Drivers of antimicrobial resistance in East Africa

Gerald Mboowa is a bioinformatics scientist at the African Center of Excellence in Bioinformatics & Data Intensive Sciences of the Infectious Diseases Institute, College of Health Sciences, Makerere University in Uganda. He is also a Grand Challenges Africa (GC Africa) grantee. GC Africa seeks to promote Africa-led scientific innovations to help countries better achieve the Sustainable Development Goals by awarding seed and full grants to the continent’s most impressive solutions. GC Africa is implemented through AESA (Alliance for Accelerating Excellence in Science in Africa), a funding, agenda setting and programme management platform of the AAS and the African Union Development Agency (AUDA-NEPAD) in partnership with the Bill & Melinda Gates Foundation.

In this blog, Gerald describes some practices and behaviours that drive emergence and spread of anti-microbial resistance (AMR) and how generating knowledge, developing innovation and deploying interventions have the potential to address AMR.

This research builds on my training in immunology and both human and pathogen genomics. While working with Mycobacterium tuberculosis, which causes tuberculosis and takes up to eight weeks to be isolated and grown in the laboratory, and Brucella isolation through microbiological cultures, I was introduced to non-microbiological diagnostic tests, such as whole-genome sequencing. This technique generates genomic data that requires use of sophisticated bioinformatics tools or workflows (pipelines). These proved to be an obstacle to implementation of next-generation sequencing (NGS)-based approaches in clinical microbiology laboratories. This problem redirected my research career from wet laboratory work to the application of bioinformatics pipelines to analyse micro-organisms such as bacteria and our own (human) DNA.

We have developed an automated and easy-to-use microbial pipeline for analysing and interpreting bacterial DNA data (rMAP Rapid Microbial Analysis and Profiling pipeline). This will be deployed to identify the specific bacteria, their antimicrobial resistance profiles, virulence factors, relatedness (phylogenetic analysis), mutations, and reconstruct their original DNA sequences (genome assembly).

Why antimicrobial resistance is important

Antibiotics revolutionized modern medicine, contributing greatly to reduction in morbidity and mortality, mostly through treatment of infections and ensuring safe surgical procedures. However, these advances are currently threatened by the emergence and spread of antimicrobial resistance (AMR), a growing global public health threat of major concern.  Moreover, it is shaping a post-antibiotic era in which even minor infections become fatal due to resistance to and ineffectiveness of currently available antibiotics. Such cases are on the increase world-wide. The post-antibiotic era, once considered an apocalyptic fantasy, has now become real.

It is estimated that at least 700,000 people die annually from infections that are resistant to currently available antibiotics worldwide, and that by 2050, antibiotic-resistant infections will kill an estimated 10 million people per year worldwide, including 4 million in Africa. If the problem is not tackled, the global economic loss due to antimicrobial resistance is projected to be approximately $100 trillion between now and 2050.

Although the drivers of AMR are well-understood, accurate projections for its magnitude are essential for formulation, deployment and monitoring of an effective response to AMR. Africa is most affected by infectious diseases, yet accurate and reliable data on AMR, especially pertaining to its emergence, burden and spread within a wide range of pathogens, are not available. It is essential to accelerate research and to develop and deploy interventions based on innovations with the best potential to improve AMR awareness, pathogen surveillance and AMR characterisation and profiling, and to reduce incidence of infections, optimize use of antimicrobial agents, understand the practices and behaviours driving AMR, and define the role of ecosystems in AMR.

Lessons

In our study titled “understanding acquisition & transmission dynamics of AMR at referral hospitals & community settings in East Africa”, conducted in Mwanza, Tanzania and Kampala, Uganda we found that majority of patients were found to be positive for carrying antibiotic resistant bacteria (ARB) on admission (i.e. within 24 hours of hospital stay); for those patients who were negative on admission, the presence of ARB was reported for many after 48 hours of hospital stay. A few patients remained negative for ARB 72 hours after admission. Most patients reported that they had been sick and referred from other health facilities or wards within referral hospitals.

Findings from this analysis include:

• There is good understanding of the need for handwashing hygiene and other infection control methods. Study participants reported handwashing as the most widely known method of infection prevention and control (IPC) with the potential to halt the spread of infections. Participants also reported having heard about these measures across several platforms (e.g., media, trainings, conferences, and workshops). These findings reaffirm other studies findings that hand washing/hygiene is critical in curbing the spread of AMR.
• There is poor understanding of AMR and its drivers. The majority of study participants, despite stating they know what antibiotics are, had never heard of AMR.
• Self-medication with antibiotics is a factor: In this study, some individuals reported changing the antibiotic dosage during the course of self-medication and sometimes completely switching the antibiotics due to their failure to work, or because they finished their supply and there were alternative cheaper antibiotics. The majority of study participants stated their belief that self-medication was a “good” and/or “acceptable” practice.
• Most patients obtain antibiotics from community pharmacies. Participants reported community pharmacies as the single greatest sources of antibiotics used in self-medication.

First year as a Grand Challenges Africa (GC Africa) grantee

I prepared for my research and set up a research team ahead of the GC Africa initiation grant period, in order to be as productive as possible during the funded research period. Fortunately, I had learned much of grant management informally from my mentors at Makerere University. Because the study sites were in two countries, Uganda and Tanzania, two experienced research teams were required to implement the project in each country, each site had specific research requirements to execute the same study protocol.  Institutional support as well as choosing a team which had prior experience in research and grant management has enabled smooth implementation of this grant.

Why is funding innovation important for Africa?

Africa has the world’s fastest growing population, faced with a high burden of infectious diseases. To find solutions to the continent’s health and economic challenges, there must be more resources for training and funding early-career researchers to transition to independence. African-led solutions to African challenges are more likely to be sustainable, and result in improved health, development and economic growth.

What impact has the GC Africa programme had on your career?

The journey from postdoctoral to principal investigator (PI) in Africa is a daunting one. The GC Africa programme has provided a launchpad for me at the critical early-career, postdoctoral researcher stage, enabling me to become a PI and now be poised to build a research team at Makerere University.