Exploring a One Health Approach to AMR in Pakistan
Antimicrobial resistance (AMR) is a major public health concern worldwide. Bacterial resistance to antibiotics can lead to ineffective medical treatment, often requiring the use of more toxic medications and resulting in increased treatment failure and mortality. These complications are already having a severe impact. A 2019 report indicated that nearly 5 million deaths worldwide were associated with drug-resistant bacteria, with almost 1/4 of these deaths (1.27 million) being directly attributed to AMR. Importantly, AMR-related deaths are not distributed equally around the globe: nearly 90% occurred in under-resourced countries.
This means global efforts to counter AMR will only be successful if they can be applied across all countries, regardless of economic status. This article will use the situation in Pakistan (an under-resourced country) as a case study, examining the current impact of AMR in Pakistan, discussing previous plans to combat AMR and highlighting examples of how the challenge of AMR is being addressed in the country. The hope is that these examples will provide key insights into strategies that can be spread worldwide, including a One Health approach.
The Status of AMR in Pakistan
Pakistan ranks 176th out of 204 nations in AMR-related mortality per 100,000 people. In 2019, the Global Research on Antimicrobial Resistance Project reported 59,200 deaths in Pakistan directly attributable to AMR, with an additional 221,300 deaths listed as AMR-associated. AMR was therefore the third-leading cause of death for Pakistanis in 2019, behind only cardiovascular disease and maternal/neonatal disorders.
The majority of AMR-related deaths in Pakistan are caused by a select group of bacteria, including Salmonella enterica, Staphylococcus aureus, Streptococcus pneumoniae and carbapenem-resistant Enterobacterales and non-Enterobacterales, that appear on the World Health Organization's (WHO) list of “priority pathogens." The growing threat represented by these deadly microbes is tangible. In 2016, a report out of Hyderabad in Pakistan highlighted the first case of extensively drug-resistant Salmonella enterica serotype Typhi (XDR typhoid). This XDR strain was resistant to ampicillin, cotrimoxazole, quinolone, chloramphenicol and third generation cephalosporins.
Yet, while these are the most prominent, they certainly are not the only drug-resistant microbes in Pakistan. New Delhi metallo-β-lactamase-1 (NDM-1) is a β-lactam enzyme that provides resistance to several antibiotics, such as carbapenems, which are broad-class antibiotics that are often used against drug-resistant bacteria. First identified in 2008, the NDM-1 gene has subsequently been found in pediatric and neonatal septicemia patients in Pakistan.
mcr-1 is a plasmid-encoded gene that imparts resistance to polymyxin E (colistin), which is considered a last resort antibiotic for carbapenem-resistant bacteria infections. After first being identified in animals and humans in China in 2016, the mcr-1 gene was soon found in Pakistan, first in a clinical isolate of Escherichia coli, and followed shortly thereafter in human clinical samples.
The Challenges of Combating AMR in Pakistan
Several factors raise challenges to addressing AMR in the country. With a population of 241 million people, Pakistan is the world’s fifth most-populated country and has a doctor-to-patient ratio of approximately 1:1300; by comparison, the doctor-to-patient ratio in China is approximately 1:400.
Such a low doctor-to-patient ratio contributes to low health literacy and a lack of patient education about AMR. Overall, around 63% of the population in Pakistan is literate. In addition, there is a low awareness among medical experts in Pakistan of effective treatments for resistant organisms.
Economics presents another challenge. Pakistan is one of the world’s poorest countries. As of 2022, per capita income was measured at $6,836, ranking 135th out of 204 countries. This means that the average person living in Pakistan cannot afford the cost of a doctor's appointment.
Overuse and Misuse of Antibiotics
The overall result of these combined factors is a high prevalence of misuse and overuse of antibiotics, 2 main drivers for the development of AMR in bacteria. Physicians administer antibiotics to 70% of patients. This prescribing pattern is particularly prevalent among general physicians in public sector hospitals, who tend to prescribe more than 3 drugs per patient.
In addition, more than 60% of the population in Pakistan self-medicates, given the prevalence of unlicensed pharmacies. Companies in Pakistan currently possess 647 operational licenses for drug production from the Drug Regulatory Authority of Pakistan (DRAP). However, none of these licensed production units have obtained approval from the United States Food and Drug Administration (FDA). By contrast, neighboring Bangladesh has 5 pharmaceutical plants approved by the FDA, while India has around 200.
Pharmacists in Pakistan are also able to provide antibiotics, often without a physician's prescription. Patients therefore have easy over-the-counter access to “Watch” (azithromycin, ceftriaxone, ciprofloxacin, meropenem and vancomycin) and “Reserve” (ceftazidime/avibactam, colistin, Fosfomycin, linezolid and polymyxin B) antibiotics.
The use of antimicrobials in livestock production, known as antimicrobial utilization (AMU), also contributes to the dissemination of AMR. Nearly 70% of antibiotics worldwide are used in livestock to prevent sickness, encourage growth and increase feed production. One study found that AMU by growers in Pakistan for broiler chickens alone was greater than every country in the world other than China, reaching nearly 568 tons annually.
Success Stories of One Health Approaches in Pakistan
Despite these challenges, Pakistan is making significant progress toward addressing and combating AMR. Like other nations, Pakistan is emphasizing a One Health approach to AMR. One Health is an interdisciplinary concept that recognizes the relationship between human health, animal health and environmental health.
One Health is an interdisciplinary concept that recognizes the relationship between human health, animal health and environmental health.
Source: Wikimedia Commons. The Pak One Health Alliance (POHA), a non-governmental organization, promotes One Health strategies, policies and interventions across the country. POHA regularly conducts meetings and workshops to raise public awareness about One Health-related issues and the emergence and re-emergence of infectious diseases in Pakistan, working with stakeholders like ASM.
Additionally, the U.S. National Academy of Sciences, Engineering and Medicine (NASEM), in partnership with the Pakistan Academy of Sciences, has established a fellowship program to build the capacity of early- and mid-career scientists in Pakistan in One Health research. The program also encourages collaboration and cooperation in preparedness and response to zoonotic diseases and other shared environmental health risks.
In 2017, Pakistan released its National Action Plan on AMR (NAP), testifying to the nation's firm commitment to battling this global crisis. The NAP included initiatives for health care, agriculture and the environment to combat AMR. It also aimed to promote sensible antibiotic usage, strengthen surveillance and improve infection prevention and control across health care settings in the country.
Antibiotic production has also improved. In 2018, the moxifloxacin tablets manufactured by Getz Pharma Pvt., Ltd. attained the distinction of being the first-ever pharmaceutical product from Pakistan to receive prequalification by the WHO.
The National Institutes of Health, Pakistan has also played a crucial role. The implementation of the Global Antimicrobial Surveillance System in 2016 led to the establishment of the Pakistan AMR Surveillance System in 2018, which has provided a strong platform for monitoring and controlling AMR. Moreover, Pakistan's efforts extend to initiatives such as the AMR Tricycle program and point prevalence surveys on antimicrobial consumption.
Pakistan is engaged in various global initiatives, including developing a microbiology laboratories database for microbiologists and a data sharing portal for the Pakistan AMR Surveillance System. Whole-genome sequencing is utilized to monitor antimicrobial resistance, and resources like the "Microbiology and Antimicrobial Resistance" Virtual Journal Club hosted by the NIH, Pakistan are available for health care workers, early to mid-career microbiologists and infection disease control experts.
Pakistan's ongoing efforts and initiatives demonstrate the country's collaborative approach toward addressing AMR, both at the national and international levels. The NAP-AMR is a comprehensive plan that addresses future strategies and regulatory challenges related to AMR, using a One Health method through its core objectives of the Global Action Plan.
To effectively implement this plan, it is necessary to have ongoing stakeholder participation from politicians, policymakers, pharmaceutical industries, agriculture sectors, civil society, media and international organizations, like the WHO, the World Organization for Animal Health and the United Nations Food and Agriculture Organization. Dedicated funding from the government of Pakistan and international collaborators is also required for specified AMR reduction efforts.
Coordination between central and provincial governments within Pakistan is crucial for achieving the aims and outcomes of the NAP on AMR. Furthermore, pharmaceutical companies, agriculture sectors and non-governmental organizations should collaborate to achieve the desired outcomes. Health care personnel should also support antimicrobial stewardship and infection prevention and control programs. Measures to limit the self-purchasing of antibiotics and the excessive use of broad-spectrum antibiotics at the community and hospital levels are expected to lower overall consumption.
My research has focused on AMR for the past 15 years, leading to the publication of more than 75 scholarly papers on the subject. My current research is focused on the surveillance and investigation of the molecular mechanisms that lead to the development of antimicrobial resistance in pathogens, within the context of the One Health approach. I am also studying the patterns of antibiotic usage in both human and veterinary sectors, determining antimicrobial residue in food-producing animals, examining how AMR impacts hospital-acquired infections (HAIs) and investigating bloodstream infections in children. Furthermore, my research group is actively involved in exploring new therapeutic options, such as phages, nanoparticles, synthetic compounds and natural products.
By continuing to undertake these efforts, Pakistan can provide an example for the rest of the world to follow in the fight against AMR.
In This Issue:
- Lessons From a Decade of Antimicrobial Resistance Policy
- Growing Resistance: How Plant Agriculture Contributes to AMR
- Understanding the Risks of Antifungal Resistance
- Experts in East Africa Propose Equitable AMR Interventions
- Wastewater As a Key Driver of AMR
- Exploring a One Health Approach to AMR in Pakistan
- Federally Qualified Health Centers Lead AMR Stewardship
- Updating Breakpoints in Antimicrobial Susceptibility Testing
- Hunting for Antibiotics in Unusual and Unculturable Microbes
- What's Hot in the Microbial Sciences