obtained from the implicated formula shared the same typing pattern in each of these investigations.
In addition, the stomach of newborns, especially of premature babies, is less acidic than that of adults: a possible important factor contributing to the survival of an infection with E. sakazakii in infants. The frequency of intrinsic E. sakazakii contamination in powdered infant formula is of concern, even though intrinsic concentration levels of E. sakazakii appear to be typically very low.
In a study of the prevalence of E. sakazakii contamination in 141 powdered infant formulas, 20 were found culture-positive, yet all met the microbiological specifications for coliform counts in powdered infant formula (<3 cfu/g) of the current Codex code (Van Acker et al., 2001; Muytjens, Roelofs-Willemse, and Jasper, 1988). Such formula has been linked to outbreaks (Van Acker et al., 2001). Furthermore, outbreaks have occurred in which the investigators have failed to identify lapses in formula preparation procedures (Van Acker et al., 2001; CDC, 2002). Thus, it seems that neither high levels of contamination nor lapses in preparation hygiene are necessary to cause infection from E. sakazakii in powdered infant formula. While it can be assumed that lapses in preparation hygiene or extended holding at non-refrigerated temperatures could lead to increases in the levels of contamination at the time of consumption, it is not possible to assess the contribution that these factors have on the cases of infection that have been associated with powdered infant formula that contained low levels of E. sakazakii. Thus it must be currently assumed that low levels of E. sakazakii in infant formula (<3 cfu/100 g) can lead to infections.
Formula preparation equipment contaminated by E. sakazakii has been demonstrated to have caused two outbreaks (Noriega et al., 1990; Block et al., 2002), but the original source of E. sakazakii was not determined in either case. Environmental swabbing of formula preparation areas in the course of outbreak investigations has not demonstrated E. sakazakii in the general environment. E. sakazakii has been identified in the environments of milk powder production facilities and other food production facilities, as well as in households (Kandhai, Reij, and Gorris, 2004). Not all infants with E. sakazakii infection have been exposed to powdered infant formula, and E. sakazakii infections can also occur in adults (Lai, 2001). Thus, although an environmental source of E. sakazakii infection other than infant formula has not been strictly identified, other sources undoubtedly exist. The relative contribution of powdered infant formula sources and other sources to the burden of E. sakazakii disease is unknown.
There is very little known about virulence factors and pathogenicity of E. sakazakii. The work done by Pagotto et al. (2003) was the first describing putative virulence factors for E. sakazakii. Enterotoxin-like compounds were produced by some strains. Using tissue cultures, some strains produced a cytotoxic effect. Two strains (out of 18 isolates) were capable of causing death in suckling mice by the peroral route. Therefore, there appear to be differences in virulence among E. sakazakii strains, and some strains may be non-pathogenic. Brain abscesses due to E. sakazakii and the related bacterium (Citrobacter koseri) are morphologically similar and may be due to similar virulence mechanisms (Kline, 1988).
Posted from ftp.fao.org/docrep/fao/007/y5502e/y5502e00.pdf