Berkley Center

Background: Dr. Sadia Shakoor was a participant in a Rome workshop in April 2019 on the roles that faith-linked institutions can play in responding to the global crisis of antimicrobial resistance (AMR). She spoke to Katherine Marshall on the margins of the meeting about her work at the Aga Khan hospital, based in Karachi, Pakistan, and about how AMR presents itself in the context where she practices.

How did you get involved in the AMR issue?

AMR is something that I've been seeing since I began my studies. Everyone, at least in countries where there's a high burden of infections and a high burden of resistance, is familiar with it, in one form or another. Maybe not as “AMR,” but everyone knows about antibiotics failing in patients with infections. When we saw a lot of typhoid in undergraduate years, we knew that you don't treat it with certain antibiotics, because they don't work anymore. You treat it with ciprofloxacin, and it worked then, and then soon, say in ten years, we knew that ciprofloxacin does not work anymore, and then you have to give ceftriaxone and that's what you work with, and then all of a sudden you have an outbreak where that doesn't work anymore. So by default, we have seen a lot of antibiotic resistant infections. AMR is something that clinical microbiology laboratories and physicians always diagnose and know about. That's what they work with. I've been working with that for a very, very long time as a permanent focus.

My mentor, professor Rumina Hasan, also a clinical microbiologist, was my supervisor during my postgraduate years. Her two areas of work were TB and antibiotic resistance. She set up a surveillance website, the Pakistan Antimicrobial Resistance Network. I was very lucky to have seen its inception, and how people were actually recruited and moved in. There's no money involved there. It is a website where people working on AMR upload their data to share with colleagues. The website gave AMR impetus in Pakistan. That was the beginning of a surveillance network in Pakistan and I've been involved since then. We do stewardship rounds (we've been doing them since undergraduate days), where we advise on antibiotic therapy. We do it in the most critical areas of the hospital. We see patients with resistant hospital-acquired or community-acquired infections that are sometimes very severe, where the situation has progressed to a point where we now have no effective antibiotics. Where the culture shows that some bugs are resistant to every known antibiotic.

This sometimes happens in neonates, a very challenging clinical situation. These neonates are usually very sick, they have very low birth weight, can't withstand infections, and lower immunities, they need antibiotics, and there is absolutely no option. And then you have to decide, okay, we're going to give them combination therapy; which antibiotic are we going to choose? Is there something else that we can test? Is there something else available out there? What else can we test, even if there are no guidelines to test for it? So these are things that we struggle with every other day.

Is the situation in Pakistan more severe than in other places, or are you describing a very normal picture?

I don't think it is more severe in Pakistan than in other places. I'm pretty sure the situation in Bangladesh is similar. I think that, because of the presence of the Aga Khan University and the level of services that are available and the network, we identify it more. Others do as well. The Child Health Research Foundation in Bangladesh, the ICCDRB in Bangladesh, and amazing centers in India, also recognize the phenomenon, but not all of them have a network of diagnostics in many cities. They also have lots of antibiotic resistance that they recognize and diagnose. Because of our network and the level of diagnostics and the quality assurance that is available in our setup, we have an excellent perspective on what is going on. In terms of surveillance, we have more of a hold of where the resistance is, what is happening these days, and how is it happening, because we cater to large populations in Pakistan.

What is your sense of the main reasons behind AMR?

That is a very, very difficult question to address. We know what the main reasons and drivers are but we can't always quantify them. We don't know if most of AMR is because of misuse of antibiotics in humans, or misuse of antibiotics in animals. I believe it differs by pathogen. The TB pathogen is different from others; there are studies that show the mutation rate is less. There are pathogens where the mutation rate is very, very high. There also zoonoses, that come from animals, and that's where of course the antibiotic use in animals is going to lead AMR. For other pathogens that are environmental and human, obviously the antibiotic concentrations in sewage and water where pathogens can just sit together and exchange genes can then lead to AMR. At the molecular, clinical level, that's the situation. It means that it's not just misuse of antibiotics in humans. It's also misuse in animals, food, the way we treat our food, food packaging, all of those processes.

The problem is that in Pakistan, most of that is unregulated, and also in India and Bangladesh, let's just say in low-, middle-income countries in Africa and South Asia. Southeast Asia has control of that a little bit, but still over there, there are unregulated markets and unregulated pharmaceutical markets. There is a lack of education in people. All these multiple things combine to give rise to it. That is why it's so difficult, why it's such a complex thing to address, because you need improvement in multiple sectors to control AMR.

You describe what sounds a common phenomenon that you see daily. You hear about stubborn infections in the US, but it is often seen as relatively unusual. But you say you encounter the problem every day.

We see it every day, absolutely. Clinical microbiologists and infectious disease physicians in our part of the world see it every day. It's our daily struggle. Of course, naturally there's more antibiotic resistance in patients who've been to healthcare and who are sicker, but even patients coming from the community have more antibiotic resistance than you would expect these patients to have. A scenario we see often is a person with a urinary tract infection, who has never been to healthcare centers before, has never been sick before, who will have a bug in the urine culture which will be resistant to several antibiotics, which means that sometimes they have to be given injectable antibiotics for the simplest infection. It becomes very difficult to manage. It's not just about the resistance or the surveillance. It's actually the patient management that suffers.

We have had to switch from oral to routine injectable treatment in sick patients with typhoid now, which is more expensive than what we had to provide to them before, and in many of these situations, the expense is significant. That is not the only cost of AMR: adverse reactions to antibiotics also incur a cost, and these are antibiotics that are not even ideal for these infections. Sometimes you have to just give patients multiple antibiotics that bugs are resistant to, because you don't have any antibiotics that these bugs are susceptible to. Globally, antibiotic discovery or development really is not progressing at the same rate as antibiotic resistance.

So that's our reality. Many physicians in the US also deal with it, but you're right, we see and live with AMR as a much more common phenomenon. We see it every day.

We have spoken during the workshop here in Rome about national action plans for AMR. Are you aware of the Pakistan plan and have you been part of it? How relevant is it or how action-focused is it?

Yes, we were certainly involved in the development of the national action plans. The National Institute of Health (NIH) in Islamabad has issued it, and it is endorsed by the Ministry of Health, including its departments and provincial offices. It was finalized in 2017. We have not really been involved in the implementation, but, as we have been discussing throughout at the workshop here, implementation is not very simple. There are several things that you have to do, across multiple sectors. The action plan is based on the WHO framework and objectives, and incorporates the Global Antimicrobial Resistance Surveillance System (GLASS). The WHO EMRO office were also involved in preparing this action plan.

In Pakistan, currently we are at the stage where we're formalizing all of our surveillance systems. We have been involved with the GLASS surveillance system in Pakistan which the NIH, Islamabad leads, and the one held in the animal sector. We are not very closely involved with the animal sector, though we do work with them on some research studies. In terms of controlling irrational use of antibiotics: It's all easier said than done. In a region where infectious diseases are very common, we have to carefully balance antibiotic access with usage guidelines. In terms of implementation, actually getting things off the ground in all four provinces which have different predominant agricultural and predominant veterinary sectors, is challenging to say the least. There are efforts that are ongoing, though it is difficult to pinpoint exactly where we are right now. Also the Drug Regulatory Agency of Pakistan is becoming more active, especially in terms of approval of antibiotic brands, testing drug quality, and so on. AMR control is progressing slowly, not as fast as we would have hoped, but I think that is understandable. We have to consider the difficulties that are faced by policymakers and implementers alike. I appreciate what the NIH in Islamabad are doing at a steady rate.

A question I have is how many national action plans a country has these days, across many different topics and sectors, other than AMR. Are there ways to help see the links among them?

Yes, that's an interesting question. They don't always link well. During the formulation of the national action plan, all the actors were at the table. Many people were involved in the actual making of the national action plan. I was struck by a colleague’s comment (Dr Mpundu) that national action plans will also have to be updated. That's an important point, alongside making the links. Some other existing action plans may be pertinent, for example for agricultural industries etc. You're right that what AMR needs is intersectoral collaboration. At some level it does happen, but I think we should actually re-examine our national action plans from a broader perspective, intersectoral collaboration, and updating it in that light, for example to link with policies of the agriculture sector, the veterinary sector, or sewage disposal.

What about action plans for various diseases? For women, children, etc? Is there something of an overload?

There are indeed many vertical programs and broader plans. There are plans for TB and malaria, as an example. But it's not feasible to suddenly change the vertical programs that have been existing for ages, a structure that people are very comfortable with, and turn them into horizontal programs. That would be a complete rehaul of the healthcare system. That is perhaps something we can dream about, but it's not possible in the short term. I think that vertical programs will continue to exist. But what is important is that we link them up. We do try. There are examples, where linkages exist between different vertical programs, but we need more such linkages.

What about simple overload as an issue, because there are so many programs? It could make focus difficult when you have many different approaches coming at similar problems from different directions.

I think that's the reason why we need horizontal programs and not vertical. A patient doesn't come to you saying, "I have tuberculosis (TB)." A patient comes to you with a chronic cough, which could be TB, or it could be something else. Difficulties in appreciating the linkages is a source of frustration for us. I recently did an analysis of TB in pediatrics; a lot of children were diagnosed with TB who actually had alternative disorders. However, most patients are evaluated for “TB,” because there is a vertical program and it provides clear guidelines and processes for diagnosis and management of TB. Sadly, if a child with a cough does not have TB, they're not included on the TB program register. But where does the patient end up in the healthcare system? Probably in a secondary care hospital where they would be evaluated for their symptoms but because guidelines and management protocols are not straightforward or well-defined, they would be “lost” in the system. So yes, holistic or integrated approach does suffer because of vertical programs that are focused on a single disease entity only. For better alignment of patients seeking care and appropriate healthcare service, physicians in the system, even in vertical programs, need better training to at least develop a list of possible diagnoses and then clinical pathways to be able to refer patients so they are managed timely and properly.

On AMR, is there an institutional focus? In other words, is somebody responsible overall, or at different levels? A colleague at our meeting advanced the principle: “First who, then what.”

The NIH in Islamabad is a national focal institution; they're responsible for AMR action plans and implementation. They have also nominated a focal person. The WHO has appointed a resource or focal person in the country office for AMR. And when you say that that person is responsible, I think that person's answerable as to what is happening with the national action program. But I think we're all responsible.

Do they have responsibility for funding? 

Pakistan is a Fleming Fund-supported country. Other than Pakistan, Nepal and Ghana have received country grants. So one source of funding is the Fleming Fund. We hope that the Pakistan country grant will be announced soon. Other than that, the CDC in the US has been supporting NIH for a very long time, establishing it as a national reference center for diagnostics (not for treatment). The WHO also supports NIH. NIH is a federal body, though, and the government system in Pakistan has devolved. Provinces are autonomous now, which on the ground, it is the provincial departments of health that are responsible for implementation.

This does, however, present another set of difficulties. While there has really been no dissonance or disagreement between federal or provincial governments in terms of policies, when we talk about implementation, there is clearly a gap.

Priorities and funding, I imagine, are the issues.

Absolutely. Priorities are often set globally, but these have a local impact. For example, in times of impending outbreaks, health authorities may be too busy grappling with Zika or influenza, and AMR then becomes a lower priority.

You've talked about the vertical issues that are all too familiar. In the global SDG framework, universal health coverage is supposed to address excessive focus on such programs. How is that playing out in Pakistan?

Again, that's a very difficult question for me to address. We have been talking about universal health coverage and agree with the principles, but how to finance it is another problem, the greatest problem by far. I’m not the best person to address what is happening at the policy level for UHC. But high-level and academic conversations mean and show that there is interest in achieving it. The Pakistani health system has “basic health units” with defined catchment populations, but this does not capture the entire population. However, these basic health units work very closely with populations, and are well positioned to deliver UHC, but they don’t reach out to all sectors. People have to access private healthcare providers, but they charge a fee, and people don’t have the capacity to pay – more than 20 percent of the population lives below the poverty line.

How far is insurance an issue? 

We don't have an insurance-based system. Healthcare in the public system, for the whole of Pakistan, is free. The basic health units offer and provide free healthcare, as do secondary hospitals and tertiary care hospitals in the government sector. But there are services that have to be paid for out of patients' pockets. TB, for example, requires patients to seek care for years and years: once the primary infection is treated, patients often have sequelae that cause symptoms. The way we calculate catastrophic costs is, have you fallen below the poverty line? If people are already below the poverty line, you can't calculate catastrophic costs or take the poor into account. And when they fall sick, the poor go deeper and deeper into debt. They are supported by charity institutions, to a degree. A very important feature of the healthcare system in our part of the world is the fact that there are several charity organizations. They are not all faith-inspired, but the way it works in an Islamic republic is that most would fall into that category.

The Indus Hospital, one of the largest hospitals. is supported by philanthropists. There are also Christian-based institutes that are charity-based. The Marie Adelaide Leprosy Center is an example, one that has been around for ages and ages. Dr. Ruth Pfau passed away a few years ago, but the Marie Adelaide Leprosy Center continues, with many branches.

So very poor people might go to those places?

Yes, as they have limited access to the government-funded healthcare system. One must not forget thought that this government-funded system has its strong points. An example of the public service are our lady healthcare workers or LHWs, whose statutory duties include community education. They are supported by some vertical programs; that is, they are employed by the government but are also deployed by specific programs as part of educational packages, leading to a complex situation. Because they're supported by the these vertically funded and operated programs, they will go to the community and teach everybody about specific diseases, but can become overburdened when you expect them to be able to cover a broad range of health education topics and services. We have employed the LHWs in many of our research studies, and it's a great system, but I don't think that we have enough LHWs or enough coverage. Perhaps that system can be strengthened or built up to be able to provide better service within communities. The LHWs have the confidence and trust of the communities, so it's a good system to build on.

Do you work with them in the Aga Khan Hospital?

The Aga Khan Health Services employ LHWs to support its community programs. It's a parallel system. There are some communities where AKU has a strong presence. It's not a parallel system in conflict. The Aga Khan Health Services and some other organizations, such as People's Primary Healthcare Initiative (PPHI, https://www.healthynewbornnetwork.org/partner/peoples-primary-healthcare-initiative-pphi-sindh/), Aga Khan University and Hospital have a very strong department of community health sciences in the Karachi campus, and through its research programs, this department has recently provided support to the provincial LHW program in revising their curriculum and thus support community health initiatives. The AKU is one of the premier medical universities in the country with a very strong community health sciences department, focused on primary health care, social science, as well as health economy. I would say that what the AKU has is quite unique.

Can you describe how the Aga Khan Hospital works in Pakistan? What is your position now?

The Aga Khan Hospital, a tertiary care hospital, is in Karachi, part of the university campus. There are also a number of secondary care hospitals in Karachi including two maternity hospitals. The Aga Khan University is part of the Aga Khan Development Network (AKDN), which has also established the Aga Khan Health Services of Pakistan (AKHSP), which is present throughout Pakistan. These facilities are non-governmental, not-for-profit, but we also work within the government setups, though that is informal.

The clinical laboratory has branches throughout the country. That's another service that we provide across Pakistan. It's not the only laboratory service in Pakistan, but it is really a reference-level setup. So a lot of people utilize these laboratory services, and a lot of hospitals liaise with us for patient testing.

Is the hospital entirely Pakistan-focused?

Where I work is Pakistan-focused. But the Aga Khan University has a humongous presence in Kenya; in Uganda, there's a nursing school, but there's also going to be a medical campus, and then a hospital very soon, we hope; and then Tanzania; and then there is presence in Central Asia: Tajikistan and Kyrgyzstan. There is also the Institute for the Study of Muslim Civilisations (ISMC) in London. Among many other health and social initiatives throughout the world.

And what is hoped in the future -- speaking on behalf of the President, Board of Trustees, is that there will be a faculty of arts and sciences in Karachi as well. AKU, Pakistan was never just a medical university, because there has been focus on Islamic Studies and architecture, but we will be expanding the center in Karachi to include arts and social sciences, which is an exciting development.

By topic, but also by location?

Yes. By topic and by location: we kind of transcend all of it. The university, like others, transcends borders, national but also political or even religious. We work in many different situations.

Do you work in Bangladesh?

The Aga Khan Development network (AKDN) works in Bangladesh and India, but AKU Pakistan also works with partners in Bangladesh and India, collaborating on infectious disease research, symptoms of diarrhea, and so on, and that has been very rewarding. These partnerships are welcomed and nurtured at the university and at the AKDN level. It is very beneficial to both ends. It is something that comes from the overarching drive to decrease diarrhea mortality or pneumonia mortality in countries, and so there are excellent examples of multi-center, multi-country studies where we've been a part of all of that, primarily for Pakistan.

How is the hospital linked to the Ismaili community in Pakistan? Is the community concentrated in one area?

It is all over. The Aga Khan University was founded by the chancellor, Prince Karim Aga Khan, the religious leader of the Ismaili Shia community. The charter of the Aga Khan University states that it is a general university inspired by Islamic principles. It is linked to the Aga Khan Development Network (AKDN), which is run by the Ismaili community. There is a very strong community in Pakistan, with very close ties and a strong sense of civic responsibility, that you don't find in a lot of other communities in Pakistan. There are a few other communities involved in public service, but they don't have a university-level service that they offer to the rest of the country, irrespective of their religion or faith. So the hospital or the university are not “run” by the Ismaili community, but it links with the AKDN, which is predominantly the Ismaili community.

What are the links between the University and hospital and the Pakistani Ismaili community. Is it institutionalized, or is it informal?

I don't think it's institutional- there is a board of trustees for the university, which is actually pretty diverse. It doesn't just have Ismaili members, but it has some. But I wouldn't say it's a Pakistani institution. The medical university in Pakistan and East Africa are separately defined as such. There have been conversations around forging linkages more at the grassroots level though. We have been linking with Kenyan counterparts more, and also with Uganda. Kenyan counterparts have been invited over to the Pakistan university. There have also been student exchange programs in the school of nursing. for AMR and infectious diseases, have monthly clinicopathological conferences with Kenya where we discuss challenging clinical cases.

How does the University and the AKDN navigate some of Pakistan’s well known religious tensions? I know the community and network focuses on excellence and avoids being enmeshed in conflicts but am curious as to how that plays out. 

I would say that it really is remarkable how the AKU has stayed its course in being a recognized university. There are a lot of religious tensions; it's not an easy subject to address, and it is recognized as an Ismaili community project, which it primarily is, though in the charter it's an open health service system. So far, I think because of the level of commitment and the level of service that the Aga Khan University has provided and continues to provide, it has played out very well. It's the quality that drives it.

And of course, everyone wants good healthcare.

Everybody wants good healthcare. We offer a great amount of welfare services to patients. But of course it can't be offered to everyone, and again, the number of hospital beds are limited. You can't cater to the whole country, all the sickest of the sick. Fortunately, more hospitals are coming up that also provide quality healthcare in Pakistan. AKU as a university and a leading academic healthcare institution has also evolved and will continue to evolve, but traditionally, it's the quality and excellence of service that we've been providing that has really welcomed and embedded AKU into the healthcare system in Pakistan, and that's still recognized and very well respected.

Are there any issues or tensions around women's health? 

Everything that affects healthcare affects women, but I cannot think of tensions specific to women. However, issues and social mores vary. We found that for TB, it is reported more in women than in men, from the north of Pakistan than in the south. That was a surprise to us, as we had expected that even if women had a higher rate of TB, they would not present to healthcare due to social pressures etc. In community clinics also, we have observed that women are more likely to seek healthcare, but may be less likely to follow advice where social pressures intervene such as independent decisions on contraceptives or family planning advice.

With large gender gaps in Pakistan relative to other countries, how obvious is that when you're treating people on a daily basis? How might, some of the differing religious perspectives play out?

It's frustrating. But at a larger level, I could not answer as to how it plays out, and how it relates to religious differences. I don't think we've looked at it that way. Perhaps religious discrimination, and gender discrimination are part and parcel of community ethos. It's difficult to deal with it, because tensions rise and the physician must be a neutral person. It's very difficult, especially when you're dealing with a patient who's a woman. So yes, it is a very challenging situation.

How did you come to your current position and work? Why did you study medicine?

I graduated in Karachi in Pakistan, where I have lived all my life.

To be honest, I wasn't like some other friends who had always wanted to become physicians. I was more geared in other directions. But where I always came from, what I always wanted to do, was to discover more. When you are going to medicine, for med school interviews and everything, people simply want to hear, and many think other people want to hear, or interviewers want to hear, that you want to help people. But everybody wants to help people; as an empathetic person, you just want to help others. So I don't think that was my primary motivation to begin with, because at that time, at that age, my drive was towards discovering things. I might have gone in different directions, but medicine was plan A. I come from a family of physicians, so seeing that around you, learning every day from my father and my father's friends, you grow up with that. That was the natural thing to do. But, being a rebel, I wasn't very happy with the straight path but, with medicine the most obvious option, I went for it.

You were at the Aga Khan University?

I was at AKU. It has a difficult selection process, and is a great university. I was very happy there. A large amount of hard work is required, and there's lots of discovery, lots of science to study, things to do. But beyond that, both I and my parents believe that in the process of becoming a physician, you become a more empathetic person; you develop more than the simple skills needed. I think that empathy is really something that all human beings should have, so I don't think it should be specific to medicine, but it somehow probably is –and I did develop that.

What I didn't really quite see is the amount of misery and the amount of pain around me. That didn't quite make itself obvious or known to me during the undergraduate years. When I graduated in medicine, I was very sure that I would like to do pediatric surgery.

In the last year of medical college, we took electives, which could be anywhere in the world. I took one month in the UK, but after that I stayed in Pakistan. Many graduates leave to pursue postgraduate education elsewhere, which I had also wanted to do, but I took my other two months of electives in another hospital in Karachi, which was a government pediatric hospital, where I got to see more patients from a more diverse background than in a private hospital. So I wasn't really familiar with the full range of social issues surrounding medical problems among the poor. Don't get me wrong, at the AKU, we had an amazing community medicine program where we experienced medicine in that environment. Also, AKU offers a lot of welfare, and so we did see patients from lower socioeconomic backgrounds, and a lot of refugees as well. But I got from my electives and working in government hospitals, a real sense of what healthcare was like in the rest of the country, perhaps 80 percent of the healthcare available to 90 percent of people. And that's what opened my eyes to what was really going on. There was a lot of pain but I experienced a general lack of empathy in people. I remember that the parents often seemed numb.

They showed empathy for their children?

No, a lack of it. Because these parents had 13 or 14 children each, and if one child fell sick, they couldn't really stay at the hospital caring for them. We rarely saw that in our private setup in the private institute, or even in community medicine when you went out in well cared for communities where there were programs. In the government hospitals there was much suffering and it was shocking.

During my internship year I felt that it was important to experience medicine elsewhere so I went to a public-sector hospital where there was a lot of infectious disease. That's when I decided I couldn't do pediatrics and that I wanted to do infectious diseases. I changed my decision.

What were the main infectious disease issues?

Typhoid and TB continue to be widespread. And on top of that, there are a lot of others, like dengue. It keeps cropping up always.

I wrote to one of my professors who is still my mentor, saying that I would like to do infectious diseases. She said "We don't have a fellowship yet, so why don't you try and do microbiology first?" And I saw that as an amazing idea, because microbiology goes to what the diseases are based on. You have to know the bug to know the drug. I took eight months of a medical officer position in microbiology, and I found it was amazing: it combined my passion for science with patient care; and I really loved it. I was not really distracted from infectious disease, so I did try to pursue more training in that as well. But I stuck with clinical microbiology. That's where I still am.

There are many unknown or undiscovered infectious agents out there and we see outbreaks, that can be both exciting and frustrating. There is still a lot of pain and misery. Sometimes there are things you can't do; but there is also pathogen discovery. There are sophisticated techniques that you can't use, especially coming from a lower-resource setting and at the community level (not at the hospital). We sometimes can't get access to patient samples in remote settings, or are not able to follow up patients. So sometimes it is frustrating, but I think it's part of the challenge. What we do here is really critical to recognition of infectious diseases.

The Aga Khan University will have its 22nd National Health Sciences Research Symposium on Antimicrobial Resistance in 2019. Read more at http://www.aku.edu/nhsrs.