BACKGROUND:Both 20-valent (PCV20) and 15-valent (PCV15) pneumococcal conjugate vaccines are recommended in the US pediatric immunization program. Static models previously have found PCV20 cost-effective compared to PCV15 and a 13-valent vaccine (PCV13). The objective of this study is to assess the health and economic impact of PCV20 compared to PCV15 or PCV13 using a dynamic transmission model (DTM). METHODS:An age-structured, compartmental DTM was developed to simulate the transmission dynamics of Streptococcus pneumoniae in the US, calibrated to historical invasive pneumococcal disease (IPD) incidence. The model estimated the impact of PCV20 versus PCV15 and PCV13 in the routine pediatric vaccination program in the US. Pneumococcal pneumonia (PP) and otitis media (OM) incidence were assumed a proportional relationship to IPD. Outcomes included disease cases, quality-adjusted life-years (QALYs), direct medical costs (2025 USD), and incremental cost-effectiveness ratio for the entire US population (328,239,522) over a 10-year horizon. RESULTS:Compared with PCV15, PCV20 pediatric vaccination averted 4.0 million disease cases (31,361 IPD, 0.889 million PP, and 3.1 million pneumococcal OM) with cost savings of $4.027 billion over 10 years. PCV20 resulted in an additional 17,717 QALY versus PCV15, thus PCV20 was dominant (cost saving and more effective) compared with PCV15. PCV20 was also dominant versus PCV13, with incremental cost savings of $5.940 billion and 26,099 additional QALY over 10 years. CONCLUSIONS:Pediatric PCV20 use is projected to reduce pneumococcal disease burden and healthcare costs in the US compared with PCV15 or PCV13. Results support the health and economic value of adopting a higher-valent pediatric vaccination approach using PCV20.

Dengue virus (DENV) circulates in two distinct transmission cycles: one, termed the sylvatic cycle, is enzootic to canopy-living hosts, including non-human primates and primatophilic mosquitoes, and the other, initiated by spillover from the sylvatic cycle, is endemic to humans and anthropophilic mosquitoes. Transmission dynamics of sylvatic DENV in non-human hosts has not been well characterized, and the identity of reservoir and amplification hosts is still to be determined. We investigated the role of the three common species of monkeys in the Kédougou region of Senegal in the sylvatic transmission cycle of DENV. Longitudinal surveillance of primatophilic mosquitoes in this region dating back to the 1970s revealed that sylvatic DENV-2, the only one of the four DENV serotypes found to circulate in a sylvatic transmission in West Africa, is amplified cyclically at intervals of approximately eight years based on the isolation of the virus from mosquitoes. Subsequent to the detection of DENV-2 in primatophilic mosquitoes in Kédougou in 2008, 737 monkeys, including 3 species: Chlorocebus sabaeus (n = 219), Erythrocebus patas (n = 78), and Papio papio (n = 440) were captured from 2010 to 2012 for the current study. Their age was determined using dentition and other morphological measurements. Evidence of DENV-2 infection was detected via neutralizing antibody in sera, and the annual hazard of DENV-2 infection was estimated per species using catalytic models. These analyses revealed annual hazard ranging from 0.09 to 0.42 across the three species, consistent with high levels of transmission in these populations. Furthermore, seroprevalence was moderate in individuals under one year of age, despite the lack of detection of DENV-2 in primatophilic mosquitoes for up to three years prior, suggesting that non-primate hosts contributed to the maintenance of sylvatic DENV in this region.

BACKGROUND:Despite the significant impact of longstanding pediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial. Higher valent vaccines, such as the 20‑valent PCV (PCV20), could reduce this burden, yet their value in the contemporary UK setting has not been fully assessed using recent data. RESEARCH DESIGN AND METHODS:An age-structured dynamic transmission model used post-COVID-19 UK epidemiology (2001-2023) to compare pediatric PCV20 (2 + 1 and 1 + 1) with PCV13 (1 + 1) and PCV15 (1 + 1). Over 10 years, we assessed cost-effectiveness and number needed to vaccinate (NNV), capturing disease cases, deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Sensitivity and scenario analyses examined key uncertainties. RESULTS:Over 10 years, both PCV20 schedules were dominant versus PCV13 and PCV15. Versus PCV13, PCV20 1 + 1 and 2 + 1 were projected to avert 448,432 and 499,151 disease cases and save £1.509 and £1.306 billion, respectively. Versus PCV15, PCV20 1 + 1 and 2 + 1 were projected to avert 409,459 and 460,179 disease cases and save £1.424 and £1.221 billion, respectively. NNVs versus PCV13 were lower for PCV20 than PCV15 across both dosing schedules. Sensitivity and scenario results were consistent with the base case. CONCLUSION:Pediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency.

While pneumococcal conjugate vaccines (PCVs) are typically administered to infants using a three- or four-dose regimen, children may receive less immunogenic regimens due to missed doses or alternative schedules. The level of direct protection in children vaccinated with a single dose of PCV remains unclear. We performed a systematic review of observational studies published during 2000–2024 on vaccine effectiveness (VE) of a single dose of PCV7, PCV10, or PCV13 against vaccine-type invasive pneumococcal disease (IPD) in children. Results were stratified by vaccine and age at administration, and meta-analysis performed to generate pooled VE estimates. Twenty-seven studies met the inclusion criteria: nine reported VE for PCV7, four for PCV10, seven for PCV13, and seven reported VE separately for more than one PCV. For PCV7, pooled VE was 64.6

Antimicrobial resistance (AMR) is a substantial global health threat and economic burden. Vaccines reduce antibiotic use and prevent resistant infections, combating AMR. However, their economic and health benefits are often underestimated because economic analyses do not consider vaccines’ broader impacts, such as effects on AMR. We conceptualize a framework for estimating the impacts of vaccination on AMR using pneumococcal conjugate vaccines (PCVs) as an example. The proposed framework includes three pathways: population and pathogen, care, and health outcomes. Operationalizing this framework requires extensive detailed data, such as serotype distribution, disease incidence, resistance profile, antibiotic use, and treatment failure, derived from multiple sources, such as national surveillance systems, epidemiological studies, and hospital records, which are often unavailable. However, considering vaccines’ impact on AMR is crucial because of potential future health and cost issues. Therefore, we adopted a simplified framework leveraging all available data related to antibiotic prescriptions and resistance to estimate the impact on critical outcomes. Routine PCV20 vaccination was estimated to prevent up to 23,509,406 antibiotic prescriptions and 14,050,115 antibiotic-resistant infections over 25 years compared to PCV13 and 12,087,128 antibiotic prescriptions and 7,245,908 antibiotic-resistant infections compared to PCV15, demonstrating the potential impact of PCV infant immunization on AMR cases and antibiotic prescriptions. A simplified model can effectively incorporate critical AMR parameters for a more comprehensive evaluation of PCVs. Our framework also identifies key data gaps that should be addressed for future modeling efforts.

Epidemiological models of mosquito-borne virus transmission often lack accurate estimates of host-to-vector transmission probability. Here, we estimated this probability for two strains of Zika virus (ZIKV)-one sylvatic and one human-endemic-from two monkey species to Aedes albopictus mosquitoes using experimental infection data. Viral dynamics did not differ between monkey species, although one (cynomolgus macaque) is a native ZIKV host and the other (squirrel monkey) a novel host, but did differ between strains, with viremia for the human-endemic strain peaking later and lower than the sylvatic strain. Only the sylvatic strain was transmitted to mosquitoes. Within mosquitoes, anatomical barriers influence viral progression to salivary glands, complicating host infectiousness estimation. We quantified the probability of viral dissemination to the legs in Ae. albopictus, which increased with host viral load and was higher after feeding on squirrel monkeys than on cynomolgus macaques. We also found a positive relationship between virus titre in mosquito legs and virus detection in saliva after a 14-day extrinsic incubation period. Combining these factors, we found that squirrel monkeys were on average 1.5 times more infectious to Ae. albopictus than cynomolgus macaques. These estimates will help assess ZIKV's potential to establish an enzootic, sylvatic cycle in the Americas.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic cycles involving monkey hosts, spilled over into human transmission, and were translocated to the Americas, creating potential for spillback into neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We exposed native (cynomolgus macaque) or novel (squirrel monkey) hosts to mosquitoes infected with either sylvatic DENV or ZIKV and monitored viremia, natural killer cells, transmission to mosquitoes, cytokines, and neutralizing antibody titers. Unexpectedly, DENV transmission from both host species occurred only when serum viremia was undetectable or near the limit of detection. ZIKV replicated in squirrel monkeys to much higher titers than DENV and was transmitted more efficiently but stimulated lower neutralizing antibody titers. Increasing ZIKV viremia led to greater instantaneous transmission and shorter duration of infection, consistent with a replication-clearance trade-off.

During outbreaks of emerging infectious diseases, internationally connected cities often experience large and early outbreaks, while rural regions follow after some delay. This hierarchical structure of disease spread is influenced primarily by the multiscale structure of human mobility. However, during the COVID-19 epidemic, public health responses typically did not take into consideration the explicit spatial structure of human mobility when designing non-pharmaceutical interventions (NPIs). NPIs were applied primarily at national or regional scales. Here we use weekly anonymized and aggregated human mobility data and spatially highly resolved data on COVID-19 cases, deaths and hospitalizations at the municipality level in Mexico to investigate how behavioural changes in response to the pandemic have altered the spatial scales of transmission and interventions during its first wave (March - June 2020). We find that the epidemic dynamics in Mexico were initially driven by SARS-CoV-2 exports from Mexico State and Mexico City, where early outbreaks occurred. The mobility network shifted after the implementation of interventions in late March 2020, and the mobility network communities became more disjointed while epidemics in these communities became increasingly synchronised. Our results provide actionable and dynamic insights into how to use network science and epidemiological modelling to inform the spatial scale at which interventions are most impactful in mitigating the spread of COVID-19 and infectious diseases in general.

Viruses transmitted by Aedes mosquitoes (e.g., dengue [DENV], Zika [ZIKV]) have demonstrated high potential to spill over from their ancestral, sylvatic cycles in non-human primates to establish transmission in humans. Epidemiological models require accurate knowledge of the contact structure between hosts and vectors, which is highly sensitive to any impacts of virus infection in mosquitoes or hosts on mosquito feeding behavior. Current evidence for whether these viruses affect vector behavior is mixed. Here we leveraged a study on sylvatic DENV-2 and ZIKV transmission between two species of monkey and Aedes albopictus to determine whether virus infection of either host or vector alters vector feeding behavior. Engorgement rates varied from 0% to 100%, but this was not driven by vector nor host infection, but rather by the individual host, host species, and host body temperature. This study highlights the importance of incorporating individual-level heterogeneity of vector biting in arbovirus transmission models.

The contact structure between vertebrate hosts and arthropod vectors plays a key role in the spread of arthropod-borne viruses (arboviruses); thus, it is important to determine whether arbovirus infection of either host or vector alters vector feeding behavior. Here we leveraged a study of the replication dynamics of two arboviruses isolated from their ancestral cycles in paleotropical forests, sylvatic dengue-2 (DENV-2) and Zika (ZIKV), in one non-human primate (NHP) species from the paleotropics (cynomolgus macaques, Macaca fascicularis) and one from the neotropics (squirrel monkeys, Saimiri boliviensis) to test the effect of both vector and host infection with each virus on completion of blood feeding (engorgement) of the mosquito Aedes albopictus. Although mosquitoes were starved and given no choice of hosts, engorgement rates varied dramatically, from 0% to 100%. While neither vector nor host infection systematically affected engorgement, NHP species and body temperature at the time of feeding did. We also interrogated the effect of repeated mosquito bites on cytokine expression and found that epidermal growth factor (EGF) and macrophage migration inhibitory factor (MIF) concentrations were dynamically associated with exposure to mosquito bites. This study highlights the importance of incorporating individual-level heterogeneity of vector biting in arbovirus transmission models.

Background: The successful development of multiple COVID-19 vaccines has led to a global vaccination effort to reduce severe COVID-19 infection and mortality. However, the effectiveness of the COVID-19 vaccines wane over time leading to breakthrough infections where vaccinated individuals experience a COVID-19 infection. Here we estimate the risks of breakthrough infection and subsequent hospitalization in individuals with common comorbidities who had completed an initial vaccination series.Methods: Our study population included vaccinated patients between January 1, 2021 to March 31, 2022 who are present in the Truveta patient population. Models were developed to describe 1) time from completing primary vaccination series till breakthrough infection; and 2) if a patient was hospitalized within 14 days of breakthrough infection. We adjusted for age, race, ethnicity, sex, and year-month of vaccination.Results: Of 1,218,630 patients in the Truveta Platform who had completed an initial vaccination sequence between January 1, 2021 and March 31, 2022, 2.85, 3.42, 2.75, and 2.88 percent of patients with CKD, chronic lung disease, diabetes, or are in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.46 percent of the population without any of these four comorbidities. We found an increased risk of breakthrough infection and subsequent hospitalization in individuals with any of the four comorbidities when compared to individuals without these four comorbidities.Conclusions: Vaccinated individuals with any of the studied comorbidities experienced an increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the people without any of the studied comorbidities. Individuals with immunocompromising conditions and chronic lung disease were most at risk of breakthrough infection, while people with CKD were most at risk of hospitalization following breakthrough infection. Patients with multiple comorbidities have an even greater risk of breakthrough infection or hospitalization compared to patients with none of the studied comorbidities. Individuals with common comorbidities should remain vigilant against infection even if vaccinated. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction Demonstrated health inequalities persist in the United States. SARS-CoV-2 (COVID) has been no exception, with access to treatment and hospitalization differing across race or ethnic groups. Here, we aim to assess differences in treatment with remdesivir and hospital length of stay across the four waves of the pandemic. Materials and methods Using a subset of the Truveta data, we examine the odds ratio (OR) of in-hospital remdesivir treatment and risk ratio (RR) of in-hospital length of stay between Black or African American (Black) to White patients. We adjusted for confounding factors, such as age, sex, and comorbidity status. Results There were statistically significant lower rates of remdesivir treatment and longer in-hospital length of stay comparing Black patients to White patients early in the pandemic (OR for treatment: 0.88, 95% confidence interval [CI]: 0.80, 0.96; RR for length of stay: 1.17, CI: 1.06, 1.21). Rates became close to parity between groups as the pandemic progressed. Conclusion While inpatient remdesivir treatment rates increased and length of stay decreased over the beginning course of the pandemic, there are still inequalities in patient care.

Dengue (DENV) and Zika (ZIKV) viruses are maintained in sylvatic cycles between non-human primate (NHP) hosts and arboreal mosquitoes in Africa and Asia. DENV was introduced to the Americas centuries ago, while ZIKV was introduced within the last decade. Despite its long history of transmission in the neotropics, there is no evidence that DENV has established a sylvatic cycle there, but whether ZIKV will do so is an open and urgent question. Key determinants of sustained transmission in a novel environment are patterns of viral replication within novel hosts and the impact of within-host replication dynamics on transmission to vectors. We analyzed parameters of DENV and ZIKV sylvatic transmission dynamics through statistical and mathematical modeling. We used Aedes albopictus mosquitoes to infect native (cynomolgus macaques) and novel (squirrel monkeys) hosts with sylvatic strains of DENV-2 and ZIKV. We monitored host viremia and transmission to mosquitoes over the course of infection. We showed that neither vector or host infection status impacted engorgement rates of Ae. albopictus. However, the proportion of engorged mosquitoes was higher on cynomolgus macaques than squirrel monkeys. DENV showed low levels of replication in both host species, and transmission to mosquitoes occurred only when viremia was low to undetectable. We fitted a mechanistic within-host compartmental model to ZIKV viral dynamics in native and novel hosts. The within-host R0 of ZIKV – the mean number of new infected cells produced by one infected cell introduced into an entirely susceptible target-cell population – was 3.25 (95% highest density interval [2.2 ; 4.9]) in squirrel monkeys and 6.1 [3.0 ; 14.3] in cynomolgus macaques. We fitted dose-response relationships within-vector, and estimated that in squirrel monkeys, the probability to produce a saliva-positive Ae. albopictus was above 50% between days 3 and 5 post ZIKV-infection. We highlighted heterogeneities in transmission potential between native and novel NHP hosts of DENV and ZIKV. Our results suggest that a ZIKV sylvatic cycle could be established in the neotropics, as we find efficient transmission between squirrel monkeys and Ae. albopictus. Combining these results with ecological factors will be necessary to assess sylvatic ZIKV epidemic potential in the neotropics.

[This corrects the article DOI: 10.1371/journal.pmed.1003793.].

Controlling the spread of infectious diseases―even when safe, transmission-blocking vaccines are available―may require the effective use of non-pharmaceutical interventions (NPIs), e.g., mask wearing, testing, limits on group sizes, venue closure. During the SARS-CoV-2 pandemic, many countries implemented NPIs inconsistently in space and time. This inconsistency was especially pronounced for policies in the United States of America (US) related to venue closure. Here, we investigate the impact of inconsistent policies associated with venue closure using mathematical modeling and high-resolution human mobility, Google search, and county-level SARS-CoV-2 incidence data from the USA. Specifically, we look at high-resolution location data and perform a US-county-level analysis of nearly 8 million SARS-CoV-2 cases and 150 million location visits, including 120 million church visitors across 184,677 churches, 14 million grocery visitors across 7662 grocery stores, and 13.5 million gym visitors across 5483 gyms. Analyzing the interaction between venue closure and changing mobility using a mathematical model shows that, across a broad range of model parameters, inconsistent or partial closure can be worse in terms of disease transmission as compared to scenarios with no closures at all. Importantly, changes in mobility patterns due to epidemic control measures can lead to increase in the future number of cases. In the most severe cases, individuals traveling to neighboring jurisdictions with different closure policies can result in an outbreak that would otherwise have been contained. To motivate our mathematical models, we turn to mobility data and find that while stay-at-home orders and closures decreased contacts in most areas of the USA, some specific activities and venues saw an increase in attendance and an increase in the distance visitors traveled to attend. We support this finding using search query data, which clearly shows a shift in information seeking behavior concurrent with the changing mobility patterns. While coarse-grained observations are not sufficient to validate our models, taken together, they highlight the potential unintended consequences of inconsistent epidemic control policies related to venue closure and stress the importance of balancing the societal needs of a population with the risk of an outbreak growing into a large epidemic.

Seasonal influenza kills hundreds of thousands every year, with multiple constantly changing strains in circulation at any given time. A high mutation rate enables the influenza virus to evade recognition by the human immune system, including immunity acquired through past infection and vaccination. Here, we capture the genetic similarity of influenza strains and their evolutionary dynamics with genotype networks. We show that the genotype networks of influenza A (H3N2) hemagglutinin are characterized by heavy-tailed distributions of module sizes and connectivity indicative of critical behavior. We argue that (i) genotype networks are driven by mutation and host immunity to explore a subspace of networks predictable in structure and (ii) genotype networks provide an underlying structure necessary to capture the rich dynamics of multistrain epidemic models. In particular, inclusion of strain-transcending immunity in epidemic models is dependent upon the structure of an underlying genotype network. This interplay is consistent with self-organized criticality where the epidemic dynamics of influenza locates critical regions of its genotype network. We conclude that this interplay between disease dynamics and network structure might be key for future network analysis of pathogen evolution and realistic multistrain epidemic models.