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1.
Immunity ; 49(2): 363-374.e10, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30029854

RESUMO

Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Ebolavirus/imunologia , Glicoproteínas/imunologia , Doença pelo Vírus Ebola/imunologia , Células 3T3 , Adulto , Animais , Células CHO , Linhagem Celular , Chlorocebus aethiops , Cricetulus , Modelos Animais de Doenças , Drosophila , Feminino , Furões , Cobaias , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/virologia , Humanos , Imunoglobulina G/imunologia , Células Jurkat , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Células THP-1 , Células Vero
2.
J Immunol ; 212(11): 1693-1705, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578283

RESUMO

NK cells in the peripheral blood of severe COVID-19 patients exhibit a unique profile characterized by activation and dysfunction. Previous studies have identified soluble factors, including type I IFN and TGF-ß, that underlie this dysregulation. However, the role of cell-cell interactions in modulating NK cell function during COVID-19 remains unclear. To address this question, we combined cell-cell communication analysis on existing single-cell RNA sequencing data with in vitro primary cell coculture experiments to dissect the mechanisms underlying NK cell dysfunction in COVID-19. We found that NK cells are predicted to interact most strongly with monocytes and that this occurs via both soluble factors and direct interactions. To validate these findings, we performed in vitro cocultures in which NK cells from healthy human donors were incubated with monocytes from COVID-19+ or healthy donors. Coculture of healthy NK cells with monocytes from COVID-19 patients recapitulated aspects of the NK cell phenotype observed in severe COVID-19, including decreased expression of NKG2D, increased expression of activation markers, and increased proliferation. When these experiments were performed in a Transwell setting, we found that only CD56bright CD16- NK cells were activated in the presence of severe COVID-19 patient monocytes. O-link analysis of supernatants from Transwell cocultures revealed that cultures containing severe COVID-19 patient monocytes had significantly elevated levels of proinflammatory cytokines and chemokines, as well as TGF-ß. Collectively, these results demonstrate that interactions between NK cells and monocytes in the peripheral blood of COVID-19 patients contribute to NK cell activation and dysfunction in severe COVID-19.


Assuntos
COVID-19 , Comunicação Celular , Técnicas de Cocultura , Células Matadoras Naturais , Ativação Linfocitária , Monócitos , SARS-CoV-2 , Humanos , Células Matadoras Naturais/imunologia , COVID-19/imunologia , Monócitos/imunologia , SARS-CoV-2/imunologia , Ativação Linfocitária/imunologia , Comunicação Celular/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Citocinas/imunologia , Citocinas/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/imunologia , Células Cultivadas
3.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35110410

RESUMO

Despite more than 300,000 rVSVΔG-ZEBOV-glycoprotein (GP) vaccine doses having been administered during Ebola virus disease (EVD) outbreaks in the Democratic Republic of the Congo (DRC) between 2018 and 2020, seroepidemiologic studies of vaccinated Congolese populations are lacking. This study examines the antibody response at 21 d and 6 mo postvaccination after single-dose rVSVΔG-ZEBOV-GP vaccination among EVD-exposed and potentially exposed populations in the DRC. We conducted a longitudinal cohort study of 608 rVSVΔG-ZEBOV-GP-vaccinated individuals during an EVD outbreak in North Kivu Province, DRC. Participants provided questionnaires and blood samples at three study visits (day 0, visit 1; day 21, visit 2; and month 6, visit 3). Anti-GP immunoglobulin G (IgG) antibody titers were measured in serum by the Filovirus Animal Nonclinical Group anti-Ebola virus GP IgG enzyme-linked immunosorbent assay. Antibody response was defined as an antibody titer that had increased fourfold from visit 1 to visit 2 and was above four times the lower limit of quantification at visit 2; antibody persistence was defined as a similar increase from visit 1 to visit 3. We then examined demographics for associations with follow-up antibody titers using generalized linear mixed models. A majority of the sample, 87.2%, had an antibody response at visit 2, and 95.6% demonstrated antibody persistence at visit 3. Being female and of young age was predictive of a higher antibody titer postvaccination. Antibody response and persistence after Ebola vaccination was robust in this cohort, confirming findings from outside of the DRC.


Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Imunogenicidade da Vacina/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Criança , República Democrática do Congo , Surtos de Doenças/prevenção & controle , Feminino , Glicoproteínas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Vacinação/métodos , Proteínas do Envelope Viral/imunologia , Adulto Jovem
4.
Emerg Infect Dis ; 30(1): 172-176, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38019211

RESUMO

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb.


Assuntos
Mpox , Humanos , Mpox/epidemiologia , Monkeypox virus/genética , República Democrática do Congo/epidemiologia , Reação em Cadeia da Polimerase/métodos
5.
Emerg Infect Dis ; 30(4): 761-765, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38526165

RESUMO

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.


Assuntos
Mpox , Poxviridae , Suipoxvirus , Humanos , Animais , Suínos , Mpox/epidemiologia , Monkeypox virus/genética , República Democrática do Congo/epidemiologia
6.
N Engl J Med ; 384(13): 1240-1247, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789012

RESUMO

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).


Assuntos
Ebolavirus/genética , Doença pelo Vírus Ebola/transmissão , Adulto , Teorema de Bayes , República Democrática do Congo/epidemiologia , Vacinas contra Ebola/imunologia , Ebolavirus/isolamento & purificação , Evolução Fatal , Genoma Viral , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Humanos , Masculino , Mutação , Filogenia , RNA Viral/sangue , Recidiva
7.
MMWR Morb Mortal Wkly Rep ; 73(22): 507-513, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38843078

RESUMO

In 2022, a global mpox outbreak occurred, primarily affecting gay and bisexual men who have sex with men (GBMSM). To screen for mpox's reemergence and investigate potentially unsuspected cases among non-GBMSM, prospective surveillance of patients aged ≥3 months with an mpox-compatible rash (vesicular, pustular, ulcerated, or crusted) was conducted at 13 U.S. emergency departments (EDs) during June-December 2023. Demographic, historical, and illness characteristics were collected using questionnaires and electronic health records. Lesions were tested for monkeypox virus using polymerase chain reaction. Among 196 enrolled persons, the median age was 37.5 years (IQR = 21.0-53.5 years); 39 (19.9%) were aged <16 years, and 108 (55.1%) were male. Among all enrollees, 13 (6.6%) were GBMSM. Overall, approximately one half (46.4%) and one quarter (23.5%) of enrolled persons were non-Hispanic White and non-Hispanic Black or African American, respectively, and 38.8% reported Hispanic or Latino (Hispanic) ethnicity. Unstable housing was reported by 21 (10.7%) enrollees, and 24 (12.2%) lacked health insurance. The prevalence of mpox among ED patients evaluated for an mpox-compatible rash was 1.5% (95% CI = 0.3%-4.4%); all persons with a confirmed mpox diagnosis identified as GBMSM and reported being HIV-negative, not being vaccinated against mpox, and having engaged in sex with one or more partners met through smartphone dating applications. No cases were identified among women, children, or unhoused persons. Clinicians should remain vigilant for mpox and educate persons at risk for mpox about modifying behaviors that increase risk and the importance of receiving 2 appropriately spaced doses of JYNNEOS vaccine to prevent mpox.


Assuntos
Serviço Hospitalar de Emergência , Exantema , Mpox , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adolescente , Exantema/epidemiologia , Mpox/epidemiologia , Surtos de Doenças , Vigilância da População , Estudos Prospectivos
8.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33431650

RESUMO

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.


Assuntos
COVID-19 , Busca de Comunicante , Máscaras , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos
9.
Emerg Infect Dis ; 29(5): 977-987, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37081530

RESUMO

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Botsuana/epidemiologia , Tuberculose/microbiologia , Mycobacterium tuberculosis/genética , Genótipo , Genômica
10.
BMC Pregnancy Childbirth ; 23(1): 31, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647021

RESUMO

BACKGROUND: Little research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC). METHODS: We conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions. RESULTS: In total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p < 0.0001). Furthermore, the level of diagnostic certainty declined slightly across all outcomes investigated from the pre-COVID-19 to the intra-COVID-19 period. Nonetheless, diagnostic certainty was especially low for certain outcomes (i.e., stillbirth and NBSI) regardless of period; still, other outcomes, such as preterm birth and LBW, had moderate to high levels of diagnostic certainty. Results were mostly consistent when the analysis was focused on the facilities designated for COVID-19 care. CONCLUSION: This study succeeded in providing prevalence estimates for key adverse birth outcomes using GAIA criteria during the COVID-19 pandemic in Kinshasa, DRC. Furthermore, our study adds crucial real-world data to the literature surrounding the impact of the COVID-19 pandemic on maternal and neonatal services and outcomes in Africa.


Assuntos
COVID-19 , Microcefalia , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Natimorto/epidemiologia , Nascimento Prematuro/epidemiologia , Pandemias , República Democrática do Congo/epidemiologia , Estudos Retrospectivos , Microcefalia/epidemiologia , COVID-19/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Complicações na Gravidez/epidemiologia , Prontuários Médicos
11.
J Infect Dis ; 226(4): 608-615, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-33269402

RESUMO

BACKGROUND: Health care workers (HCW) are more likely to be exposed to Ebola virus (EBOV) during an outbreak compared to people in the general population due to close physical contact with patients and potential exposure to infectious fluids. However, not all will fall ill. Despite evidence of subclinical and paucisymptomatic Ebola virus disease (EVD), prevalence and associated risk factors remain unknown. METHODS: We conducted a serosurvey among HCW in Boende, Tshuapa Province, Democratic Republic of Congo. Human anti-EBOV glycoprotein IgG titers were measured using a commercially available ELISA kit. We assessed associations between anti-EBOV IgG seroreactivity, defined as ≥2.5 units/mL, and risk factors using univariable and multivariable logistic regression. Sensitivity analyses explored a more conservative cutoff, >5 units/mL. RESULTS: Overall, 22.5% of HCWs were seroreactive for EBOV. In multivariable analyses, using any form of personal protective equipment when interacting with a confirmed, probable, or suspect EVD case was negatively associated with seroreactivity (adjusted odds ratio, 0.23; 95% confidence interval, .07-.73). DISCUSSION: Our results suggest high exposure to EBOV among HCWs and provide additional evidence for asymptomatic or minimally symptomatic EVD. Further studies should be conducted to determine the probability of onward transmission and if seroreactivity is associated with immunity.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , República Democrática do Congo/epidemiologia , Surtos de Doenças , Pessoal de Saúde , Humanos , Imunoglobulina G , Fatores de Risco
12.
J Infect Dis ; 226(Suppl 3): S346-S352, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36208168

RESUMO

BACKGROUND: This study aimed to evaluate the feasibility and acceptability of engaging unhoused peer ambassadors (PAs) in coronavirus disease 2019 (COVID-19) vaccination efforts to reach people experiencing unsheltered homelessness in Los Angeles County. METHODS: From August to December 2021, vaccinated PAs aged ≥18 years who could provide informed consent were recruited during vaccination events for same-day participation. Events were held at encampments, service providers (eg, housing agencies, food lines, and mobile showers), and roving locations around Los Angeles. PAs were asked to join outreach alongside community health workers and shared their experience getting vaccinated, receiving a $25 gift card for each hour they participated. Postevent surveys evaluated how many PAs enrolled and how long they participated. In October 2021, we added a preliminary effectiveness evaluation of how many additional vaccinations were attributable to PAs. Staff who enrolled the PAs estimated the number of additional people vaccinated because of talking with the PA. RESULTS: A total of 117 PAs were enrolled at 103 events, participating for an average of 2 hours. At events with the effectiveness evaluation, 197 additional people were vaccinated over 167 PA hours ($21.19 gift card cost per additional person vaccinated), accounting for >25% of all vaccines given at these events. DISCUSSION: Recruiting same-day unhoused PAs is a feasible, acceptable, and preliminarily effective technique to increase COVID-19 vaccination in unsheltered settings. The findings can inform delivery of other health services for people experiencing homelessness.


Assuntos
COVID-19 , Pessoas Mal Alojadas , Vacinas , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Viabilidade , Humanos , Los Angeles/epidemiologia , Vacinação
13.
Clin Infect Dis ; 74(7): 1166-1173, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-34292319

RESUMO

BACKGROUND: Sentiments of vaccine hesitancy and distrust in public health institutions have complicated the government-led coronavirus disease 2019 (COVID-19) vaccine control strategy in the United States. As the first to receive the vaccine, COVID-19 vaccine attitudes among frontline workers are consequential for COVID-19 control and public opinion of the vaccine. METHODS: In this study, we used a repeated cross-sectional survey administered at 3 time points between 24 September 2020 and 6 February 2021 to a cohort of employees of the University of California, Los Angeles Health and the Los Angeles County Fire Department. The primary outcome of interest was COVID-19 vaccination intent and vaccine uptake. RESULTS: Confidence in COVID-19 vaccines and vaccine uptake rose significantly over time. At survey 1, confidence in vaccine protection was 46.4% among healthcare workers (HCWs) and 34.6% among first responders (FRs); by survey 3, this had risen to 90.0% and 75.7%, respectively. At survey 1, about one-third of participants intended to receive a vaccine as soon as possible. By survey 3, 96.0% of HCWs and 87.5% of FRs had received a COVID-19 vaccine. CONCLUSIONS: Attitudes toward vaccine uptake increased over the study period, likely a result of increased public confidence in COVID-19 vaccines, targeted communications, a COVID-19 winter surge in Los Angeles County, and ease of access from employer-sponsored vaccine distribution.


Assuntos
COVID-19 , Vacinas , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Pessoal de Saúde , Humanos , Los Angeles/epidemiologia , Vacinação
14.
Am J Obstet Gynecol ; 227(6): 849-861.e7, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35985514

RESUMO

The 2022 monkeypox outbreak, caused by the zoonotic monkeypox virus, has spread across 6 World Health Organization regions (the Americas, Africa, Europe, Eastern Mediterranean, Western Pacific, and South-East Asia) and was declared a public health emergency of international concern on July 23, 2022. The global situation is especially concerning given the atypically high rate of person-to-person transmission, which suggests viral evolution to an established human pathogen. Pregnant women are at heightened risk of vertical transmission of the monkeypox virus because of immune vulnerability and natural depletion of population immunity to smallpox among reproductive-age women, and because orthopoxviral cell entry mechanisms can overcome the typically viral-resistant syncytiotrophoblast barrier within the placenta. Data on pregnancy outcomes following monkeypox infection are scarce but include reports of miscarriage, intrauterine demise, preterm birth, and congenital infection. This article forecasts the issues that maternity units might face and proposes guidelines to protect the health of pregnant women and fetuses exposed to the monkeypox virus. We review the pathophysiology and clinical features of monkeypox infection and discuss the obstetrical implications of the unusually high prevalence of anogenital lesions. We describe the use of real-time polymerase chain reaction tests from mucocutaneous and oropharyngeal sites to confirm infection, and share an algorithm for the antenatal management of pregnant women with monkeypox virus exposure. On the basis of the best available knowledge from prenatal orthopoxvirus infections, we discuss the sonographic features of congenital monkeypox and the role of invasive testing in establishing fetal infection. We suggest a protocol for cesarean delivery to avoid the horizontal transmission of the monkeypox virus at birth and address the controversy of mother-infant separation in the postpartum period. Obstetrical concerns related to antiviral therapy with tecovirimat and vaccinia immune globulin are highlighted, including the risks of heart rate-corrected QT-interval prolongation, inaccuracies in blood glucose monitoring, and the predisposition to iatrogenic venous thromboembolism. The possibility of monkeypox vaccine hesitancy during pregnancy is discussed, and strategies are offered to mitigate these risks. Finally, we conclude with a research proposal to address knowledge gaps related to the impact of monkeypox infection on maternal, fetal, and neonatal health.


Assuntos
Mpox , Nascimento Prematuro , Recém-Nascido , Lactente , Feminino , Humanos , Gravidez , Mpox/diagnóstico , Mpox/epidemiologia , Automonitorização da Glicemia , Glicemia , Monkeypox virus
15.
PLoS Comput Biol ; 17(3): e1008837, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33780443

RESUMO

Predictions of COVID-19 case growth and mortality are critical to the decisions of political leaders, businesses, and individuals grappling with the pandemic. This predictive task is challenging due to the novelty of the virus, limited data, and dynamic political and societal responses. We embed a Bayesian time series model and a random forest algorithm within an epidemiological compartmental model for empirically grounded COVID-19 predictions. The Bayesian case model fits a location-specific curve to the velocity (first derivative) of the log transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectories. The compartmental model uses this distribution and predicts deaths using a random forest algorithm trained on COVID-19 data and population-level characteristics, yielding daily projections and interval estimates for cases and deaths in U.S. states. We evaluated the model by training it on progressively longer periods of the pandemic and computing its predictive accuracy over 21-day forecasts. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Colorado, and West Virginia. The sophistication and accuracy of this COVID-19 model offer reliable predictions and uncertainty estimates for the current trajectory of the pandemic in the U.S. and provide a platform for future predictions as shifting political and societal responses alter its course.


Assuntos
COVID-19/epidemiologia , COVID-19/mortalidade , Previsões/métodos , Modelos Estatísticos , Pandemias/estatística & dados numéricos , SARS-CoV-2 , Algoritmos , Teorema de Bayes , COVID-19/transmissão , Biologia Computacional , Humanos , Aprendizado de Máquina , Estados Unidos/epidemiologia
16.
BMC Infect Dis ; 22(1): 30, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986786

RESUMO

BACKGROUND: Vaccination efforts to eradicate polio currently focus on children under 5 years of age, among whom most cases of poliomyelitis still occur. However, in the Democratic Republic of the Congo (DRC), an outbreak of wild poliovirus type 1 occurred in 2010-2011 in which 16% of cases occurred among adults; in a related outbreak in the neighboring Republic of Congo, 75% of cases occurred among the same adult age-group. Given that infected adults may transmit poliovirus, this study was designed to assess adult immunity against polioviruses. METHODS: We assessed poliovirus seroprevalence using dried blood spots from 5,526 adults aged 15-59 years from the 2013-2014 Demographic and Health Survey in the DRC. RESULTS: Among adults in the DRC, 74%, 72%, and 57% were seropositive for neutralizing antibodies for poliovirus types 1, 2, and 3, respectively. For all three serotypes, seroprevalence tended to be higher among older age groups, those living in households with more children, and among women. CONCLUSIONS: Protection against poliovirus is generally low among adults in the DRC, particularly for type 3 poliovirus. The lack of acquired immunity in adults suggests a potentially limited poliovirus circulation over the lifetime of those surveyed (spanning 1954 through 2014) and transmission of vaccine-derived poliovirus in this age group while underscoring the risk of these outbreaks among adults in the DRC.


Assuntos
Poliomielite , Poliovirus , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , República Democrática do Congo/epidemiologia , Surtos de Doenças , Feminino , Humanos , Lactente , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacina Antipólio Oral , Estudos Soroepidemiológicos
17.
J Infect Dis ; 222(12): 2021-2029, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-32255180

RESUMO

BACKGROUND: Our understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited. METHODS: We used time-series data of case counts to compare individuals in Ebola-affected health zones in DRC, April 2018-August 2019. Exposure was number of violent events per health zone, categorized into Ebola-targeted or Ebola-untargeted, and into civilian-induced, (para)military/political, or protests. Outcome was estimated daily reproduction number (Rt) by health zone. We fit linear time-series regression to model the relationship. RESULTS: Average Rt was 1.06 (95% confidence interval [CI], 1.02-1.11). A mean of 2.92 violent events resulted in cumulative absolute increase in Rt of 0.10 (95% CI, .05-.15). More violent events increased EBOV transmission (P = .03). Considering violent events in the 95th percentile over a 21-day interval and its relative impact on Rt, Ebola-targeted events corresponded to Rt of 1.52 (95% CI, 1.30-1.74), while civilian-induced events corresponded to Rt of 1.43 (95% CI, 1.21-1.35). Untargeted events corresponded to Rt of 1.18 (95% CI, 1.02-1.35); among these, militia/political or ville morte events increased transmission. CONCLUSIONS: Ebola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission.


Assuntos
Conflitos Armados/classificação , Distúrbios Civis/classificação , Surtos de Doenças , Mapeamento Geográfico , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/transmissão , República Democrática do Congo/epidemiologia , Ebolavirus , Humanos
18.
J Infect Dis ; 219(4): 517-525, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30239838

RESUMO

Healthcare settings have played a major role in propagation of Ebola virus (EBOV) outbreaks. Healthcare workers (HCWs) have elevated risk of contact with EBOV-infected patients, particularly if safety precautions are not rigorously practiced. We conducted a serosurvey to determine seroprevalence against multiple EBOV antigens among HCWs of Boende Health Zone, Democratic Republic of the Congo, the site of a 2014 EBOV outbreak. Interviews and specimens were collected from 565 consenting HCWs. Overall, 234 (41.4%) of enrolled HCWs were reactive to at least 1 EBOV protein: 159 (28.1%) were seroreactive for anti-glycoprotein immunoglobulin G (IgG), 89 (15.8%) were seroreactive for anti-nucleoprotein IgG, and 54 (9.5%) were VP40 positive. Additionally, sera from 16 (2.8%) HCWs demonstrated neutralization capacity. These data demonstrate that a significant proportion of HCWs have the ability to neutralize virus, despite never having developed Ebola virus disease symptoms, highlighting an important and poorly documented aspect of EBOV infection and progression.


Assuntos
Anticorpos Antivirais/sangue , Ebolavirus/imunologia , Pessoal de Saúde , Estudos Soroepidemiológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , República Democrática do Congo , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
19.
Clin Infect Dis ; 68(8): 1388-1393, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30107392

RESUMO

BACKGROUND: Clinical sequelae of Ebola virus disease (EVD) have not been described more than 3 years postoutbreak. We examined survivors and close contacts from the 1995 Ebola outbreak in Kikwit, Democratic Republic of Congo (DRC), and determined prevalence of abnormal neurological, cognitive, and psychological findings and their association with EVD survivorship. METHODS: From August to September 2017, we conducted a cross-sectional study in Kikwit, DRC. Over 2 decades after the EVD outbreak, we recruited EVD survivors and close contacts from the outbreak to undergo physical examination and culturally adapted versions of the Folstein mini-mental status exam (MMSE) and Goldberg anxiety and depression scale (GADS). We estimated the strength of relationships between EVD survivorship and health outcomes using linear regression models by comparing survivors versus close contacts, adjusting for age, sex, educational level, marital status, and healthcare worker status. RESULTS: We enrolled 20 EVD survivors and 187 close contacts. Among the 20 EVD survivors, 4 (20%) reported at least 1 abnormal neurological symptom, and 3 (15%) had an abnormal neurological examination. Among the 187 close contacts, 14 (11%) reported at least 1 abnormal neurologic symptom, and 9 (5%) had an abnormal neurological examination. EVD survivors had lower mean MMSE and higher mean GADS scores as compared to close contacts (MMSE: adjusted coefficient: -1.85; 95% confidence interval [CI]: -3.63, -0.07; GADS: adjusted coefficient: 3.91; 95% CI: 1.76, 6.04). CONCLUSIONS: EVD survivors can have lower cognitive scores and more symptoms of depression and anxiety than close contacts more than 2 decades after Ebola virus outbreaks.


Assuntos
Doença pelo Vírus Ebola/fisiopatologia , Doença pelo Vírus Ebola/psicologia , Ansiedade , Cognição , Estudos Transversais , República Democrática do Congo/epidemiologia , Depressão , Surtos de Doenças , Feminino , Doença pelo Vírus Ebola/epidemiologia , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Sobreviventes
20.
Emerg Infect Dis ; 25(5): 911-918, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002071

RESUMO

We conducted a serologic survey of 2,430 serum samples collected during 1997-2012 for various studies to determine the prevalence of the hemorrhagic fever virus Ebola virus (EBOV) in equatorial Africa. We screened serum samples for neutralizing antibodies by using a pseudotype microneutralization assay and a newly developed luciferase immunoprecipitation system assay. Specimens seroreactive for EBOV were confirmed by using an ELISA. Our results suggest a serologic prevalence of 2%-3.5% in the Republic of the Congo and the Democratic Republic of the Congo, which have reported outbreaks of infection with EBOV. In addition we detected a seroprevalence of 1.3% in southern Cameroon, which indicated a low risk for exposure in this region.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola/epidemiologia , África Central/epidemiologia , Anticorpos Antivirais/sangue , Ebolavirus/imunologia , Ensaio de Imunoadsorção Enzimática , Células HEK293 , Doença pelo Vírus Ebola/sangue , Humanos , Imunoprecipitação , Nucleoproteínas/imunologia , Estudos Soroepidemiológicos , Proteínas do Core Viral/imunologia , Proteínas do Envelope Viral/imunologia
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