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IntroductionInappropriate antibiotic use is a major driver of antimicrobial resistance. However, the scope of literature and its prevalence across world regions remain largely unknown, as do the most common indicators and study designs used. In this study, we summarised the current literature on inappropriate use of antibiotics by world regions. We also provided the first global estimates of the overall amount of antibiotics that are potentially used inappropriately each year. MethodsWe considered both patient and provider-mediated inappropriate antibiotic use. We reviewed 412 studies published between 2000 and 2021 and used beta regression and marginal contrasts to compare prevalence of inappropriate use by study design, indicator, world region, and national income level. Country-level sales of antibiotics from 2022 were combined with inappropriate antibiotic use estimates derived from two study designs (clinical audits and patient interviews) and one indicator (lack of indication) to estimate the amount of antibiotics inappropriately used globally. ResultsClinical audits (50.1%, 208/412) and ‘non-prescription’ use (37.1%, 153/412) were the most common study design and indicator, respectively, used to estimate inappropriate antibiotic use. Inappropriate antibiotic use prevalence was ~6% higher in low-income and middle-income than in high-income countries. However, this difference disappeared after accounting for a proxy of access to care: physicians per capita. Globally, based on clinical audits, patient interviews and lack of indication, the estimated proportion of inappropriate antibiotic use was 29.5%, 36.5% and 30.8%, respectively, with an average of ~30% (~13 000 000 kg) the equivalent of the annual antibiotic consumption in China. ConclusionsInappropriate antibiotic use is highly prevalent across all countries regardless of national income level, with a third of global antibiotic consumption potentially due to unnecessary prescription (‘lack of indication’). Antibiotic stewardship efforts and defining internationally standardised indicators are needed to track progress in reducing the occurrence of inappropriate antibiotic use where necessary, as well as identifying gaps in access to care. 

Broader coverage can have economic, climate-related, animal welfare, and human health benefits 

Abstract BackgroundThe emergence of antimalarial drug resistance poses a major threat to effective malaria treatment and control. This study aims to inform policymakers and vaccine developers on the potential of an effective malaria vaccine in reducing drug-resistant infections. MethodsA compartmental model estimating cases, drug-resistant cases, and deaths averted from 2021 to 2030 with a vaccine againstPlasmodium falciparuminfection administered yearly to 1-year-olds in 42 African countries. Three vaccine efficacy (VE) scenarios and one scenario of rapidly increasing drug resistance are modeled. ResultsWhen VE is constant at 40% for 4 years and then drops to 0%, 235.7 (Uncertainty Interval [UI] 187.8–305.9) cases per 1000 children, 0.6 (UI 0.4–1.0) resistant cases per 1000, and 0.6 (UI 0.5–0.9) deaths per 1000 are averted. When VE begins at 80% and drops 20 percentage points each year, 313.9 (UI 249.8–406.6) cases per 1000, 0.9 (UI 0.6–1.3) resistant cases per 1000, and 0.9 (UI 0.6–1.2) deaths per 1000 are averted. When VE remains 40% for 10 years, 384.7 (UI 311.7–496.5) cases per 1000, 1.0 (0.7–1.6) resistant cases per 1000, and 1.1 (UI 0.8–1.5) deaths per 1000 are averted. Assuming an effective vaccine and an increase in current levels of drug resistance to 80% by 2030, 10.4 (UI 7.3–15.8) resistant cases per 1000 children are averted. ConclusionsWidespread deployment of a malaria vaccine could substantially reduce health burden in Africa. Maintaining VE longer may be more impactful than a higher initial VE that falls rapidly. 

BackgroundDespite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths.Klebsiella pneumoniae(K.pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden ofK.pneumoniaeneonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths ofK.pneumoniaeneonatal sepsis and project the global effects of routine immunization of pregnant women with theK.pneumoniaevaccine as antimicrobial resistance (AMR) increases. Methods and findingsWe developed a Bayesian mixture-modeling framework to estimate the effects of a hypotheticalK.pneumoniaematernal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality—with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive forK.pneumoniae. We analyzed 9,070K.pneumoniaegenomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes inK.pneumoniaeisolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination.Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistantK.pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends inK.pneumoniaeneonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. ConclusionsAK.pneumoniaematernal vaccine could have widespread, sustained global benefits as AMR inK.pneumoniaecontinues to increase. 

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant’s importation time, its infectiousness advantage and, its cross-infection on the novel variant’s detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention’s effectiveness due to the variants’ competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant’s basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions’ regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population. 

Despite vast improvements in global vaccination coverage during the last decade, there is a growing trend in vaccine hesitancy and/or refusal globally. This has implications for the acceptance and coverage of a potential vaccine against COVID-19. In the United States, the number of children exempt from vaccination for “philosophical belief-based” non-medical reasons increased in 12 of the 18 states that allowed this policy from 2009 to 2017 ( 1 ). Meanwhile, the overuse and misuse of antibiotics, especially in young children, have led to increasing rates of drug resistance that threaten our ability to treat infectious diseases. Vaccine hesitancy and antibiotic overuse exist side-by-side in the same population of young children, and it is unclear why one modality (antibiotics) is universally seen as safe and effective, while the other (vaccines) is seen as potentially hazardous by some. In this review, we consider the drivers shaping the use of vaccines and antibiotics in the context of three factors: individual incentives, risk perceptions, and social norms and group dynamics. We illustrate how these factors contribute to the societal and individual costs of vaccine underuse and antimicrobial overuse. Ultimately, we seek to understand these factors that are at the nexus of infectious disease epidemiology and social science to inform policy-making.