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Creators/Authors contains: "Lewnard, Joseph A."

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  1. ; ; ; ; ; ; ; ; ( , PLOS Medicine)
    Background

    Despite 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 findings

    We 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.

     Conclusions

    AK.pneumoniaematernal vaccine could have widespread, sustained global benefits as AMR inK.pneumoniaecontinues to increase.

     
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    Free, publicly-accessible full text available May 22, 2024
  2. ; ; ; ; ; ; ; ; ; ; et al ( , Journal of The Royal Society Interface)
    null (Ed.)
    School closures may reduce the size of social networks among children, potentially limiting infectious disease transmission. To estimate the impact of K–12 closures and reopening policies on children's social interactions and COVID-19 incidence in California's Bay Area, we collected data on children's social contacts and assessed implications for transmission using an individual-based model. Elementary and Hispanic children had more contacts during closures than high school and non-Hispanic children, respectively. We estimated that spring 2020 closures of elementary schools averted 2167 cases in the Bay Area (95% CI: −985, 5572), fewer than middle (5884; 95% CI: 1478, 11.550), high school (8650; 95% CI: 3054, 15 940) and workplace (15 813; 95% CI: 9963, 22 617) closures. Under assumptions of moderate community transmission, we estimated that reopening for a four-month semester without any precautions will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1) and elementary school teachers (4.1%, 95% CI: −1.7, 12.0). However, we found that reopening policies for elementary schools that combine universal masking with classroom cohorts could result in few within-school transmissions, while high schools may require masking plus a staggered hybrid schedule. Stronger community interventions (e.g. remote work, social distancing) decreased the risk of within-school transmission across all measures studied, with the influence of community transmission minimized as the effectiveness of the within-school measures increased. 
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