RESUMO
Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 104 and 1.4 × 104 gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE.
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COVID-19 , Tobamovirus , Humanos , SARS-CoV-2/genética , RNA Viral/genética , Tobamovirus/genéticaRESUMO
Randomized controlled trials (RCTs) evaluate hypotheses in specific contexts and are often considered the gold standard of evidence for infectious disease interventions, but their results cannot immediately generalize to other contexts (e.g., different populations, interventions, or disease burdens). Mechanistic models are one approach to generalizing findings between contexts, but infectious disease transmission models (IDTMs) are not immediately suited for analyzing RCTs, since they often rely on time-series surveillance data. We developed an IDTM framework to explain relative risk outcomes of an infectious disease RCT and applied it to a water, sanitation, and hygiene (WASH) RCT. This model can generalize the RCT results to other contexts and conditions. We developed this compartmental IDTM framework to account for key WASH RCT factors: i) transmission across multiple environmental pathways, ii) multiple interventions applied individually and in combination, iii) adherence to interventions or preexisting conditions, and iv) the impact of individuals not enrolled in the study. We employed a hybrid sampling and estimation framework to obtain posterior estimates of mechanistic parameter sets consistent with empirical outcomes. We illustrated our model using WASH Benefits Bangladesh RCT data (n = 17,187). Our model reproduced reported diarrheal prevalence in this RCT. The baseline estimate of the basic reproduction number [Formula: see text] for the control arm (1.10, 95% CrI: 1.07, 1.16) corresponded to an endemic prevalence of 9.5% (95% CrI: 7.4, 13.7%) in the absence of interventions or preexisting WASH conditions. No single pathway was likely able to sustain transmission: pathway-specific [Formula: see text] for water, fomites, and all other pathways were 0.42 (95% CrI: 0.03, 0.97), 0.20 (95% CrI: 0.02, 0.59), and 0.48 (95% CrI: 0.02, 0.94), respectively. An IDTM approach to evaluating RCTs can complement RCT analysis by providing a rigorous framework for generating data-driven hypotheses that explain trial findings, particularly unexpected null results, opening up existing data to deeper epidemiological understanding.
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Doenças Transmissíveis , Saneamento , Humanos , Água , Ensaios Clínicos Controlados Aleatórios como Assunto , Higiene , Doenças Transmissíveis/epidemiologiaRESUMO
BACKGROUND: Varicella zoster virus (VZV) is one of the eight known human herpesviruses. Initial VZV infection results in chickenpox, while viral reactivation following a period of latency manifests as shingles. Separate vaccines exist to protect against both initial infection and subsequent reactivation. Controversy regarding chickenpox vaccination is contentious with most countries not including the vaccine in their childhood immunization schedule due to the hypothesized negative impact on immune-boosting, where VZV reactivation is suppressed through exogenous boosting of VZV antibodies from exposure to natural chickenpox infections. METHODS: Population-level chickenpox and shingles notifications from Thailand, a country that does not vaccinate against either disease, were previously fitted with mathematical models to estimate rates of VZV transmission and reactivation. Here, multiple chickenpox and shingles vaccination scenarios were simulated and compared to a model lacking any vaccination to analyze the long-term impacts of VZV vaccination. RESULTS: As expected, simulations suggested that an introduction of the chickenpox vaccine, at any coverage level, would reduce chickenpox incidence. However, chickenpox vaccine coverage levels above 35% would increase shingles incidence under realistic estimates of shingles coverage with the current length of protective immunity from the vaccine. A trade-off between chickenpox and shingles vaccination coverage was discovered, where mid-level chickenpox coverage levels were identified as the optimal target to minimize total zoster burden. Only in scenarios where shingles vaccine provided lifelong immunity or coverage exceeded current levels could large reductions in both chickenpox and shingles be achieved. CONCLUSIONS: The complicated nature of VZV makes it impossible to select a single vaccination scenario as universal policy. Strategies focused on reducing both chickenpox and shingles incidence, but prioritizing the latter should maximize efforts towards shingles vaccination, while slowly incorporating chickenpox vaccination. Alternatively, countries may wish to minimize VZV complications of both chickenpox and shingles, which would lead to maximizing vaccine coverage levels across both diseases. Balancing the consequences of vaccination to overall health impacts, including understanding the impact of an altered mean age of infection for both chickenpox and shingles, would need to be considered prior to any vaccine introduction.
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Varicela , Vacina contra Herpes Zoster , Herpes Zoster , Varicela/epidemiologia , Varicela/prevenção & controle , Vacina contra Varicela , Criança , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Humanos , Vacinação , Vacinas AtenuadasRESUMO
The role of human papillomavirus (HPV) as a causative agent for epithelial cancers is well-known, but many open questions remain regarding the downstream gene regulatory effects of viral proteins E6 and E7 on the cell cycle. Here, we extend a cell cycle model originally presented by Gérard and Goldbeter (2009) in order to capture the effects of E6 and E7 on key actors in the cell cycle. Results suggest that E6 is sufficient to reverse p53-induced quiescence, while E7 is sufficient to reverse p16INK4a-induced quiescence; both E6 and E7 are necessary when p53 and p16INK4a are both active. Moreover, E7 appears to play a role as a "growth factor substitute", inducing cell division in the absence of growth factor. Low levels of E7 may permit regular cell division, but the results suggest that higher levels of E7 dysregulate the cell cycle in ways that may destabilize the cellular genome. The mechanisms explored here provide opportunities for developing new treatment targets that take advantage of the cell cycle regulatory system to prevent HPV-related cancer effects.
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Alphapapillomavirus , Infecções por Papillomavirus , Carcinogênese , Ciclo Celular , Divisão Celular , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Accurate estimates of the total burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to inform policy, planning, and response. We sought to quantify SARS-CoV-2 cases, hospitalizations, and deaths by age in Michigan. Coronavirus disease 2019 cases reported to the Michigan Disease Surveillance System were multiplied by age and time-specific adjustment factors to correct for under-detection. Adjustment factors were estimated in a model fit to incidence data and seroprevalence estimates. Age-specific incidence of SARS-CoV-2 hospitalization, death, vaccination, and variant proportions were estimated from publicly available data. We estimated substantial under-detection of infection that varied by age and time. Accounting for under-detection, we estimate the cumulative incidence of infection in Michigan reached 75% by mid-November 2021, and over 87% of Michigan residents were estimated to have had ≥1 vaccination dose and/or previous infection. Comparing pandemic waves, the relative burden among children increased over time. In general, the proportion of cases who were hospitalized or who died decreased over time. Our results highlight the ongoing risk of periods of high SARS-CoV-2 incidence despite widespread prior infection and vaccination. This underscores the need for long-term planning for surveillance, vaccination, and other mitigation measures amidst continued response to the acute pandemic.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Criança , Humanos , Michigan/epidemiologia , Pandemias , Estudos SoroepidemiológicosRESUMO
Environmental pathogen surveillance is a sensitive tool that can detect early-stage outbreaks, and it is being used to track poliovirus and other pathogens. However, interpretation of longitudinal environmental surveillance signals is difficult because the relationship between infection incidence and viral load in wastewater depends on time-varying shedding intensity. We developed a mathematical model of time-varying poliovirus shedding intensity consistent with expert opinion across a range of immunization states. Incorporating this shedding model into an infectious disease transmission model, we analysed quantitative, polymerase chain reaction data from seven sites during the 2013 Israeli poliovirus outbreak. Compared to a constant shedding model, our time-varying shedding model estimated a slower peak (four weeks later), with more of the population reached by a vaccination campaign before infection and a lower cumulative incidence. We also estimated the population shed virus for an average of 29 days (95% CI 28-31), longer than expert opinion had suggested for a population that was purported to have received three or more inactivated polio vaccine (IPV) doses. One explanation is that IPV may not substantially affect shedding duration. Using realistic models of time-varying shedding coupled with longitudinal environmental surveillance may improve our understanding of outbreak dynamics of poliovirus, SARS-CoV-2, or other pathogens.
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COVID-19 , Poliomielite , Poliovirus , Surtos de Doenças/prevenção & controle , Monitoramento Ambiental , Humanos , Lactente , Israel/epidemiologia , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Saúde Pública , SARS-CoV-2 , Eliminação de Partículas ViraisRESUMO
We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018-20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection in college-age participants reporting no lifetime sexual partners. Reporting a single recent partner was associated with a lower oral HPV prevalence (PR 0.39, 95% CI: 0.16, 0.96) than reporting no recent (but at least one ever) partner. No similar protective effect was seen for cervicogenital HPV. Both oral and cervicogenital prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and the age 23+ populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US.
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Doenças da Boca , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Michigan/epidemiologia , Doenças da Boca/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de Risco , Comportamento Sexual , Adulto JovemRESUMO
Structural stigma shapes men who have sex with men's (MSM's) mental health and sexual behaviours. The aim of this study was to examine how stigmatizing policies interact with downstream anxiety/depression and sexual behaviours to structurally pattern HIV disparities among European MSM. We conducted a secondary data analysis of the European Men-who-have-sex-with-men Internet Survey (EMIS) from 2017. We included a total of 98,600 participants living in 39 European countries. We used the Rainbow Index, a score given to countries based on their sexual and gender minority policies as the predictor of HIV diagnosis. We conducted adjusted random intercept and slope multi-level logistic regressions. In adjusted models, higher Rainbow Index scores was associated with lower predictive probabilities of diagnosed HIV, regardless of the number of condomless intercourse partners. The predictive probability of HIV diagnosis was also lower, regardless of severity of anxiety/depression, where the Rainbow Index score was better. Country-level policies interact with downstream sexual behaviours and anxiety/depression to structurally influence HIV diagnosis among MSM in Europe.
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Infecções por HIV , Minorias Sexuais e de Gênero , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/psicologia , Humanos , Masculino , Saúde Mental , Políticas , Comportamento SexualRESUMO
BACKGROUND: HIV has been shown to increase the likelihood of oral HPV infection. In this study, we evaluated the risk of oral HPV in HIV infected patients compared with HIV-negative controls. METHODS: 101 healthy adult volunteers (HIV-) and 245 adults living with HIV infection (HIV+) were recruited from 5 academic medical centers. Questionnaires and saliva samples were obtained every 3-8 months over a period of 2 years (2015-2017). DNA was isolated from the saliva samples and tested for 18 high- and low-risk genotypes. RESULTS: Oral HPV was detected in 23% of HIV + vs. 10% of HIV- participants (p < 0.0001). Men had a higher oral HPV prevalence than women (27% vs. 15% HIV+, p = 0.03, 16% vs. 5% HIV-, p = 0.01). Risk factors among HIV + participants included more lifetime deep kissing and oral sex partners, and history of AIDS. Persistent oral HPV was detected in 23% of HIV + vs. 5% of HIV- participants (p < 0.001). Among 8 HIV + participants with CD4 counts <200 cell/µL none had cleared their HPV infection during the study. CONCLUSIONS: Risk of oral HPV infection and persistence was significantly higher in HIV + adults with a history of poorly controlled HIV, which may put them at increased risk of HPV-associated cancer.
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Alphapapillomavirus , Infecções por HIV , Doenças da Boca , Infecções por Papillomavirus , Adulto , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Doenças da Boca/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de RiscoRESUMO
OBJECTIVES: The Michigan HPV and Oropharyngeal Cancer study aimed to evaluate patterns of oral and cervicogenital human papillomavirus (HPV) infection prevalence, incidence, and clearance as well as their relationship to sexual behaviours. DESIGN: Cohort SETTING: General public in and around Ann Arbor, Michigan. PARTICIPANTS: 394 college-age and older-adult participants of both sexes provided oral samples, and 325 completed at least 2 visits. 130 who provided a cervicogenital samples, and 127 completed at least 2 visits. OUTCOMES: Incidence and clearance rates as well as HRs for oral and cervicogenital HPV. RESULTS: Oral HPV infections were transient, with only 16% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 46 days (95% CI 37 to 58). In contrast, cervicogenital infections were more persistent, with 56% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 87 days (95% CI 74 to 102). HPV vaccination was associated with reduced incidence of cervicogenital HPV infection (HR 0.63; 95% CI 0.47 to 0.83) but not oral HPV infection. Incidence of oral HPV infection was associated with 2+ recent deep kissing partners (HR 2.00; 95% CI 1.13 to 3.56). Incidence of both oral (HR: 1.70; 95% CI 1.08 to 2.68) and cervicogenital (HR 2.46; 95% CI 1.69 to 3.59) was associated with 2+ recent sexual partners. CONCLUSIONS: Detection of oral HPV was highly transient, but incidence was associated with recent deep kissing and sexual partners. Detection of cervicogenital HPV was more persistent, and incidence was positively associated with recent sexual partners and negatively associated with HPV vaccination.
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Neoplasias Orofaríngeas , Infecções por Papillomavirus , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Fatores de Risco , Comportamento SexualRESUMO
OBJECTIVES: Vaccine hesitancy is a growing threat to health in the United States. Facing the fourth highest vaccine exemption rate in the United States in 2014, Michigan changed its state Administrative Rules, effective January 1, 2015, requiring parents to attend an in-person vaccine education session at their local health department before obtaining a nonmedical exemption (NME). In this article, we evaluate the longer-term impact of this policy change on the rate, spatial distribution, and sociodemographic predictors of NMEs in Michigan. METHODS: Using school-level kindergarten vaccination data from Michigan from 2011 to 2018, we evaluated sociodemographic predictors of NMEs before and after this Administrative Rule change using Bayesian binomial regression. We measured the persistence and location of school district-level geographic clustering using local indicators of spatial association. RESULTS: Immediately after the rule change, rates of NMEs fell by 32%. However, NME rates rebounded in subsequent years, increasing by 26% by 2018, although income disparities in NME rates decreased after the rule change. Philosophical, religious, and medical vaccine exemptions exhibited distinct geographic patterns across the state, which largely persisted after 2015, illustrating that NME clusters remain a concern despite this rule change. CONCLUSIONS: Although Michigan's Administrative Rule change caused a short-term decline in NME rates, NME rates have risen dramatically in the following 4 years since the policy was implemented. Michigan's administrative effort to require parental education at the local health department before receiving an exemption did not cause a sustained reduction in the rate or spatial distribution of NMEs.
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Educação em Saúde , Recusa de Vacinação/estatística & dados numéricos , Vacinação/legislação & jurisprudência , Criança , Pré-Escolar , Escolaridade , Humanos , Renda , Michigan , PaisRESUMO
Varicella zoster virus (VZV) is a herpesvirus that causes chickenpox and shingles. The biological mechanisms underpinning the multidecadal latency of VZV in the body and subsequent viral reactivation-which occurs in approximately 30% of individuals-are largely unknown. Because chickenpox and shingles are endemic worldwide, understanding the relationship between VZV transmission and reactivation is important for informing disease treatment and control. While chickenpox is a vaccine-preventable childhood disease with a rich legacy of research, shingles is not a notifiable disease in most countries. To date, population-level studies of shingles have had to rely on small-scale hospital or community-level data sets. Here, we examined chickenpox and shingles notifications from Thailand and found strong seasonal incidence in both diseases, with a 3-month lag between peak chickenpox transmission season and peak shingles reactivation. We tested and fitted 14 mathematical models examining the biological drivers of chickenpox and shingles over an 8-year period to estimate rates of VZV transmission, reactivation, and immunity-boosting, wherein reexposure to VZV boosts VZV-specific immunity to reinforce protection against shingles. The models suggested that the seasonal cycles of chickenpox and shingles have different underlying mechanisms, with ambient levels of ultraviolet radiation being correlated with shingles reactivation.
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Herpesvirus Humano 3 , Estações do Ano , Infecção pelo Vírus da Varicela-Zoster/transmissão , Varicela/epidemiologia , Varicela/transmissão , Surtos de Doenças/estatística & dados numéricos , Herpes Zoster/epidemiologia , Herpes Zoster/transmissão , Humanos , Reinfecção/etiologia , Reinfecção/virologia , Tailândia/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/epidemiologiaRESUMO
OBJECTIVE: Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination. METHODS: We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature. RESULTS: A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold. CONCLUSION: Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.
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Gastroenterite , Norovirus , Criança , Análise Custo-Benefício , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos/epidemiologia , VacinaçãoRESUMO
BACKGROUND: Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms. METHODS: We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted 'immunity'), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data. RESULTS: Including immunity in the model led to attack rates that were consistent with the data. However, immunity alone resulted in the majority of outbreak durations being relatively short. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data. CONCLUSIONS: The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. More studies on how best to design interventions which leverage population immunity and encourage more rigorous individual exclusion may improve venue-level control measures. See video abstract at http://links.lww.com/EDE/B795.
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Infecções por Caliciviridae , Gastroenterite , Norovirus , Infecções por Caliciviridae/epidemiologia , Criança , Surtos de Doenças , Gastroenterite/epidemiologia , Humanos , Instituições AcadêmicasRESUMO
There is an emerging consensus that achieving global tuberculosis control targets will require more proactive case finding approaches than are currently used in high-incidence settings. Household contact tracing (HHCT), for which households of newly diagnosed cases are actively screened for additional infected individuals is a potentially efficient approach to finding new cases of tuberculosis, however randomized trials assessing the population-level effects of such interventions in settings with sustained community transmission have shown mixed results. One potential explanation for this is that household transmission is responsible for a variable proportion of population-level tuberculosis burden between settings. For example, transmission is more likely to occur in households in settings with a lower tuberculosis burden and where individuals mix preferentially in local areas, compared with settings with higher disease burden and more dispersed mixing. To better understand the relationship between endemic incidence levels, social mixing, and the impact of HHCT, we developed a spatially explicit model of coupled household and community transmission. We found that the impact of HHCT was robust across settings of varied incidence and community contact patterns. In contrast, we found that the effects of community contact tracing interventions were sensitive to community contact patterns. Our results suggest that the protective benefits of HHCT are robust and the benefits of this intervention are likely to be maintained across epidemiological settings.
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Busca de Comunicante , Tuberculose/metabolismo , Tuberculose/transmissão , Algoritmos , Simulação por Computador , Progressão da Doença , Características da Família , Saúde Global , Humanos , Incidência , Probabilidade , Informática em Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tuberculose/epidemiologiaRESUMO
BACKGROUND: Given the challenges in implementing widespread testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is increasing interest in alternative surveillance strategies. METHODS: We tested nasopharyngeal swabs from 1094 decedents in the Wayne County Medical Examiner's Office for SARS-CoV-2. All decedents were assessed using a coronavirus disease 2019 (COVID-19) checklist, and decedents flagged using the checklist (298) were preferentially tested. A random sample of decedents not flagged using the checklist were also tested (796). We statistically analyzed the characteristics of decedents (age, sex, race, and manner of death), differentiating between those flagged using the checklist and not and between those SARS-CoV-2-positive and not. RESULTS: A larger percentage of decedents overall were male (70% vs 48%) and black (55% vs 36%) compared with the catchment population. Seven-day average percent positivity among flagged decedents closely matched the trajectory of percent positivity in the catchment population, particularly during the peak of the outbreak (March and April 2020). After a lull in May to mid-June, new positive tests in late June coincided with increased case detection in the catchment. We found large racial disparities in test results; SARS-CoV-2-positive decedents were substantially more likely to be black than SARS-CoV-2-negative decedents (82% vs 51%). SARS-CoV-2-positive decedents were also more likely to be older and to have died of natural causes, including of COVID-19 disease. CONCLUSIONS: Disease surveillance through medical examiners and coroners could supplement other forms of surveillance and serve as a possible early outbreak warning sign.
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COVID-19 , SARS-CoV-2 , Negro ou Afro-Americano , Médicos Legistas , Surtos de Doenças , Feminino , Humanos , MasculinoRESUMO
The United States experienced historically high numbers of measles cases in 2019, despite achieving national measles vaccination rates above the World Health Organization recommendation of 95% coverage with two doses. Since the COVID-19 pandemic began, resulting in suspension of many clinical preventive services, pediatric vaccination rates in the United States have fallen precipitously, dramatically increasing risk of measles resurgence. Previous research has shown that measles outbreaks in high-coverage contexts are driven by spatial clustering of nonvaccination, which decreases local immunity below the herd immunity threshold. However, little is known about how to best conduct surveillance and target interventions to detect and address these high-risk areas, and most vaccination data are reported at the state-level-a resolution too coarse to detect community-level clustering of nonvaccination characteristic of recent outbreaks. In this paper, we perform a series of computational experiments to assess the impact of clustered nonvaccination on outbreak potential and magnitude of bias in predicting disease risk posed by measuring vaccination rates at coarse spatial scales. We find that, when nonvaccination is locally clustered, reporting aggregate data at the state- or county-level can result in substantial underestimates of outbreak risk. The COVID-19 pandemic has shone a bright light on the weaknesses in US infectious disease surveillance and a broader gap in our understanding of how to best use detailed spatial data to interrupt and control infectious disease transmission. Our research clearly outlines that finer-scale vaccination data should be collected to prevent a return to endemic measles transmission in the United States.
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Epidemias/estatística & dados numéricos , Vacina contra Sarampo/administração & dosagem , Sarampo/epidemiologia , Modelos Estatísticos , Conglomerados Espaço-Temporais , Vacinação/estatística & dados numéricos , Viés , Confiabilidade dos Dados , Epidemias/prevenção & controle , Monitoramento Epidemiológico , Humanos , Sarampo/prevenção & controle , Vacina contra Sarampo/uso terapêutico , Estados UnidosRESUMO
BACKGROUND: Anatomical site is strongly associated with head and neck cancer etiology, and etiology and patient sociodemographic characteristics are prognostic factors for survival. It is not known whether the effects of these predictors persist over the postdiagnosis period or are strongest proximal to the time of diagnosis. METHODS: Using survival times and causes of death for 180,434 patients with head and neck cancer in the Surveillance, Epidemiology, and End Results cancer registry (1973-2015), the empirical cumulative incidences of cancer-specific death and other-cause death were calculated with a competing risks framework, and the time-dependent effects (hazard ratios) of anatomical tumor site (oropharynx, oral cavity, or hypopharynx/larynx), age, sex, race, and year of diagnosis on cancer-specific death and other-cause death, stratified by tumor stage, were estimated. RESULTS: All effects were significantly time-varying (P < .001). Patients with nonoropharyngeal cancer had a higher hazard of cancer-specific death but a similar cumulative fraction of deaths because of a higher rate of death from other causes. Cancer-specific survival has not changed for patients with nonoropharyngeal cancer over the past decades but has improved since 2000 for patients with oropharyngeal cancer. The effects of age and sex on cancer survival were strongest proximal to the diagnosis, whereas the effect of race persisted over time. CONCLUSIONS: Recent improvements in survival for patients with oropharyngeal cancer may be due more to an increasing fraction of cancers attributable to human papillomavirus than to increasing treatment effectiveness. The prognostic strength of anatomical site and other predictors changes over the postdiagnosis period. LAY SUMMARY: It is generally assumed that the effects of tumor and personal characteristics on the survival of patients with head and neck cancer are fixed over time, but this study shows that many factors are most important only in the first few years after diagnosis. Also, recent improvements in the survival of patients with head and neck cancer appear to benefit only patients with cancers of the oropharynx. The improvements may be due more to an increasing fraction of cancers caused by human papillomavirus (which generally have better outcomes) than to advances in head and neck cancer treatment overall.