Addressing the transmission of antimicrobial resistance in low-resource settings

Published in Microbiology
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We are living through an antimicrobial resistance crises that is an under-mitigated, anthropomorphic disaster. The biological basis for resistance is the same everywhere but contextual factors determine whether newly-evolved resistance fizzles out or amplifies and persists. Place is an important determinant of resistance:     the resistance crises is amplifying globally but the peculiarities are playing out somewhat differently in developing countries.  Here, essential and avoidable antimicrobial use is driven by a higher burden of infectious diseases and lower per-capita access to prescribing health professionals, pharmacists, or testing laboratories required for stewardship. Worse still, pervasive inadequacies in water sanitation and hygiene foster unfettered transmission of evolved resistant strains among humans, animals and the environment. The close-knit interaction that humans in LMICs often have with livestock, even in urban settings, due to open wet markets and unregulated and widespread “backyard” production enables resistant bacteria to easily spread. And because of their higher infectious disease burdens and fewer antimicrobial options, low-resource settings will pay more for resistance.

 

Key contributors of AMR spread in LMICs include ease of accessibility and misuse of antimicrobials; and poor surveillance of AMR development in human, animal and environmental settings; inadequate sanitation and hygiene conditions; weak infection prevention and control systems; lower AMR awareness as priority areas for intervention . These are mentioned in the WHO Global Action Plan on Antimicrobial Resistance, and the direction from WHO that countries develop their own National Action Plans emphasizes the importance of local input in prioritizing, designing, implementing and evaluating interventions.  National Action Plans, in many cases short of implementation funds, rightly aim for a multipronged strategy to address resistance.  But which approaches should be prioritized?  Many evidence-based resistance containment solutions were devised and evaluated in high-income settings with good regulatory structures.  Other AMR case-studies are just emerging.  However, in general, for problems requiring a multipronged approach, ranging from malaria control to disease eradication, bottom-up approaches have worked better in low- and middle-income countries.  As countries renew their antimicrobial resistance National Action Plans, we propose that a bit more thought and evidence generation needs to go into interventions that can be successfully used in informal economies with limited resources

 

A number of antimicrobial resistance interventions rightly focus on selective pressure.  Less emphasis is made on the dissemination of resistance, even though it is acknowledged that transmission is rife in developing countries.  Here, increased access to safe and clean water, improvements in sanitary conditions, as well as the concomitant reduction in the incidence of infectious diseases in animal and human populations using vaccines and other preventative tools will markedly reduce the spread of AMR and should be priority interventions.  All of these inadequately implemented but essential interventions have evidenced potential to reduce the overall infectious disease burden.  This in turn would reduce the need to use antimicrobials in the first place, potentially ultimately ratchetting selective pressure downwards, and having a similar effect on burden from ill health and antimicrobial resistance. 

 

We have the privilege of being part of the tremendous progress that has been made in recent years on antimicrobial resistance surveillance in LMICs.  As at January 2021, Sixty-six (n=66) Low and middle-income countries and territories have been enrolled into the Global Antimicrobial Surveillance System (GLASS) by the World Health Organization (WHO) (https://www.who.int/initiatives/glass/country-participation). While surveillance is not yet adequate or representative, we have a better sense of the scale of the problem than ever before.  This offers the potential to measure the impact of interventions, including those we suggest in our paper.  In addition to the aforementioned more general interventions to control transmission, however, there is also the potential for targeted technological approaches with grassroots deployment potential.  More targeted approaches, in turn, require us to understand what is being transmitted via which pathways and how best to block it.  Pandemic lineages of many priority organisms have been highlighted but less is known about their epidemiology and ecology in lesser-studied parts of the world and locally circulating successful clones are often unknown to science.  Our co-author group worked with other stakeholders to introduce genomics to antimicrobial resistance surveillance in four low- and middle-income countries and we are engaged in other activities aimed at expanding access to these powerful technologies.  It was therefore important for us to highlight that using genomic methods to address these questions is now possible as whole genome sequencing costs are falling and templates for starting up genomic surveillance are now in place.  We hope that readers will see why genomic methods need to be applied more in LMIC settings.

 

Reversing the worrying antimicrobial resistance trajectory will require better implementation of existing approaches and technologies, as well as a focused analysis of innovation needs for low resource settings, such as – but not limited to – those we lay out.

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