Episode Summary Afreenish Amir, Ph.D., Antimicrobial Resistance (AMR) Project Director at the National Institute of Health in Pakistan, highlights significant increases in extensively drug-resistant typhoid and cholera cases in Pakistan and discusses local factors driving AMR in Asia. She describes the development and implementation of a National Action Plan to combat AMR in a developing country, emphasizing the importance of rational antimicrobial use, surveillance and infection control practice. Ashley's Biggest Takeaways

• AMR is a global and One Health issue.
• Pakistan has a huge disease burden of AMR.
• Contributing factors include, but are not limited to, overcrowding, lack of infection control practices, poor waste management practices and over-the-counter prescription practices.
• Promoting the rational use of antimicrobials is imperative at all levels—from tertiary care to primary care practitioners.
• Typhoid and cholera are high-burden infections in Pakistan, with typhoid being a year-round issue and cholera being seasonal.
• A holistic approach, involving various sectors and disciplines, is necessary in order to address the global AMR threat.
• Amir highlights the need for better communication and collaboration to bridge gaps and build trust between different organizations.

Featured Quotes: I've been working at the National Institutes of Health for the last 7 years now. So, I've been engaged in the development and the implementation of the national action plan on AMR, and that gave me the opportunity to explore the work in the field of antimicrobial resistance. Reality of AMR in Pakistan [Pakistan] is an LMIC, and we have a huge disease burden of antimicrobial resistance in the country right now. A few years back, there was a situational analysis conducted, and that has shown that there is presence of a large number of resistant pathogens within the country. And National Institutes of Health, they have started a very standardized surveillance program based upon the global antimicrobial use and surveillance system back in 2017. And [those datasets have] generated good evidence about the basic statistics of AMR within the country. So, for example, if I talk about the extensively drug-resistant typhoid, typhoid is very much prevalent in the country. Our data shows that in 2017 there were 18% MDR typhoid cases through the surveillance data. And in 2021 it was like 60%. So that has shown that how the resistance has increased a lot. A number of challenges are associated with this kind of a thing, overcrowded hospitals, poor infection prevention and control (IPC) measures. So, there is AMR within the country—there's a huge burden—and we are trying to look for the better solutions.  Local Factors Driving AMR Bacteria, they do not know the borders. We have a close connection with the other Asian countries, and we have a long border connected with the 2 big countries, which are Afghanistan and India and Bangladesh and China. So, we see that it's not limited to 1 area. It's not regional. It’s also a history of travel. When the people travel from one area to the other, they carry the pathogen as a colonizer or as a carrier, and they can infect [other] people. So, it's really connected, and it's really alarming as well. You never know how the disease is transmitted, and we have the biggest example of COVID—how things have spread from 1 country to the other, and how it has resulted in a massive pandemic. AMR is similar. We have seen that it's not limited to 1 region. We are part of this global community, and we are contributing somehow to the problem. First, I'll talk about the health care infrastructure. We do have the capacities in the hospitals, but still, there's a huge population. Pakistan is a thickly populated country. It's a population of around 241 million. And with the increasing population, we see that the infrastructure has not developed this much. So now the existing hospitals are overcrowded, and this has led to poor infection control practices within the hospitals. The staff is not there. In fact, ID consultants are not available in all the hospitals. Infection control nurses are not available in all the hospitals. So, this is one of the main areas that we see, that there is a big challenge. The other thing that can contribute is the poor waste management practices. Some of the hospitals—private and public sectors—they are following the waste management guidelines—even the laboratories. But many of the hospitals are not following the guidelines. And you know that AMR is under one health. So, whatever waste comes from the hospital eventually goes to the environment, and then from there to the animal sector and to the human sector. [Another big] problem that we are seeing is the over-the-counter prescription of antimicrobials. There is no regulation available in the country right now to control the over-the-counter prescription of antibiotics. They are easily available. People are taking the antibiotics without a prescription from the doctors, and the pharmacist is giving the patients any kind of medicine. And either it is effective/not effective, it's a falsified, low-quality antibiotic for how long in duration antibiotic should be taken. So, there are multiple of things or reasons that we see behind this issue of AMR. Rational Use of Antimicrobials It is a complex process how we manage this thing, but what we are closely looking at in the country right now is that we promote the rational use of antimicrobials at all levels—not only at the tertiary care levels, but also at the general practitioner level. They are the first point of contact for the patients, with the doctors, with the clinicians. So, at this point, I think the empirical treatment needs to be defined, and they need to understand the importance of this, their local antibiograms, what are the local trends? What are the patterns? And they need to prescribe according to those patterns. And very recently, the AWaRE classification of WHO, that is a big, big support in identifying the rational use of antimicrobials—Access, Watch and Reserve list—that should be propagated and that should be understood by all the general practitioners. And again, I must say that it's all connected with the regulations. There should be close monitoring of all the antibiotic prescriptions, and that can help to control the issue of AMR. National Action Plan on AMR So, when I joined NIH, the National Election plan had already been developed. It was back in 2017, and we have a good senior hierarchy who has been working on it very closely for a long period of time. So, the Global Action Plan on AMR, that has been our guiding document for the development of the national action plan on AMR, and we are following the 5 strategic objectives proposed in the global action plan. The five areas included:

1. The promotion of advocacy and awareness in the community and health care professionals.
2. To generate evidence through the data, through the surveillance systems.
3. Generation of support toward infection prevention and control services IPC.
4. Promoting the use of antimicrobials both in the human sector and the animal sector, but under the concept of stewardship, antimicrobial consumption and utilization.
5. Invest in the research and vaccine and development.

So, these are some of the guiding principles for us to develop the National Action Plan, and it has already been developed. And it's a very comprehensive approach, I must say. And our institute has started working on it, basically towards recreating awareness and advocacy. And we have been successful in creating advocacy and awareness at a mass level. Surveillance We have a network of Sentinel surveillance laboratories engaged with us, and they are sharing the data with NIH on a regular basis, and this is helping NIH to understand the basic trends on AMR and what is happening. And eventually we plan to go towards this case-based surveillance as well, but this is definitely going to take some time because to make people understand the importance of surveillance, this is the first thing. And very recently, the Institute and country has started working towards the hospital acquired infection surveillance as well. So, this is a much-needed approach, because the lab and the hospital go hand in hand, like whatever is happening in the lab, they eventually reach the patients who are in the hospitals. Wastewater surveillance is the key. You are very right. Our institute has done some of the work toward typhoid and cholera wastewater surveillance, and we were trying to identify the sources where we are getting these kinds of pathogens. These are all enteric pathogens. They are the key source for the infection. And for the wastewater surveillance mechanism, we can say that we have to engage multiple stakeholders in this development process. It's not only the laboratory people at NIH, but we need to have a good epidemiologist. We need to have all the water agencies, like the public health engineering departments, the PCRWR, the environmental protection agencies who are working with all these wastewater sites. So, we need to connect with them to make a good platform and to make this program in a more robust fashion. Pathogens and Disease Burdon For cholera and typhoid within Pakistan, I must say these are the high burden infections or diseases that we are seeing. For typhoid, the burden is quite high. We have seen a transition from the multidrug-resistant pathogens to the extensively drug-resistant pathogens, which now we are left with only azithromycin and the carbapenems. So, the burden is high. And when we talk about cholera, it is present in the country, but many of the times it is seasonal. It comes in during the time of the small zone rains and during the time of floods. So, every year, during this time, there are certain outbreaks that we have seen in different areas of the country. So, both diseases are there, but typhoid is like all year long—we see number of cases coming up—and for cholera, it's mainly seasonal. Capacity Building and ASM's Global Public Health Programs

Capacity building is a key to everything, I must say, [whether] you talk about the training or development of materials. I've been engaged with ASM for quite some time. I worked to develop a [One Health] poster in the local language to create awareness about zoonotic diseases. So, we have targeted the 6 zoonotic diseases, including the anthrax, including the Crimean-Congo hemorrhagic fever and influenza. And we have generated a very user-friendly kind of layout in the local language, trying to teach people about the source of transmission. What are the routes of transmission, if we talk about the CCHF? And then how this can be prevented. So, this was one approach. And then I was engaged with the development of the Learnamr.com. This is online platform with 15 different e-modules within it, and we have covered different aspects—talking about the basic bacteriology toward the advanced, standardized methods, and we have talked about the national and global strategies [to combat] AMR, One Health aspects of AMR, vaccines. So, it's a huge platform, and I'm really thankful to ASM for supporting the program for development. And it's an online module. I have seen that there are around more than 500 subscribers to this program right now, and people are learning, and they are giving good feedback to the program as well. We keep on improving ourselves, but the good thing is that people are learning, and they are able to understand the basic concepts on AMR.

Links for This Episode:

• Experts Discuss One Health in Pakistan: Biosafety Education Inside and Outside the Lab. 

• Explore ASM’s Global Public Health Programs. 

• Download poster about zoonotic disease in English or Urdu. 

• Progress on the national action plan of Pakistan on antimicrobial resistance (AMR): A narrative review and the implications. 

• Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from 13,000 Salmonella Typhi genomes. 

• Wastewater based environmental surveillance of toxigenic Vibrio cholerae in Pakistan. 

• Point Prevalence Survey of Antimicrobial Use in Selected Tertiary Care Hospitals of Pakistan Using WHO Methodology: Results and Inferences. 

• Overcoming the challenges of antimicrobial resistance in developing countries. 

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