International Journal of

Environmental Research
and Public Health

Review
Antimicrobial Resistance in Rural Settings in Latin America:
A Scoping Review with a One Health Lens
Maria Luisa Medina-Pizzali 1 , Stella M. Hartinger 1,2,3, * , Gabriela Salmon-Mulanovich 1,4 , Anika Larson 1,5 ,
Maribel Riveros 6 and Daniel Mäusezahl 2,3

1 School of Public Health and Administration, Universidad Peruana Cayetano Heredia,

Av. Honorio Delgado 430, San Martin de Porres, Lima 31, Peru; [email protected] (M.L.M.-P.);
[email protected] (G.S.-M.); [email protected] (A.L.)
2 Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57,
4057 Basel, Switzerland; [email protected]
3 Swiss Tropical and Public Health Institute, University of Basel, Petersplatz 1, 4051 Basel, Switzerland
4 Institute for Earth, Nature and Energy at Pontificia Universidad Catolica del Peru, Av. Universitaria 1801,
San Miguel, Lima 32, Peru
5 Department of Environmental and Occupational Health Sciences, University of Washington,
Seattle, WA 98195, USA
6 School of Medicine, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martin de Porres,
Lima 31, Peru; [email protected]
* Correspondence: [email protected]



Abstract: Antimicrobial resistance (AMR) in rural Latin America is not fully understood. The transmission


pathways are partially known since research predominantly focuses on the urban hospital setting.
Citation: Medina-Pizzali, M.L.; The contribution to AMR from environmental factors is usually only mentioned in large-scale animal
Hartinger, S.M.; Salmon-Mulanovich,
production. To understand the state of the literature on AMR in rural LA, we carried out a scoping
G.; Larson, A.; Riveros, M.;
review using the One Health (OH) perspective. OH recognises the concomitant contributions and
Mäusezahl, D. Antimicrobial
interconnectedness of humans, animal, and the environment, thus, we used the OH perspective to
Resistance in Rural Settings in Latin
select those articles adopting a holistic view of the problem. We searched original articles in English,
America: A Scoping Review with a
One Health Lens. Int. J. Environ. Res.
Spanish, and Portuguese in four peer-reviewed databases and included 21 publications in the analysis.
Public Health 2021, 18, 9837. https:// We charted data on bibliometrics, design, data collection sources, and instruments. We identified
doi.org/10.3390/ijerph18189837 the human, animal, and environmental contributions to AMR in rural locations, and information
gaps on AMR transmission routes and AMR drivers. Intensive and non-intensive animal production
Academic Editors: Jay Graham, systems and agricultural practices were the most frequently found human contributions to AMR.
Ayse Ercumen and Beth J. Feingold Poultry, swine, cattle, and fish were the most frequent livestock mentioned as sources of AMR
bacteria. Animal carriage and/or transfer of AMR determinants or bacteria was recognised as the
Received: 6 August 2021 primary contribution of livestock to the problem, while water, soil, and farming were predominant
Accepted: 14 September 2021
environmental contributions. We found that only 1 article out of 21 considered the OH approach as a
Published: 18 September 2021
framework for their sampling scheme, whereas 5 out 21 discussed all the three OH components. There
were hardly any descriptions of humans or human waste as reservoirs for AMR in rural locations,
Publisher’s Note: MDPI stays neutral
and rural health centres or hospitals and wildlife were not represented. No studies identified mining
with regard to jurisdictional claims in
as an anthropogenic activity driving AMR. More OH-oriented studies, with emphasis on molecular
published maps and institutional affil-
iations.
approaches—for identification and comparison of AMR genes—are sorely needed to understand
better the existence of a network of interconnected transmission routes in rural Latin America and
provide efficient strategies to prevent further AMR emergence.

Keywords: anthropogenic activities; livestock; environment; Latin America; one health;

Copyright: © 2021 by the authors.
antimicrobial resistance
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
1. Introduction
creativecommons.org/licenses/by/ Antimicrobial resistance (AMR) is a global public health issue [1–3], which is occurring
4.0/). among a wide range of microorganisms with increasing prevalence [2]. AMR is a natural

Int. J. Environ. Res. Public Health 2021, 18, 9837. https://doi.org/10.3390/ijerph18189837 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2021, 18, 9837 2 of 18

phenomenon [1] that can arise from mutations or through AMR genes transmitted within
the same microbial species or horizontally among different species [4,5]. Drug-resistant mi-
croorganisms are found in people, animals, food, plants, and the environment and threaten
our ability to treat common infections [6]. The One Health (OH) concept is used by the
United Nations (World Health Organization, World Organization for Animal Health, and
Food and Agriculture Organization) to address global health issues, specifically AMR [7].
The OH concept recognises that “human health and animal health are interdependent and
bound to the health of the ecosystems in which they exist” [8]. Several national actors
adopt a OH perspective when analysing human, animal, and environmental health [9]
or apply a OH approach when implementing control measures [10].
Using the OH lens, we find that in humans, AMR is linked to diverse social factors
such as non-adherence to regimens or doses, self-medication, and misperceptions regarding
antibiotics [11]. Likewise, diverse anthropogenic activities also drive AMR, among them,
the presence of hospitals, industries (i.e., mining, pharmaceutical), and urbanization,
generating chemical waste and faecally-contaminated water. These activities pollute the
environment with antimicrobials, biocides, heavy metals, bacteria with AMR, and AMR
genes which are known drivers of AMR [3,12]. On the other hand, wild or domestic animals,
animal production, and animal-based agricultural systems are linked to the spread of AMR
to humans and the environment [13]. The excessive or inadequate use of antibiotics in
animal farming drives AMR [14] by favouring the increase in the number of resistant
strains in farm animals, animal origin-food, and animal manure [15,16]. AMR bacteria in
animal-origin food may cause foodborne-disease outbreaks, remain as commensals, and
bring about drug-resistant infections later [17]. Aquaculture stands out as a very important
AMR contributor because it promotes significant genetic exchange and recombination
at a fast rate [18]. In addition, antimicrobial residues in feed and animal waste pollute
soil and water [14]. Thus, animal-based agricultural systems and fish farming are a direct
source for the transmission of AMR bacteria and antimicrobial residues to wildlife, humans,
and the whole ecosystem [14,19]. In short, the most important routes for the spread of
AMR drivers into the environment are communal and industrial wastewater, human and
animal waste (i.e., the application of animal manure and sewage sludge for land fertilising),
and aquaculture [12].
Specifically, in Latin America (LA), human and veterinary use of antibiotics is loosely
regulated, and antibiotics are readily available over the counter without prescription [20–22].
In addition to urban clinical settings [23–25], rural environments have been linked to
AMR in Latin America [17,26,27]. In such settings, small-scale animal farming is predomi-
nant [28,29] and animal excreta are a key driver of faecal contamination in domestic human
environs [30]. Thus, rural settings may be an important eco-sphere for the dissemination of
AMR. However, in rural settings of low- and middle-income countries—including Latin
American countries [22], AMR transmission routes are not clearly documented, and the
evidence shown is limited. Reasons may include: AMR surveillance of agricultural and
animal production management is limited and/or poor [14,22]; the available literature
is sparse and often lacks scientific rigor, providing insufficient information for an ade-
quate overview [13,22], and there is scarcity of OH research, involving the human, animal,
and environment domains [13].
This study aims at identifying research that focuses on AMR in rural settings in
Latin America (LA) using the OH lens as a framework to identify their human, animal,
and environmental contributions to AMR. In addition, this work seeks to pinpoint knowl-
edge gaps on AMR transmission routes and AMR drivers to inform researchers and
raise awareness in policymakers. Specifically, this review answers the following research
question: What are the concomitant contributions of humans, farm animals, and the
environment on antimicrobial resistance in rural settings in LA?
Int. J. Environ. Res. Public Health 2021, 18, 9837 3 of 18

2. Materials and Methods

The steps included for our review followed the checklist outlined in the PRISMA
Extension for Scoping Reviews (PRISMA-ScR) by Tricco et al. [31] and the guidelines
provided by Peters et al. [32].

2.1. Inclusion Criteria

The study period spanned from January 2001 until December 2018. Only original,
peer-reviewed articles published in Spanish, Portuguese, and English were considered.
A search strategy was designed using terminology associated with the three domains of
OH and antimicrobial resistance in rural geographic environments for human populations
in Latin American countries. We developed and refined key search terms with online
databases prior to the article search (Table A1).

2.2. Exclusion Criteria

We excluded grey literature. Reviews and meta-analyses were excluded, but their
reference lists were scanned. Articles not acknowledging or discussing all three OH
components were excluded.
We consulted the following electronic databases concentrating on peer-reviewed
articles only: PubMed (biomedical sciences), Web of Science (multidisciplinary), Scopus
(multidisciplinary), and SciELO (multidisciplinary for LA and the Caribbean). We carried
out the search from 13 November to 3 December 2018. All articles were uploaded to a
Mendeley database [33].
A multi-step process was applied for the analysis of inclusion (Figure 1). Our initial
search produced 7936 articles. After screening for duplicates and evaluating the search
criteria (AMR link, rural link, environmental link, animal or agriculture link, and LA
country link), we screened 1151 publications. After evaluating the titles and abstracts of
the articles in our Mendeley database, we created an initial list of 294 articles meeting the
eligibility criteria. These selected articles were then read in full and evaluated for inclu-
sion; 21 publications were finally included for the qualitative synthesis. Five reviewers
conducted all stages of the scoping review, from relevance screening to data extrac-
tion. The five reviewers individually selected the studies for each phase of elimination.
In the process, the reviewers met and discussed each study they had identified, and jointly
agreed on including or excluding the study for analysis. If no agreement could be reached,
the senior author (SH) decided.

2.3. Article Selection

We defined relevant publications as any original peer-reviewed article published
between 1 January 2001 to 3 December 2018; in English, Spanish, and Portuguese language
that presented data from LA countries only (Argentina, Bolivia, Brazil, Chile, Colombia,
Costa Rica, Cuba, Dominic Republic, Ecuador, El Salvador, Guatemala, Haiti, Honduras,
Mexico, Nicaragua, Panama, Paraguay, Peru, Uruguay, and Venezuela); referred to a rural
human setting and to agricultural and/or animal-based food production activities, linked
to environmental aspects, and focused on the topic of AMR. To be included, an article
needed to refer to any aspects of AMR and to partially or totally match the concept of AMR
as defined by the WHO: “Antimicrobial resistance (AMR) is the ability of a microorganism
(like bacteria, viruses, and some parasites) to stop an antimicrobial (such as antibiotics,
antivirals, and antimalarials) from working against it. As a result, standard treatments
become ineffective; infections persist and may spread to others” [34].
Considering an OH perspective, and using it as a screening tool, we searched for
articles that linked to human populations in rural settings (e.g., rural hospitals or health
services, rural communities, farms), had a connection with agricultural and/or animal
production activities (e.g., cattle, fish, poultry, swine farming or animal keeping, transporta-
tion, slaughtering, meat-processing), and described a strong connection with AMR and the
environment. All the inclusion criteria needed to be met, and thus, the criteria needed to be
Int. J. Environ. Res. Public Health 2021, 18, x FOR PEER REVIEW 4 of 18

Int. J. Environ. Res. Public Health 2021, services,

18, 9837rural communities, farms), had a connection with agricultural and/or animal 4 of 18
production activities (e.g., cattle, fish, poultry, swine farming or animal keeping,
transportation, slaughtering, meat-processing), and described a strong connection with
AMR and the environment. All the inclusion criteria needed to be met, and thus, the
explicitly stated to
criteria needed and/or discussed
be explicitly in the
stated article.
and/or Finally, we
discussed excluded
in the article. studies
Finally,on
weAMR that
excluded
focused only on topics that were remotely linked to agricultural and animal-based-food
studies on AMR that focused only on topics that were remotely linked to agricultural and
production activities,production
animal-based-food such as articles describing
activities, suchurban hospitaldescribing
as articles settings or industrial food
urban hospital
production settings; peripherally related to environmental aspects such
settings or industrial food production settings; peripherally related to environmental as publications
dealing
aspects with
such economic impacts;
as publications loosely
dealing linked
with to AMR
economic discussing
impacts; molecular/kinetics
loosely linked to AMR
analyses
discussing of molecular/kinetics
enzymes responsible for AMR,
analyses and describing
of enzymes research
responsible for AMR,in parks and zoos
and describing
within urban spaces, since they would not qualify as “rural”.
research in parks and zoos within urban spaces, since they would not qualify as “rural”.

Figure1.1.Flowchart
Figure Flowchartof
ofthe
thestudy
studyselection
selectionprocess.
process.

2.4.
2.4. Data
Data Management
Management and and Characterisation/Charting
Characterisation/Charting
We tabulated data extracted
We tabulated data extracted from
fromthethe
selected articles,
selected including
articles, authors,
including year of
authors, pub-
year of
lication, title, research objectives, DOI, URL, location of the study, language,
publication, title, research objectives, DOI, URL, location of the study, language, and and summary
of the findings.
summary of theWe used a charting
findings. We used spreadsheet
a charting established
spreadsheeta priori as a guide,
established which
a priori as awas es-
guide,
tablished through team discussions when reviewing the preliminary
which was established through team discussions when reviewing the preliminary results. results.
IfIfinvestigators
investigatorsfrom
fromindividual
individualstudies
studies were
were contacted,
contacted, their
their clarifications
clarifications were
were included.
included.
2.5. Analysing, Summarising, and Reporting the Results
2.5. Analysing, Summarising, and Reporting the Results
The analysis and synthesis of literature included quantitative analysis (i.e., descriptive
The analysis and synthesis of literature included quantitative analysis (i.e.,
statistics) and qualitative analysis (i.e., content analysis). For the qualitative analysis, re-
descriptive statistics) and qualitative analysis (i.e., content analysis). For the qualitative
viewers extracted common themes that emerged from the findings, and the team discussed
the results. Each article was analysed to identify the approach to study AMR and findings
regarding each theme.
Int. J. Environ. Res. Public Health 2021, 18, 9837 5 of 18

3. Results
3.1. Literature Profile
A total of 19 articles were included in the analysis, and 2 articles were added after
browsing their references (Figure 1).
The 21 studies included in the analysis originated from 8 Latin American countries:
Brazil, Ecuador, Colombia, Argentina, Chile, Mexico, El Salvador, and Peru, with Brazil
providing the most articles (9 of 21). All articles but one were published in 2010 and
onwards, peaking with five publications in 2014. All of them were written in the English
language. Nineteen studies were funded by research funders, public agencies; two did
not declare their funding source. One study was partially funded by a microbiological
laboratory which supplied Salmonella spp. strains, and three studies were partially funded
by private LA universities.
All studies were quantitative and had a cross-sectional design except for one, which
was qualitative. Two articles addressed AMR only through molecular methods, six com-
bined phenotypic profiling and molecular techniques (PCR), and eight only through mi-
crobiological methods. Three studies analysed microbiological and epidemiological data.
Only one article included a chemical identification analysis of antibiotics in samples in
addition to molecular genetic analysis. All eligible research works addressed AMR in a
rural site, but four studies also took samples in urban or peri-urban sites for comparison.
In one study, we assumed the location was rural (poultry production sites), based on
current poultry production practices, but it was not explicit in the article. Table 1 presents
the 21 publications included in our review and their characteristics are summarised in
Table 2. Table 3 outlines the methods used in each of the research works.

Table 1. Summary of selected publications.

Human Animal Environment

One Health Important Results
Citation Contribution Contribution Contribution Location
Component 1 (Summary)
to AMR to AMR to AMR
FQ resistance Higher FQ 3 resistance in E.
FQ 3 resistance
linked to coli isolates from chickens than
linked to
Armas- food- in rural human isolates. The
humans, Water samples
Freire producing latter showed higher rates of
AH, HH especially in collected but Ecuador
2015 animals, no qnrB genes compared to
clinical settings not discussed.
[35] restriction to chicken isolates. Urban clinical
where its use is
the use of FQ human isolates: low
widespread. 3. occurrence of qnrB genes.
Expansion of Farm animals’
aquacul- pathogens can E. coli strains isolated from fish
Barbosa Water gets
ture/incorrect colonise fish for human consumption, 43%
2014 HH, EH polluted with Brazil
animal and become were EPEC. MDR 12 was high
[36] animal faeces.
husbandry carriers of in isolates.
practices. AMR.
Animal
Potential
production
extrinsic
systems boost
sources of Surfaces of Higher levels of AMR in
and are sources
resistance: poultry coops: bacteria from production
Braykov for AMR. Broad
birds could AMR profiles versus household birds.
2016 HH, AH, EH spectrum Ecuador
become most similar to Prevalence of AMR in
[37] antibiotics used
colonised by samples from production birds declined
in humans
resistant poultry. with bird age.
contributed to
strains from
AMR in
hatcheries.
poultry.
Int. J. Environ. Res. Public Health 2021, 18, 9837 6 of 18

Table 1. Cont.

Human Animal Environment

One Health Important Results
Citation Contribution Contribution to Contribution Location
Component 1 (Summary)
to AMR AMR to AMR
Pig farming
E. coli isolates in pig faeces,
production
Pig faeces water, and soil samples:
systems
Brisola contaminated MDR 12 isolates 37.04% showed MDR 12 , 7.41%
contaminate
2019 HH, AH, EH environment with found in water Brazil were ESBL 10 producers. Most
environment
[38] E. coli carrying and soil. MDR 12 strains presented a
and spread
MDR genes. high risk of transmission to
AMR/MDR 12
humans.
resistant genes.
Environs not
the source of
Resistance to NA
5 in Salmonella AMR; they Some strains isolated from two
Overuse of QN
Campioni 4 in poultry become sources were
enteritidis isolates
2014 HH, AH contaminated Brazil indistinguishable. Forty-four
production from chicken; the
[39] by chicken strains were resistant to NA 5 .
spreads AMR. pathogen is
breeders QN 4 resistance was present.
vehicle for AMR.
sharing the
same strains.
Swine
production
Pigs carry AMR Flies are an
generates Resistance detected in 2 out of
zoonotic bacteria, environmental
Cervelin manure and 4 antibiotics tested (used in
which are factor of
2018 HH, AH overuses Brazil human or veterinary
pathogenic to importance in
[40] antibiotics, medicine). Some farms
animals and the spread of
fostering AMR showed MDR 12 bacteria.
humans. AMR.
spread through
vectors.
Animal farming
impacts on
quality of Animal faeces Water unsafe
surface and contaminate for human
Gambero groundwater by water. High consumption Source of faecal contamination
2018 HH, EH spreading AMR proportion E. coli due to E. coli Argent-ina in water is mainly animal
[41] E. coli. Small resistant to concentrations, residues.
proportion of E. veterinary which foster
coli resistant to antimicrobials. AMR spread.
antibiotics used
in humans.
Meat Lack of
Human use of Individuals taking “any
consumption of protection of
antibiotics antibiotic” increased children’s
animals excreta and
Kalter impacts on risk risk for resistant E. coli.
produced water play a
2010 HE, HH of AMR Peru Residence in zones where
commercially role in
[42] bacteria home-raised chicken was
drives AMR increasing
carriage in consumed protected against
carriage risk in AMR carriage
children. carrying resistant E. coli.
humans. risk in children.
Handling and
Animal Qualitative study. Handling
Small-scale consumption of
environment and consumption of sick and
livestock sick and dead
sanitation not dead animals and
Lowen- production animals:
addressed. over-the-counter purchase of
stein could have an perceived risk
AH, HH Animals and Ecuador veterinary drugs increase
2016 impact on the factor for AMR
humans zoonoses risk and AMR
[43] risk of zoonosis spread.
sharing water spread. Commercial poultry
and spread of Unregulated use
sources and considered less healthy due to
AMR. of veterinary
living spaces. antibiotics.
antimicrobials.
Int. J. Environ. Res. Public Health 2021, 18, 9837 7 of 18

Table 1. Cont.

Human Animal Environment

One Health Important Results
Citation Contribution Contribution Contribution Location
Component 1 (Summary)
to AMR to AMR to AMR
Poultry house
Animals’
Use of environment is Poultry house environment
contribution
antibiotics as major produced more AMR isolates.
is explained
growth contributor to Highest resistance: SA 6 . Most
Mattiello by their
promoters. AMR. resistant isolates: sul genes.
2015 HH, EH carrying Brazil
Improper Environmental Twenty-one isolates with
[44] AMR
sanitation isolates showed reduced susceptibility to
pathogenic
favours MDR 12 MDR 12 to b-lactams and had blaTEM,
Salmonella
Salmonella. human blaCMY and/or blaCTX-M.
enterica.
antibiotics.
Poultry and egg Salmonella prevalence: 33%;
Feed and water
industry two isolates were MDR 12 .
carried
malpractices Hens and Farm practices as potential
Rodriguez Salmonella.
promote eggs carry risk factors for Salmonella
2015 AH, HH Farm workers’ Colom-bia
dissemination AMR spread: on-farm feed milling,
[45] faecal samples
of pathogenic Salmonella. inappropriate sanitation, egg
collected but
and resistant storage, and inadequate
not discussed.
Salmonella spp. construction material.
Grassland-
Grasslands:
based
cattle are Remarkable presence of tet
production
reservoirs of Soil and water genes. Predominant
systems
Santamaría TCN 7 are reservoirs of distribution of tet(W) and tet
(antibiotics only
2011 EH, AH resistance TCN 7 Colom-bia (Q) in both animal and
for disease
[46] genes and are resistance environmental reservoirs.
control) still
more diverse genes. Probable gene transmission
create
than from animals to environment.
reservoirs for
environment.
AMR bacteria.
AMR in aquatic
AMR
environments
AMR transferred
dos increased by
transferred from shrimps to More than 90.5% of strains of
Vieira indiscriminate
AH, EH, HH from animals the Brazil Escherichia coli showed a
2010 use of
to humans environment variety of AMR profiles.
[47] antimicrobials
through food. (pond water
(human and
and sediment).
veterinary).
Prophylactic Poor fish
therapy in farming Water and feed:
Miranda Gram-negative OXT
Chilean salmon management likely reservoirs 8 -resistant
2002 AH, HH, EH Chile bacteria recovered.
farming and incorrect of MDR 12
[48] MDR 12 was frequent.
produces use of antimi- bacteria.
higher AMR. crobials.
Antimicrobials
in livestock
linked to AMR Farm animals, Rain,
in animals and manure, fish agricultural 54 different AMR profiles;
humans. farming, and runoff, and 49.5% of isolates with AMR.
Palhares
Inadequate wild animals river flow MDR 12 : 18% of isolates. Link
2014 HH, AH, EH Brazil
animal husbandry, contribute to contribute to among animal-based
[49]
agricultural, AMR AMR agriculture, Salmonella and
and environmental Salmonella Salmonella AMR.
practices favour spread. spread.
presence of
Salmonella.
Int. J. Environ. Res. Public Health 2021, 18, 9837 8 of 18

Table 1. Cont.

Human Animal Environment

One Health Important Results
Citation Contribution Contribution Contribution Location
Component 1 (Summary)
to AMR to AMR to AMR
Rural site: soil
Subsistence
faecally
farming:
contaminated
antibiotic use Rural site:
with human Large network of AMR genes
Pehrsson without backyard
and animal Salvador shared: microbial
2016 HH, EH, AH prescription farming
AMR genes. and Peru communities of humans,
[50] and inadequate contributed to
Limited access animals, and environment.
excreta AMR spread.
to drinking
management
water and
favour AMR.
sanitation.
Extensive cattle
production TCN 7 - No differences in isolates from
Faecally
impacts resistance environmental samples vs.
contaminated
Lopez 2 environment genes can animal samples. TCN 7
soil can pollute
2012 EH, AH and animals, flow from Colom-bia resistance in grasslands likely
underground
[51] creating AMR animal waste caused by horizontal gene
and surface
reservoirs to soil and transfer from animals to
water.
despite low water. environment.
antibiotic use.
Use of manure
Poultry, cattle, Manure application associated
as fertiliser
and swine with antibiotic residues and
drives
Camotti manure Fertilised soils AMR in soils. Swine manure
accumulation of
2018 EH, AH contaminate contaminate Brazil had highest antibiotic
pharmaceutical
[52] soils and forest soils. concentrations. Extended
residues or
disseminate dairy cow grazing linked to
induces AMR
AMR bacteria. high SA 6 resistance.
bacteria in soils.
Effluent use
Cattle manure Biodigestion
from ambient 55.65% of isolated bacteria
recycling may of cattle
Resende temperature were MDR 12 . Some isolates
impact animal, manure does
2014 AH, EH biodigesters Brazil recovered from biodigestor
human, and not guarantee
[53] contaminates (influent and effluent) were
environmental “safe”
soil with AMR AMR.
health. fertiliser.
bacteria.
Compost use,
Agricultural and animal Workers’ hands,
practices and waste: water, and soil High resistance to TCN 7 and
Corzo-
sewage water sources of can AMP 9 . 3.5% were
Ariyama
HH, EH contribute to contamina- contaminate Mexico MDR 12 . Potential consumer
2019
spread of AMR tion for produce with risk: AMR, pathogenicity, and
[54]
pathogenic E. pathogenic pathogenic biofilm formation.
coli. and resistant AMR bacteria.
strains.
Human
Animals can
contribution
carry variety
not discussed. Water samples
of potentially
Cicuta ESBL collected but Neither phenotypically ESBL
10 -producing pathogenic 10 nor CB 11 -producing
2014 HH, AH not discussed Argent-ina
ESBL
[55] enterobacteria 10 -producing nor linked to bacteria detected.
more frequent other samples.
enterobacte-
in humans and
ria.
animals.
1 HH: Human Health; AH: Animal Health; EH: Environmental Health; 2 Both publications belong to the same project and share the
same sample; 3 Fluoroquinolones; 4 Quinolones; 5 Nalidixic acid; 6 Sulfonamides; 7 Tetracyclines; 8 Oxytetracycline; 9 Ampicillin;
10 Extended-spectrum beta-lactamases; 11 Carbapenemase; 12 Multidrug resistance/multidrug resistant.
Int. J. Environ. Res. Public Health 2021, 18, 9837 9 of 18

Table 2. Basic details of included publications.

Number (n =); Included Article Number in

Study Characteristics
Articles, n (%) References
Type
Quantitative research 20 (95.2) [35–42,44–55]
Qualitative research 1 (4.8) [43]
Country of origin
Brazil 9 (42.9) [36,38–40,44,47,49,52,53]
Ecuador 3 (14.3) [35,37,43]
Colombia 3 (14.3) [45,46,51]
Argentina 2 (9.5) [41,55]
Chile 1 (4.8) [48]
Mexico 1 (4.8) [54]
Peru * 2 (9.5) [42,50]
El Salvador * 1 (4.8) [50]
Publication year
2001–2005 1 (4.8) [48]
2006–2010 2 (9.5) [42,47]
2011–2016 13 (61.9) [35–37,39,43–46,49–51,53,55]
2017–2019 5 (23.8) [38,40,41,52,54]
Language
English 21 (100) [35–55]
Approach used to study AMR
Microbiological and molecular 6 (28.6) [35,38,39,44,51,54]
Molecular 2 (9.5) [46,50]
Microbiological 8 (38.1) [36,40,41,47–49,53,55]
Microbiological and
3 (14.3) [37,42,45]
epidemiological
Chemical and molecular 1 (4.8) [52]
Other (qualitative) 1 (4.8) [43]
* The study carried out in El Salvador also included Peru.

Table 3. Data collection sources/instruments used in selected publications.

Number (n =); Included Article Number in

Type of Data Collection
Articles, n (%) References
Animal collection (cloacal
swabs, faeces, manure,
16 (76.2) [35–39,42,44–51,53,55]
compost, muscle, eggs,
veterinary clinical samples)
Environment collection (soil,
water, pond mud, surfaces, 18 (85.7) [35–42,44–52,54]
workers’ hands, vectors, feed)
Human collection (faeces) 4 (19.1) [35,42,45,50]
Questionnaires and
4 (19.1) [37,42,43,45]
interviews, observation
Produce collection 1 (4.8) [54]

3.2. Antimicrobial Resistance through the One Health Lens

Figure 2 shows AMR contributions from animal, environmental, and human domains,
applying the OH perspective; it describes how various specific human activities, animal-
related factors, and environmental factors are connected based on the information extracted
from the selected articles.
 extracted from the selected articles.
As shown in Table 1, in most articles, only two OH components were considered,
either in the discussion or the description of the sampling procedures. Only Braykov et al.
[37], Brisola et al. [38], dos Vieira et al. [47], Miranda et al. [48], and Palhares et al. [49]
discussed
Int. J. Environ. Res. Public Health 2021, 18, 9837 all three components, but their study designs did not include sampling for10allof 18
of them. Pehrsson et al. [50] took samples of human, animal, and environmental origin
but did not discuss the relevance or impact of their results on animal health.

Figure 2. Proposed
Figure pathways
2. Proposed for the
pathways forspread of antimicrobials
the spread and/orand/or
of antimicrobials AMR genes
AMR ingenes
rural in
settings, based on based
rural settings, the publications
on the
publications included
included in the review. in the review.

3.2.1.
AsHuman
shownContribution
in Table 1, in most articles, only two OH components were considered,
either Anthropogenic
in the discussion or theofdescription
drivers AMR included of theintensive
samplingand procedures. Only(small-
non-intensive Braykov
etscale/extensive)
al. [37], Brisola animal
et al. [38], dos Vieira
production et al. [47],
systems Miranda
[35–51] et al. [48], and
and agricultural Palhares
practices et al. [49]
[49,50,52–
discussed
54], suchallas three components,
the use of recycledbut ortheir study designs
composted animal did not include
or human sampling
manure for all of
as fertiliser.
them.
ResendePehrsson et al.showed
et al. [53] [50] took samples of human,
microbiological evidenceanimal, and environmental
of survival of AMR bacteria origin
afterbut
did not discuss
biodigestion the relevance
treatment or manure,
of cattle impact ofwhich
their could
resultscontaminate
on animal health.
soils when applied as
fertiliser. Camotti et al. [52] found that each type of manure used as fertiliser in
3.2.1. Human soils
agricultural Contribution
had a unique concentration of antibiotic residues and AMR genes,
specific to the particular
Anthropogenic animal
drivers production
of AMR includedsystem it originated
intensive from. Perhsson(small-scale/
and non-intensive et al. [50]
and Kalter et al. [42] identified inadequate human excreta management
extensive) animal production systems [35–51] and agricultural practices [49,50,52–54], as an important
human
such AMR-promoting
as the use of recycledfactor in rural sites.
or composted animal Only three articles
or human manure[35,42,50] identified
as fertiliser. Resende
unrestricted, unregulated, or recent use of antimicrobials in humans
et al. [53] showed microbiological evidence of survival of AMR bacteria after biodigestion as a human
contribution
treatment to themanure,
of cattle problem.which
Cicutacould
et al. contaminate
[55] did not identify
soils when any applied
human input but
as fertiliser.
acknowledged the need to have an interdisciplinary approach to implement
Camotti et al. [52] found that each type of manure used as fertiliser in agricultural soils human and
had a unique concentration of antibiotic residues and AMR genes, specific to the particular
animal production system it originated from. Perhsson et al. [50] and Kalter et al. [42]
identified inadequate human excreta management as an important human AMR-promoting
factor in rural sites. Only three articles [35,42,50] identified unrestricted, unregulated, or
recent use of antimicrobials in humans as a human contribution to the problem. Cicuta
et al. [55] did not identify any human input but acknowledged the need to have an
interdisciplinary approach to implement human and animal health-oriented research. Only
Perhsson et al. [50] gave direct evidence of the human role in the generation of AMR; they
proved that humans modify microbiomes and resistomes in rural settings by interacting
with animals and the environment by means of horizontal transfer of AMR determinants.
Int. J. Environ. Res. Public Health 2021, 18, 9837 11 of 18

3.2.2. AMR and Contributions from Animals

Poultry was the most common livestock [35,37,39,42–45,49,50,52], but fish [36,48],
swine [38,40–43,49], and cattle [41,42,46,49,51] were also studied. Only dos Vieira et al. [47]
focused on AMR in shrimp production. Some studies considered the input of other do-
mestic animal species [41–43,55] such as sheep, ducks, pigeons, horses, dogs, or guinea
pigs. Corzo-Ariyama et al. [54] did not specify the type of animal under study; their
focus was solely on identifying AMR patterns from bacteria in produce; therefore, they
recognised the animal role in the spread of AMR more generally. By far, animal AMR
carriage and/or transfer of AMR determinants or bacteria was the most widely identified
animal contribution [36–38,44,46–48,50–54], while several studies mentioned the inade-
quate or unregulated use of veterinary antimicrobials [39–41,43,47–49]. The role of food of
animal origin in the spread of AMR bacteria in the human food chain was mentioned as
well [35,36,38,39,42,46,47].
In contrast, Cicuta et al. [55] did not acknowledge any of the above-mentioned contri-
butions of animals to the generation and spread of AMR, but only discussed the phenotypic
resistance screening results and their likely cellular resistance mechanisms.
Armas-Freire et al. [35], Brisola et al. [38], Campioni et al. [39], Mattiello et al. [44],
and Lopez et al. [51] showed strong evidence of the animal role as reservoirs or carriers of
AMR genes obtained by molecular methods—allowing identification and comparison of
AMR genes [56]—combined with phenotypic resistance testing—based on viable culturable
bacteria [57]. Santamaria et al. [46] and Pehrsson et al. [50] used only molecular methods
to study AMR, but the latter applied metagenomics to compare entire resistomes. Camotti
et al. [52] used a combined molecular and chemical methodology to identify AMR genes
and antimicrobial molecules. Braykov et al. [37], Kalter et al. [42], and Rodriguez et al. [45]
included an epidemiological methodology and one of them provided sound evidence
regarding the risk and protective factors for AMR presence in humans. One of the
main risk factors for AMR were children’s or household members’ recent antibiotic use.
At the same time, AMR was less often described among older children and those living in
a community where a greater proportion of homes consumed home-raised chicken [42].
Most of the above-mentioned articles proposed a one-way transmission pathway of AMR
genes from animals to the environment. However, Brisola et al. [38] and Pehrsson et al. [50]
proposed a more complex scenario of interactions where the dissemination of AMR oc-
curs simultaneously and in two opposite directions linking all reservoirs: human, animal,
and environmental, although Brisola et al. [38] pointed at the animal reservoir as the origin.

3.2.3. Environment Contribution

More than half of the articles identified water as a contributing factor for AMR
spread [36–38,41,42,46–52,54]. Other environmental inputs included: soil [37,38,46,49–54],
farm/bird coop’s environment (which included surfaces, feed, shoe soles, and/or hands of
workers) [37,44,45,54], vectors (flies) [40], and pond sediments [47]. Lopez et al. [51] recog-
nised the importance of soil-containing faeces in the contamination of underground and
surface water. Santamaría et al. [46] and Palhares et al. [49] highlighted the importance of
runoff in disseminating AMR genes into the environment. Lowenstein et al. [43] considered
questions about the use of shared animal-human drinking water sources and shared living
spaces. Interestingly, Miranda et al. [48] pointed at feed and influent water—as opposed to
effluent water—as reservoirs for AMR bacteria in salmon farms. On the other hand, Armas
Freire et al. [35] and Cicuta et al. [55] did not address any environmental contributions to
the AMR problem.
Brisola et al. [38], Campioni et al. [39], Mattielo et al. [44], Santamaria et al. [46],
Pehrsson et al. [50], Lopez et al. [51], and Camotti et al. [52] produced sound evidence
regarding the role of the environment in the maintenance and dissemination of AMR.
All these articles agreed that the faecally-contaminated environments are a persistent
source or reservoir for AMR bacteria from which AMR could easily disseminate. Most
of them considered animals as the contamination source but Pehrsson et al. [50] verified
Int. J. Environ. Res. Public Health 2021, 18, 9837 12 of 18

the contribution of both animal and human faecal matter in this contamination of the
environment. Strong microbiological/epidemiological evidence was provided by Braykov
et al. [37] and Kalter et al. [42] for the role of the environment in the spread of AMR.

3.3. Information Gaps

As shown in Figure 2, neither of the selected articles investigated nor identified the
contribution of effluents of rural hospitals or health services to the environment and their
impact on rural populations, animals, and ecosystems. Four articles included human
faecal samples in their studies, but human waste collective discharges were not sampled.
Likewise, the link between mining and AMR in rural settings was not the focus of any of
the eligible studies, despite the role of metals as drivers of AMR [12] and the contribution
of mining to metal pollution [58,59]. Moreover, wild animal reservoirs and/or their
contribution to the AMR problem in rural locations were not discussed in the selected
articles. Even though many studies published in Portuguese or Spanish language were
found at the initial steps of the search, none of them met the inclusion criteria, so they were
not represented in our selection.

4. Discussion
This review identified key contributors to AMR in LA considering the OH concept.
The following anthropogenic activities were identified as drivers for AMR dissemination
in rural Latin American settings: animal husbandry, fish farming, agriculture, and other
related practices such as animal waste recycling. The carriage and/or transfer of AMR
determinants were the most frequent animal contributions, in addition to the inadequate
or unregulated use of veterinary antimicrobials and the role of food of animal origin in the
spread of AMR bacteria in the human food chain. Water was the most commonly identified
environmental contributor for AMR spread but also soil, farm/bird coops, vectors (flies),
and pond sediments were also important contributors mentioned.
Nearly half of the eligible studies showed robust evidence confirming the human, animal,
or environmental contributions to the generation or the spread of AMR. However, only one
study [50] provided evidence embracing a OH framework to suggest a global scenario in
which all the reservoirs—human, animal, and environmental—contribute to the problem,
sharing AMR genes through horizontal transfer. Rather than illustrating a mere pathway,
this work embraces the numerous interactions between human, animal, and environmental
domains portraying an intricate network of AMR spread. Pehrsson et al. [50] took samples of
human, animal, and environmental origin simultaneously and compared their resistomes,
allowing them to produce strong evidence for the interconnectedness of human, animal,
and environmental drivers of AMR. As these AMR drivers converge, the environment
might function as both a reservoir and a bridge for antimicrobial determinants giving rise
to other potential pathways of AMR transmission to non-contaminated wildlife, humans,
and animals [12].
Most of the assessed articles studied the AMR problem from a single viewpoint
or emphasised one of the OH components. Five studies [37,38,47–49] considered the
importance of animal, human, and environment inputs to the AMR generation and spread,
but did not collect samples from all these interconnected sources or omitted discussing the
results in an integrated manner. The reasons were not explicit.
One of the most important insights from our study is the scarce research on humans
or human waste as sources of AMR determinants in rural locations described in the Latin
American literature. Studies focusing on AMR in rural health centres or rural hospitals
were not found in the articles eligible for analysis. However, the impacts of rural hospital
effluents on the environment and hence, on human and animal microbiomes cannot be
ignored [60], mainly because wastewater collection and treatment in rural settings are
significantly reduced or absent compared to urban settings in LA [61,62].
We found some information gaps in the selected literature. Mining is an important
economic activity in many countries in LA [63] and it has been identified as a contributor
Int. J. Environ. Res. Public Health 2021, 18, 9837 13 of 18

to the spread of AMR, however, we did not find any studies on the topic. Mining activities
lead to the release of metal-containing effluents into the environment, driving AMR in
bacteria due to shared mechanisms of resistance to both metals and antimicrobials [12].
Wildlife is a neglected likely significant contributor to the spread of AMR in rural
LA. Although it was not identified as a contributor in the eligible articles, the interaction
between humans, wild animals, and farm and domestic animals occurs in rural settings,
sharing AMR bacteria [64]. Thus, studying wild animals’ AMR gene sources and their
genetic similarity in farm animals, human, and environmental reservoirs in LA, should be
the focus for future research worth working on. More public health research focusing on
wildlife is needed to better understand the impacts of human activities on the environment
(habitat fragmentation, land-use change, urbanisation) and the role of wildlife species—
as reservoirs, melting pots, and/or vectors for AMR determinants—in the dissemination of
resistance [65]. Our findings underscore the importance of adopting an OH approach as a
framework for the design of future studies aimed at understanding the interconnections
among its three components to assess AMR more efficiently and propose better strategies
to prevent AMR emergence in LA.
Only one article used qualitative methods [43]. Qualitative approaches are useful
when trying to elucidate the reasons behind practices, knowledge, attitudes and percep-
tions, and prove useful in understanding the complexity of AMR transmission pathways.
We suggest incorporating a qualitative approach in AMR research since it could be a signif-
icant added value to quantitative studies. Mixed-methods approaches allow researchers
to identify any contradictions between the quantitative and qualitative findings [66],
and could be valuable for identifying deficiencies in sanitation and biosecurity practices
in animal production and agricultural systems, knowledge and attitudes regarding these
practices, and the structural and economic limitations contributing to AMR dissemination
in LA rural settings.
On the other hand, the most robust evidence for the role of animals, humans, and/or
the environment in the spread of AMR originated from studies combining molecular
methods, phenotypic resistance screening methods, sound study design and sampling,
and an integrated OH perspective. A few studies relied upon a combined phenotypic
resistance testing and an epidemiological approach, thus identifying risk factors and pro-
tective factors for AMR. However, due to the limitations of culturing in assessing AMR,
they could not give insight into the specific AMR determinants associated with the AMR
phenotypes [56]. Phenotypic resistance profiling enables cultivation of target bacteria.
However, assessing AMR through culture-based methods carries an inherent bias since
these methods cannot detect cells in a viable but non-culturable state [57]. In contrast,
molecular methods provide information regarding the underlying mechanism of resistance,
identifying the determinants for that resistance, even if they are not always expressed in
the host bacteria [56,67]. In addition, with the use of genomic tools, typing, comparing,
and tracing specific allele profiles, it is now possible [68]. Thus, it is necessary to apply
molecular methods along with phenotypic profiling methods to have a more detailed
and complete picture when assessing AMR [57]. We believe that studies focusing on
the total environment using microbiological, epidemiological, and molecular approaches
in an integrative way are needed to better understand the existence of a network of in-
terconnected transmission routes. Additionally, given the cross-sectional nature of the
eligible studies, they could not demonstrate the directionality of their proposed path-
ways of transmission of AMR, which—in most cases—pointed at a one-way path only,
from animals to the environment.
It is important to note that only one study in Brazil [47], mentioned that local govern-
mental agencies were concerned with the results of the antibiotics’ indiscriminate use in
aquaculture. However, no other mention was made to the uptake of research findings by
local authorities or any other local actors in any sector. This finding may imply the need of
a more effective dissemination of scientific findings from academia to government agencies
and local actors in LA. Likewise, an OH approach to provide robust evidence on AMR
Int. J. Environ. Res. Public Health 2021, 18, 9837 14 of 18

emergence and transmission is key to translate AMR’s research results when designing
public health and animal production policies.
We did not include grey literature, which we believe would have enriched our find-
ings. There was no systematic way to search for country-level surveillance reports. Since
most literature reviews only include publications in the English language, we purposedly
looked for articles produced in LA written in Spanish and Portuguese languages, finding a
considerable number during the screening process. However, none of them fulfilled the
eligible criteria for this review. This limitation may be due to the kind of settings in which
these studies have been conducted—urban as opposed to rural—and the AMR perspective
applied, which may be one-sided, favouring any of the OH components but not comprising
the three domains, as we specified in our inclusion criteria. Since AMR was recognised as
a global threat to public health, virtually all countries adopted a national action plan to
tackle the problem [69]; however, actions developed in LA may not have had an explicit
focus on an integrated OH approach.
Other reasons may explain the scarcity of truly integrated OH research works in
LA—as in other low- and middle-income regions. Establishing OH research involves
facing barriers such as lack of OH training and expertise, and difficulty in establishing
collaboration among multiple and cross-sectoral actors—resulting in scarcity of multidisci-
plinary training programs—and limited government support and research funding [70,71].
Funding bias could partially explain the absence of articles written in these languages:
most comprehensive and well-funded AMR studies adopting an OH approach tended to
be published in English.

5. Conclusions
This scoping review on AMR in rural settings in LA identified the human, animal,
and environmental contributions to AMR using an OH lens, and pinpointed the informa-
tion gaps on AMR transmission routes and AMR drivers in the literature. Human activities
contributed to the spread of AMR through animal husbandry (mainly poultry), fish farm-
ing, agriculture, and animal waste recycling (composting). Farm animals contributed
by carrying and/or transferring resistant genes or resistant bacteria. Main environmen-
tal contributors are faecally-contaminated water, contaminated soil or pond sediments,
and farm environments.
Adopting an OH lens proved useful as a framework to determine whether the selected
articles considered the impact of AMR on the three aspects of health, animal, human,
and environment, and to what extent they did so. However, a small percentage of articles
took into account the three OH components in the sampling or in the discussion. Thus,
we recommend following the OH approach as a framework for the design of future
studies—emphasising on the use of mixed methods and a combination of approaches—
molecular-, epidemiological-, and culture-based—to tackle AMR more efficiently and to
tailor strategies to prevent AMR emergence in the region, where these efforts are still scant
and considerably needed.
Future research efforts should give more attention to the role of mining, wildlife,
and rural hospitals’ or health services’ effluents on the emergence and spread of AMR in
rural Latin America, given that these aspects were not identified in the selected literature
and were considered information gaps.

Author Contributions: M.L.M.-P. and S.M.H. conceived the original idea for this review; D.M.
and S.M.H. obtained the funding; M.L.M.-P., S.M.H., G.S.-M., M.R. and A.L. analysed and interpreted
the data; M.L.M.-P. wrote the first draft of the manuscript; S.M.H., G.S.-M., M.R., A.L. and D.M.
interpreted the data, contributed to the writing and performed critical revisions of the manuscript.
All authors have read and agreed to the published version of the manuscript.
Funding: This study received financial support from the Novartis Foundation (grant number 18A059).
The sponsor had no involvement in the decision to submit the article for publication.
Int. J. Environ. Res. Public Health 2021, 18, 9837 15 of 18

Institutional Review Board Statement: The study was conducted according to the guidelines of the
Declaration of Helsinki, and approved by the Institutional Review Board for humans and animal
subjects of the Universidad Peruana Cayetano Heredia, protocol code 418-16-18.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data presented in this study are available in Table 1. Additional
data are available on request from the corresponding author.
Conflicts of Interest: The authors declare no conflict of interest.

Appendix A
Table A1 shows the full electronic search strategy used in this review.

Table A1. Keywords (with synonyms) and syntax used for the literature search.

#4: “Animal
#1: #2: “Type of #3:
Handling or #5: “Countries in LA” #6: Combined
“Antimicrobial Geographical “Environmental”
Agriculture” Terms Search
Resistance” Terms Setting” Terms Terms
Terms
(“antimicrobial (Argentina OR Bolivia
drug resistances” OR Brazil OR Chile
OR “antimicrobial OR Colombia OR
(“animal
drug resistance” “Costa Rica” OR Cuba
production” OR
OR “antibiotic OR “Dominican
(rural OR “rural animal OR
resistance” OR Republic” OR Ecuador
populations” OR (environment * OR livestock OR #1 AND #2
“drug resistances, OR “El Salvador OR
“rural settings” OR water OR soil OR agricultur * OR AND #3 AND
microbial”) OR” Guatemala OR Haiti
“rural health lixiviation) AND “animal #4 AND #5
antibiotic OR Honduras OR
services”) AND husbandry” OR
resistance, Mexico OR Nicaragua
poultry OR food)
microbial” OR OR Panama OR
AND
“antimicrobial Paraguay OR Peru OR
resistance” Uruguay OR
AND Venezuela)

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