Emerging Infectious Diseases, Antimicrobial Resistance
and Millennium Development Goals: Resolving the Challenges through One
Emerging Infectious Diseases, Antimicrobial Resistance and
Millennium Development Goals: Resolving the Challenges through One
G. V. Asokan1, R. K. Kasimanickam2
1Public Health Program, College of Health
Sciences, University of
Bahrain, Manama, Bahrain; 2Department of
Veterinary Clinical Sciences,
College of Veterinary Medicine, Washington State University, Pullman,
Most emerging infectious diseases are zoonoses, which could severely
hamper reaching the targets of millennium development goals (MDG). Five
out of the total eight MDG’s are strongly associated with the Emerging
Infectious Diseases (EIDs). Recent emergence and dissemination of
drug-resistant pathogens has accelerated and prevent reaching the
targets of MDG, with shrinking of therapeutic arsenal, mostly due to
antimicrobial resistance (AMR). World Health Organization (WHO has
identified AMR as 1 of the 3 greatest threats to global health.
Until now, methicillin-resistant staphylococcus aureus (MRSA) and
vancomycin-resistant enterococci (VRE) have been observed in
hospital-acquired infections. In India, within a span of three years,
New Delhi metallo-β-lactamase prevalence has risen from three percent
in hospitals to twenty- fifty percent and is found to be colistin
resistant as well. Routine use of antimicrobials in animal husbandry
accounts for more than 50% in tonnage of all antimicrobial production
to promote growth and prophylaxis. This has consequences to human
health and environmental contamination with a profound impact on the
environmental microbiome, resulting in resistance.
Antibiotic development is now considered a global health crisis. The
average time required to receive regulatory approval is 7.2 years.
Moreover, the clinical approval success is only 16%. To overcome
resistance in antimicrobials, intersectoral partnerships among medical,
veterinary, and environmental disciplines, with specific
epidemiological, diagnostic, and therapeutic approaches are needed.
Joint efforts under “One Health”, beyond individual professional
boundaries are required to stop antimicrobial resistance against
zoonoses (EID) and reach the MDG.
Keywords: Emerging infectious diseases, Zoonoses,
Antimicrobial resistance, Millennium development goals, One health
Emerging infectious diseases (EID), mostly zoonoses, pose enormous
threats, which could severely hamper reaching the targets of the
health-related United Nations Millennium Development Goals (MDG) set
for 2015.1 The following five out of the total eight MDG’s are strongly
associated with the EIDs:
1. Reducing child mortality rates;
2. Improving maternal health;
3. Combating HIV/AIDS, malaria, and other diseases;
4. Ensuring environmental sustainability; and
5. Developing a global partnership for development.
Of all known infectious diseases, zoonoses constitute about 60%. Within
emerging infectious diseases, approximately 75% are of zoonotic origin.
By classification, 40% of fungi, 50% of bacteria, 70% of protozoa, 80%
of viruses, and 95% of helminths that infect human beings are zoonotic.
It has been recognized that more than 50% of human pathogens can infect
other vertebrate hosts.2 Only 100 of the approximately 400 known
emerging pathogens occur as human pathogens.3 Among the marine mammal
pathogens at least 49% are zoonotic, and 28% are emerging zoonoses.4
Emerging zoonoses, such as hendra, nipha, avian influenza, and severe
acquired respiratory syndrome (SARS) are a growing threat to global
health and have caused huge economic loss in the past 20 years. There
is poor understanding of how zoonotic pathogens evolve from natural
ecology and cause disease, and how various circumstances, such as
animal production, extraction of natural resources, and antimicrobial
application alter the dynamics of disease exposure to human beings.5 To
counter the shared risks between animals and humans, the concept of
“one health” was developed during the early 21st century and is based
on a systems approach.6 One health has been defined as "the
collaborative effort of multiple disciplines working locally,
nationally, and globally to attain optimal health for people, animals,
and the environment."7 The purpose of this review is to look at the
challenges faced due to antimicrobial resistance in EID particularly
zoonoses and find solutions under a “one health” approach to reach the
targets of the MDG.
Microorganisms have evolved over the ages and have an innate ability to
survive by developing resistance to antimicrobial compounds
administered. Antimicrobial resistance (AMR), sometimes known as drug
resistance, occurs when microorganisms such as bacteria, viruses, fungi
and parasites change ways to render the existing standard medications
such as antibacterials (antibiotics -MRSA), antifungals (candida
resistance to fluconazole), antivirals (H1N1 resistance to
oseltamivir), and antiparasitics (Chloroquine resistance to malarial
In recent times, the emergence and dissemination of drug-resistant
pathogens has accelerated, proving to be global, extremely dangerous,
and preventing reach of the set targets of MDG. With no borders between
ecosystems, the spread of drug resistance is linked to the following:
human life activity and travel, animals and the food trade, wild
animals, migration, transportation, as well as water and wind flow.
Further, EID are becoming untreatable and uncontrollable due to
shrinking of the existing therapeutic arsenal, mostly due to AMR.
Sensing the public health threat and having identified AMR as one of
the three greatest threats to global health, the World Health
Organization (WHO) announced the theme for World Health Day 2011 as
“Antimicrobial resistance: no action today, no cure tomorrow.”8
Moreover, the emergence of “superbugs” occurs when microorganisms
become resistant to most antimicrobials currently available. These
resistant superbug infections are of great concern, since this may
spread and cause death, placing burden on health care expenditures.
AMR in humans
In humans, antimicrobials are commonly used for the treatment and
control of infectious diseases that address three of the eight MDG,
namely: reducing child mortality rates, improving maternal health and
combating HIV/AIDS, malaria, and other diseases. Besides,
antimicrobials are used for treatment and prophylaxis of complex
surgeries, intensive care, organ transplants, care of premature babies
and the elderly, and survival of the immunosuppressed.
Severe problems of AMR are associated with multidrug-resistant
tuberculosis and extensively drug-resistant tuberculosis. Rarely,
mycobacterial infections of livestock are treated with antimicrobials,
which could therefore add to the pool of tuberculosis. Falciparum
malaria parasites resistant to artemisinins are emerging. New
resistance mechanisms, such as the beta-lactamase (New Delhi
metallo-β-lactamase- NDM-1) have emerged among several gram-negative
bacilli. The beta-lactamase resistant strains of Escherichia coli from
India have spread to other countries.9
Until recently, such completely resistant bacteria have only been found
in hospitals, such as methicillin-resistant staphylococcus aureus
(MRSA) and vancomycin-resistant enterococci (VRE) in hospital-acquired
infections. In India, within a span of three years, NDM-1 prevalence
has gone up from three percent in hospitals to 20 to 50 percent, and
patients were found to be resistant to colistin which is used against
multi resistant gram negative bacteria.10 Other causes of AMR in humans
include: over-the-counter selling of antimicrobials without a licensed
physicians prescriptions has been rampant mostly in the developing
world and pharmaceutical incentives to the physicians for
AMR in animals and environment
Manifestation of antimicrobial resistance in veterinary medicine is
intricate because of the number of animal species, the diversity of
environmental conditions in which the animals are reared, the
differences in the microbes involved and pathogenicity mechanisms, and
the complex epidemiology.11 In most parts of the world, routine use of
antimicrobials in animal husbandry account for more than 50% of the
tonnage of all antimicrobial production to promote growth and for
prophylaxis in food-producing animals of cattle, poultry, swine, fish,
and honeybee. In the United States alone, 80% of all antibiotics sold
are administered to food producing animals for growth promotion and
prophylaxis.12 It has been estimated that antibiotic use in animals and
fish is far greater than the usage in humans (as much as 1,000-fold
higher).13 Risk quantification by the use of antimicrobials in animal
husbandry is not possible due to the vast dispersal area from run-off
and other sources of environmental contamination.14
Further, use of antimicrobial agents in food-producing animals has also
contributed to the development of resistant pathogens with resistance
genes. The direct effect was observed more than 35 years ago, with high
rates of AMR in the intestinal flora of farm animals and farmers.15
Molecular detection tools have shown that resistant bacteria in food
producing animals reach consumers through meat products.16 Usually,
resistant microbes in animals are transferred to people, not only
through consumption of food but also through direct contact with
food-producing animals or through environmental spread. As an indirect
impact, it has been observed that up to 90% of antimicrobials given to
animals are excreted in urine and stool and then widely dispersed
through fertilizer, surface runoff, and groundwater, with a profound
impact on the environmental microbiome. This has implications on two
MDG’s namely: ensuring environmental sustainability, and developing a
global partnership for development.
Various environmental samples of different geological age have proved
that resistance genes in the environment are higher than those found in
pathogens, and have existed for thousands of years. The word
‘resistome’ refers to the population of resistant genes in nature.16,17
This has resulted in human infections with resistant microbes to
antimicrobial agents and is difficult or impossible to cure. Extensive
use of invasive procedures, and high rates of antimicrobial use,
results in a nosocomial “environmental resistome.” Of special concern
is resistance to antimicrobial agents classified by the World Health
Organization (WHO) as critically important for human medicine, such as
fluoroquinolones, third- and fourth-generation cephalosporins, and
Research and development of new antimicrobial agents
The discovery of antibiotics in the 1930s and 1940s transformed
medicine from a diagnostic to a therapeutic discipline.19 Sulphonamides
and penicillin came into use in the 1940s. Selman Waksman discovered
streptomycin in 1943 which propelled important findings related to the
‘secondary metabolites’ produced by actinomycetes,20 and the next 40
years was considered as the golden era of antimicrobials. New classes
of antibiotics were discovered, existing antibiotics were modified, and
synthetic components were constantly tailored to combat emerging AMR by
improving the clinical qualities. Until the late 1980s, the problem was
not considered significant as many new substances were developed and
marketed when resistance rendered existing drugs inefficient.
However, views changed, as few new antibiotics have been introduced
since the 1990s. In addition, financial challenges for antibiotic
development showed a poor investment return, as they are taken as a
short course to cure the targeted disease. In contrast, drugs that
treat non communicable diseases, such as high blood pressure, are
continuously taken for the patient’s life. This can be illustrated in
terms of net present value (NPV): at discovery, an antibiotic has a NPV
of –$50 million and are generally priced at a peak charge of
$1,000–$3,000 per course, whereas, NPV for a new musculoskeletal drug
is estimated to a +$1 billion and a chemotherapy for cancer sometimes
costs >$80, 000.21
Antibiotic development is now considered a global health crisis. The
average time required to take a product from the start of clinical
testing to regulatory approval is 7.2 years, this excludes phases of
discovery, research, preclinical and animal testing.22 Moreover, the
clinical approval success rate (the likelihood that a compound entering
clinical testing will eventually reach the marketplace) is only 16%.23
A report published in 2004 showed that, of 506 drugs in development by
15 large pharmaceutical companies and seven major biotechnology
companies, only six were antibiotics. This has declined further; by
2008, eight of the 15 major pharmaceutical companies had abandoned
antibiotic discovery programs and two others had reduced them.24
Approval of new antibacterial agents by the United States Food and Drug
administration has shown a decrease of 56% between 1998 and 2002, and a
75% decrease in systemic antibacterials approved from 1983 through
2007;25 evidence of continued decrease in approvals was noticed between
2003 and 2007.26 Yet another discouraging report mentions that no new
class of antibiotics for gram negative bacilli has been found in the
last four decades; only 2 drugs with new microbial targets (linezolid
and daptomycin) have been introduced since 1998.27 Recently, a study on
antibiotic development involving small firms as well as large
pharmaceutical companies revealed that only 15 of 167 antibiotics under
development had a new mechanism of action.28 Subsequently, a review
identified that eight out of nine synthetic compounds are derived from
quinolones, a class of antibiotic that may only require minor
chromosomal mutations to gain resistance.29 It is estimated that over
the next 5–10 years, the number of approved antibacterials will plateau
at a level similar to that of the past 5 years which may approximate 1
drug per year.30
The association between disease status and antimicrobials is
illustrated in Figure 1. While the drug development process diminishes
the disease load in a population it is countered by an increased
disease load in humans, animals including aquatic and the environment
Figure 1. Association between disease status and
Most of the emerging infectious diseases are zoonoses, which have a
direct influence on the majority of MDG. The emergence and spreading of
drug-resistant pathogens, particularly zoonoses, has accelerated due to
overuse, not following the prescribed length of use, misuse, and abuse
of antimicrobials. More essential medicines are failing. The speed with
which these drugs fail and are being lost far outpaces the development
of replacement drugs. AMR challenges control of infectious diseases,
hampers MDG, threatens a return to the pre-antibiotic era, increases
the health care budget, jeopardizes health-care gains achieved,
compromises health security, and damages trade and economies.
In order to reach the MDG, antimicrobial conservation must be one of
the essential strategies. With limited health care resources, achieving
a balance between conserving the effectiveness of existing
antibacterial drugs and developing new ones is attracting attention
among policy circles that will best serve public health, such as in
viral respiratory tract infections a “delayed prescription” (any
prescription for an antimicrobial where the patient is advised to delay
getting the antimicrobial agent). Preventing use of these drugs in
self-resolving disease with uncertain evidence of effectiveness would
limit the spread of antimicrobial resistance. In addition, maximizing
hospital infection-control practices, antimicrobial surveillance and
restricting the use of antibiotics in humans and animal husbandry can
achieve conservation of antimicrobials.
Finally, to overcome microbial evolution, issues in antibiotic
pipeline, and resistance in antimicrobials, intersectoral partnerships
in research among medical, veterinary medical, and environmental
disciplines, with specific epidemiological, diagnostic and therapeutic
approaches needed. The “10 x '20” initiative of the Infectious Disease
Society of America is one such initiative. Diagnostic tests to identify
resistant organisms with new approaches (i.e. procalcitonin levels) are
markers to facilitate decisions for when to use or stop antibiotics as
these levels reflect bacterial replication. Evidence has come from a
meta-analysis and has shown that decisions guided by procalcitonin
levels reduced antibiotic use by 51% without altering outcome.31 Joint
efforts are required under the “One Health”
multidisciplinary/interdisciplinary collaborative approach, beyond
individual professional boundaries, to stop antimicrobial resistance
against zoonoses (EID) and reach the MDG.
1. United Nations. United Nations Millennium Development Goals.
http://www.un.org/millenniumgoals/reports.shtml. Accessed July 27,
2. Taylor LH, Latham SM, Woolhouse MEJ. Risk factors for human disease
emergence. Phil Trans R Soc Lond B. 2001;356(1411):983-989.
3. Woolhouse MEJ, Taylor LH, Haydon DT. Population biology of multihost
pathogens. Science. 2001;292(5519):1109-1112.
4. Venn-Watson S, Stamper A, Rowles T. Thinking outside the terrestrial
box: How high-priority, emerging, and zoonotic marine mammal pathogens
reflect those of human pathogens. Eco Health. 2011;7.
5. Karesh WB, Dobson A, Lloyd-Smith JO, et al. Ecology of zoonoses:
Natural and unnatural histories. Lancet. 2012;380(9857):1936-1945.
6. American Veterinary Medical Association. One Health.
Accessed May 23, 2013.
7. One Health Initiative. www.onehealthinitiative.com. Accessed October
8. World Health Organization. WHO World Health Day.
http://www.who.int/world-health-day/2011/en/index.html. Accessed August
9. Thoen CO, Steele JH, Gilsdorf MJ. Mycobacterium bovis infection in
animals and humans, 2nd edition. Emerg Infect Dis. 2006;12(8):1306.
10. Castanheira M, Deshpande LM, Farrell SE, Shetye S, Shah N, Jones
RN. Update on the prevalence and genetic characterization of
NDM-1-producing Enterobacteriaceae in Indian hospitals during 2010.
Diagn Microbiol Infect Dis. 2013;75(2):210-213.
11. Acar JF, Moulin G, Page SW, Pastoret PP. Antimicrobial resistance
in animal and public health: Introduction and classification of
antimicrobial agents. Rev Sci Tech. 2012;31(1):15-21.
12. US Food and Drug Administration. 2010 summary report on
antimicrobials sold or distributed for use in food producing animals.
Accessed August 15, 2013.
13. Marshall BM, Levy S. Food animals and antibiotics: Impacts on human
health. Clin Microbiol Rev. 2011;24(4):718-733.
14. Aarestrup FM, Jensen VF, Emborg HD, Jacobsen E, Wegener HC. Changes
in the use of antimicrobials and the effects on productivity of swine
farms in Denmark. Am J Vet Res. 2010;71(7):726-733.
15. Ansari F, Molana H, Goossens H, Davey P. ESAC II Hospital Care
Study Group. Development of standardized methods for analysis of
changes in antibacterial use in hospitals from 18 European countries:
the European Surveillance of Antimicrobial Consumption (ESAC)
longitudinal survey. Antimicrob Chemother. 2010;65(12):2685-2691.
16. Wright GD. Antibiotic resistance in the environment: A link to the
clinic. Curr Opin Microbiol. 2010;13(5):589-594.
17. D'Costa VM, King CE, Kalan L, et al. Antibiotic resistance is
ancient. Nature. 2011;477(7365):457-461.
18. Aidara-Kane A. Containment of antimicrobial resistance due to use
of antimicrobial agents in animals intended for food: WHO perspective.
Rev Sci Tech. 2012;31(1):277-287.
19. Infective Diseases Society of America (IDSA). Combating
antimicrobial resistance: policy recommendations to save lives. Clin
Infect Dis. 2011;52(5):S397-428.
20. Aminov RI. A brief history of the antibiotic era: lessons learned
and challenges for the future. Front Microbiol. 2010;1:134.
21. Sharma P, Towse A. New drugs to tackle antimicrobial resistance:
analysis of EU policy options.
Accessed July 9, 2013.
22. Kaitin KI. Deconstructing the drug development process: The new
face of innovation. Clin Pharmacol Ther. 2010;87(3):356-361.
23. The NIH Common Fund. Common Fund Initiative.
http://nihroadmap.nih.gov/initiatives.asp. Accessed May 16, 2013.
24. Taubes G. The bacteria fight back. Science. 2008;321(5887):356-361.
25. Infectious Diseases Society of America. The 10×20 Initiative:
Pursuing a global commitment to develop 10 new antibacterial drugs by
2020. Clin Infect Dis. 2010;50(8):1081-1083.
26. Spellberg B, Guidos R, Gilbert D, et al. The epidemic of antibiotic
resistant infections: A call to action for the medical community from
the Infectious Diseases Society of America. Clin Infect Dis.
27. Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE. Trends in
antimicrobial drug development: Implications for the future. Clin
Infect Dis. 2004;38(9):1279-1286.
28. Braine T. Race against time to develop new antibiotics. Bull World
Health Organ. 2011;89(2):88-89.
29. Butler MS, Cooper MA. Antbiotics in the clinical pipeline in 2011.
J Antibiot (Tokyo). 2011;64(6):413-425.
30. Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no
ESKAPE! An update from the Infectious Diseases Society of America. Clin
Infect Dis. 2009;48(1):1-12.
Tang H, Huang T, Jing J, Shen H, Cui W. Effect of procalcitonin guided
treatment in patients with infections: A systematic review and
meta-analysis. Infection. 2009;37(6):497-507.