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1.
bioRxiv ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38559148

ABSTRACT

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.

2.
Nat Commun ; 15(1): 2682, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538621

ABSTRACT

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic (forest) cycles involving monkeys and canopy-living Aedes mosquitoes. Both viruses spilled over into human transmission and were translocated to the Americas, opening a path 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 infected a native, Asian host species (cynomolgus macaque) and a novel, American host species (squirrel monkey) with sylvatic strains of DENV-2 or ZIKV via mosquito bite. We then monitored aspects of viral replication (viremia), innate and adaptive immune response (natural killer (NK) cells and neutralizing antibodies, respectively), and transmission to mosquitoes. In both hosts, ZIKV reached high titers that translated into high transmission to mosquitoes; in contrast DENV-2 replicated to low levels and, unexpectedly, transmission occurred only when serum viremia was below or near the limit of detection. Our data reveal evidence of an immunologically-mediated trade-off between duration and magnitude of virus replication, as higher peak ZIKV titers are associated with shorter durations of viremia, and higher NK cell levels are associated with lower peak ZIKV titers and lower anti-DENV-2 antibody levels. Furthermore, patterns of transmission of each virus from a Neotropical monkey suggest that ZIKV has greater potential than DENV-2 to establish a sylvatic transmission cycle in the Americas.


Subject(s)
Aedes , Dengue Virus , Dengue , Zika Virus Infection , Zika Virus , Animals , Humans , Viremia
3.
Res Sq ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38343798

ABSTRACT

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.

5.
bioRxiv ; 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37425901

ABSTRACT

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.

6.
Vaccine ; 41(15): 2447-2455, 2023 04 06.
Article in English | MEDLINE | ID: mdl-36803895

ABSTRACT

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.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Humans , COVID-19/epidemiology , COVID-19 Vaccines , Breakthrough Infections , Hospitalization , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology
7.
PNAS Nexus ; 1(4): pgac143, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36060623

ABSTRACT

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.

8.
Am J Trop Med Hyg ; 107(4): 863-872, 2022 10 12.
Article in English | MEDLINE | ID: mdl-36096407

ABSTRACT

The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34% to 57% and 65% to 77% reduction in measles infection and mortality and 56% to 60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.


Subject(s)
Malnutrition , Measles , Child , Dietary Supplements , Humans , Infant , Measles/prevention & control , Measles Vaccine/therapeutic use , Vaccination
9.
Commun Med (Lond) ; 2: 41, 2022.
Article in English | MEDLINE | ID: mdl-35603276

ABSTRACT

Background: The emergence of the Brazilian variant of concern, Gamma lineage (P.1), impacted the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Methods: We sequenced 305 SARS-CoV-2 whole-genomes and performed phylogenetic analyses to identify introduction events and the circulating lineages. Additionally, we use epidemiological data of COVID-19 cases, severe cases, and deaths to measure the impact of vaccination coverage and mortality risk. Results: Here we show that Gamma introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of seven circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection in January 2021. Moreover, Gamma variant is associated with increased mortality risk and severity of COVID-19 cases in younger age groups, which corresponds to the unvaccinated population at the time. Conclusions: Our findings highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.

10.
ArXiv ; 2022 Feb 10.
Article in English | MEDLINE | ID: mdl-35169597

ABSTRACT

Most models of epidemic spread, including many designed specifically for COVID-19, implicitly assume mass-action contact patterns and undirected contact networks, meaning that the individuals most likely to spread the disease are also the most at risk to receive it from others. Here, we review results from the theory of random directed graphs which show that many important quantities, including the reproduction number and the epidemic size, depend sensitively on the joint distribution of in- and out-degrees ("risk" and "spread"), including their heterogeneity and the correlation between them. By considering joint distributions of various kinds, we elucidate why some types of heterogeneity cause a deviation from the standard Kermack-McKendrick analysis of SIR models, i.e., so-called mass-action models where contacts are homogeneous and random, and some do not. We also show that some structured SIR models informed by realistic complex contact patterns among types of individuals (age or activity) are simply mixtures of Poisson processes and tend not to deviate significantly from the simplest mass-action model. Finally, we point out some possible policy implications of this directed structure, both for contact tracing strategy and for interventions designed to prevent superspreading events. In particular, directed graphs have a forward and backward version of the classic "friendship paradox" -- forward edges tend to lead to individuals with high risk, while backward edges lead to individuals with high spread -- such that a combination of both forward and backward contact tracing is necessary to find superspreading events and prevent future cascades of infection.

11.
medRxiv ; 2022 Feb 06.
Article in English | MEDLINE | ID: mdl-35169816

ABSTRACT

Background: Co-circulating respiratory pathogens can interfere with or promote each other, leading to important effects on disease epidemiology. Estimating the magnitude of pathogen-pathogen interactions from clinical specimens is challenging because sampling from symptomatic individuals can create biased estimates. Methods: We conducted an observational, cross-sectional study using samples collected by the Seattle Flu Study between 11 November 2018 and 20 August 2021. Samples that tested positive via RT-qPCR for at least one of 17 potential respiratory pathogens were included in this study. Semi-quantitative cycle threshold (Ct) values were used to measure pathogen load. Differences in pathogen load between monoinfected and coinfected samples were assessed using linear regression adjusting for age, season, and recruitment channel. Results: 21,686 samples were positive for at least one potential pathogen. Most prevalent were rhinovirus (33·5%), Streptococcus pneumoniae (SPn, 29·0%), SARS-CoV-2 (13.8%) and influenza A/H1N1 (9·6%). 140 potential pathogen pairs were included for analysis, and 56 (40%) pairs yielded significant Ct differences (p < 0.01) between monoinfected and co-infected samples. We observed no virus-virus pairs showing evidence of significant facilitating interactions, and found significant viral load decrease among 37 of 108 (34%) assessed pairs. Samples positive with SPn and a virus were consistently associated with increased SPn load. Conclusions: Viral load data can be used to overcome sampling bias in studies of pathogen-pathogen interactions. When applied to respiratory pathogens, we found evidence of viral-SPn facilitation and several examples of viral-viral interference. Multipathogen surveillance is a cost-efficient data collection approach, with added clinical and epidemiological informational value over single-pathogen testing, but requires careful analysis to mitigate selection bias.

12.
PLoS One ; 17(1): e0262466, 2022.
Article in English | MEDLINE | ID: mdl-35061793

ABSTRACT

OBJECTIVE: Pakistan was one of the first South-Asian countries to introduce the ten-valent pneumococcal conjugate vaccine (PCV10) at the national level, using a 3+0 schedule without catchup, in 2013. METHODS: From 2014-18, fifteen children <2 years old were recruited every week in Matiari, Sindh, and nasopharyngeal swabs were collected. The samples were cultured, and pneumococcus was further serotyped through multiplex PCR at the Aga Khan University Hospital as per the method described by the Centers for Disease Control and Prevention, USA. RESULTS: Pneumococcus was detected in 2370/3140 (75%) children. Vaccine type (VT) and non-vaccine type (NVT) serotypes were carried by 379 and 1990 children. There was a significant decline in VT carriage (by 40.3%, p-value <0.001), whereas overall NVT carriage remained the same. The prevalence of VT serotypes 6B, 9V/9A, and 19F showed a significant decline by 58.8%, 79.3%, and 56%, respectively. The prevalence of NVT serotypes 19A, 21, and 10A increased by 70%, 33.3%, and 65.6%, respectively, whereas serotypes 13 and 9N/9L decreased by 53.4% and 51.8%, respectively. Serotype-specific vaccine effectiveness estimates that reached statistical significance were for 9V/9A (VE = 65.0, 95% CI 26.0-83.5%), 19F (VE = 55.3, 95% CI 15.5-76.4%) and for the vaccine related serotype 6A (VE = 28.4, 95% CI 0.9-48.2%). CONCLUSION: The emergence of NVT serotypes, primarily 19A replacing VT serotypes in this rural community, necessitates continuous monitoring of serotypes in the carriage and invasive disease to evaluate the utility of existing vaccine formulations.


Subject(s)
Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/therapeutic use , Carrier State/epidemiology , Cross-Sectional Studies , Female , Humans , Immunization , Immunization Programs , Infant , Infant, Newborn , Male , Pakistan/epidemiology , Prevalence , Rural Population , Serogroup , Streptococcus pneumoniae/immunology , Treatment Outcome , Vaccines, Conjugate
13.
Front Public Health ; 10: 1074775, 2022.
Article in English | MEDLINE | ID: mdl-36711416

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , United States/epidemiology , COVID-19/epidemiology , Length of Stay , White People , Hospitals
14.
Epidemics ; 37: 100529, 2021 12.
Article in English | MEDLINE | ID: mdl-34871942

ABSTRACT

BACKGROUND: Long-term suppression of SARS-CoV-2 transmission will involve strategies that recognize the heterogeneous capacity of communities to undertake public health recommendations. We highlight the epidemiological impact of barriers to adoption and the potential role of community-led coordination of support for cases and high-risk contacts in urban slums. METHODS: A compartmental model representing transmission of SARS-CoV-2 in urban poor versus less socioeconomically vulnerable subpopulations was developed for Montserrado County, Liberia. Adoption of home-isolation behavior was assumed to be related to the proportion of each subpopulation residing in housing units with multiple rooms and with access to sanitation, water, and food. We evaluated the potential impact of increasing the maximum attainable proportion of adoption among urban poor following the scheduled lifting of the state of emergency. RESULTS: Without intervention, the model estimated higher overall infection burden but fewer severe cases among urban poor versus the less socioeconomically vulnerable population. With self-isolation by mildly symptomatic individuals, median reductions in cumulative infections, severe cases, and maximum daily incidence were 7.6% (IQR: 2.2%-20.9%), 7.0% (2.0%-18.5%), and 9.9% (2.5%-31.4%), respectively, in the urban poor subpopulation and 16.8% (5.5%-29.3%), 15.0% (5.0%-26.4%), and 28.1% (9.3%-47.8%) in the less socioeconomically vulnerable population. An increase in the maximum attainable percentage of behavior adoption by the urban slum subpopulation was associated with median reductions of 19.2% (10.1%-34.0%), 21.1% (13.3%-34.2%), and 26.0% (11.5%-48.9%) relative to the status quo scenario. CONCLUSIONS: Post-lockdown recommendations that prioritize home-isolation by confirmed cases are limited by resource constraints. Investing in community-based initiatives that coordinate support for self-identified cases and their contacts could more effectively suppress COVID-19 in settings with socioeconomic vulnerabilities.


Subject(s)
COVID-19 , Communicable Disease Control , Epidemiological Models , Humans , Liberia/epidemiology , SARS-CoV-2 , Vulnerable Populations
15.
PLoS Med ; 18(10): e1003793, 2021 10.
Article in English | MEDLINE | ID: mdl-34665805

ABSTRACT

BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.


Subject(s)
Biomedical Research/standards , COVID-19/epidemiology , Checklist/standards , Epidemics , Guidelines as Topic/standards , Research Design , Biomedical Research/methods , Checklist/methods , Communicable Diseases/epidemiology , Epidemics/statistics & numerical data , Forecasting/methods , Humans , Reproducibility of Results
16.
Nat Hum Behav ; 5(7): 834-846, 2021 07.
Article in English | MEDLINE | ID: mdl-34183799

ABSTRACT

Social and behavioural factors are critical to the emergence, spread and containment of human disease, and are key determinants of the course, duration and outcomes of disease outbreaks. Recent epidemics of Ebola in West Africa and coronavirus disease 2019 (COVID-19) globally have reinforced the importance of developing infectious disease models that better integrate social and behavioural dynamics and theories. Meanwhile, the growth in capacity, coordination and prioritization of social science research and of risk communication and community engagement (RCCE) practice within the current pandemic response provides an opportunity for collaboration among epidemiological modellers, social scientists and RCCE practitioners towards a mutually beneficial research and practice agenda. Here, we provide a review of the current modelling methodologies and describe the challenges and opportunities for integrating them with social science research and RCCE practice. Finally, we set out an agenda for advancing transdisciplinary collaboration for integrated disease modelling and for more robust policy and practice for reducing disease transmission.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks/prevention & control , Health Behavior , Hemorrhagic Fever, Ebola/epidemiology , Primary Prevention/organization & administration , COVID-19/prevention & control , Developing Countries , Health Policy , Hemorrhagic Fever, Ebola/prevention & control , Humans
17.
JAMA Netw Open ; 4(4): e214514, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33871619

ABSTRACT

Importance: Sepsis disproportionately affects recipients of allogeneic hematopoietic cell transplant (allo-HCT), and timely detection is crucial. However, the atypical presentation of sepsis within this population makes detection challenging, and existing clinical sepsis tools have limited prognostic value among this high-risk population. Objective: To develop a full risk factor (demographic, transplant, clinical, and laboratory factors) and clinical factor-specific automated bacterial sepsis decision support tool for recipients of allo-HCT with potential bloodstream infections (PBIs). Design, Setting, and Participants: This prognostic study used data from adult recipients of allo-HCT transplanted at the Fred Hutchinson Cancer Research Center, Seattle, Washington, between June 2010 and June 2019 randomly divided into 70% modeling and 30% validation data sets. Tools were developed using the area under the curve (AUC) optimized SuperLearner, and their performance was compared with existing clinical sepsis tools: National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), and Systemic Inflammatory Response Syndrome (SIRS), using the validation data set. Data were analyzed between January and October of 2020. Main Outcomes and Measures: The primary outcome was high-sepsis risk bacteremia (culture confirmed gram-negative species, Staphylococcus aureus, or Streptococcus spp bacteremia), and the secondary outcomes were 10- and 28-day mortality. Tool discrimination and calibration were examined using accuracy metrics and expected vs observed probabilities. Results: Between June 2010 and June 2019, 1943 recipients of allo-HCT received their first transplant, and 1594 recipients (median [interquartile range] age at transplant, 54 [43-63] years; 911 [57.2%] men; 1242 individuals [77.9%] identifying as White) experienced at least 1 PBI. Of 8131 observed PBIs, 238 (2.9%) were high-sepsis risk bacteremia. Compared with high-sepsis risk bacteremia, the full decision support tool had the highest AUC (0.85; 95% CI, 0.81-0.89), followed by the clinical factor-specific tool (0.72; 95% CI, 0.66-0.78). SIRS had the highest AUC of existing tools (0.64; 95% CI, 0.57-0.71). The full decision support tool had the highest AUCs for PBIs identified in inpatient (0.82; 95% CI, 0.76-0.89) and outpatient (0.82; 95% CI, 0.75-0.89) settings and for 10-day (0.85; 95% CI, 0.79-0.91) and 28-day (0.80; 95% CI, 0.75-0.84) mortality. Conclusions and Relevance: These findings suggest that compared with existing tools and the clinical factor-specific tool, the full decision support tool had superior prognostic accuracy for the primary (high-sepsis risk bacteremia) and secondary (short-term mortality) outcomes in inpatient and outpatient settings. If used at the time of culture collection, the full decision support tool may inform more timely sepsis detection among recipients of allo-HCT.


Subject(s)
Decision Support Techniques , Hematopoietic Stem Cell Transplantation/adverse effects , Machine Learning/standards , Sepsis/diagnosis , Adult , Female , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Immunocompetence , Male , Middle Aged , ROC Curve , Random Allocation , Retrospective Studies , Risk Assessment , Sepsis/blood , Sepsis/etiology , Sepsis/microbiology
19.
Sci Rep ; 11(1): 5163, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33664311

ABSTRACT

It is uncertain whether clinical severity of an infection varies by pathogen or by multiple infections. Using hospital-based surveillance in children, we investigate the range of clinical severity for patients singly, multiply, and not infected with a group of commonly circulating viruses in Nha Trang, Vietnam. RT-PCR was performed to detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients. We apply a novel clinical severity score and examine associations with the odds of being severe and differences in raw severity scores. We find no difference in severity between 0-, 1-, and 2-concurrent infections and little differences in severity between specific viruses. We find RSV and HMPV infections to be associated with 2- and 1.5-fold increase in odds of being severe, respectively, and that infection with ADV is consistently associated with lower risk of severity. Clinically, based on the results here, if RSV or HMPV virus is suspected, PCR testing for confirmatory diagnosis and for detection of multiple coinfecting viruses would be fruitful to assess whether a patient's disease course is going to be severe.


Subject(s)
Coinfection/diagnosis , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Tract Infections/diagnosis , Virus Diseases/diagnosis , Alphaherpesvirinae/genetics , Alphaherpesvirinae/isolation & purification , Alphaherpesvirinae/pathogenicity , Child , Child, Hospitalized , Child, Preschool , Coinfection/genetics , Coinfection/pathology , Coinfection/virology , Female , Humans , Infant , Infant, Newborn , Male , Metapneumovirus/genetics , Metapneumovirus/isolation & purification , Metapneumovirus/pathogenicity , Nasopharynx/pathology , Nasopharynx/virology , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/pathology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/isolation & purification , Respiratory Syncytial Virus, Human/pathogenicity , Respiratory Tract Infections/genetics , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology , Vietnam , Virus Diseases/genetics , Virus Diseases/pathology , Virus Diseases/virology
20.
Am J Trop Med Hyg ; 104(5): 1694-1702, 2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33684067

ABSTRACT

The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. Whereas case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events in the SSA region. To capture epidemiological details related to early transmission events into and within countries, a line list was developed from publicly available data on institutional websites, situation reports, press releases, and social media accounts. The availability of indicators-gender, age, travel history, date of arrival in country, reporting date of confirmation, and how detected-for each imported case was assessed. We evaluated the relationship between the time to first reported importation and the Global Health Security Index (GHSI) overall score; 13,201 confirmed cases of COVID-19 were reported by 48 countries in SSA during the 54 days following the first known introduction to the region. Of the 2,516 cases for which travel history information was publicly available, 1,129 (44.9%) were considered importation events. Imported cases tended to be male (65.0%), with a median age of 41.0 years (range: 6 weeks-88 years; IQR: 31-54 years). A country's time to report its first importation was not related to the GHSI overall score, after controlling for air traffic. Countries in SSA generally reported with less publicly available detail over time and tended to have greater information on imported than local cases.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2 , Adolescent , Adult , Africa South of the Sahara/epidemiology , Aged , Aged, 80 and over , COVID-19/transmission , Child , Child, Preschool , Female , Global Health , Humans , Infant , Male , Middle Aged , Travel , Young Adult
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