Antibiotic Resistance and Wastewater - Correlation, Impact and Critical Human Health Challenges
Antibiotic Resistance and Wastewater - Correlation, Impact and Critical Human Health Challenges
A R T I C L E I N F O A B S T R A C T
Keywords: The spread of bacterial antibiotic resistance (due to over and non-judicious use of antibiotics) is an apprehensive
Antibiotic over-use subjects matter and the role of wastewater treatment plants has been attracting particular interest. These stations
Antibiotic resistance bacteria are a reservoir of resistant bacteria, and the amount of bacteria released into the environment is very high and
Water pollution dangerous. The reuse of treated wastewater for irrigation is a practical solution for surmounting scarcity of
Wastewater treatment
water, but there are several health-related and environmental risks associated with this practice. It may increase
Health hazardous
antibiotic resistance (AR) levels in soil and water. Wastewater treatment plant effluents have been recognised as
significant environmental AR reservoirs due to selective pressure generated by antibiotics that are frequently
discharged in water. It also enhanced the possibility of horizontal gene transfer by increasing the abundance of
the resistance gene. This review focuses on the emergence of antibiotic resistance in waste water, waste water
treatment, challenges and their impact on human health. Based on the current state of the art, we conclude that
the improvements in wastewater treatment technologies are required that not only remove solids, organic
matter, and nutrients but also they could remove AR element and bacteria.
⁎
Corresponding author at: Department of Chemical Engineering National Institute of Technology Raipur, Chhattisgarh, 492010, India.
E-mail address: [email protected] (D. Pal).
https://doi.org/10.1016/j.jece.2017.11.059
Received 15 September 2017; Received in revised form 18 November 2017; Accepted 21 November 2017
Available online 22 November 2017
2213-3437/ © 2017 Elsevier Ltd. All rights reserved.
A. Kumar, D. Pal Journal of Environmental Chemical Engineering 6 (2018) 52–58
hotels, and residential care facilities) and commercial facilities (in- than sewage sludge or soil due to low movement of bacteria in both
cluding hospitals) are known contributors of antibiotics to municipal soils and sediments as compared to the free water phase. Besides, it has
wastewater [12]. been reported that antibiotics emanated from its production plants
The development of antibiotic-resistant bacteria has poses an in- ranges to several mg/L and may contribute significantly; however, it
creasing concern. The widespread and often inappropriate administra- was considered of less concern [24,25]. It is worth to mention here that,
tion of antibiotics in livestock, pets, and humans has been shown to in contrast to general expectation, hospitals are not the main source of
result in the development of antibiotic-resistant bacteria and is gen- pharmaceuticals in municipal sewage [26,27]. Now a day’s to promote
erally accepted to be a primary pathway for their proliferation in the the growth or for the prevention or therapy of animal, antibiotics are
environment. There is further concern that antibiotic-resistant bacteria used in modern breeding and fattening to achieve a lower percentage of
might develop from long-term environmental exposure to low con- fat and higher protein content in the meat [28]. Some antibiotics are
centrations of antibiotics (ng/L–μg/ L), such as those present in was- used in bee-keeping and for other purposes such as streptomycins are
tewater and surface water. One study has shown the increased pre- being used for growing fruits. The main purpose of antibiotics use in
valence of antibiotic-resistant Acinetobacter spp. in sewers receiving aquaculture is therapeutic and also as a prophylactic agent. Antibiotics
hospital and pharmaceutical plant wastewater effluent [13]. Genotoxic such as oxytetracycline, florfenicol, premix, sarafloxacin, erythromycin,
substances are often mutagenic and carcinogenic and are, therefore, the sulphonamides are commonly used in aquaculture [29,30]. In has been
potential suspect in the development of antibiotic resistant organisms. noted that, selection of resistance in pathogenic bacteria may arise even
Although several studies have detected the occurrence of antibiotics in due to low amounts of antibiotics.
hospital effluent [12,13], little is known about their persistence in
conventional wastewater treatment processes or their fate or effects in 3. Wastewater treatment and reuse
the environment [14]. The resistant organisms may enter into human
bodies directly or indirectly, and the resistance genes are distributed in Wastewater treatment is conventionally a combination of a primary,
various environmental media and disseminated widely by horizontal secondary and infrequently a tertiary process. Each treatment stage
gene transfer mechanism in the environment [15]. Discharged factors consists of different biological and physicochemical processes. Primary
in waste water, such as gene cassettes, integrons, plasmids, and heavy treatment is generally common in most of the treatment plants and
metals, play important roles in the exchange of resistance and con- mainly consists of filtration and sedimentation with primary objective
tribute to resistance retention [16]. Therefore, the focus of research is to remove the solid content of the wastewater (oils & fats, sand, and
should be shifted on the study that will have significant implications for settleable solids etc) [31]. Whereas the main purpose of secondary
the elimination of antibiotics from the environment. Effective ap- treatment is to remove organic matter (nutrients) with aerobic or
proaches (additional treatment steps, downstream of conventional anaerobic systems through the biological process such as membrane
biological process, such as membrane processes [17], adsorptive bioreactors, moving bed biofilm reactor, or fixed bed bioreactors etc;
treatment processes [18], advanced oxidation processes [19], and the most common being the conventional activated sludge. In the plants
combined ones [20]) have been suggested to limit/eliminate the oc- based on activated sludge, for the growth of biological floc dissolved
currence of antibiotics and multi-drug resistant bacteria in the aquatic oxygen is utilized, that substantially removes the organic material and
environment and to monitor their concentration properly. This review nitrogen. Tertiary wastewater treatment processes can be applied at the
compiles useful information on various sources for antibiotics, waste- last stage for the precipitation of phosphorus on a filter [32]. Disin-
water treatment techniques to remove antibiotics, antibiotic resistance fectant such as chlorine, UV radiation, and ozonization is also applied
in waste water and its impact on public health and mechanism of an- in few cases for the wastewater disinfection processes before its release
tibiotic resistance and prevention of its spread. into the environment.
Traditionally, antibiotics are being used since the 50 s to control During the biological treatment, antibiotics removal and modifica-
certain bacterial diseases of valuable flora & fauna such as apple, pear, tion can be biotic (mainly bacterial and fungal biodegradation) and
and related ornamental trees. Even today use of streptomycin with abiotic (e.g. sorption, hydrolysis, homo or hetro photolysis). Sorption
oxytetracycline is very common. Numerous antibiotic of different types on the sewage sludge and their degradation or transformation during
is being used with world-wide estimated consumption ranging from 0.1 the treatment is the main mechanism involved in removal of antibiotics.
to 0.2 million ton per annum [21]. It has been estimated that (in the For few cases hydrolysis is the key step, whereas, photolysis is less
USA) half of the antimicrobials use is for humans and rest is for animals, common due to low light exposure of the substances during wastewater
agriculture and aquaculture mainly to promote the growth of cattle, treatment. Hydrophobic (or non-polar) antibiotic residues have a
hogs, and poultry [22]. Extensive use of antibiotics is prevalent both as greater affinity to solids and thus, remain concentrated in the organic-
human and veterinary medicine, in addition, to plant agriculture and rich sewage sludge [33]. For the removal of antibiotics from aqueous
aquaculture for treating microbial infections and for prophylaxis. It is solutions, techniques such as polar hydrophilic interactions, complex
also found that ß-lactam antibiotics, including the sub-groups of peni- formation with metal ions, and ion exchange may be employed
cillins, cephalosporins, carbapenems, and others make up the largest [34].Generally, sludge sorption constants, Kd (L/kg) is used as the
share (50–70%) of total human antibiotic consumption. Moreover, ex- measure of the affinity of antibiotics sorbed to sludge. Higher sorption
cretion rates for the unchanged active compound cover a broad range of to sludge is marked by the higher Kd values [35].According to Rogers
10–90%., with an average metabolic rate estimated to be 30% [23], (1996) sorption potential of organic contaminants could be estimated
that is seventy percent is excreted unchanged into waste water. In using octanol-water partition coefficient (KOW) an can be classified as:
general, the high water solubility of metabolites as compared to parent (i) low sorption potential (logKOW < 2.5, such as sulfonamides, tet-
compounds causes their excretion with urine. Nevertheless, formed racyclines, aminoglycosides etc.), (ii) medium sorption potential
metabolites may be more toxic to humans as compared to the parent (2.5 < logKOW < 4.0, such as macrolides, b-lactams etc.), and (iii)
compound. high sorption potential (logKOW > n4.0, like glycopeptides)
In view of precise risk assessment antibiotics of natural origin is [36].Nonetheless, antibiotics mainly remain in the aqueous phase of the
highly crucial. Soil bacteria may produce different antibiotics like wastewater by virtue of their hydrophilicity and biological resistance.
aminoglycosides, streptomycins ß-lactams etc. In addition, the free In the wastewater treatment, influential operational parameters for the
water phase also contains bacteria, though the concentration is lower removal of antibiotic from biological residues are, (i) biochemical
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A. Kumar, D. Pal Journal of Environmental Chemical Engineering 6 (2018) 52–58
oxygen demand (ii) hydraulic retention time (iii) sludge retention time 3.4. Advanced oxidation processes (AOPs)
(iv) anoxic and anaerobic compartment size (v) mixed liquor suspended
solids (vi) suspended solids (vii) food-microorganism ratio (viii) tem- Advanced oxidation processes (AOPs) have emerged as an efficient
perature, and (ix) pH [37,38]. Thus, in wastewater treatment complete and novel method for the removal of antibiotics from wastewater ef-
elimination of antibiotics cannot be achieved by employing biological fluents [49,50]. AOPs primarily rely on the use of generated short-lived
treatment alone [31]. Therefore, alternative post-treatment is essential species, the hydroxyl radical (OH%) [51]. Organic matter is oxidized
for further elimination of contaminants present in wastewater effluents and mineralized by powerful oxidizing agent, hydroxyl radical [52].
to avoid harmful human exposure to living beings. Alternative techni- The effectiveness of oxidative processes for degrading antibiotics de-
ques often used for the removal of antibiotics from wastewater such as pends on the specific water matrix though; such effects on antibiotics
membrane process, adsorption, and advanced oxidation processes removal are not well established. For instance, the presence of nitrates,
(AOPs) have been presented in the subsequent sub-sections. carbonates and dissolved organic, may reduce the effectiveness of the
AOP method applied, by interfering with the chosen antibiotic. The
existence of different production routes of radicals OH* make AOPs a
3.2. Membrane processes versatile treatment method. AOPs such as UV-radiation photolysis;
combinations of H2O2, O3 and UV-radiation; Fenton reagent based
Elimination of antibiotics by means of membrane processes takes homo-photocatalysis, hetro-photocatalysis (based on semiconductor
place via various mechanisms simultaneously. Strong hydrogen- materials like TiO2), and sonolysis under UV radiation, have been
bonding (or hydrophobic) antibiotics adsorption occurs on membranes widely evaluated and reported [31,53].
at early filtration step. In other cases, removal of uncharged solutes
takes place through steric effects or combined steric and electrostatic 4. Antibiotic resistance in waste water and its impact on public
effects for charged solutes. According to Le-Minh et al., actual me- health
chanisms is dependent on the solution (ionic strength, pH), physico-
chemical properties of compound (hydrophobicity & hydrophilicity, Rigorous use of antibiotics a since long time in human/animal
molecular weight cut-off, pKa), and characteristics of the membrane therapy and livestock is resulting in serious environmental and public
(surface morphology, pore size, material) [33]. During wastewater health problems. It is due to the increasing concentration of antibiotic
treatment, lower membrane pore size in nanofiltration (NF, 0.001 mm) residues in wastewaters and ultimately the development of antibiotic-
and reverse osmosis (RO, < 0.001 mm) are quite suitable to effectively resistance in bacteria. Antibiotics are highly applicable drugs till date
remove the pharmaceuticals (antibiotics) having low-molecular-weight that are used in the prevention and treatment of microbial infections in
[31]. Removal (as high as 90%) has been reported for various anti- humans and other animals [54]. When bacteria are attacked by anti-
biotics such as tetracyclines, sulfonamides, quinolones, and trimetho- biotics in wastewater, they use these tactics to combat the drugs and to
prim [38,39]. A study undertaken by Zhang et al. (2006) reported more develop resistance not only against single drug but also against multiple
than 99% removal efficiency for amoxicillin from wastewater, using RO antibiotics and those bacteria is known as multidrug resistant bacteria.
[40]. To achieve an overall enhanced performance (up to 99%) of the Due to long term presence of these components in most water systems
treatment processes; the combined approach of MBR and NF/RO and pressures selection at sub-inhibitory concentrations of various an-
membrane filtration has ample potential to be explored for removal of tibiotics upon microorganisms, resulting in the development of anti-
antibiotics [41,42]. biotic resistance genes (ARG) in bacteria which is known as antibiotic-
resistant bacteria (ARB) [55]. Waste of hospitals are major source and
path of vast antibiotic-resistant bacteria spectrum contributes to waste
3.3. Adsorptive treatment water/sludge and ultimately waste water treatment plants and thus
contaminating surface water/groundwater and agricultural soil. Safety
It has been established that adsorption consists of following sub- measures issue before hospital waste discharge and reliable testing of
sequent steps: (a) solute (adsorbate) transport in the bulk (adsorbent) discharge samples must be employed to detect the contents of resistant
(b) film diffusion (transport of adsorbate) (c) pores diffusion, and (d) bacterial strains and antimicrobial residue/agents in order to adopt
adsorptive interaction [43]. Le-Minh et al. have studied the use of ac- necessary control measures. Effective disinfection is one of the most
tivated carbon for removing hydrophobic and charged pharmaceuticals important parts to prevent dissemination of ARB [55]. According to
from water [33]. During activated carbon adsorptive treatment effec- Exner et al., there is no risk of emergence of ARB provided disinfectants
tiveness of the removal is influenced by the properties of the adsorbent are used in the correct dosage, except for few disinfectants like triclosan
(such as porosity, specific surface area, physical shape, and polarity of and quaternary ammonium compounds. They are the active agents and
the surface), as well as on the characteristics of the compound (namely; suspected to trigger resistance, especially when used in sub-lethal
charge, hydrophobicity shape, and size). Furthermore, in addition to doses. They probably cause outer membrane damage in gram-negative
the pH, temperature and the presence of other species in the solution, bacteria and finally cause killing of the microbes. This finding shows
efficiencies of sorption on to activated carbon are highly dependent on that continuous research and development in disinfection is also es-
the initial concentrations of selected antibiotics [44]. In the adsorption sential to eliminate ARB from waste discharge.
process of antibiotics by activated carbon, van der Waals interactions Antibiotics are daily discharged by living beings into the environ-
(dispersive interactions) seem to play a major role. Nevertheless, it is ment through faeces and urine. It is a mixture of partially metabolized
the electrostatic interactions of ionic antibiotics (polar) with the surface bioactive compounds and unchanged xenobiotic compounds by humans
charge of activated carbon, which is critical for adsorptive removal and animals. This antibiotic release is the major contributor to this
[45]. Mostly, for the removal of antibiotics from wastewater treatment, problem in the network of municipal sewers, sewage sludge, and the
biological treatment followed by a powdered activated carbon treat- soil. The municipal wastewater contains high levels of inorganic and
ment has been utilized [46,47]. More than 94% removal of amoxicillin organic matter and also contains high concentrations of microorgan-
from wastewater was claimed using activated carbon by Putra et al. isms (including commensal, pathogenic, and environmental bacteria)
[48]. It was found that during treatment of wastewater effluents, the and adapted to the growth and spread of antibiotic resistances [56,57].
adsorption efficiency of activated carbon for antibiotics and other micro Waste water treatment plant receives these things and it is a potential
pollutants decreases due to the presence of dissolved organic matter in hot spot for promoting the spread of antibiotic resistance. Therefore,
wastewater matrix [45]. the wastewater treatment plant is the meeting point of most of ARB,
particularly in those with activated sludge or percolator biological
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A. Kumar, D. Pal Journal of Environmental Chemical Engineering 6 (2018) 52–58
filters for the biological treatment. It acts as an important reservoir of would pose a risk to public health and further research is needed on this
Enterobacteriaceae carrying ARG genes and they contribute to its subject. Along with the ecological concern, there is a growing interest
transfer. At these locations, bacterial density is very high, and due to of research about the potential public health impacts due to the pre-
selective pressure for resistance and increased availability of nutrients; sence of ARB and ARGs in the waste water. Studies reported an increase
the horizontal ARG transfer to the newly arrived bacterial population in antibiotic resistance pathogenic bacterial strains with one or more
takes place which favours the increase of bacterial resistance and un- antibiotics might be transferred from the environment to humans
controlled discharge of untreated urban waste contributed to an overall [62,63]. Water treatment plants can offer conducive conditions to es-
increase of ARB and ARGs in the environment [57–59]. Some recent tablishment and propagation of ARB. Diseases and death caused by
studies showed higher percentages of multiresistant bacteria in the ef- resistant bacteria are increasing day bay day. ARB and ARGs growth
fluent than in the affluent of treated wastewater [56,59] and concluded can increase the chances of human pathogens for acquiring resistance.
that once antibiotics enter the ecosystems, they have been raised about The spread of resistance genes in ecosystems can challenge the popu-
the potential impact of their remnants in the aquatic environment. lation dynamics. The growth and release of bacteria enriched in re-
Therefore, removal of ARB from the aquatic ecosystem is urgently re- sistance elements increase the possibility of acquiringresistance de-
quired because microbial contamination remains one of the major terminants by human-linked bacteria [59,64]. Bacteria resistant to
threats to public health. antibiotics have been found downstream waste water treatment plant,
Waste water treatment determines a significant reduction in the multi-resistance genes was found in drinking water, and multi-resistant
bacterial numbers, including the total numbers of resistant bacteria but Salmonella were present in water sprayed on vegetables in developing
differences in treatment plant designs and their operation may influ- countries [65,66]. Multi-resistant enterohaemorrhagic E. coli epidemic
ence the fate of ARB and ARGs in wastewater. Even after the treatment was reported in Europe, which was originated from water sprayed ve-
process of waste water, microbial growth and health risks still exist. getables [67]. High concentration of antibiotics and large amounts of
Some studies reported that bacteria in drinking water are able to pro- bacteria in waste water is a major concern facing modern medicine and
liferate in distribution system pipes after chlorination [59,60]. Chlor- consequently, all the multidrug resistance phenotypes impose further
ination initially lowered the total number of bacteria may have sub- limitations on the therapeutic options. The wastewater treatment,
stantially increased the proportion of antibiotic-resistant bacteria. aiming the removal of ARB and ARG contaminants from the effluent
Huang et al. [61], have examined the effect of chlorination on anti- and consequently the mitigation of potential negative impacts on other
biotic-resistant bacteria in the secondary effluents of a waste water water resources, is, therefore, a crucial point for the management of the
treatment plant and they advocated that reactivation of antibiotic-re- environment. The choice of the type of waste water treatment to be
sistant bacteria occurred, specially, for chloramphenicol, ampicillin, used will depend on the nature of the wastewater and their final use.
and penicillin-resistant bacteria, whereas the reactivation of chlor- The improvement in wastewater treatment technologies and un-
amphenicol-resistant bacteria exceeded 50%. The increase in the ARB necessary use of antibiotics are also needed to overcome the threat of
content could be due to many reasons, including an increase of anti- ARB infection (Fig. 1). Efforts to slow the spread of antibiotic resistance
biotic-resistant bacteria or a decrease of antibiotic-sensitive bacteria in should ideally focus on ARGs, as well as the antibiotics that select for
the bacterial population of the effluent. It also depends on the type of them. The waste water treatment plant design has been mastered for
antibiotic resistance or on the dose of chlorination. Therefore, the risk the removal of solids, organic matter, and nutrients, but they will have
of ARB prevalence in treated water still exists and it is not clear whether to be designed for removal of antibiotics and ARB. Yet little is known
re-growth or reactivation of ARB is a common phenomenon but it about effective treatment and removal of ARB and ARG. Researchers
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A. Kumar, D. Pal Journal of Environmental Chemical Engineering 6 (2018) 52–58
have to fill the key knowledge gaps in this area and enhance the re- antibiotics in aquaculture, and in the treatment of human infection
search needs. There are many problems that still remain to be solved, enters in the food chain, and finally, resistance persists [70]. We are
particularly safety issues related to public health. The search for local speeding up the process of antibiotic resistance dramatically by using
solutions to avoid the environmental spreading of these pollutants re- too many antibiotics often in the wrong contexts. We need to slow down
quires the knowledge of the specific residues and the antibiotic resistant the process so that the antibiotics continue to work for a long time and
determinants present in the wastewater. There is the urgent need for resistance does not spread. Time to time world health organization
public health research to accelerate its pace to keep up and go forwards (WHO) prescribes how to stop antibiotic resistance [71] and we have to
in water sustainability technologies. Further, more research work is follow the recommendations of the WHO. According to WHO, clinicians
required for the application of effective treatment and disinfection should not prescribe or dispense any antibiotic unless they are strictly
methods for the complete elimination of ARB in waste water treatment necessary to the patient. Clinician should make all efforts to test and
plants because the environmental and public health risks bring high confirm which antibiotic is necessary for the treatment of human/an-
challenges. imal. Today, it is seen that antibiotics are prescribed for viral infection,
where they do not work. It is also seen that people take antibiotic
without any consultation. A person should take antibiotics only when
5. Mechanism of antibiotic resistance and prevention of its spread
prescribed by certified medical professionals. If someone takes an an-
tibiotic, always complete the full prescription, even if the person feel
Antibiotics are either naturally occurring or man-made drugs, which
better, because stopping treatment early or in between diagnosis pro-
are widely used for the prevention and treatment of infections caused
motes the spread of resistance. Abuse of antibiotics in livestock, aqua-
by pathogenic bacteria. The first antibiotic was of natural origin but the
culture, and crops is a key factor contributing to antibiotic resistance
majority of antibiotics are synthetic chemical compounds. A number of
and its spread into the environment, food chain and humans. Therefore,
diseases are caused by bacteria in human throughout the globe: tu-
farmers should ensure that antibiotics given to animals are used only to
berculosis, leprosy, plague, fever, gonorrhoea, syphilis etc and they
control or treat the bacterial infection under strong veterinary super-
have cured by the use of antibiotics. Antibiotics are divided into dif-
vision. Maintenance of hygienic animal husbandry condition and
ferent classes, such as aminoglycosides, carbapenems, cephalosporins
proper vaccination to animals can reduce the spread of resistance. We
beta-lactams, macrolides, quinolones, sulfonamides, tetracyclines and
also need strong national action plans to embark upon the resistance of
they are used against infections. The rate of antibiotic use is con-
antibiotics. Government agencies should make strong surveillance of
tinuously increasing that ultimately leads to resistance of antibiotic in
antibiotic-resistant, and regulate the appropriate use of quality medi-
bacteria. It is the ability of bacteria to survive even in the presence of
cines. People should be also educated about the dangers of overuse of
antibiotics this resistance is encoded in segments of DNA/gene of bac-
antibiotics. People in developing or low-income countries are seeking
teria which is known as ARGs. There are various mechanisms, which
medical support to strengthen their health systems and need proper
enable bacteria to fight antibiotics, such as degrading or modifying the
guidance to ensure essential use of antibiotics with responsibility.
antibiotic, modifying the cellular target, pumping it out of the cell i.e
efflux of antibiotics, preventing uptake of drugs (Fig. 2). ARB survives
and multiplies better than susceptible ones in the presence of antibiotics 6. Discussion
and thus enriching resistant strains during the course of antibiotic
treatment. Emergence of antibiotic resistant bacteria in water is due to huge
The ARG is transferred or shared among bacteria through horizontal knowledge gap between sustainable water systems and antibiotic
gene transfer [68]. Sharing of genes among bacteria is facilitated misuse. Development of antibiotic resistance in water represents mag-
through their mobile genetic elements transposons, plasmids and they nificent challenges that must be addressed in the coming time seriously.
are driven by various gene transfer methods such as conjugation Continued innovation and investment in research, technology, and
(transfer of DNA between two microbes via mating), transformation policy is greatly needed mainly in those areas where these challenges
(uptake of extracellular DNA from dead cells), and transduction (viral traverse. Fig. 1 illustrates few aspects that contribute to the spread of
mediated DNA transfer). Plasmids carrying tetracycline resistance in E. antibiotic resistance and emphasizes the future research action. The
coli was isolated from hospital wastewater [69]. Extensive use of value of efforts in this direction by engineers is to design a high
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A. Kumar, D. Pal Journal of Environmental Chemical Engineering 6 (2018) 52–58
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