Marc Lipsitch's research while affiliated with Centers for Disease Control and Prevention and other places
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Publications (726)
Background
Antibiotic-resistant infections are a major public health concern. To better understand the burden of these infections, we analyzed incidence and antibiotic resistance trends for nine important organisms in the US Veterans Affairs (VA) Healthcare System from February 2007 to March 2022.
Example plot of reporting resistance burden.
The ba...
Background
Infectious disease models, including individual based models (IBMs), can be used to inform public health response. For these models to be effective, accurate estimates of key parameters describing the natural history of infection and disease are needed. However, obtaining these parameter estimates from epidemiological studies is not alwa...
Public health surveillance for pathogens presents an optimization problem: we require enough sampling to identify intervention-triggering shifts in pathogen epidemiology, such as new introductions or sudden increases in prevalence, but not so much that costs due to surveillance itself outweigh those from pathogen-associated illness. To determine th...
Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity...
Background
Many severe acute respiratory syndrome coronavirus 2 infections have not been detected, reported, or isolated. For community testing programs to locate the most cases under limited testing resources, we developed and evaluated quantitative approaches for geographic targeting of increased coronavirus disease 2019 testing efforts.
Methods...
When respiratory viruses co-circulate in a population, individuals may be infected with multiple pathogens and experience possible virus-virus interactions, where concurrent or recent prior infection with one virus affects the infection process of another virus. While experimental studies have provided convincing evidence for within-host mechanisms...
Postexposure vaccination has the potential to prevent or modify the course of clinical disease among those exposed to a pathogen. However, due to logistical constraints, postexposure vaccine trials have been difficult to implement in practice. In place of trials, investigators have used observational data to estimate the efficacy or optimal timing...
While some studies have previously estimated lives saved by COVID-19 vaccination, we estimate how many deaths could have been averted by vaccination in the US but were not because of a failure to vaccinate. We used a simple method based on a nationally representative dataset to estimate the preventable deaths among unvaccinated individuals in the U...
Background. Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees in a given season. Understanding the underlying causes requires consideration of within-season waning and recent infection.
Methods. Using the US Flu Vaccine Effectiveness (VE) Network data over 8...
Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with improvements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity...
Wolff Sagy et al. (Nature Medicine 2023) report that a single dose of MVA-BN mpox vaccine was 86% effective in preventing incidence of diagnosed mpox. In their cohort study, all eligible men were enrolled on July 31, 2022 and followed until they tested positive for mpox or December 25, 2022, whichever was earlier. Individuals vaccinated after July...
The COVID-19 epidemic in the United States has been characterized by two stark disparities. COVID-19 burden has been unequally distributed among racial and ethnic groups and at the same time the mortality rates have been sharply higher among older age groups. These disparities have led some to suggest that inequalities could be reduced by vaccinati...
Vaccine allocation decisions during emerging pandemics have proven to be challenging due to competing ethical, practical, and political considerations. Complicating decision making, policy makers need to consider vaccine allocation strategies that balance needs both within and between populations. When vaccine stockpiles are limited, doses should b...
Policy reset and convergence on governance are needed
While some studies have previously estimated lives saved by COVID-19 vaccination, we estimate how many deaths could have been averted by vaccination in the US but were not because of a failure to be vaccinated. We used a simple method based on a nationally representative dataset to estimate the preventable deaths among unvaccinated individuals in t...
There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis). We estimated that for the Kaiser Permanente Northern California population during 2010-2018, 3.4% (2.8%-4%) of all macrolide prescriptions (fills), 2.7% (...
Background:
The COVID-19 pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: for example, reports suggest 271,900 per million people have been infected in Europe versus 8,800 per million people in Africa. While Africa is the second largest continent by population, its reported COVID-...
Background
The World Health Organization recommends mass drug administration (MDA) of the antibiotic azithromycin for children 1-11 months of age in areas with high infant and child mortality. Notwithstanding the substantial potential benefits in lowering childhood mortality, MDA raises understandable concerns about exacerbating antibiotic resistan...
Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain s...
Background
The COVID-19 pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: for example, reports suggest 271,900 per million people have been infected in Europe versus 8,800 per million people in Africa. While Africa is the second largest continent by population, its reported COVID-19...
Background:
Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age.
Methods:
Using data from the largest health care organization in Israel, we identified a cohort of children...
Nirmatrelvir/ritonavir (Paxlovid) is a combination protease inhibitor that blocks replication of SARS-CoV-2 (the virus that causes COVID-19) and has been shown to reduce the risk for hospitalization and death among patients with mild to moderate COVID-19 who are at risk for progression to severe disease* (1). In December 2021, the Food and Drug Adm...
Abtract:
Epidemiologic surveillance has revealed decoupling of COVID-19 hospitalizations and deaths from case counts following emergence of the Omicron (B.1.1.529) SARS-CoV-2 variant globally. However, assessment of the relative severity of Omicron variant infections presents challenges because of differential acquired immune protection against Om...
Background:
Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions...
Background:
With large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose.
Methods:
To ev...
When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right...
Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use–resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use–resistance relationship across 3 species ( Staphylococcus aureus , Escherich...
Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence.
Methods: To elucidate patterns of HIV sp...
Vaccines against SARS-CoV-2 were authorized at the end of 2020 and are effective in preventing deaths; however, many persons remain unvaccinated. We used weekly publicly available CDC data from 26 U.S. jurisdictions, which include COVID-19 death rates by age and vaccination status, to estimate the number of excess deaths that might have been averte...
Background
The COVID-19 epidemic in the United States has been characterized by two stark disparities. COVID-19 burden has been unequally distributed among racial and ethnic groups and at the same time the mortality rates have been sharply higher among older age groups.
These disparities have led some to suggest that higher equity could be attained...
Recent studies have provided key information about SARS-CoV-2 vaccines' efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptibles between vaccinated and unvaccinated groups. Here we...
Protection, whether direct or not
Vaccination provides both direct protection of vaccinated individuals and indirect protection of individuals living in vaccinated communities. Two studies based on data from Israel investigated the efficacy and indirect protection of the Pfizer/BioNTech messenger RNA vaccine (see the Perspective by Dean and Hallora...
The Omicron (B.1.1.529) variant of SARS-CoV-2 rapidly achieved global dissemination following its emergence in southern Africa in November, 2021. 1,2 Epidemiologic surveillance has revealed changes in COVID-19 case-to-hospitalization and case-to-mortality ratios following Omicron variant emergence, 3–6 although interpretation of these changes prese...
Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain s...
[This corrects the article DOI: 10.1371/journal.pcbi.1008409.].
Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in fully vaccinated individuals are receiving intense scrutiny because of their importance in determining how long restrictions to control virus transmission will need to remain in place in highly vaccinated populations as well as in determining the need for a...
Background:
SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Be...
SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from acquired immunity. Much effort has been devoted to measuring these phenotypes, but understanding their impact on the course of the pandemic – especially that of immune escape – has remained a challenge. Here, we use a mathematical model to sim...
Background
Many countries are experiencing a resurgence of COVID-19, driven predominantly by the delta (B.1.617.2) variant of SARS-CoV-2. In response, these countries are considering the administration of a third dose of mRNA COVID-19 vaccine as a booster dose to address potential waning immunity over time and reduced effectiveness against the delt...
To evaluate the effectiveness of the BNT162b2 messenger RNA vaccine in pregnant women, we conducted an observational cohort study of pregnant women aged 16 years or older, with no history of SARS-CoV-2, who were vaccinated between 20 December 2020 and 3 June 2021. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregn...
Background
On Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths av...
Determining policies to end the SARS-CoV-2 pandemic will require an understanding of the efficacy and effectiveness (hereafter, efficacy) of vaccines. Beyond the efficacy against severe disease and symptomatic and asymptomatic infection, understanding vaccine efficacy against virus transmission, including efficacy against transmission of different...
SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from infection- and vaccine-induced immunity. Much effort has been devoted to measuring these phenotypes, but predicting their impact on the course of the pandemic - especially that of immune escape - remains a challenge. Here, we use a mathematica...
Background
Preapproval trials showed that messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse e...
Background
Nipah virus (NiV) is an emerging, bat-borne pathogen that can be transmitted from person-to-person. Vaccines are currently being developed for NiV, and studies have been funded to evaluate their safety and immunogenicity. An important unanswered question is whether it will be possible to evaluate the efficacy of vaccine candidates in pha...
Background:
BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine's effect on infectivity is thus a critical priority.
Methods:
Among all 9650 HCW of a large tertiary medical center in Israel, we calculated the prevale...
Background
Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity.
Met...
Recent studies have provided key information about SARS-CoV-2 vaccines' efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptibles between vaccinated and unvaccinated groups. Here we...
Background: As mass vaccination campaigns against COVID-19 accelerate worldwide, there remains only limited evidence regarding vaccine effectiveness (VE) among pregnant women. Pregnant women have been shown to be at risk for severe COVID-19, resulting in adverse obstetrics outcomes, and their immune system is known to undergo alterations during pre...
Test-negative designs (TNDs) can be used to estimate vaccine effectiveness by comparing the relative rates of the target disease and symptomatically similar diseases among vaccinated and unvaccinated populations. However, the diagnostic tests used to identify the target disease typically suffer from imperfect sensitivity and specificity, leading to...
Mathematical models predict that community–wide access to HIV testing–and–treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test–and–treat HIV prevention trials in high–prevalence epidemics demonstrated variable reduction in population–level incidence. To elucidate patterns of HIV spread in universal tes...
Vaccine allocation decisions during the ongoing COVID-19 pandemic have proven to be challenging due to competing ethical, practical, and political considerations. Complicating decision making, policy makers need to consider vaccine allocation strategies that balance needs both within and between populations. Due to limited vaccine stockpiles, vacci...
Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four co...
Added value of PCR testing for COVID-19
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, polymerase chain reaction (PCR) tests were generally reported only as binary positive or negative outcomes. However, these test results contain a great deal more information than that. As viral load declines exponentially, the P...
Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50-95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, em...
Randomized controlled trials (RCTs) have shown high efficacy of multiple vaccines against SARS-CoV-2 disease (COVID-19), and recent studies have shown the vaccines are also effective against infection. Evidence for the effect of each of these vaccines on ability to transmit the virus is also beginning to emerge. We describe an approach to estimate...
Introduction:
Advance planning of vaccine trials conducted during outbreaks increases our ability to rapidly define the efficacy and potential impact of a vaccine. Vaccine efficacy against infectiousness (VEI) is an important measure for understanding a vaccine's full impact, yet it is currently not identifiable in many trial designs because it re...
Background: The impact of variable infection risk by race and ethnicity on the dynamics of SARS CoV-2 spread is largely unknown.
Methods: Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk changes across groups.
Results: A simple mod...
On 30 December 2019, the Program for Monitoring Emerging Diseases notified the world about a pneumonia of unknown cause in Wuhan, China (1). Since then, scientists have made remarkable progress in understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogenesis, and mitigation by vaccin...
Determining policies to end the SARS-CoV-2 pandemic will require an understanding of the efficacy and effectiveness (hereafter, efficacy) of vaccines. Beyond the efficacy against severe disease and symptomatic and asymptomatic infection, understanding vaccine efficacy against transmission will help model epidemic trajectory and determine appropriat...
Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practice...
When vaccines are in limited supply, expanding the number of people who receive some vaccine, such as by halving doses or increasing the interval between doses, can reduce disease and mortality compared with concentrating available vaccine doses in a subset of the population. A corollary of such dose-sparing strategies is that the vaccinated indivi...
There has been an increased focus on the public health burden of antimicrobial resistance (AMR). This raises conceptual challenges such as determining how much harm multi-drug resistant organisms do compared to what, or how to establish the burden. In this viewpoint we will present a counterfactual framework and provide guidance to harmonize method...
Randomized controlled trials (RCTs) have shown high efficacy of multiple vaccines against SARS-CoV-2 disease (COVID-19), but evidence remains scarce about vaccines’ efficacy against infection with, and ability to transmit, the virus. We describe an approach to estimate these vaccines’ effects on viral positivity, a prevalence measure which under re...
Although vaccines against SARS-CoV-2 have now been found safe and efficacious, there remains an urgent global health need to test both these vaccines and additional vaccines against the same virus. Under variable conditions, either standard or unusual designs would for both familiar and often-missed reasons make continued testing possible and ethic...
Background:
As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel's largest health care organization were used to evaluate the effectiveness of the BNT162b...
Background
Empirical antibiotic use is common in the hospital. Here, we characterize patterns of antibiotic use, infectious diagnoses, and microbiological lab results among hospitalized patients and aim to quantify the proportion of antibiotic use that is potentially attributable to specific bacterial pathogens.
Methods
We conducted an observation...
In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiou...
Designing public health responses to outbreaks requires close monitoring of population-level health indicators in real-time. Thus an accurate estimation of the epidemic curve is critical. We propose an approach to reconstruct epidemic curves in near real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regio...
Vaccine prioritization
There is likely to be high demand for the limited supplies of vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so how should vaccine distribution be prioritized? Bubar et al. modeled across countries how uncertainty about a vaccine's characteristics affects prioritization strategies for reducing d...
The impact of variable infection risk by race and ethnicity on the dynamics of SARS-CoV-2 spread is largely unknown. Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk changes across racial and ethnic groups. A proportionate mixing m...
Early in the COVID-19 pandemic, predictions of international outbreaks were largely based on imported cases from Wuhan, China, potentially missing imports from other cities. We provide a method, combining daily COVID-19 prevalence and flight passenger volume, to estimate importations from 18 Chinese cities to 43 international destinations, includin...
Streptococcus pneumoniae can be divided into many strains, each a distinct set of isolates sharing similar core and accessory genomes, which co-circulate within the same hosts. Previous analyses suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus negative frequency-dependent selection (N...
Background
A vaccine trial with a conventional challenge design can be very fast once it starts, but it requires a long prior process, in part, to grow and standardize challenge virus in the laboratory. This detracts somewhat from its overall promise for accelerated efficacy testing of SARS-CoV-2 vaccine candidates, and from the ability of developi...