Research at the AKU Medical College (MC) focuses on advancing knowledge across the health sciences spectrum – from bench to bedside to community. The MC's research is targeted towards making a difference in six priority areas:
- Cardiometabolic Diseases
- Neurosciences and Mental Health
- Cancer
- Reproductive, Maternal, Neonatal, Child Health (RMNCH)
- Communicable Diseases
- Trauma and Emergency
These areas intersect with foundational and cross-cutting themes for the MC i.e. Data Science, Family Medicine, Community Health Sciences and Genomics and Translational Research, with the objective of developing large-scale impact. Research priorities are aligned with national health needs, the University’s vision, and its comparative advantage in terms of expertise and infrastructure.
“2021 has been a record-breaking year for research at the Medical College. Hard work of our faculty and research staff, facilitation of our support departments, and improvements in policies and procedures have culminated in this year being one of the most productive in our 40-year history. The Medical College received over $49 Million in extramural research grants and published over 670 indexed research articles. Our faculty is serving at many important national and provincial platforms, often in leading roles. Contributions in the fight against the Covid-19 pandemic have been particularly relevant and impactful. Being the leading health research institute in Pakistan comes with great responsibility to produce new knowledge that helps our society. The potential to make a difference is immense, and we are just starting on this journey!” - Dr Syed Asad Ali, Associate Dean Research.
1. Public private partnerships for primary health care in Sindh
19 hospitals, 143 rural health centres and 1225 basic health units across Sindh have been actively engaged in World Bank Washington’s technical assistance project since 2017. This flagship reform project entails public-private partnerships (PPPs) where the government finances the co-management of a public primary health care (PHC) facility with NGOs like AKU. The PPP works to revitalise public PHC facilities back to a functional state through improvement in quality of care, also leading to increased uptake in use of the facilities. The evaluation stage has been completed by the AKU team; findings demonstrate opportunities and obstacles on part of both, the private and public stakeholders. The AKU team has created a report with recommendations to all stakeholders to reduce risks while improving service quality, through hiring third-party monitoring agencies, implementing output-oriented targets that can be measured against the United Nations Sustainable Development Goals etc. On the basis of the AKU team’s report, the government created their first-ever five-year plan with support of World Bank to strengthen existing PPPs while also diversifying to create new models of PPPs and conducting further research.
2. South Asia self harm research capability building initiative
In 1990, AKU’s Department of Psychiatry established a registry for cases of self-harm which is now known as the AKUH self-harm management system (SHMS). WHO recognises the critical importance of AKUH-SHMS by stating that it “remains the only database for self-harm in the country and provides an excellent example of a low-cost, low resource intensive health facility-based system on data collected routinely. This is particularly useful for LMICs that lack national surveillance systems for self-harm.” Pakistan needs to understand its national burden of self-harming behaviour and completed suicides; In collaboration with the University of Manchester, the AKU team is advancing the self-harm prevention mission for Pakistan by initiating a national-level self-harm registry through a monitoring and evaluation system at public hospital Jinnah Postgraduate Medical Centre. This registry, collecting quantitative and qualitative date, will be the first step to understand and manage the magnitude of self-harming behaviour. The team will also analyse patterns of reporting self-harm incidents to better understand the cultural stigma surrounding the issue. As data is collected and analysed, the evidence-backed findings can inform a national strategy to tackle the problem across Pakistan through preventative measures. Dr Nargis mentioned that “self-harming thoughts and behaviours can occur in all age groups” so any future strategy will be tailored to varying age groups and subcultures.
3. Evaluating the efficacy and safety of SCY-078 (Ibrexafungerp) in patients with fungal diseases that are refractory to or intolerant of standard antifungal treatment (FURI)
Antifungal drug development has been relatively slow in the past, with few antifungal agents available in the market worldwide. As fungal infection incidence rates and varieties are increasing, a new antifungal drug, SCY-078 (Ibrexafengerp), has been developed. This first-class drug is the only antifungal drug in this class and the study is examining its role in the treatment of fungal infections which have failed to respond to conventional therapy. Dr Mahmood shared “It’s exciting because it’s not often that we get to kickstart a new drug, and it’s also good for our patients (at AKU) because we will give them access to therapy which would otherwise be impossible for them to get.” SCY-078 is a very safe low-risk drug that is administered orally, making it easy for patients to make the switch to it. There is not much resistance to the antifungal drug and as it has a high safety profile while covering a wide range of fungi, it will prove to be a novel advancement for the treatment of multiple conditions.
4. Is low Vitamin D associated with higher fracture risk in children under 10 years of age?
Vitamin D, something that is essential in maintaining a healthy and strong body, is found to be deficient in 50% of the Pakistani population. Researchers at AKU are investigating the relationship between this prevalent deficiency and risk of fractures in the paediatric population, with the aim of developing evidence-based guidelines to inform the care and management of at-risk children. Presently, there is a dearth of LMIC-specific research conducted on this topic and in fact, this study will be the first to identify and assess specific detailed outcomes and risk factors that may be associated with fracture risk in Pakistani children. Primary caregivers have a duty to prevent future factures or at least reduce the risk of future fractures in children especially because fractures are a heavy burden for the Pakistani healthcare system to bare, and they often cause financial and mental problems for the patients and their families. The guidelines being developed by the researchers will inform the holistic care for fractures in Pakistan’s paediatric population, and the data obtained will serve as evidence for early provision of Vitamin D supplementation to reduce long term risks of fractures and associated health problems.
5. Phylo- and immuno- dynamics of SARS-CoV-2 infection in Pakistan: relating Covid-19 disease severity with viral diversity
This study explores something that has been on the minds of people worldwide; why does Covid-19 affect different people so differently? A research team from AKU is examining the disease biology of Covid-19 to understand what protects against severe disease. They are investigating genetic differences between individuals with asymptomatic, mild, moderate and severe infection, studying which genes are turned ‘on’ or ‘off’ between these groups. Study of gene expression patterns employ a microarray gene chip which allows the study of 21,000 targets simultaneously. By comparing data of Covid-19 patients with healthy control groups, the study has identified the largest difference to be in the type I Interferon (IFN) response in those who have minimal disease. Type I IFNs have effective anti-viral properties and have proven to clear viral infections such as influenza and hepatitis. This study demonstrates an association between highly effective Interferon Stimulated Genes and asymptomatic Covid-19 infections. The team hopes to conduct a clinical trial to test if administration of type I IFNs can be used to treat Covid-19. This discovery is especially exciting because IFNs are a low-cost and locally available resource commonly used in the treatment of other diseases, therefore providing a new and easy solution for treatment of Covid-19 in Pakistan. The study has been accepted for publication in Scientific Reports within Nature journal.
6. Does the use of achar (fermented pickles) improve the microbiome of women of reproductive age in Pakistan?
From a pool of two hundred applicants, AKU’s team was one of only five whose application was chosen through a competitive Grand Challenges call at the Gates Foundation. Pakistan’s culture is rooted in the ancient Indus Civilisation and studies have found that even some 2000 years ago, locals were making fermented foods in the form of achaar and it is is now a household staple across Pakistan. Focusing on treatments for malnutrition and childhood stunting, researchers are investigating the extent to which achaar improves the microbiome of expecting mothers. They will begin with a modest sample size of 30 women to test for changes in the expecting mothers’ microbiomes through faecal and blood samples. If any changes in the microbiome are detected, the study will expand to a larger sample size from which evidence can be generated to advocate for the medical use of achaar to improve maternal and foetal nutrition during pregnancy. Indigenous solutions to local problems prove their long-term sustainability in production and use, while also enabling treatment access for a large audience within low-resource LMICs such as Pakistan.
7. Estimating the prevalence of forced labour in Pakistan's brick kiln industry
Over 90 percent of brick kiln workers in Pakistan are estimated to have taken a loan at the time of starting work. This is a bonded labour system which particularly impacts rural and marginalised populations and migrants belonging to low socio-economic groups. Studies estimating the prevalence of bonded labour are limited, hampering implementation of 2018 Prevention of Trafficking in Persons Act. This comprehensive (qualitative and quantitative) study will gain an enhanced understanding of the issue, and will contribute to improved understanding of methodologies best suited to measure forced labour in hard-to-reach populations. The study will also contribute to the evidence base on forced labour risks in the brick kiln industry in Sindh, to guide implementation and monitoring of policies protecting brick kiln workers in Pakistan and globally. Following this first study, the second phase of the project is designed to reduce the prevalence of bonded labour in brick kiln workers in Sindh by testing interventions such as registration and formalisation of brick kiln industries and workers, access to legal aid for workers in debt bondage, provision of non-formal education for children, and occupational health and safety support and education.
8. Developing gut enteroids from control subject/ human small intestinal organoids model of SARS-CoV-2 replication
Working in collaboration with Harvard University and Moore Lab at University of Virginia, researchers developed an organoids model which uses stem cells isolated from human biopsies and grow them into miniature organs. This model goes beyond conducting studies on animals by developing cells close to healthy human cells. The research group was previously using the model to understand diseases like tropical enteropathy in malnourished children but upon the onset of Covid-19, they swiftly adapted the study to explore the impact of SARS-CoV-2 on malnourished children. The group had already collected biopsy samples and developed enteroids from well-nourished children in the USA, so they went on to collect such samples from well-nourished children and malnourished children from Pakistan to draw reliable and valid comparisons while advancing scientific knowledge. The organoids model is a patient-specific model, allowing for customised investigations to be conducted and customised treatments to be developed. Researchers are working to understand why the virus affects people so differently, and also to specifically understand the effects on malnourished children as they are prone to vaccine failure and to suffering from severe illnesses from vaccine-preventable infectious agents.
9. The Azithromycin and Cefixime treatment of typhoid in South Asia Trial (ACT-South Asia trial)
Typhoid and paratyphoid fever affects over 11 million people globally each year, of which seven million cases occur in South Asia. Up to one per cent of patients who get typhoid may die, and the survivors often face a prolonged period of ill health and heavy financial costs. Over the past two decades, treatment of typhoid fever with a 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime or azithromycin has led to patient recovery in four to six days without necessitating expensive hospitalisation. There is increasing antimicrobial resistance in the region which reduces the effectiveness of common treatments and increases the risk of prolonged illness and severe disease. The recent emergence of a particularly resistant typhoid strain in Pakistan, and the threat of its international spread, adds urgency to this problem. Treatment through combinations of antimicrobials may be more effective for treating typhoid fever and mitigating drug resistance. This multi-country and multi-centre study includes sites in Bangladesh, India, Nepal and Pakistan, and it will compare a combination of azithromycin and cefixime with azithromycin alone in the outpatient treatment of typhoid fever. Both antimicrobials are widely used and have excellent safety profiles. The team will assess whether treatment outcomes improve after one week of treatment and if the combination treatment is better than the single antibiotic treatment. Researchers will additionally investigate the financial implications for families and health systems.
10. Effectiveness of unconditional cash transfers combined with lipid-based nutrient supplement and/or behaviour change communication to prevent stunting among children in Pakistan.
Over half of the global burden of child stunting is in Asia. In Pakistan, prevalence of stunting in children under five-years of age has remained above the WHO critical threshold for over two decades. Child stunting is the devastating result of poor nutrition during the first 1,000 days of life; these children face a higher risk of morbidity, mortality, reduced cognition, and poorer performance in education and earning wages which contributes to intergenerational cycles of malnutrition and poverty. The AKU research team hypothesised that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behaviour change communication (SBCC) will prevent stunting among children 6-23 months of age. This study was a four-arm, community-based, cluster randomised controlled trial conducted in the district with highest prevalence of child stunting in Pakistan, Rahim Yar Khan. A total of 1729 children were enrolled at 6 months of age and measured monthly for 18 months until the age of 24 months. The team concluded that while UCT+SBCC was ineffective in reducing the child stunting prevalence, UCT+LNS and UCT+LNS+SBCC proved to be effective among children aged 6-23 months in marginalized populations. The study has been published in the American Journal of Clinical Nutrition (click here to view).
Acknowledging the hard work, dedication and contribution of all project's co-investigators, researchers, administrators and all other team members. The huge success of these projects is a collaborative effort that would not be possible without each project's entire team of experts.