The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis

Abstract

Background: A critical and persistent challenge to global health and modern health care is the threat of antimicrobial resistance (AMR). Previous studies have reported a disproportionate burden of AMR in low-income and middle-income countries, but there remains an urgent need for more in-depth analyses across Africa. This study presents one of the most comprehensive sets of regional and country-level estimates of bacterial AMR burden in the WHO African region to date.

Methods: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO African region in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). We obtained data from research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings: In the WHO African region in 2019, there were an estimated 1·05 million deaths (95% UI 829 000-1 316 000) associated with bacterial AMR and 250 000 deaths (192 000-325 000) attributable to bacterial AMR. The largest fatal AMR burden was attributed to lower respiratory and thorax infections (119 000 deaths [92 000-151 000], or 48% of all estimated bacterial pathogen AMR deaths), bloodstream infections (56 000 deaths [37 000-82 000], or 22%), intra-abdominal infections (26 000 deaths [17 000-39 000], or 10%), and tuberculosis (18 000 deaths [3850-39 000], or 7%). Seven leading pathogens were collectively responsible for 821 000 deaths (636 000-1 051 000) associated with resistance in this region, with four pathogens exceeding 100 000 deaths each: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Third-generation cephalosporin-resistant K pneumoniae and meticillin-resistant S aureus were shown to be the leading pathogen-drug combinations in 25 and 16 countries, respectively (53% and 34% of the whole region, comprising 47 countries) for deaths attributable to AMR.

Interpretation: This study reveals a high level of AMR burden for several bacterial pathogens and pathogen-drug combinations in the WHO African region. The high mortality rates associated with these pathogens demonstrate an urgent need to address the burden of AMR in Africa. These estimates also show that quality and access to health care and safe water and sanitation are correlated with AMR mortality, with a higher fatal burden found in lower resource settings. Our cross-country analyses within this region can help local governments to leverage domestic and global funding to create stewardship policies that target the leading pathogen-drug combinations.

Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Figure 1

Age-standardised mortality associated with and attributable to AMR in Africa in 2019 (A) Age-standardised mortality associated with AMR. (B) Age-standardised mortality attributable to AMR. (C) Age-standardised mortality associated with and attributable to AMR in relation to the status of NAPs for the countries in the WHO African region. Data from Angola on AMR NAPs were last reported in the 2018−19 survey responses. Algeria last reported on the 2021−22 survey responses. AMR=antimicrobial resistance. NAP=national action plan.

Figure 2

Deaths (count) associated with bacterial antimicrobial resistance by pathogen−drug combinations, 2019 3GC=third-generation cephalosporins. 4GC=fourth-generation cephalosporins. Anti-pseudomonal=anti-pseudomonal penicillin or β-lactamase inhibitors. BL-BLI=β-lactam or β-lactamase inhibitors. Group A Streptococcus=Streptococcus pyogenes. Group B Streptococcus=Streptococcus agalactiae. MDR=multidrug resistance. Mono INH=isoniazid mono-resistance. Mono RIF=rifampicin mono-resistance. NA=not applicable. Penicillin=natural pencillins susceptible to penicillinases (benzylpenicillin, phenoxymethylpenicillin, procaine benzylpenicillin, and benzathine benzylpenicillin). Resistance to 1+=resistance to one or more drugs. S Paratyphi=Salmonella enterica serotype Paratyphi. S Typhi=Salmonella enterica serotype Typhi. TMP-SMX=trimethoprim-sulfamethoxazole. XDR=extensive drug resistance.

Figure 3

Deaths (count) attributable to bacterial antimicrobial resistance by pathogen−drug combinations, 2019 3GC=third-generation cephalosporins. 4GC=fourth-generation cephalosporins. Anti-pseudomonal=anti-pseudomonal penicillin or β-lactamase inhibitors. BL-BLI=β-lactam or β-lactamase inhibitors. Group A Streptococcus=Streptococcus pyogenes. Group B Streptococcus=Streptococcus agalactiae. MDR=multidrug resistance. Mono INH=isoniazid mono-resistance. Mono RIF=rifampicin mono-resistance. NA=not applicable. Penicillin=natural pencillins susceptible to penicillinases (benzylpenicillin, phenoxymethylpenicillin, procaine benzylpenicillin, and benzathine benzylpenicillin). Resistance to 1+=resistance to one or more drugs. S Paratyphi=Salmonella enterica serotype Paratyphi. S Typhi=Salmonella enterica serotype Typhi. TMP-SMX=trimethoprim-sulfamethoxazole. XDR=extensive drug resistance.