1AC

Antibiotic resistance, known as ABR or superbugs are on the rise now

Beaubien 22, Jason. “Antibiotic-resistant bacteria kill 1.2 million a year — more than HIV/AIDS :
Goats and Soda.” NPR, 20 January 2022,
https://www.npr.org/sections/goatsandsoda/2022/01/20/1074373834/why-humans-are-losing-the-race-agai
nst-superbugs

Drug-resistant bacteria — also known as superbugs — are on the rise globally, and they're now killing
more people each year than either HIV/AIDS or malaria. And low- and middle-income countries are being hit the hardest by the rise in antibiotic-resistant
infections. "That resistance out there is actually now one of the leading causes of death in the world," says Dr. Chris Murray, the director of the Institute for Health Metrics and Evaluation.

infections directly killed 1.2 million

Murray is one of the authors of a new study, published in the medical journal The Lancet, that finds that in 2019, drug-resistant

people and played a role in 5 million more deaths worldwide. Murray and his colleagues set out to
quantify how much of a problem antibiotic resistance is globally, and they found that bacteria are
mutating to evade antibiotics at a pace far faster than many researchers had previously forecast. These deadly new
strains of bacteria are causing untreatable blood infections, fatal pneumonia, relentless urinary tract infections, gangrenous wounds and terminal cases of sepsis, among other conditions. The
conventional wisdom used to be that the failure of antibiotics was a "First World" problem. But Murray says this new study shows it happening all over the world. "In the past, we all thought that
you had to be rich enough to use a lot of antibiotics inappropriately to have this problem," he says. "But that's not the case." The researchers calculate that deaths caused directly by antibiotic
resistance are the highest in sub-Saharan Africa, causing 24 deaths per 100,000 population annually, compared with an average fatality rate of 13 per 100,000 in high-income countries. Australia
has the lowest mortality rate globally from antibiotic resistance, at 6 deaths per 100,000. Latin America is right in the middle. But Fiorella Krapp Lopez, an infectious disease physician in Lima,
Peru, says being in the middle is still quite bad. "We do have a very high frequency of resistance to different types of antibiotics, first line and second line [antibiotics]," Krapp says. "And the
problem has been increasing in the last years." She says antibiotic resistance is affecting every level of health care in Peru. "Unfortunately, I think it's everywhere. We are seeing it in the
community with infections that used to be very simple to treat, like urinary infections," she says. Physicians are seeing minor wounds that in the past may have needed only a bandage but now are
turning into multidrug-resistant infections. "And we also see it in very sick patients with bloodstream infections or very severe pneumonia. So unfortunately, it's across the full spectrum of
bacterial infectious diseases right now in Peru," she says. Krapp was one of dozens of researchers around the world who contributed to the new Lancet report. She provided data specifically on
available to
drug resistance in Peru. She says there are many reasons that this problem is harder to address in low- and middle-income countries. First, antibiotics are often readily

anyone without a prescription. Misuse and overuse of these drugs fuels mutations in bacteria, leading to
more resistance. Second, the systems to flag and test for potentially drug-resistant infections are not as robust as in some wealthier countries. Third, low- and middle-income countries in general report higher rates of
infections in hospitals than high-income countries do, and those infections are more likely to be drug resistant. Fourth, while some new, more powerful antibiotics are being developed, lower-income countries are still dependent on

older, cheaper, less-effective drugs. Krapp says the COVID-19 crisis exacerbated all of these problems in Peru. And while it's too early to tell, she worries that the coronavirus pandemic has led
to a significant increase in drug resistance. "First, there was a lot of antibiotic use during the pandemic," she says. As the COVID-19 crisis pounded Peru,
many people who contracted the virus did not want to go anywhere near the overcrowded hospitals, so they self-medicated at home. "It is still very easy to get antibiotics in the local pharmacy
without a prescription," Krapp notes. "Unfortunately, more than 70, 80% of [COVID-19] patients that arrived to the hospital were already using antibiotics at home." They believed the drugs
would aid in their recovery. But antibiotics target bacteria and wouldn't be of much help against a coronavirus. This scenario may be one of the reasons that Peru has had the world's highest per
capita death rate from COVID-19. At times, hospitals and clinics were barely able to function as they were inundated with patients. "We believe that a lot of the high COVID mortality that we
had in Peru was due to secondary infections acquired in the hospitals rather than just by COVID-19," Krapp says. Whether or not that happened is hard to say. Monitoring for antibacterial
resistance in Peru — and in many other lower-income countries — is limited during the best of times but especially unlikely when hospitals are overflowing with COVID-19 patients. "During the
pandemic, the hospitals were overloaded. A lot of patients went into ICUs that were understaffed. That was just the perfect storm to have a very high transmission of these [drug-resistant]
pathogens," she says. It's unclear if that was happening because as health care workers were simply trying to keep COVID-19 patients breathing, testing bacterial samples for resistance fell low
on the priority list. Krapp says that overall she's very concerned that are evolving and learning how to evade what had been some of the world's most powerful drugs. "We are in a race, and
bacteria

bacteria are moving faster than we are," she says. "They are becoming resistant much faster than we humans are able to
these

create new antibiotics and make those antibiotics accessible to the most vulnerable populations."

Phages are natural predators to bacteria and fight superbugs

Yale Medicine 19
“How Phage Therapy Kills Superbugs: Weaponizing Viruses to Fight Infections.” Yale Medicine, 18
November 2019, https://www.yalemedicine.org/news/phage-therapy. Accessed 25 August 2022.

Phage therapy—using specific viruses to fight difficult bacterial infections—shows great promise as a
tool for solving the problem of antibiotic-resistant bacteria (also called superbugs). Here at Yale
Medicine, the experimental treatment has already been used to benefit some patients—good news given
that antibiotic-resistant bacteria are now considered one of the most alarming public health problems. A
recent report from the Centers for Disease Control and Prevention (CDC) blames the problem for a death
every 15 minutes here in the U.S. Since the discovery of penicillin, doctors have used antibiotics to cure
people of once lethal bacterial infections. But now we know that, over time, bacteria have the ability to
protect themselves by evolving and becoming stronger and more complex (called antibiotic resistance).
Researchers have found that viruses can be a powerful tool that can be used against them. Specifically, a
type of friendly virus called bacteriophage (sometimes referred to as just phage) can be weaponized to
fight even the most difficult bacterial infections. This works because, unlike viruses that make us sick, phages can only infect
bacteria—and they are even selective about which bacteria they target. These phages are not rare; phages come from nature and are found nearly
everywhere in the world. This gives them the power to become, potentially, superheroes in our battle against resistant superbugs. This video
explains how Yale research scientist Benjamin Chan, PhD, collaborates with Yale Medicine doctors like Jonathan Koff, MD, to not only develop
phage therapy, but to use them to treat people who are especially vulnerable to infection (for instance, patients with cystic fibrosis). The goal is to
develop a library of effective treatments for specific types of bacteria and make these treatments available to patients with antibiotic-resistant
infections when other options are exhausted. “It’s definitely the dream,” says Chan. “It’s fantastic to go from doing basic research and then
bringing it to a patient in the clinic.”

Phage banks and research already found in NATO countries

Principi et al 21
Principi, Nicola, et al. “Learning From Mistakes: The Role of Phages in Pandemics.” Frontiers, 17 March
2021, https://www.frontiersin.org/articles/10.3389/fmicb.2021.653107/full. Accessed 6 September 2022.

Need for a Phage-Based Regulatory Framework and Future Perspectives. The current regulatory framework worldwide is not allowing the use of
phage therapy in Western Europe and the United States (Parracho et al., 2012). Hence, the phage community calls for new and specific standards
to implement phage therapy. The
phage therapy-based regulatory framework should include providing
well-characterized phages, including isolation and purification, defining host range, sequencing, and
storage in phage banks. These will provide an available well-defined collection ready-to-use for clinical care. Importantly, patients
should be informed of the phage therapy and given the option to decide to try it. It is also worth mentioning that it is recommended by the FDA to
follow phage manufacturing under Good Manufacturing Practice (GMP) guidelines and infrastructure. However,
the implementation
of GMP is considered for a large phage production whereas phage-specific patients are produced for a
limited number of phages, thus, a simpler GMP system is recommended. Phage banks are already
increasing, and some of them are located in Belgium, Republic of Georgia, Russia, Germany, Switzerland,
Finland, and Canada (Moelling et al., 2018). In addition, Phage Directory, an online database of phage
laboratories, phages, and bacterial hosts, in which phage researchers, regulators, and biotech companies
are communicated, is an interesting example of a network to implement the use of phages in clinics. This
huge phage database provides an opportunity to continue working on research to form therapeutic phages,
even as a form of individualized medicine. Political authorities, stakeholders, academics, and researchers
around the world must be aware of the need for urgency to treat a high number of people suffering from
MDR infections, which are predicted to be much higher as a primary and as a secondary infection during
the current pandemics, being a major global health threat. This can be achieved by the establishment of a
phage therapy-related regulation to allow for phage therapy research development and to increase
incentives in order to increase basic research and translate it to proper clinical trials.

Superbugs kill 5 million people every year - will only increase

Beaubien 1-20-22
Beaubien, Jason. “Antibiotic-resistant bacteria kill 1.2 million a year — more than HIV/AIDS : Goats and
Soda.” NPR, 20 January 2022,
https://www.npr.org/sections/goatsandsoda/2022/01/20/1074373834/why-humans-are-losing-the-race-agai
nst-superbugs. Accessed 26 August 2022.

Drug-resistant bacteria — also known as superbugs — are on the rise globally, and they're now killing
more people each year than either HIV/AIDS or malaria. And low- and middle-income countries are
being hit the hardest by the rise in antibiotic-resistant infections. "That resistance out there is actually now
one of the leading causes of death in the world," says Dr. Chris Murray, the director of the Institute for
Health Metrics and Evaluation. Murray is one of the authors of a new study, published in the medical
journal The Lancet, that finds that in 2019, drug-resistant infections directly killed 1.2 million people and
played a role in 5 million more deaths worldwide. Murray and his colleagues set out to quantify how
much of a problem antibiotic resistance is globally, and they found that bacteria are mutating to evade
antibiotics at a pace far faster than many researchers had previously forecast. These deadly new strains of
bacteria are causing untreatable blood infections, fatal pneumonia, relentless urinary tract infections,
gangrenous wounds and terminal cases of sepsis, among other conditions. The conventional wisdom used to be that
the failure of antibiotics was a "First World" problem. But Murray says this new study shows it happening all over the world. "In the past, we all
thought that you had to be rich enough to use a lot of antibiotics inappropriately to have this problem," he says. "But that's not the case." The
researchers calculate that deaths caused directly by antibiotic resistance are the highest in sub-Saharan Africa, causing 24 deaths per 100,000
population annually, compared with an average fatality rate of 13 per 100,000 in high-income countries. Australia has the lowest mortality rate
globally from antibiotic resistance, at 6 deaths per 100,000. Latin America is right in the middle. But Fiorella Krapp Lopez, an infectious disease
physician in Lima, Peru, says being in the middle is still quite bad. "We do have a very high frequency of resistance to different types of
antibiotics, first line and second line [antibiotics]," Krapp says. "And the problem has been increasing in the last years." She
says antibiotic resistance is affecting every level of health care in Peru. "Unfortunately, I think it's everywhere. We are seeing it in the community
with infections that used to be very simple to treat, like urinary infections," she says. Physicians are seeing minor wounds that in the past may
have needed only a bandage but now are turning into multidrug-resistant infections. "And we also see it in very sick patients with bloodstream
infections or very severe pneumonia. So unfortunately, it's across the full spectrum of bacterial infectious diseases right now in Peru," she says.
Krapp was one of dozens of researchers around the world who contributed to the new Lancet report. She provided data specifically on drug
resistance in Peru. She says there are many reasons that this problem is harder to address in low- and middle-income countries. First, antibiotics
are often readily available to anyone without a prescription. Misuse and overuse of these drugs fuels mutations in bacteria, leading to more
resistance. Second, the systems to flag and test for potentially drug-resistant infections are not as robust as in some wealthier countries. Third,
low- and middle-income countries in general report higher rates of infections in hospitals than high-income countries do, and those infections are
more likely to be drug resistant. Fourth, while some new, more powerful antibiotics are being developed, lower-income countries are still
dependent on older, cheaper, less-effective drugs. Krapp says the COVID-19 crisis exacerbated all of these problems in Peru. And while it's too
early to tell, she worries that the coronavirus pandemic has led to a significant increase in drug resistance. "First, there was a lot of antibiotic use
during the pandemic," she says. As the COVID-19 crisis pounded Peru, many people who contracted the virus did not want to go anywhere near
the overcrowded hospitals, so they self-medicated at home. "It is still very easy to get antibiotics in the local pharmacy without a prescription,"
Krapp notes. "Unfortunately, more than 70, 80% of [COVID-19] patients that arrived to the hospital were already using antibiotics at home."
They believed the drugs would aid in their recovery. But antibiotics target bacteria and wouldn't be of much help against a coronavirus. This
scenario may be one of the reasons that Peru has had the world's highest per capita death rate from COVID-19. At times, hospitals and clinics
were barely able to function as they were inundated with patients. "We believe that a lot of the high COVID mortality that we had in Peru was due
to secondary infections acquired in the hospitals rather than just by COVID-19," Krapp says. Whether or not that happened is hard to say.
Monitoring for antibacterial resistance in Peru — and in many other lower-income countries — is limited during the best of times but especially
unlikely when hospitals are overflowing with COVID-19 patients. "During the pandemic, the hospitals were overloaded. A lot of patients went
into ICUs that were understaffed. That was just the perfect storm to have a very high transmission of these [drug-resistant] pathogens," she says.
It's unclear if that was happening because as health care workers were simply trying to keep COVID-19 patients breathing, testing bacterial
samples for resistance fell low on the priority list. Krapp says that overall she's very concerned that bacteria are evolving and learning how to
evade what had been some of the world's most powerful drugs. "We are in a race, and these bacteria are moving faster than we
are," she says. "They are becoming resistant much faster than we humans are able to create new
antibiotics and make those antibiotics accessible to the most vulnerable populations."

Antibiotic resistance will result in extinction

Farrah 20
Farrah, Matt. “A Threat Deadlier Than Climate Change: Antibiotic Resistance.” AMR Insights, 20
August 2020, https://www.amr-insights.eu/a-threat-deadlier-than-climate-change-antibiotic-resistance/.
Accessed 6 September 2022.

In 2019, England’s Chief Medical Officer warned that antimicrobial resistance might cause the death of
around 10 million people every year. This is a threat that may overtake climate change in causing
humanity’s extinction. What are antibiotics? Antibiotics are drugs that are designed to either destroy bacteria or slow down their growth.
They can cost billions of euros and take years to develop. Unfortunately, they don’t work against fungal or viral infections which means there’s no
point in taking them for coughs, colds or influenza. The problem is that resistance to these drugs is growing rapidly. Professor Dame Sally Davies
noted that the number of bugs immune to antibiotics is on the rise, with a variety of causes being cited, including: The high volume of people
carrying harmful bacteria Overuse of antibiotics Non-adherence to prescribed hygiene practice These are also the primary reasons why numerous
large infection outbreaks occur in hospital. In this setting, many patients are susceptible due to their weak immune systems. When a particular
bacteria strain becomes resistant to antibiotics, treatment is often difficult or even impossible. There are also cases where these resistant bacteria
will pass their genes to other strains. Antibiotic resistance in farming and the environment The farming industry also uses antibiotics to protect
livestock from bacterial infection. However, in some countries, farmers administer these drugs in low doses as a preventive measure or even to
promote growth. Unfortunately, both the drug and the anti-resistant bacteria can escape farms and contaminate the local food chain and
environment. Nurses.co.uk published an article in which Dame Sally proposed that, in order to protect the British public, the UK should stop
importing beef and other meats from countries that misuse antibiotics. Why do humans need antibiotics? Every day, you can encounter bacteria
that could potentially be harmful to your health. For instance: Due to injury, even if it’s just a small scratch When you have been exposed to a
contaminated environment After undergoing a medical procedure (ranging from dental work to cancer therapy) Doctors administer antibiotics to
people with a bacterial infection, a condition where the uncontrolled growth of harmful bacteria can cause cell damage. These bacteria also
excrete toxins that are harmful to the human body. Usually, people’s immune systems can fight off the bacteria. However, if the infection is too
strong, they will need antibiotics to help the body recover. Currently, around 46,000 people die from sepsis in the UK every year, it is a severe
condition where harmful bacteria invade an individual’s bloodstream or tissues. The primary treatment for sepsis is antibiotics. Otherwise, the
infection could lead to organ failure, shock and ultimately death. The UK’s response By 2014, the UK had reduced antibiotic use by almost 10%
and by around 40% in livestock. However, drug-resistant
infections still increased by more than 30% between 2013
and 2017. Dame Sally laments the apparent lack of concern for the potential doomsday disaster. In her
view, despite the vital importance of this subject, not enough is being done in terms of research.
Conclusion If the current antibiotics being used are no longer effective, then even minor infections such
as a skin wound could cause death. There is a need to reduce the usage of antibiotics in both humans and
agriculture. It is pointless continuing to manufacture powerful drugs if bacteria can develop resistance to
them in a short period of time. Antibiotics should only be used when necessary. Furthermore, medical
researchers should find safer alternatives that can overcome resistant bacteria and therefore treat people
and animals successfully.

Poverty leads to conflict

Marks 16
Marks, Zoe. “Poverty and conflict.” GOV.UK, October 2016,
https://assets.publishing.service.gov.uk/media/5980670a40f0b61e4b00003e/Poverty-and-conflict_RP.pdf.
Accessed 7 September 2022.

Poverty and conflict are widely understood to be closely interconnected; with poverty making countries
more prone to civil war, and armed conflict weakening governance and economic performance, thus
increasing the risk of conflict relapse (Goodhand 2001). The selected readings in this pack move beyond
reductive and harmful assumptions about ‘pathologies’ of poverty to examine the latest research into the
poverty-conflict nexus. Earlier studies identified macro-level factors that made countries more likely to
experience armed conflict. For example, low per capita income and large populations correlate with civil
war, whereas ethnic and religious diversity does not make countries more prone to conflict (Fearon &
Laitin 2003). Newer research examines the processes and mechanisms that precipitate and shape violence
on the ground. At the state level, poverty can lower resilience to conflict by weakening government
institutions, stripping capacity for public goods provision, and limiting the projection of power and
authority, whether soft or coercive. Poverty also compounds vulnerability to insurgency at the individual
and community level by lowering the opportunity cost of mobilising for violence. High rates of
unemployment and inequality, combined with low levels of education and development, are thought to
soften the ground for recruitment and provide motives to fight (Humphreys & Weinstein 2008).1 These
individual correlates of poverty often follow systematic patterns that lead to ‘horizontal inequalities’.
Horizontal inequalities occur when members of ethnic, religious, or other identity groups have unequal
access to public goods, opportunities and resources. Group-level inequalities can generate social and
economic polarisation that increases the risk of violent conflict (Østby 2008; Stewart 2009). Of course,
these dynamics alone do not start wars. Political grievances and conflict proneness are most likely to lead
to violence—from terrorism to civil war—when poverty and inequality combine with repression,
particularly in anocracies, regimes that are neither strongly democratic, nor wholly autocratic (Abadie
2004; Mousseau et al. 2003). Yet, governance can also mitigate the link between poverty and conflict.
Resource governance plays a key role in shaping countries’ economic and structural vulnerability to
conflict (Ross 2004; Thies 2010). While social welfare spending, particularly on education and
healthcare, and stable aid flows reduce the risk of war, aid shocks and excessive military spending
increase its likelihood (De Ree & Nillesen 2009; Nielsen et al. 2011; Savun & Tirone 2011; Taydas &
Peksen 2012). Similarly, economic shocks, such as the 2008 spike in global food prices, can spark social
unrest that escalates into armed conflict in vulnerable political settings (Blattman & Miguel 2010; Lagi et
al. 2011). Once conflict breaks out, it hits the poor the hardest: social welfare is depleted as goods and
services are diverted to the war effort; rural infrastructure is destroyed in contested territory; and justice
and security provision retracts into urban areas and elite enclaves. Conflict causes and compounds
poverty. First depleting labour and human capital, then destroying productive assets and financial capital, and finally, eroding the social capital
of trust and cooperation upon which strong political and economic systems depend (Mercier et al. 2016). The war economies and institutions that
are created in conflict are overwhelmingly extractive, and tend to warp local political economies through their reliance on smuggling and
coercion (Keen 1997). These practices can become conflict drivers in their own right, and can perpetuate conflict-related violence and inequality
even after war has officially ended (Justino 2013). Our understanding of the effects of conflict over time is still nascent. Evidence from Burundi
suggests that households exposed to violence at the local level are more likely to face long-term poverty and deprivation than those who were
spared. Exposure to violence also hurts those who participate in armed groups, as they have to overcome an education deficit, social stigma, and
psychological distress that can leave them economically alienated and socially marginalised (Annan et al. 2011). At the country-level, this leads
to what some call the ‘conflict trap’ (Hegre et al. 2011). The strongest predictor of civil war onset is whether a country has recently experienced
vicious
civil war, with harmful ‘neighbourhood effects’ making surrounding countries similarly vulnerable to conflict spillover. However,
cycles of conflict that exacerbate poverty, slow economic growth, destabilise weak institutions and lead to
violent relapse are not inevitable. The international response to post-conflict reconstruction can support a
potential ‘phoenix effect’ of strengthened economic growth, where infrastructure development, debt relief
and foreign aid, and currency stabilisation help to generate private investment (Addison et al. 2001; Kang
& Meernik 2005). More importantly, local communities have proven remarkably resilient in rebuilding
trust, social cohesion and civic engagement after war ends (Bellows & Miguel 2009; Blattman 2009;
Gilligan et al. 2014; Voors et al. 2012).

Civil war and poverty are linked

Patricia, et. al 12
Justino, Patricia, ' War and Poverty', in Michelle R. Garfinkel, and Stergios Skaperdas (eds), The Oxford
Handbook of the Economics of Peace and Conflict, Oxford Handbooks (2012; online edn, Oxford
Academic, 21 Nov. 2012), https://doi.org/10.1093/oxfordhb/9780195392777.013.0027
This article surveys the existing empirical evidence on the interlinkages between civil war and poverty.
Conflict can impair economic performance, and poor economic performance provides fertile ground for
the outbreak of war within nations. The survey highlights these interlinkages, focusing on the decision
making of individuals and households. Considering at the same time how social norms and forms of
institutional organization change during civil wars, and how such changes imply different constraints on
individual decision making, it also sheds light on the various factors that influence the duration of civil
conflict.

Poverty disproportionately harms marginalized groups

Beech et al 21
Beech, Bettina M et al. “Poverty, Racism, and the Public Health Crisis in America.” Frontiers in
public health vol. 9 699049. 6 Sep. 2021, doi:10.3389/fpubh.2021.699049
Conceptual Framework of Poverty and Health. Socioeconomically disadvantaged populations across the
globe bear a disproportionate burden of chronic diseases and are least likely to receive evidence-based
care leading to optimal clinical outcomes (51, 52). A basic understanding of the vulnerabilities of the
marginalized and oppressed populations will facilitate the adaptation and adoption of the necessary
policies to support disease treatment and prevention guidelines (52). The WHO has identified three key
tenets to improving health at a global level that each reinforces the impact of socioeconomic factors: (1)
improve the conditions of daily life; (2) tackle the inequitable distribution of power, money, and
resources, the structural drivers of those conditions of daily life, globally, nationally, and locally; and (3)
develop a workforce trained in the social determinants of health and raise public awareness about social
needs and the social determinants of health (53). Social factors and health behaviors have contributed
substantially to the growing non-communicable disease epidemics (e.g., obesity, diabetes, hypertension,
and mental health disorders). A deeper understanding and integration of social and behavioral sciences is
needed to equip medical and public health communities to address the challenge of providing quality care
in the setting of contrasting financial and public health policies to control costs (54). A conceptual
framework emphasizing the key pathways through which poverty and structural racism may influence
wellness and health outcomes is shown in Figure 1.

Including a laundry list of impacts

Beech et al 21
Beech, Bettina M et al. “Poverty, Racism, and the Public Health Crisis in America.” Frontiers in
public health vol. 9 699049. 6 Sep. 2021, doi:10.3389/fpubh.2021.699049
Perniciousness of Persistent Poverty. The Social Determinants of Health (SDoH) are macro-level factors that shape the economic, physical, psychological, and social
environments in which people live (56). They are often viewed as having the capacity to enhance or diminish the resources available to individuals to promote health,
including but not limited to the food supply, housing, economic and social relationships, transportation, employment, criminal justice, education, and health care,
whose distribution across populations effectively determines length and quality of life and the programs and policies that direct them (23). The World Health
Organization Commission on Social Determinants of Health has found that the poor health status of low resource persons, communities, and nations is directly related
to the unequal distribution of power, income, goods, and services (53). Social structures and institutions with unequal and unfair social policies, economic
arrangements, and practices have contributed to much of the health inequity present in the world. A brief overview of select medical conditions follows.
Communicable diseases: Poverty can contribute to many communicable diseases including many acute
and chronic infectious diseases. Poverty and the associated disadvantage of personal and social resources often
lead to unsafe habitation and lack of cleanliness, unhealthy diets, and malnutrition (including maternal-fetal), poor
water quality, increased exposure to infectious diseases, environmental pollution and toxins, and more (57). The
rates of infectious disease morbidity and mortality in low resource households, communities, and nations over
decades bear witness to the considerable impact of economic inequality on health (53). Maternal and child health:
Poverty has been strongly linked with poor reproductive outcomes, both independently and in combination
with exposure to discrimination (58–61). Maternal and child health among low-income and racial/ethnic
minority groups are particularly susceptible to psychological stress, nutrition, substance use, and more
(58, 62, 63). Incarcerated youth: Globally and in the US, incarceration rates are higher among poor and
marginalized groups (64). For children within the criminal justice system or otherwise deprived of liberty
are at particularly high risk of violence, rape and sexual assault, sexually transmitted diseases, substance
use disorders, mental illnesses, and physical disorders, many of which will continue throughout the life
course (65, 66). Furthermore, adult incarceration can create health deficits in familial youth (64). Chronic
non-communicable diseases: Similar patterns of disparities negatively are observed in the incidence and
prevalence of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, and others
(67–70). Poverty can also have indirect implications for health (5, 71). Race-based economic
disadvantages can influence other social determinants as the intersection with poverty can further limit
housing, educational, and employment opportunities, and these have also been linked to worse health
outcomes (58, 72–74). Poverty can also influence individual perceptions and behaviors (75). Relative and
absolute economic deprivation can shape expectations and perceived life chances in a manner that
individuals focus on surviving rather than thriving. Mental health: In addition to the more traditional
mental health conditions that may limit daily functioning, the additional chronic stress associated with
navigating basic needs in a state of poverty can impair cognitive processing and the ability to remember
and to perform implementation tasks (76), along with mistrust which may impact the ability of the
individual to follow up on medical appointments, provider recommendations and more to conspire to limit
health outcomes (77). In summary, the impact of poverty on both the physical and psychological aspects of a person can play an important role in the many dimensions
associated with the development and progression of diseases. The socioeconomic status of the individual may considerably impact the perception of the individual of many life issues, such as
food, education, language, and time (75). While these concepts may be apparent and easily recognizable in other social disciplines, their presence and implications may be lost or concealed to
many health care providers. Therefore, an understanding of how poverty may influence worldviews is critical for health professionals to truly understand the diverse group of patients they care
for and how to better connect with those in an impoverished situation to optimize the effectiveness of traditional and alternative health strategies and recommendations. Table 1 highlights the
influence of socioeconomic class including income on the context of patient-specific needs, values, and preferences, as well as considerations as to how racism may be operating in that setting.

Phages decrease food-borne illness - 420,000 deaths annually

Sokolowska 19
Sokołowska, Barbara. “Bacteriophages—a new hope or a huge problem in the food industry.” NCBI, 24
October 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946638/. Accessed 24 August 2022.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946638/

Food is the primary route of transmission for more than 200 known diseases. The leading bacterial
food-borne pathogens of concern are Salmonella, Campylobacter, Shiga toxin-producing E. coli, and
Listeria monocytogenes [32]. Each of them can be associated with serious gastrointestinal infections.
Food-borne diseases remain a major cause of hospitalization and death worldwide, despite many advances
in modern technologies including food sanitation techniques and pathogen surveillance. As estimated by
the World Health Organization (WHO), 600 million—almost one in 10 people in the world—fall ill after
eating contaminated food and 420 000 die every year [33]. Several approaches are used to improve the
safety of our foods, but food-borne outbreaks occur relatively frequently. A new multihurdle approach
identified to prevent the food-borne bacterial pathogens from reaching the consumers is the use of lytic
bacteriophages for targeting specific food-borne bacteria in foods, without deleteriously impacting their
normal—and often beneficial—microflora. This approach is termed ‘bacteriophage or phage biocontrol’
[34]. Table 1 summarizes the list of studies on bacteriophage biocontrol of the more important food-borne
pathogens. Since the regulatory acceptance of the first phage-based product, ListShield™ (approved in
2006 as ‘generally recognized as safe’), for use in the control of L. monocytogenes in meat and poultry
products, the attempts to develop new phage-based technologies for pathogen control in postharvest foods have increased [3],[35]. The main
organizations approving bacteriophage cocktails for use in agri-food sector are the European Food Safety Authority (EFSA) and the US Food and
Drug Administration (FDA).The production of commercially available bacteriophage cocktails should be carried out according to the good
manufacturing practices. Bacteriophages used in phage-based products should be strictly lytic (use of lysogenic phages for phage therapy is
undesirable due to horizontal gene transfer) and effective against the highest possible number of strains belonging to the target bacterium [8]. It is
recommended to use cocktails consisting of a mixture of bacteriophages to achieve improved efficiency and avoid the formation of strains
resistant to bacteriophages [3],[36]. Changes in the composition of phage cocktails should be made systematically; however, this may be
associated with additional difficulties in the production of these cocktails. For example, according to the EU regulations (1107/2009 EC), changes
in the composition of plant protection products based on bacteriophages may require a new registration [8]. Campylobacter infections are among
the most frequently encountered food-borne bacterial infections around the world. Handling and consumption of raw or
undercooked poultry products have been identified to be the main route of transmission of these
infections. Studies have analyzed the use of phages to target the Campylobacter bacteria growing on the surface of chicken carcasses, raw
chicken meat, and raw and cooked beef [37]–[39]. The Shiga toxin-producing E. coli serotype O157:H7 can invade the human gastrointestinal
tract and trigger disease, with symptoms including abdominal cramping and hemorrhagic diarrhea. Recent work has demonstrated that E.
coli-specific phage preparation was effective in inhibiting this serotype [41]–[46]. Listeria monocytogenes is a major food-borne pathogen of
public health concern associated with a high mortality rate in individuals at risk such as pregnant women, neonates, immunocompromised
individuals, and the elderly [61]. It is therefore critically important to ensure the safety of the food chain, especially in the case of ready-to-eat
(RTE) foods. The
application of bacteriophages to assorted foods has been shown to be effective at reducing
contamination with L. monocytogenes (Table 1). Food-borne Salmonella infections are a major public health concern worldwide. All
Salmonella phages reported so far have been able to decrease the number of viable cells present in raw meats, processed and RTE foods, and fresh
products but not on apple slices. This indicates that the acidic pH of the apples may have inactivated the phages [17]. The concept of hurdle
technology has been applied in the food industry following the observations that the rate of microorganism survival decreases greatly when the
organisms are confronted with multiple antimicrobial factors or hurdles [62]. Several studies demonstrated the synergistic effect of using a
bacteriophage with another food-grade antimicrobial such as nisin [57] and trans-cinnamaldehyde oil [46]. The antibacterial effect was also
reported to be improved when phages were combined with a protective culture or modified atmosphere packaging [45],[49]. The Listeria-specific
phage was effective against L. monocytogenes when used alone, and additionally, enhanced the effectiveness of other antimicrobials such as
sodium diacetate and potassium lactate when used together [51],[52]. In recent years, an
increasing number of phage products
have been commercially used for pathogen control, as shown in Table 2.
Studies prove phage cocktails are effective against food borne diseases
Picozzi et. al 21, Picozzi Claudia, Garcia Pilar and Vives Martha. Editorial: Bacteriophages to Fight
Food-Borne Pathogens/Phages Struggling for Food Safety.” Frontiers, 23 September 2021,
https://www.frontiersin.org/articles/10.3389/fmicb.2021.741387/full
In recent years, the application of phage therapy for the control of pathogenic bacteria has been experiencing a new renaissance driven by the emergence of multidrug-resistant bacteria (Gordillo Altamirano and Barr, 2019).
Bacteriophages are natural predators of bacteria, presenting several benefits, the main ones related to their high specificity and their harmlessness to humans, animals, and plants. The interactions between phages and their hosts play an
important role in the evolutionary ecology mechanisms of bacterial resistance and phage infectivity (“antagonistic coevolution”). Some failures in the application of phage therapy are indeed due to bacterial mutations that led to
resistance (Buckling and Rainey, 2002). To be considered as excellent candidates as biocontrol agents in foods, phages should be strictly lytic and possibly have a broad host range. To overcome this limitation, formulations with more
than one phage (phage cocktails) can be used. But how many and which isolates should compose these cocktails? The optimum formulation should provide a compromise between achieving a high reduction on the bacterial load and
minimizing the side effects (cost of production, dysbiosis, risk of horizontal transfer of toxins, antibiotic resistance, or virulence genes) of an increasing cocktail complexity. Molina et al. tackled these challenging questions proposing a
new pipeline for designing phage cocktails. Their analysis started with the building of a phage-bacteria infection network (PBIN) from host range matrices using two different algorithms, a genetic and a heuristic one. The first one led
to the lower temperature, i.e., increased nestedness, simplifying the identification of phages with the broadest host range. They performed a meta-analysis of 35 host range matrices and proposed a new metric (Φ) for estimating phage
cocktail size. At the end they applied an agglomerative hierarchical clustering on their data, developing a cocktail that was able to reduce bacterial counts of cheese-isolated Escherichia coli of five orders of magnitude. To further
validate these results, Molina et al. submitted another work where they characterized coliphages isolated from ewe feces and E. coli strains isolated from goat and sheep raw milk cheeses. Several phages showed a broad host range,
making them good candidates for E. coli biocontrol. However, they highlighted that phage virulence decreased as bacterial susceptibility range increased, until reaching a plateau, revealing a local gene-for-gene coevolution between
hosts and phages that explained the ability of the phages they isolated to propagate on host strains from different niches. They concluded that, when devising long-term and short-term biocontrol strategies, different phage cocktail

The formulation of a
formulations might be required. Their results affirm the importance of knowing the specific interactions between phages and bacteria to develop successful phage applications.

cocktail is also the basis of the work of Mangieri et al. which shows the relevance of this particular step in
any phage therapy endeavor. The aim of the authors was to formulate a cocktail able to reduce the counts
of pathogenic E. coli (Shiga toxin-producing E. coli-STEC) in food. They analyzed 20 different
bacteriophages isolated from feces, sewage, and bedding material for their lytic ability toward a
population of STEC strains belonging to different serogroups and with different antibiotic-resistance
profiles. Three of these phages were selected, also taking into account their RAPD (Random
Amplification of Polymorphic DNA) profile and the absence of antibiotic-resistance genes and
virulence-encoding genes. This cocktail was then tested directly on a food matrix (cucumber) at different
temperatures resulting in a 2-log reduction of E. coli cells after 24 h both at 4 and 25°C, suggesting
possible application in biocontrol of different STEC serogroup on raw products and RTE foods.
Considering that foodborne diseases were estimated to cause 600 million illnesses resulting in 420,000
deaths (Havelaar et al., 2015), the possibility to use bacteriophages and their derivatives to prevent or kill
food pathogens is extremely crucial. This work shows the potential of using phages in fresh vegetables
and opens new possibilities for upcoming studies on its applications. Another important benefit of
bacteriophages is that they will not cause any problem in consumers nor affect the taste, color, smell, and
texture of the food products. Starting from this assumption, Ahmadi et al. investigated the effectiveness of using
bacteriophages added as an ingredient in a cooked meat product to control the growth of Listeria monocytogenes. They
elaborated different scenarios for bacteriophage application and pathogen contamination where phage and sensitive strain were
introduced inside or on the surface of the cooked meat stored at 4°C. Only when phage was applied directly on top of L.
monocytogenes inoculated on the surface of cooked meat was there a reduction in cell number below the detection limit. As
concerning other applications where phage and bacteria were mixed and inoculated in meat or when only the bacteriophage was
inoculated in meat and L. monocytogenes spread on the surfaces, or vice versa, they were not able to obtain any reduction in cell
numbers. The main reason is probably the immobilization of phages and bacteria inoculated in a solid food matrix that limits
bacteriophage-host interactions. Therefore, more studies are needed to increase the access of phages to their hosts in complex
matrixes, and integration of fields such as food technology, nanomaterials, active compound-controlled delivery, and food
compatible bio-emulsifiers. Overall, bacteriophages undoubtedly have a great potential in a food safety context. Since more
research is necessary to achieve a suitable cocktail or phage-derived product to cover the current industrial sector needs, this
emerging and exciting area is an open field for interdisciplinary research and innovations.
 Plan
The United States federal government should substantially increase its security
cooperation with the North Atlantic Treaty Organization in the area of
biotechnology by partnering with NATO through the Science for Peace and Security
program to work on developing phage therapy.
 Solvency
NATO key for existing SPS framework to connect scientists
Funds for NGOs 5-31
“CFPs: NATO Science for Peace and Security Program.” fundsforNGOs, 31 May 2022,
https://www2.fundsforngos.org/information-technology/cfps-nato-science-for-peace-and-security-progra
m/. Accessed 6 September 2022.

The North Atlantic Treaty Organization Science for Peace and Security (SPS) Programme is accepting
proposals for Multi-Year Projects and Events (Advanced Research Workshops, Advanced Training
Courses and Advanced Study Institutes). The SPS Programme enhances civil science and technology to
address emerging security challenges and their impact on international security. It connects scientists,
experts and officials from NATO and partner nations to work together to address these challenges, by
supporting security-relevant activities in the form of four established grant mechanisms, which are:
Multi-Year research and development Projects (MYP)
Events, in the following formats:
Advanced Research Workshops (ARW)
Advanced Training Courses (ATC)
Advanced Study Institutes (ASI)
Through the SPS Programme, NATO has demonstrated its longstanding commitment to science,
innovation and practical cooperation with partners. The SPS Programme offers funding, expert advice and
support to tailor-made, civil security-relevant activities that respond to NATO’s strategic objectives.
Participation in the SPS Programme enables experts and scientists to develop innovative solutions to
today’s security challenges, and to build partnerships with their peers in NATO and partner nations.
Themes
Proposals focusing on the convergence and integration of different technologies and disciplines with the
purpose of serving a common goal (i.e. integration of engineering, biotechnologies, physical sciences, data
science, computation, life sciences, social sciences, etc.) can also be accepted.
Topics In preparation to the upcoming 2022 NATO Summit and in line with the NATO 2030 agenda, proposals addressing the topics below are especially encouraged.
Security-related advanced technology
Climate change and security
Defence against CBRN agents
Resilience
Eligibility Criteria
Applications for funding must be developed jointly by a NATO country Co-Director (NPD) and a Partner country Co-Director (PPD). To be deemed eligible for funding, proposals submitted to
the SPS Programme must:
Contribute towards NATO’s Strategic Objectives and have a clear link to security;
Address at least one of the SPS Key Priorities;
Be led by a co-director who is a national of, resident and employed in a NATO member country, and a co-director who is a national of, resident and employed in a partner nation;
Be developed and implemented by co-directors affiliated with a government, academic, or other non-profit institutions. For-profit private companies are not eligible for SPS funding;
Include realistic plans and budgets;
Be developed and managed in alignment with rules and regulations outlined in the SPS handbooks, which are regularly updated and made available at the time of publication of new calls for
proposals.
NATO Countries: Albania, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Iceland, Italy, Latvia, Lithuania, Luxembourg,
Montenegro, Netherlands, the Republic of North Macedonia, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Turkey, United Kingdom, United States.
NATO Partners: Afghanistan, Algeria, Armenia, Australia, Austria, Azerbaijan, Bahrain, Belarus, Bosnia and Herzegovina, Colombia, Egypt, Finland, Georgia, Iraq, Ireland, Israel, Japan,

Phages show rates of success - higher than antibiotics and no side-effects

Sulakvelidze et al 2001
Sulakvelidze, Alexander, et al. “Bacteriophage Therapy - PMC.” NCBI, March 2001,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/. Accessed 3 September 2022.
The international literature contains several hundred reports on phage therapy in humans, with the majority of recent publications coming from researchers in Eastern Europe and the former Soviet Union and only a few reports (1, 30,
73) published in other countries. In the English language literature, several reviews of phage therapy have recently been published (3, 8, 14). In addition, comprehensive information about the discovery of bacteriophages and the
history of phage therapy has been published recently by Yale University Press (68) and included in a web page (http://www.evergreen.edu/user/t4/phagetherapy/phagethea.html). Clearly, it would be impossible to summarize all of
these publications in this minireview; therefore, we have focused our minireview primarily on papers published in the non-English literature not widely accessible to the international scientific community. Overall, we have reviewed
over a hundred phage therapy publications available in the Georgian, Russian, and English literature, including Ph.D. theses and meeting presentations from the former Soviet Union. However, theses and meeting presentations (all
speaking in favor of phage therapy) are not discussed here, and we have focused primarily on reports published in peer-reviewed journals. Some of the major human phage therapy studies from Poland and the former Soviet Union are
summarized in Table ​Table1.1.
TABLE 1

Some of the major human phage therapy studies performed in Poland and the former Soviet Union
 Reference(s) Infection(s) Etiologic agent(s) Comments

Babalova et al. (7) Bacterial dysentery Shigella Shigella phages were successfully used for prophylaxis of bacterial dysentery.

Bogovazova et al. Infections of skin K. ozaenae, K. Adapted phages were reported to be effective in treating Klebsiella infections in all of the 109 patients.
(11) and nasal mucosa rhinoscleromatis,
and K. pneumoniae

Cislo et al. (17) Suppurative skin Pseudomonas, Thirty-one patients having chronically infected skin ulcers were treated orally and locally with phages. The
infections Staphylococcus, success rate was 74%.
Klebsiella, Proteus,
and E. coli
Ioseliani et al. (22) Lung and pleural Staphylococcus, Phages were successfully used together with antibiotics to treat lung and pleural infections in 45 patients.
infections Streptococcus, E.
coli, and Proteus
Kochetkova et al. Postoperative Staphylococcus and A total of 131 cancer patients having postsurgical wound infections participated in the study. Of these, 65 patients
(25) wound infections in Pseudomonas received phages and the rest received antibiotics. Phage treatment was successful in 82% of the cases, and
cancer patients antibiotic treatment was successful in 61% of the cases.
Kucharewicz-Kruko Various infections Staphylococcus, Immunogenicity of therapeutic phages was analyzed in 57 patients. The authors concluded that the phages'
wska and Slopek (27) Klebsiella, E. coli, immunogenicity did not impede therapy.
Pseudomonas, and
Proteus
Kwarcinski et al. (29) Recurrent E. coli Recurrent subphrenic abscess (after stomach resection) caused by an antibiotic-resistant strain of E. coli was
subphrenic abscess successfully treated with phages.
Litvinova et al. (32) Intestinal E. coli and Proteus Phages were successfully used together with bifidobacteria to treat antibiotic-associated dysbacteriosis in 500
dysbacteriosis low-birth-weight infants.
Meladze et al. (33) Lung and pleural Staphylococcus Phages were used to treat 223 patients having lung and pleural infections, and the results were compared to 117
infections cases where antibiotics were used. Full recovery was observed in 82% of the patients in the phage-treated group,
as opposed to 64% of the patients in the antibiotic-treated group.
Miliutina and Bacterial dysentery Shigella and The effectiveness of treating salmonellosis using phages and a combination of phages and antibiotics was
Vorotyntseva (35) and salmonellosis Salmonella examined. The combination of phages and antibiotics was reported to be effective in treating cases where
antibiotics alone were ineffective.

Perepanova et al. (40) Inflammatory Staphylococcus, E. Adapted phages were used to treat acute and chronic urogenital inflammation in 46 patients. The efficacy of
urologic diseases coli, and Proteus phage treatment was 92% (marked clinical improvements) and 84% (bacteriological clearance).
Sakandelidze and Peritonitis, Staphylococcus, Phages administered subcutaneously or through surgical drains in 236 patients having antibiotic-resistant
Meipariani (45) osteomyelitis, lung Streptococcus, and infections eliminated the infections in 92% of the patients.
abscesses, and Proteus
postsurgical wound
infections
Sakandelidze (46) Infectious Staphylococcus, A total of 1,380 patients having infectious allergoses were treated with phages (360 patients), antibiotics (404
allergoses (rhinitis, Streptococcus, E. patients), or a combination of phages and antibiotics (576 patients). Clinical improvement was observed in 86, 48
pharyngitis, coli, Proteus, and 83% of the cases, respectively.
dermatitis, and enterococci, and P.
conjunctivitis) aeruginosa
Slopek et al. (52–58) Gastrointestinal Staphylococcus, A total of 550 patients were treated with phages. The overall success rate of phage treatment was 92%.
tract, skin, head, Pseudomonas, E.
and neck infections coli, Klebsiella, and
Salmonella
Stroj et al. (67) Cerebrospinal K. pneumoniae Orally administered phages were used successfully to treat meningitis in a newborn (after antibiotic therapy
meningitis failed).
Tolkacheva et al. (69) Bacterial dysentery E. coli and Proteus Phages were used together with bifidobacteria to treat bacterial dysentery in 59 immunosuppressed leukemia
patients. The superiority of treatment with phage-bifidobacteria over antibiotics was reported.

Weber-Dabrowska et Suppurative Staphylococcus and Orally administered phages were used to successfully treat 56 patients, and the phages were found to reach the
al. (74) infections various patients' blood and urine.
gram-negative
bacteria
Zhukov-Verezhnikov Suppurative Staphylococcus, The superiority of adapted phages (phages selected against bacterial strains isolated from individual patients)
et al. (77) surgical infections Streptococcus, E. over commercial phage preparations was reported in treating 60 patients having suppurative infections.
coli, and Proteus
Polish papers. The most detailed English language reports on phage therapy in humans were by Slopek et al., who published a series of six papers (52–57) on the effectiveness of phages against infections caused by several bacterial pathogens, including multidrug-resistant mutants. Their seventh paper (58) summarized the results of all these studies, and it is discussed in some detail here. Five hundred fifty patients having bacterial septicemia and ranging in age from 1 week to 86 years were treated at a total of 10
clinical departments and hospitals located in three different cities. Antibiotic treatment (no information was given about the specific antibiotics used) was reported to be ineffective in 518 of the patients, leading to the decision to use phage therapy. The etiologic agents in the studies of Slopek et al. (52–58) were staphylococci, Pseudomonas, Escherichia, Klebsiella, and Salmonella, and treatment was initiated after isolating the etiologic agents and selecting specific, highly potent phages from a collection of more than

al cavities; and (iii) by applying a few drops of phage suspension to the eye,
250 lytic phages. Phages were administered as follows: (i) orally, three times a day before eating and after neutralizing gastric acid by oral administration of baking soda or bicarbonated mineral water a few minutes prior to phage administration; (ii) locally, by applying moist, phage-containing dressings directly on wounds and/or pleural and peritone

middle ear, or nasal mucosa. During the course of phage treatment, the etiologic agents were continuously monitored for phage susceptibility, and if phage resistance developed, phages were replaced with different bacteriophages lytic

were applied for up to 14 days after

against the newly emerged, phage-resistant bacterial mutants. The duration of treatment was 1 to 16 weeks, and in some cas es phages
negative cultures were obtained. The rates of success (marked to complete recovery in conjunction with
negative cultures) ranged from 75 to 100% (92% overall) and were even higher (94%) with the 518
patients for whom antibiotic therapy was ineffective. Control groups without phage treatment were not
included in the study. In other publications from Poland (Table ​(Table1),1), phages were reported to be
effective in treating cerebrospinal meningitis in a newborn (67), skin infections caused by Pseudomonas,
Staphylococcus, Klebsiella, Proteus, and E. coli (17), recurrent subphrenic and subhepatic abscesses (29),
and various chronic bacterial diseases (23). In addition to being effective in the treatment of long-term suppurative infections, phage therapy was found, in a recent study (75), to normalize tumor necrosis factor alpha
(TNF-α) levels in serum and the production of TNF-α and interleukin-6 by blood cell cultures. Soviet papers. One of the most, if not the most, extensive studies evaluating the utility of therapeutic phages for prophylaxis of infectious diseases was conducted in Tbilisi, Georgia, during 1963
and 1964 (7) and involved phages against bacterial dysentery. A total of 30,769 children (6 months to 7 years old) were included in the study. Of these, children on one side of the streets (17,044 children) were given Shigella phages orally (once every 7 days), and the children on the other side
of the streets (13,725) did not receive phages. The children in both groups were visited on a once-a-week basis to administer phages and monitor their overall status. Fecal samples from all children having gastrointestinal disorders were tested for the presence of Shigella spp. and other,
unspecified diarrhea-causing bacteria. Based on clinical diagnosis, the incidence of dysentery was 3.8-fold higher in the placebo group than in the phage-treated group (6.7 and 1.76 per 1,000 children, respectively) during the 109-day study period; based on the culture-confirmed cases, the
incidence of dysentery was 2.6-fold higher in the placebo group than in the phage-treated group (1.82 and 0.7, respectively) (Fig. ​(Fig.1).1). The phage effectiveness index (disease incidence per 1,000 children in the placebo group divided by the corresponding number in the phage-treated
group) was highest in children between 6 months and 1 year of age and was lowest in children 5 to 7 years of age. An interesting outcome of the study was that there was an overall reduction (2.3-fold) in diarrheal diseases of unknown origin among children treated with phages compared to
the children in the placebo group. This may have been observed because some dysentery cases were not diagnosed as such (but were prevented with the Shigella phage preparation) or because the phage preparation, although developed specifically against Shigella species, was also active
against some additional gastrointestinal pathogens. Many similar clinical studies, albeit conducted on a smaller scale, have yielded similar results (Table ​(Table1).1). To give but a few examples, phages have been reported to be effective in treating staphylococcal lung infections (22, 33), P.
aeruginosa infections in cystic fibrosis patients (50), eye infections (43), neonatal sepsis (38), urinary tract infections (40), and surgical wound infections (39, 41). However, as with the Polish studies, controls were not included in the majority of these trials or controls were used but
information needed for rigorous evaluation of the authors' conclusions was not provided. For example, a study which was meant to be a double-blind trial evaluating the efficacy of bacteriophages for prophylaxis and/or treatment of bacterial dysentery was conducted in 1982-1983 and
included soldiers of the Red Army stationed in four distinct geographic regions of the former Soviet Union (6). The study was conducted so that all information about the patients and preparations given to them was coded (i.e., the study was performed in a double-blinded manner), and the
authors reported that the incidence of dysentery in the phage-treated groups was approximately 10-fold less than in the control group (P < 0.0001). However, information was not presented concerning the number of patients enrolled in each arm of the study and the methods used to evaluate
the results. Thus, it is impossible to evaluate rigorously the efficacy of the phage treatment used in the study. In the majority of other studies, the effectiveness of phage therapy was not questioned and controls were used only to compare the effectiveness of new or modified phage preparations
to that of prior phage preparations. For example, Zhukov-Verezhnikov et al. (77) compared the effectiveness of “adapted” bacteriophages (i.e., phages selected against bacterial strains isolated from individual patients) to that of commercially available phage preparations. The authors used
phage preparations to treat 60 patients having suppurative surgical infections. Thirty patients were treated with phages specifically adapted to strains isolated from each patient, and an equal number of patients were treated with commercially available phage preparations targeted against
staphylococci, streptococci, enteropathogenic E. coli, and Proteus. The adapted bacteriophages were reported to be five- to sixfold more effective in curing suppurative surgical infections than were the commercially available preparations, presumably because of their improved specificity.
Comparison of phages and antibiotics. Lytic phages are similar to antibiotics in that they have remarkable antibacterial activity. However, therapeutic phages have some at least theoretical advantages over antibiotics (Table ​(Table2),2), and phages have been reported to be more effective than
antibiotics in treating certain infections in humans (25, 33, 46) and experimentally infected animals (59). For example, in one study (33), Staphylococcus aureus phages were used to treat patients having purulent disease of the lungs and pleura. The patients were divided into two groups; the

The results
patients in group A (223 individuals) received phages, and the patients in group B (117 individuals) received antibiotics. Also, this clinical trial is one of the few studies using i.v. phage administration (48 patients in group A received phages by i.v. injection).

were evaluated based on the following criteria: general condition of the patients, X-ray examination,
reduction of purulence, and microbiological analysis of blood and sputum. No side effects were observed
in any of the patients, including those who received phages intravenously. Overall, complete recovery was
observed in 82% of the patients in the phage-treated group as opposed to 64% of the patients in the
antibiotic-treated group. Interestingly, the percent recovery in the group receiving phages intravenously
was even higher (95%) than the 82% recovery rate observed with all 223 phage-treated patients.

TABLE 2

Comparison of the prophylactic and/or therapeutic use of phages and antibiotics

Bacteriophages Antibiotics Comments

Very specific (i.e., usually affect only the Antibiotics target both pathogenic High specificity may be considered to be a
targeted bacterial species); therefore, microorganisms and normal microflora. disadvantage of phages because the
dysbiosis and chances of developing This affects the microbial balance in the disease-causing bacterium must be
secondary infections are avoided (15). patient, which may lead to serious identified before phage therapy can be
secondary infections. successfully initiated. Antibiotics have a
higher probability of being effective than
phages when the identity of the etiologic
agent has not been determined.

Replicate at the site of infection and are They are metabolized and eliminated from The “exponential growth” of phages at the
thus available where they are most the body and do not necessarily concentrate site of infection may require less frequent
needed (59). at the site of infection. phage administration in order to achieve
the optimal therapeutic effect.

No serious side effects have been Multiple side effects, including intestinal A few minor side effects reported (17, 58)
described. disorders, allergies, and secondary for therapeutic phages may have been due
infections (e.g., yeast infections) have been to the liberation of endotoxins from
reported (76). bacteria lysed in vivo by the phages. Such
effects also may be observed when
antibiotics are used (42).

Phage-resistant bacteria remain Resistance to antibiotics is not limited to Because of their more broad-spectrum
susceptible to other phages having a targeted bacteria. activity, antibiotics select for many
similar target range. resistant bacterial species, not just for
resistant mutants of the targeted bacteria
(47).

Selecting new phages (e.g., against Developing a new antibiotic (e.g., against Evolutionary arguments support the idea
phage-resistant bacteria) is a relatively antibiotic-resistant bacteria) is a that active phages can be selected against
rapid process that can frequently be time-consuming process and may take every antibiotic-resistant or
accomplished in days or weeks. several years (16, 51). phage-resistant bacterium by the
ever-ongoing process of natural selection.
Phage cocktails speed up process
Barron 8-31-22
Barron, Madeline. “Phage Therapy: Past, Present and Future.” American Society for Microbiology, 31
August 2022, https://asm.org/Articles/2022/August/Phage-Therapy-Past,-Present-and-Future. Accessed 7
September 2022.
Nevertheless, while phage therapy is no longer on the back burner of medicine in the U.S., it’s not at the forefront either. “One of the biggest reasons why phage therapy is not mainstream in the
West right now is because the clinical trials haven't been done to show that it's efficacious,” Strathdee explained. She noted that clinical trials form the backbone of therapeutic development in the
U.S.—anecdotal evidence and/or case studies are not enough. Finding the Right Phages Can Take Time There are 2 types of phages: lytic and temperate. Strictly lytic phages infect their host cell
and cause it to burst, thus killing the bacterium. Temperate, or lysogenic, phages don’t kill their bacterial prey outright—they integrate their genome (which may harbor AMR or toxin genes) into
the host cell. The phage may eventually lyse the cell, but this does little to immediately thwart bacterial infection, and may contribute to the spread of AMR and other virulence genes. As such, it
is critical to ensure strictly lytic phages are used for phage therapies. With that in mind, the process for identifying phages to treat an infection can be lengthy. It often involves testing phages from
existing libraries to find those that kill a patient’s bacterial isolate. “It’s like [having] a million keys and you’re trying to sort through a million locks to figure out which key matches the lock,”
Strathdee said. One study reported a range of 28 to 386 days between the time of request for phage therapy and actual administration to the patient. However, there are products being developed
a company that develops engineered phage biotherapeutics,
with a broader target range. For example, Locus Biosciences,

manufactures phage cocktail drug products for each of 4 different pathogens (Escherichia coli, Klebsiella
pneumoniae, Pseudomonas aeruginosa and Staphyloccocus aureaus) that target >95% of clinical strains.
This approach does not require culturing a patient’s isolate and screening a library for the right phages, and thus may streamline the process. Manufacturing and
Administrating Phage Therapeutics Isn't Straightforward Unlike antibiotics, where concentrations of the drug decrease within the body over time, phages multiply. This means that the dose of a
phage cocktail that a patient is administered is not necessarily the dose they receive. How this self-replicating feature of phage therapies influences treatment efficacy, and potential for adverse
effects, is still unknown. “[We need] pharmacokinetic and pharmacodynamic studies to try to figure out, ‘okay, [if] you deliver this amount of phage, but through this particular route, what
happens to the phage?’” Strathdee said. Similarly, researchers must confirm “that [the phages] perform in the matrix they’re expected to perform [in],” said Dr. Nick Conley, Vice President of
Technology at Locus Biosciences. For example, if phages are used to treat a urinary tract infection (UTI), they need to be active in urine. There are also important considerations from a
manufacturing standpoint. For instance, to create phage preparations, the phages are amplified in bacterial hosts—they infect the bacteria, the bacteria lyse and release more phages to create a
high-titer phage soup. However, upon lysis, “all of the guts of the bacteria get spilled out,” Conley explained. This includes toxins and DNA, among other cell components, which must be
removed before the phage could be, for example, injected into someone’s bloodstream. Potential for Bacterial Phage Resistance Patients generally receive mixtures (cocktails) of phages that
target bacteria in different ways. The chances of the bacteria evolving resistance to multiple phages is lower than for a single phage—lower, but not impossible. Patients receiving phage therapy
must be continuously monitored to ensure the phages are still effective against their infection. If not, researchers must find a new set of phages that can combat the pathogen. Still, the
In some cases, the modifications to the bacteria that promote phage
development of resistance is not always a bad thing.

resistance increase their susceptibility to antibiotics, and thus work synergistically with the antibiotics to
promote their efficacy.

Phage cocktails can be created within days

UCSD no date
“Phage 101 - Bacteriophage Therapy.” UC San Diego Health, no date,
https://health.ucsd.edu/news/topics/phage-therapy/pages/phage-101.aspx. Accessed 26 August 2022.
Phages may help overcome the main drawbacks to today’s antibiotics. Antibiotics are broad spectrum, meaning that in addition to killing the nefarious species causing infection, antibiotics also
destroy many beneficial bacteria making up a person’s microbiome, and that can have a variety of short- and long-term health effects. Bacteria also replicate quickly and the selective pressure of
antibiotics encourages the emergence of antibiotic-resistant strains. In contrast, phages are very specific about the bacteria they infect, so the collateral damage to other bacteria or human cells is
minimal. Though bacteria can develop resistance to phage (they can eventually shed the surface receptors that phages use to dock and enter the cells), the risk is low. What’s more, since there is a
nearly inexhaustible supply of phages in nature, if resistance does occur, researchers can now find new phages that use other receptors, as they did in Tom Patterson’s case. Such an approach can
antibiotics take years to develop, whereas a phage cocktail can be identified
be expedited with the use of phage libraries. Finally,

and matched to a patient’s specific bacterial infection and purified within a matter of days, making
personalized phage therapy-on-demand a potential reality in the future.