Intestinal carriage of Staphylococcus aureus: how does its frequency compare with that of nasal carriage and what is its clinical impact?
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- Acton, D.S., Tempelmans Plat-Sinnige, M.J., van Wamel, W. et al. Eur J Clin Microbiol Infect Dis (2009) 28: 115. doi:10.1007/s10096-008-0602-7
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The bacterial species Staphylococcus aureus, including its methicillin-resistant variant (MRSA), finds its primary ecological niche in the human nose, but is also able to colonize the intestines and the perineal region. Intestinal carriage has not been widely investigated despite its potential clinical impact. This review summarizes literature on the topic and sketches the current state of affairs from a microbiological and infectious diseases’ perspective. Major findings are that the average reported detection rate of intestinal carriage in healthy individuals and patients is 20% for S. aureus and 9% for MRSA, which is approximately half of that for nasal carriage. Nasal carriage seems to predispose to intestinal carriage, but sole intestinal carriage occurs relatively frequently and is observed in 1 out of 3 intestinal carriers, which provides a rationale to include intestinal screening for surveillance or in outbreak settings. Colonization of the intestinal tract with S. aureus at a young age occurs at a high frequency and may affect the host’s immune system. The frequency of intestinal carriage is generally underestimated and may significantly contribute to bacterial dissemination and subsequent risk of infections. Whether intestinal rather than nasal S. aureus carriage is a primary predictor for infections is still ill-defined.
Nasal colonization by Staphylococcus aureus is a well-established risk factor for acute cutaneous infections, post-operative infections, as well as most other types of S. aureus infections [1, 2, 3]. Several recent studies have suggested that lasting colonization of S. aureus in the human intestinal tract also occurs and that this may have important clinical implications. Still, compared to nasal carriage, gastro-intestinal colonization by S. aureus has been sparsely studied.
In the 1950s and 1960s, intestinal S. aureus carriage was first defined and studied as a potential cause of antibiotic-associated diarrhea (AAD) . However, after the identification of Clostridium difficile as the most common pathogen of hospital-acquired AAD in the 1970s , the role of gastro-intestinal colonization as a risk factor for (intestinal) S. aureus infection has been neglected for decades and the issue has only recently re-emerged. The pandemic rise in the incidence of methicillin-resistant S. aureus (MRSA) strains, as opposed to methicillin-sensitive S. aureus (MSSA), has contributed greatly to the renewed interest in intestinal S. aureus colonization. This covered investigations into risk factors for both AAD as well as health care-associated (HA) infections. Furthermore, community-acquired (CA) MRSA infection among individuals without “HA risk factors” was first recognized in the late 1990s. CA-MRSA is now emerging as an apparent epidemic. In recent studies, in addition to nasal carriage, rectal carriage of CA-MRSA has also been documented. In this review we will give an historical update and a systemic overview of the more recent studies related to intestinal and/or perineal carriage of S. aureus (MSSA, HA-MRSA, and CA-MRSA) and we will discuss its clinical implications.
Culture methods and definition of perineal and intestinal carriage
Techniques to determine carriage or colonization can be based on classical culture assays using selective broths or agars for MSSA, as well as novel growth-based phenotypic and molecular methods for both MSSA and MRSA detection . Methods used to define intestinal carriage include culture of stool, rectal swabs or anal swabs. Also, swabs from the perianal area (including the perineum and the groin or inguinal region) are generally accepted to define intestinal carriage. For these sites, however, it can be argued that these may also represent skin carriage. In a limited number of reports direct comparison of the frequency yields for these different sites of colonization within the same study have been presented. Rectal swabs were reported to have higher yields of S. aureus detection than stool cultures , but a more recent comparison  gave opposite results for MRSA. Other studies reported similar frequencies of carriage for both perianal and groin sites of carriage for nursing home residents and hospitalized patients respectively [9, 10]. Also, direct comparisons of the rectal and perineal sites gave similar frequencies of detection  and in another recent study screening of the perineal area, the rectum and the inguinal area gave similar frequencies of detection of MRSA , which legitimates the use of all of these sites to define intestinal carriage.
Intestinal carriage frequencies of S. aureus in adults
Frequencies of detection of S. aureus (including MRSA) with regard to intestinal and nasal carriage and intestinal carriage in the absence of nasal carriage in adults
Total number of patients screened
Intestinal carriage, percentage of total (n) or (n/total)
Nasal carriage, percentage of total (n) or (n/totala)
Intestinal carriage in the absence of nasal carriage, percentage of total (n/totala)
Intestinal carriage in the absence of nasal carriage, percentage of intestinal carriers (n/totala)
Mothers 1 week after delivery
Private SNF patients
ICU liver transplant patients
Intensive care patients
Liver transplant recipients
Nursing home residents
The prevalence of S. aureus colonization of the perineum was examined in a longitudinal study on 84 community-dwelling adults with spinal cord dysfunction . S. aureus was detected in 20 (24%) individuals. Nasal carriage was detected in 55% of all patients from a subset of 22 patients of whom 23% had intestinal carriage only. By follow-up of 30 patients with at least five cultures for 1 year, the perineal carriage pattern was assessed. They found that 10% had persistent carriage, 63% had intermittent carriage, and 27% were non-carriers, in agreement with nasal carriage patterns . Paired perineal/nasal carriage was determined for 22 participants. Of the 16 perineal carriers in this group, 5 did not have nasal carriage. Among the 11 with both perineal and nasal carriage, all but 1 carried the same spa type at both sites. Many similar studies were performed, the results of which are summarized in Table 2.
Obviously, compared with nasal carriage the intestinal carriage of S. aureus is less frequent, but still may have important clinical consequences.
Intestinal MRSA in adult patients at high risk
The MRSA intestinal carriage and nasal carriage detection frequencies in hospitalized adult patients at high risk
Total patients screened
Intestinal MRSA, percentage of total (n)
Nasal MRSA percentage of total (n/totala)
Interestingly, when frequencies of nasal and intestinal MRSA carriage are plotted and compared with those reported for S. aureus (Fig. 1) it seems that the incidence of carriage of MRSA is lower than that for S. aureus for both the nares and the intestines, which makes sense, since MRSA has been emerging and disseminating as a colonizing bacterium much more recently than S. aureus has. However, the slope of the regression of 0.53 for MRSA is the same as that determined for S. aureus (0.55), which indicates a similar relation between both sites of carriage for MRSA and suggests that antibiotic resistance does not influence the relative colonization ability for these two sites.
Distribution of MRSA detection sites
Distribution of intestinal and nasal carriage in all MRSA-colonized patients detected in the studies
Total MRSA cases
Intestinal MRSA, percentage of total (n)
Nasal MRSA, percentage of total (n/totala)
Intestinal without nasal, percentage of total (n)
Intestinal without nasal, percentage of intestinal carriers
General hospital patients, MRSA outbreak
General hospital patients, MRSA outbreak
Hospital MRSA outbreak
Private skilled nursing facility patients
Acute care patients
Acute rehabilitation unit SCI patients
Skilled care unit patients
Acute rehabilitation unit
General hospital, at risk patients
Neurosurgery unit patients
General hospital, at risk patients
University hospital, at risk patients
General hospital, at risk patients
General hospital, at risk patients
Community-dwelling SCD patients
ICU patients and other risk factors
Nursing home residents
In Table 4 the reported frequencies of intestinal MRSA carriage in the absence of nasal carriage are also summarized. For instance, in a study of an MRSA outbreak involving a total of 975 MRSA patients, perineal screening identified an additional 15% of culture-positive individuals compared with nasal screening only . In this study, the intestines were reported to be the only positive site out of five culture sites in 10% of the cases. Klotz and coworkers reported that in addition to a high frequency of 24% MRSA-positive stool cultures, 13% of the MRSA strains were first observed in the stool before detecting MRSA in other material from these patients . Similarly, in a large Canadian surveillance study , comprising more than 10,000 adult patients, the perineal area was found to be the initial site of MRSA colonization or infection in 41% of the cases. In patients older than 65 years of age, the perineum or rectum was the only positive site in 13%, indicating that nasal screening alone would be sub-optimal in elderly patients. More recently, Zhang et al.  reported that nasal screening alone would have detected 76% of MRSA carriers and that the inclusion of rectal screening increased the detection sensitivity to 96%, indicating 20% rectal carriers without nasal carriage. Reyes et al.  reported an intestinal carriage frequency without nasal carriage in 27% of their MRSA-positive patients, whereas Mody et al.  showed that 23% of their MRSA carriers were only colonized in the perianal area. Altogether, comparisons of rates of nasal and intestinal carriage of MRSA were recorded in 16 of the studies mentioned (Table 4). It can be calculated from these studies that of all MRSA colonized patients, 58% were colonized in the nares, whereas 45% were colonized in the intestines. Of the individuals with gastro-intestinal MRSA, 1 out of 3 (35%) did not carry MRSA in the nose. Of all MRSA-colonized individuals detected in these studies more than 1 out of 6 (18%) presented with intestinal carriage in the absence of nasal carriage. Such frequencies suggest that the intestines might be clinically relevant reservoirs of MRSA that should be taken into account during screening for such carriage during outbreak situations or when screening patients at risk.
Intestinal or perineal carriage as a risk factor for dissemination and infections
The perineum, as an area where S. aureus can colonize and multiply, was first recognized by Hare and Ridley , and heavy contamination from the perineum to the groin and upper parts of the thighs is often observed . Both intestinal and perineal carriage have been implicated as important contributors to environmental dissemination of S. aureus. Patients with intestinal colonization of S. aureus may serve as an important source of transmission, since they often contaminate the adjacent environment. Masaki et al.  performed a prospective culture survey to investigate a possible relationship between S. aureus types colonizing the rectum and respiratory tract and S. aureus types isolated from the environment. They simultaneously detected in both patients and the environment several S. aureus types. This indicates a potential route of contamination of the hospital environment. It was also reported that patients with intestinal and nasal colonization of S. aureus had higher frequencies of incontinence or diarrhea than patients without S. aureus colonization. This may significantly contribute to the observed trend toward increased contamination of environmental surfaces [44, 45]. The latter studies also substantiated that patients who have diarrheal stools and heavy gastro-intestinal colonization with MRSA are associated with significantly greater environmental MRSA contamination than patients without MRSA in their stools.
Data from early studies suggested an association between intestinal colonization and the occurrence of infections. For example, a study on recurrent furunculosis showed that 56% of the patients sampled had positive perineal cultures . This suggested intestinal S. aureus carriage to be an infection risk factor, although nasal carriage was not precisely assessed for those patients. Hospitalized patients who reported developing S. aureus lesions on the buttocks and lower half of the abdomen and back often had the causative strain isolated from the perineum as well . It was found that intensive care and liver transplant unit patients with both nasal and intestinal colonization had significantly increased rates of S. aureus infection of 40% compared with an infection rate of 18% in patients with nasal carriage without intestinal carriage . On the basis of these data it was concluded that rectal carriage represents a potential reservoir and simultaneous nasal and rectal carriage portended a greater risk of S. aureus infections than nasal carriage alone in ICU and liver transplant unit patients. The same authors also proposed that intestinal colonization could be associated with an increased frequency of colonization of skin sites, which was confirmed in later studies . It was found that patients with nasal and intestinal colonization were significantly more likely than those with nasal colonization only to have positive skin cultures. This group performed a prospective study involving 71 patients. The patients enrolled were divided into three groups: those without nasal or intestinal colonization, those with nasal colonization only, and those with both nasal and intestinal colonization. The development of S. aureus infections was significantly different among the three groups. Only 1 out of 32 patients without nasal or intestinal colonization developed an S. aureus infection. S. aureus infections developed more often in patients with stool colonization (8 out of 26) than in patients with only nasal colonization (2 out of 13). However, due to the small number of infected patients the power of this study was too limited to reach statistical significance. Significant differences in staphylococcal infection between patients with S. aureus in the stools and patients with negative stool cultures for S. aureus were documented . In an 8-month prospective study of inpatients known to have vancomycin-resistant enterococci (VRE) colonization, none of the 14 patients with stool cultures negative for S. aureus developed an S. aureus infection in the hospital. In contrast, more than half of S. aureus-colonized patients had an S. aureus infection documented.
Eradication of intestinal carriage
Given its relatively high incidence, prevention of or therapy for intestinal carriage should be clinically beneficial. However, most studies are focused on the elimination of nasal rather than intestinal carriage. Nasal carriage eradication with mupirocin ointment has been studied frequently (recently reviewed by Van Rijen et al. ) and is generally considered to be highly effective, at least in the short term. However, reacquisition of carriage may occur from extra-nasal sites. Dupeyron et al.  monitored mupirocin treatment of 86 patients and found treatment failure in 22. For this group, the stool carriage rate was significantly higher and stool carriage upon admission was independently associated with reacquisition of nasal carriage. Conflicting results regarding the effects of nasal carriage eradication on the prevalence of MSSA/MRSA infections have been reported. Some authors showed significantly decreased rates of nosocomial infections [52, 53], whereas others did not [54, 55].
Mupirocin treatment may only be marginally effective in the eradication of multi-site carriage and, therefore, therapies based upon combinations of nasal, skin, and intestinal carriage eradication methods have more recently been exploited. The use of oral rifampin, for treatment of intestinal carriage of S. aureus for various patient populations and healthy people was reviewed by Falagas et al. [56, 57]. Rifampin, however, showed limited success in MRSA elimination. More novel treatment modalities for intestinal MRSA elimination to control transmission or subsequent infections, e.g., using oral vancomycin, have been described merely in uncontrolled or observational studies. Oral vancomycin treatment results were reported that showed that the eradication of MRSA intestinal carriage by enteral vancomycin in subsets of adult ICU patients [58, 59, 60] as well as in pediatric patients [61, 62] was effective, but had limited effect on the prevention of transmission. The results from prospective controlled studies of intestinal MRSA decolonization are urgently awaited.
Colonization of the intestinal tract by S. aureus may have another important clinical implication. The co-existence of S. aureus and VRE was reported in more than 50% of the American patients studied . In this study, stool specimens were tested for VRE and S. aureus at enrollment (baseline) and weekly thereafter. Patients with at least three stool cultures were included in the study. Of the 37 patients who completed the study, all were colonized with VRE; 62% were colonized with S. aureus on at least one occasion, and 60% were colonized persistently. Patients with stool cultures positive for S. aureus were colonized with MRSA strains in 87% of all cases. Warren et al.  screened stools and rectal samples from 878 ICU patients for VRE and MRSA. Of 485 VRE-positive patients, 83 (17%) also had intestinal carriage of MRSA. Furuno et al.  reported that out of 57 patients with both nasal MRSA carriage and intestinal VRE, 23 (40%) also had intestinal carriage of MRSA. These studies suggest that the intestinal tract could provide an important reservoir for the emergence of vancomycin-resistant S. aureus (VRSA) isolates
The emergence of the rectal carriage of CA-MRSA has been documented in a study in which S. aureus was detected in 507 of 2,963 vaginal/rectal cultures from late pregnancy cases (17%) . Interestingly, 3% of the pregnant women had vaginal–rectal colonization of an epidemic CA-MRSA strain. A significant association between S. aureus colonization and Group B streptococcus (GBS) colonization was found. In a subsequent study this association was analyzed in more detail  and the significant association between MSSA and GBS was confirmed. Pregnant women with MSSA carriage were significantly more likely to have postpartum fever than those who were S. aureus-negative. Surprisingly, a significant negative association between CA-MRSA carriage and GBS carriage was observed. Apparently, when a certain bacterial species inhabits a given niche other species may not be able to colonize. In the case of the vaginal carriage of MRSA or MSSA such bacterial interference may lead to novel modes of intervention based on interference therapy of GBS once the microbial molecules involved have been identified.
Potential role of S. aureus in intestinal disease
How S. aureus causes intestinal infections is still ill-defined. The basic mechanisms are quite enigmatic and the etiological processes are just beginning to be identified. For instance, Froberg et al.  presented histo-pathological evidence for the existence of a specific S. aureus-induced pseudomembranous intestinal disease, distinct from that seen during C. difficile infection in an unusual case of simultaneous infection with C. difficile and MRSA. Whereas C. difficile induces colonic pseudomembranes, the MRSA infection induced loosely adherent pseudomembranes in the small bowel.
Intestinal carriage of S. aureus may impose a risk factor for intestinal infection. Antibiotic treatment can lead to the overgrowth of bacteria in the intestine and induce enteritis or AAD. The role of intestinal S. aureus as a causative agent for enteritis or AAD and as a risk factor for other infections gained renewed interest with the spreading of MRSA. MRSA has been suggested as a cause of AAD in hospitalized patients . In this study S. aureus was the only identified pathogenic micro-organism to cause AAD in 47 patients and the presence of staphylococcal enterotoxin A was strongly associated with the development of diarrhea. A German study reported intestinal carriage of S. aureus, in the absence of C. difficile in 8% of patients with AAD . Compelling evidence for the etiological role of MRSA in AAD was provided by excluding the involvement of C. difficile, numerous other bacterial pathogens and parasites, but also several enteric viruses in 11 patients with enterotoxin-producing MRSA intestinal carriage .
Intestinal S. aureus colonization and disease development in infants and young children
S.aureus intestinal carriage in infants
Hospitalized children up to 16 years
Also, in more recent Swedish studies [76, 77, 78, 79], high frequencies of intestinal S. aureus carriage during the first year of life were reported, and co-colonization of intestine and anterior nares with the same S. aureus strains, which were also found on the parents, suggested mother-to-child transmission. These studies were performed to test the hypothesis that development of allergic disease among children may be associated with differences in intestinal colonization patterns of S. aureus. Two-year-old allergic children from both Sweden and Estonia were reported to have significantly higher counts of S. aureus in the intestines than non-allergic children . In a prospective follow-up study, significantly increased S. aureus intestinal prevalence at 6 months of age was found in a group of allergic children compared with the non-allergic group. An interesting correlation between intestinal colonization with S. aureus at 2 and 4 weeks of age and the development of food allergy was observed by Lundell et al. . They also found a correlation between perinatal intestinal S. aureus colonization and expression levels of the soluble immune modulator CD14, but not the levels of CD83, and concluded that colonization with S. aureus might modulate the development of the neonatal immune system. This indicates an interrelatedness between factors involved in the host’s immune response, early colonization, and development of allergic disease. Adlerberth et al.  studied the hypothesis that infantile intestinal colonization patterns may influence sensitization to food allergens and atopic eczema. They analyzed a birth cohort of more than 300 infants from three European countries with regard to relations between intestinal colonization patterns during the first year and the development of atopic eczema and sensitization at 18 months of age. They reported a nearly significant association (p = 0.06) between early intestinal colonization with S. aureus and increased risk of atopic eczema. Kalliomaki et al.  recently observed that higher numbers of fecal S. aureus carriage at 6 and 12 months of age were associated with obesity in children.
Bisgaard et al. , who studied a Danish birth cohort of 411 infants, did not observe any correlation between neonatal airway colonization with S. aureus at 1 month of age and the development of childhood asthma. In contrast, for colonization with the classical otitis media bacteria S. pneumonia, M. catarrhalis and H. influenzae a significant association with increased persistent or acute wheezing and hospitalization for wheezing was observed. This seems to indicate a lack of influence of S. aureus colonization. However, since these studies were performed in a high-risk cohort, an alternative plausible interpretation of these data is that S. aureus to a greater extent than the other bacteria mentioned may modulate the neonatal immune system, and that the lower rates of wheezing associated with S. aureus colonization may actually reflect relative protection. This may be in line with observed differences in immune induction between gram-positive and gram-negative bacteria and the risk of childhood asthma . The potential involvement of S. aureus enterotoxins (SE) in allergic diseases in early childhood by following 510 children from birth to 5 years of age was studied by Semic-Jusufagic et al. . SE-mix-specific IgE, (SE-A, SE-C, and TSST-1) were measured to determine SE sensitization and correlated with atopic disease. Atopic children were nearly 4 times more SE-mix-sensitive than non-atopic children. Children with eczema were significantly more frequently SE-mix sensitized than children without and the SE-mix sensitization rate increased significantly with increasing eczema severity. SE-mix sensitization was also significantly associated with current wheezing. Furthermore, SE-mix-sensitized children with wheezing had significantly higher airway reactivity than wheezing children who were not sensitized to SE-mix, which suggests that enterotoxins from S. aureus might be potential modifiers of childhood wheezing and eczema.
Intestinal MRSA in infants and young children at risk
Paired analysis of nasal and intestinal colonization during separate outbreaks of MRSA in children and newborns has been reported in a limited number of studies. After identification of a single case of MRSA infection, 128 children from a child care center were assessed for MSSA/MRSA carriage by perianal, nasal, and throat swabs . This analysis identified an additional MRSA carrier only from the perianal swab, whereas the two other sites were negative. Singh et al.  found that during an MRSA outbreak at the neonatal intensive care unit of two hospitals, out of 373 infants analyzed, 24 were positive for MRSA. Of these, 7 (29%) had positive rectal cultures, of whom 1 (0.4%) was negative for nasal carriage. In 17 infants (71%) only the nasal culture was positive. Investigations during two MRSA outbreaks (one with a HA-MRSA and one with a CA-MRSA strain) were performed using paired nasal and intestinal screening . Altogether, 1,792 newborns were screened and 50 were MRSA-positive. In the first hospital, out of 25 infants positively screened, 17 (71%) had nasal carriage and 5 (21%) had carriage in the rectum, all of whom also had nasal carriage. In the second hospital, 18 out of 25 positively screened (72%) had nasal carriage and 15 out of 25 infants (60%) had rectal carriage, of whom 3 (12%) did not have nasal carriage. The use of surveillance cultures of throat and rectal swabs in a pediatric intensive care unit is important . Among 1,241 patients analyzed there were 29 MRSA carriers, of whom 14 (48%) had rectal carriage. Gustafsson et al.  described a study on MRSA carriage in 23 children adopted by Swedish families. Multiple swabs were taken from the perineum, nose, and other sites. MRSA was detected in 13 of the children. The perineum culture was positive at least once in 9 children (69%) and the nose was positive in 9 children (69%). Interestingly, 4 perineal MRSA carriers (31%) did not have nasal carriage.
Intestinal carriage of S. aureus occurs in a significant fraction of both healthy and diseased human individuals. For healthy adults and hospitalized adults at risk the incidence figure is 20%. For MRSA the average fraction of intestinal carriers amongst adult patients at risk is 9%. In young children the colonization of the intestines with S. aureus occurs at a very high frequency within the first 6 months of life, after which the frequency drops. For newborns and young children intestinal colonization with MRSA was detected in 1–2% of patients screened. This shows that the clinical impact of this phenomenon may be significant, which was corroborated in a number of studies that associated carriage and intestinal infection. Both MSSA and MRSA seem to successfully colonize the human intestines. This further emphasizes that care has to be taken: not only MSSA infections but also MRSA infection can result from intestinal carriage. Since MSSA and MRSA nasal carriage has been implicated to be a highly important risk factor for infections, the same will probably apply to intestinal carriage. Therefore, prospective controlled studies of intestinal carriage as a predictor of clinical infection need to be performed to determine the significance of this site of colonization. Prolonged intestinal carriage, also among personnel, can be an important factor in the persistence of MRSA outbreaks in hospitals and can be a source of environmental contamination. The development of rapid molecular detection methods for MRSA carriage facilitates prophylaxis . Nasally applied mupirocin very effectively eliminates nasal carriage and results in significant reductions in S. aureus infection rates. Mupirocin seems less effective for the elimination of intestinal carriage or other extra-nasal sites. Therefore, application of combined strategies, involving mupirocin in combination with oral antibiotics or other selective intestinal decontamination regiments, such as novel therapies based on polyclonal antibodies , may be more effective in cases of proven nasal and intestinal carriage. Because of the significant frequencies of intestinal carriage reported in a wide variety of patient groups and in healthy people it is recommended, in addition to nasal screening, to also include intestinal or perianal screening during surveillance.
Little is known on the age-related kinetics of intestinal carriage, but S. aureus seems to colonize the intestine of healthy newborns from very early in life onwards, and can be involved in the development of neonatal infectious disease. Later in life, intestinal carriage frequencies seem to drop. In concordance with nasal carriage, non-, intermittent and persistent intestinal carriage need to be defined in more detail. It is, therefore, of importance to determine whether specific variants of S. aureus are more proficient colonizers than others and which adhesion and virulence factors play a role in the transition from intestinal colonization to infection. Even more importantly, little is known on the environmental, bacteriological and physiological determinants of intestinal carriage. Preliminary data identify intestinal carriage as an infection risk factor and results from cohort studies suggest that there is interrelatedness among early intestinal colonization of S. aureus, the host’s immune system, and the development of disease later in life. Additional research, however, will be needed to fully appreciate the importance of intestinal S. aureus colonization in association with infection.
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