Raffaella’s Literature Update
The following message is courtesy of Dr Raffaella Ravinetto, Public Health Department, Institute of Tropical Medicine Antwerp, Belgium.
Ref. Cavany S, Nanyonga S, Hauk C, Lim C, Tarning J, Sartorius B, Dolecek C, Caillet C, Newton PN, Cooper BS. The uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance. Nat Commun. Oct 3;14(1):6153. doi: 10.1038/s41467-023-41542-w.
Dear Friends,
Happy 2024! In this first mailing of the year, I am sharing an updated version of our Informal Factsheet on Quality of medicines, sadly including new cases of contamination with diethylene glycol.
I am also sharing an interesting manuscript that investigates the link between substandard ad falsified (SF) medicines and antimicrobial resistance (AMR). Cavany and coll. discuss the ways in which SF antimicrobials could impact AMR; and what types of data and analyses would help us to better understand the relationship between SF medicines and AMR. A few loose highlights from the paper:
· The key factors that will determine how SF medicines medicines impact on drug-resistance are the % of active pharmaceutical ingredient (API) and bioavailability.
· Transmission will be moderated by the frequency of AMR in the community, spatial distribution of SF medicines, and the extent to which these overlap in space and time.
· For many potential pathogens, such as those that often form part of the normal gut flora, most antibiotic exposure occurs when they are not the target of treatment. This exposure creates a selective pressure in favor of resistant bacteria, known as bystander selection. Failure to account for this effect can lead to mistaken inferences about the effect of interventions to reduce antibiotic use (this resistance could also be transferred to other microbes via horizontal gene transfer).
· Antimicrobials are often given in combination, for synergistic effect and to guard against resistance. However, if one or more of the medicines are SF, then it could lead to a negation of the synergistic effects or even inadvertent monotherapy (inadvertent monotherapy or a reduced API could lead to increased resistance, but also to reduced resistance in the presence of multi-drug resistant strains, as inadvertent monotherapy may reduce the strength of their competitive release…). Thus, “the specific effect of SF medicines on combination therapy will depend intimately on the disease and combination in question”.
· Random surveys of the prevalence of SF medicines should include dissolution testing (and not only the measure of API content) to predict the bioavailability and therapeutic efficacy of medicines. It is also important to undertake longitudinal (rather than cross-sectional only) studies of SF medicine frequency, % API, and bioavailability. Epidemiological models could also help us understand the impact of spatio-temporal clustering of the distribution of SF medicines.
It is concluded that “SF medicines represent a scourge on health systems through large parts of the global South, and will likely lead to large health and economic costs if we do not invest in research and systems to reduce their prevalence. This includes efforts to understand their burden, their direct impact on health outcomes, the trade-routes of falsified medicines, and what types of mechanisms could ensure the quality of antimicrobials. Solving the mystery of their impact on the burden of AMR is one critical part of this endeavor”.
Have a nice reading,
Raffaella