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1.
PLoS One ; 17(8): e0271920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35925959

RESUMO

A growing number of organisations, including medical associations, recommend that research subjects should be given the option of being informed about the general outcome and results of the study. We recently completed a study involving nine serosurveys from 2018 to 2020 in five districts of India among three age groups (children 9 months to < 5 years; 5 to < 15 years of age, and women 15 to < 50 years of age before and after the measles and rubella (MR) vaccination campaigns). In Palghar district of Maharashtra all individuals in 30 selected clusters were enumerated, and 13 individuals per age group were randomly sampled. We established the procedures to return the results to the respondents for each stage of the survey. Of the 1,166 individuals selected for the measles and rubella serosurvey, 971 (83%) agreed to participate and were enrolled. Participants were informed that they will only be contacted if they test seronegative for measles and/or rubella antibodies. Overall, 140 individuals enrolled in the survey tested seronegative for IgG antibodies to measles and/or rubella viruses; were provided the reports and informed to seek medical advice. Upon follow up by phone, 10% (14) of the 140 participants reported to have been vaccinated. In this paper we discuss the procedures, experiences and considerations in returning results to participants in a community-based measles and rubella serosurvey. Although the lessons learned are specific to post measles-rubella vaccine campaign serosurvey in India, they might be helpful to those contemplating sharing results to participants of large scale survey settings.

2.
Nat Commun ; 13(1): 4234, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918315

RESUMO

Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of Th 1 immunity. Here we show application of cationic adjuvant formulation CAF08, a liposomal vaccine formulation tailored to induce Th 1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics to human dendritic cells and reveal a role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identify signaling events resulting in antigen cross-presentation. In a murine in vivo model a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protects newborn mice from RSV infection by induction of antigen-specific CD8+ T-cells and Th1 cells. Overall, we describe a pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other respiratory viral pathogens.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais , Linfócitos T CD8-Positivos , Criança , Humanos , Recém-Nascido , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Virais de Fusão
3.
Commun Chem ; 5(1): 85, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911504

RESUMO

SARS-CoV-2 infection remains spread worldwide and requires a better understanding of virus-host interactions. Here, we analyzed biochemical modifications due to SARS-CoV-2 infection in cells by confocal Raman microscopy. Obtained results were compared with the infection with another RNA virus, the measles virus. Our results have demonstrated a virus-specific Raman molecular signature, reflecting intracellular modification during each infection. Advanced data analysis has been used to distinguish non-infected versus infected cells for two RNA viruses. Further, classification between non-infected and SARS-CoV-2 and measles virus-infected cells yielded an accuracy of 98.9 and 97.2 respectively, with a significant increase of the essential amino-acid tryptophan in SARS-CoV-2-infected cells. These results present proof of concept for the application of Raman spectroscopy to study virus-host interaction and to identify factors that contribute to the efficient SARS-CoV-2 infection and may thus provide novel insights on viral pathogenesis, targets of therapeutic intervention and development of new COVID-19 biomarkers.

4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(8): 1095-1100, 2022 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-35922237

RESUMO

Objective: To determine IgG antibody levels of measles, rubella, mumps in healthy population in Shanghai from 2010 to 2020 and analyze the trend of antibody changes in different age groups. Methods: 10 828 healthy people without measles, rubella and mumps in Shanghai were included in the study from 2010 to 2020. Serum samples were collected from 12 age groups, and the serum IgG antibody of measles, rubella and mumps were detected by ELISA. The difference of antibody positive rates and antibody levels were analyzed. Results: The median age M (Q1, Q3) of 10 828 objects were 8 years old (9 months old, 20 years old). Males accounted for 48.34% (5 234/10 828) and females accounted for 50.92% (5 514/10 828). Unknown gender information accounted for 0.74% (80/10 828), and 27.03% (2 927/10 828) of participants had unknown MMR immunization history. The total positive rates of measles, rubella and mumps IgG antibody were 76.78%, 64.46% and 64.29% and their GMCs were 541.45 mIU/ml, 31.76 IU/ml and 133.73 U/ml respectively. There were significant differences in serum IgG antibody GMC of measles, rubella and mumps in each year (Fmeasles=180.74, P<0.001; Frubella=189.95, P<0.001; Fmumps=122.40, P<0.001). The positive rate of measles antibody was higher than that of rubella and mumps, and the difference was statistically significant (χ²=518.09, P<0.001). Conclusion: The level of measles IgG antibody in healthy people in Shanghai is higher, while the level of rubella and mumps IgG antibody is slightly lower.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Adulto , Anticorpos Antivirais , Criança , China/epidemiologia , Feminino , Humanos , Imunoglobulina G , Lactente , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/epidemiologia , Caxumba/prevenção & controle , Vírus da Caxumba , Rubéola (Sarampo Alemão)/epidemiologia , Rubéola (Sarampo Alemão)/prevenção & controle , Adulto Jovem
5.
Vaccine ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35927136

RESUMO

Japan is one of the countries conducting longitudinal serosurveillance of vaccine-preventable diseases. We conducted surveillance of the local measles-specific antibody titer, calculated the effective reproduction number (Re), and compared data of four terms: term 1, 2003-2006 (before the introduction of the second shot of measles-containing vaccine); term 2, 2007-2010 (early term toward measles elimination); term 3, 2011-2014 (later term toward measles elimination); and term 4, 2015-2020 (after elimination of measles in Japan). Approximately 250 sera from volunteers aged 0 to ≥ 40 years were collected and examined for measles-specific IgG using the gelatin particle agglutination (PA) method annually from 2003 to 2020. Seroprevalence and the geometric mean of the PA antibody titer were examined by term. Re was calculated using the age-dependent proportion immune and contact matrix for each term. Of the 4,716 sera, 886 in term 1, 1,217 in term 2, 1,069 in term 3, and 1,544 in term 4 were collected. The seroprevalence gradually increased from term 1 (88.3% CI 86.0-90.3) to term 4 (95.7% CI 94.6-96.7), and the seroprevalence of term 1 was significantly lower than those of other terms (Fisher's exact test, p < 0.001), with PA titer ≥ 16 as positive. By contrast, PA antibody titers significantly decreased from term 1 (median 1,024) to term 4 (median 256) (Mann-Whitney U test, p < 0.001). With the protection level (PA titer ≥ 128 and ≥ 256) as positive, Re gradually increased from term 1 (1.8 and 2.3) to term 4 (2.5 and 4.8, respectively). Waning levels of measles antibodies potentially increase the measles susceptibility in Osaka, Japan. This trend might imply a limitation of vaccine-induced immunity in the absence of a natural booster for wild strains after measles elimination. This study provides a cue for maintaining continuous measles elimination status in the future.

6.
J R Soc Interface ; 19(193): 20220123, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35919978

RESUMO

Timely forecasts of the emergence, re-emergence and elimination of human infectious diseases allow for proactive, rather than reactive, decisions that save lives. Recent theory suggests that a generic feature of dynamical systems approaching a tipping point-early warning signals (EWS) due to critical slowing down (CSD)-can anticipate disease emergence and elimination. Empirical studies documenting CSD in observed disease dynamics are scarce, but such demonstration of concept is essential to the further development of model-independent outbreak detection systems. Here, we use fitted, mechanistic models of measles transmission in four cities in Niger to detect CSD through statistical EWS. We find that several EWS accurately anticipate measles re-emergence and elimination, suggesting that CSD should be detectable before disease transmission systems cross key tipping points. These findings support the idea that statistical signals based on CSD, coupled with decision-support algorithms and expert judgement, could provide the basis for early warning systems of disease outbreaks.


Assuntos
Doenças Transmissíveis , Sarampo , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Surtos de Doenças , Previsões , Humanos , Sarampo/diagnóstico , Sarampo/epidemiologia , Modelos Biológicos
7.
Ann Otol Rhinol Laryngol ; : 34894221115757, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35923122

RESUMO

OBJECTIVE: Laryngeal abscesses are rare in the modern antibiotic era. Historically, they were associated with systemic infections including typhoid fever, measles, gonorrhea, syphilis, and tuberculosis. More recent authors have described cases resulting from iatrogenic injury and immunosuppression. This report presents a novel case of laryngeal abscess in the setting of uncontrolled diabetes and a detailed review of modern, reported cases of spontaneous laryngeal abscess. METHODS: Report of a single case. Also, PubMed was queried for cases of laryngeal abscess since 1985. CASE REPORT: A 58-year-old male with poorly controlled diabetes presented with odynophagia, dysphagia, and dyspnea. He had biphasic stridor, and flexible laryngoscopy showed reduced mobility of bilateral vocal folds and narrowed glottic airway. He was taken urgently for awake tracheostomy and microdirect laryngoscopy. Laryngoscopy demonstrated fullness and fluctuance of the right hemilarynx. The abscess cavity was entered endoscopically via paraglottic incision extending into the subglottis. The patient was treated with an 8-week course of ampicillin-sulbactam with resolution of infection. RESULTS: Seven additional cases of spontaneous laryngeal abscesses published after 1985 were identified. In total, 6 of 8 had some form of immunodeficiency (75%). The most common presenting symptoms were dysphonia (8/8, 100%), odynophagia (5/8, 62.5%), and dyspnea/stridor (4/8, 50%). All cases were treated with surgical incision and drainage. CONCLUSIONS: Laryngeal abscesses are rare in the era of modern antibiotics. This review confirms that the majority of recent episodes occurred in the setting of immunodeficiency and are caused by non-tubercular bacteria. These infections are commonly associated with impaired vocal fold mobility which may contribute to dyspnea, stridor, and airway compromise. Surgical intervention is necessary for treatment and culture-directed antimicrobial therapy. Poorly controlled diabetes is a newly described context for development of spontaneous laryngeal abscess.

8.
medRxiv ; 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35923323

RESUMO

Both private and public benefits result from vaccination for transmissible diseases, such as seasonal influenza, measles, and COVID-19. To help inform vaccination efforts for such diseases, we ask whether social preferences-concerns for the well-being of other people-influence one's decision regarding vaccination. We measure these social preferences for 549 online subjects: We give each subject $4 to play a public-good game and make contributions to public welfare. To the extent that one gets vaccinated out of concern for the health of others, contribution in this game is analogous to an individual's decision to obtain vaccination. We proxy vaccine demand with individuals' delay to initially vaccinate for COVID-19. We collect COVID-19 vaccination history separately to avoid experimenter-demand effects. We find a strong result: Contribution in the public-good game is associated with greater demand to voluntarily receive a first dose, and thus also to vaccinate earlier. Compared to a subject who contributes nothing, one who contributes the maximum ($4) is 48% more likely to obtain a first dose voluntarily in the four-month period that we study (April through August 2021). People who are more pro-social are indeed more likely to take a voluntary COVID-19 vaccination. We thus recommend further research on the use of pro-social preferences to help motivate individuals to vaccinate for transmissible diseases, such as the flu and HPV.

9.
Brasilia, D.F.; OPAS; 2022-08-03. (OPAS-W/BRA/FGL/COVID-19/22-0023).
Não convencional em Português | PAHO-IRIS | ID: phr2-56214

RESUMO

Depois de mais de 22 meses da pandemia de COVID-19 em curso na Região das Américas, onde casos e mortes por COVID-19 foram relatados em todos os 56 países e territórios na Região das Américas, os sistemas de saúde ainda estão sendo desafiados e as atividades de imunização rotineira ainda estão atrasadas na maioria dos países. A pandemia afetou o cumprimento dos indicadores de vigilância de doenças preveníveis por vacinação (VPD, sigla em inglês). Além disso, as restrições impostas ao movimento e as preocupações com a pandemia limitaram as atividades da atenção primária à saúde, incluindo serviços preventivos como a vacinação, com a consequente queda na cobertura vacinal e aumento da população suscetível.


Assuntos
Doenças Preveníveis por Vacina , Imunização , Vacinas , Difteria , Sarampo , Vacina contra Sarampo , Febre Amarela , Vacina contra Febre Amarela , Poliomielite , COVID-19 , América
10.
Microbiol Immunol ; 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35909326

RESUMO

Lactate dehydrogenase (LDH) levels in measles virus (MeV) reinfection cases for the diagnosis of measles have not been extensively studied. Thus, we evaluated the significance of serum LDH in the immune response of patients with MeV reinfection in comparison with those of patients with primary infection. Among 70 patients who tested positive for MeV-RNA, 42 with high MeV-specific IgG avidity (HA) were suspected as cases of reinfection and 28 with low MeV-specific IgG (LA) were suspected as cases of primary infection. The viral loads in the HA group were also lower than those in the LA group (p < 0.001). The titers of MeV-specific IgM and IgG in the HA group were significantly lower and higher, respectively, than those in the LA group (p < 0.001). The total LDH and LDH isozyme levels were elevated in the LA group compared with those in the HA group (p < 0.001). Through receiver operating characteristic curve analyses, we determined that the area under the curve of total LDH level was 0.87 (95% confidence interval 0.74-1.00) and that the discriminatory accuracy was high for total LDH and all isozymes. By stepwise binary logistic regression analysis considering MeV-specific IgG avidity, we developed a model using IgG, IgM, and total LDH as explanatory variables, which was optimal for distinguishing the LA and HA groups (adjusted R2 : 0.773, p < 0.001). Thus, the serum LDH level in addition to IgM and IgG may be useful parameters for differentiating MeV reinfection from primary infection. This article is protected by copyright. All rights reserved.

11.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-49069

RESUMO

Após a campanha de vacinação para a proteção das crianças e profissionais de saúde contra o sarampo, a vacina tríplice viral segue disponível nas unidades de saúde e faz parte do Calendário Nacional de Vacinação.


Assuntos
Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Programas de Imunização
12.
Front Pediatr ; 10: 896086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813375

RESUMO

Objectives: Post-measles increased susceptibility to subsequent infections seems particularly relevant in low-resource settings. We tested the hypothesis that measles causes a specifically increased rate of infections in children, also in a high-resource setting. Methods: We conducted a retrospective cohort study on a large measles outbreak in Berlin, Germany. All children with measles who presented to hospitals in Berlin were included as cases, children with non-infectious and children with non-measles infectious diseases as controls. Repeat visits within 3 years after the outbreak were recorded. Results: We included 250 cases, 502 non-infectious, and 498 infectious disease controls. The relative risk for cases for the diagnosis of an infectious disease upon a repeat visit was 1.6 (95% CI 1.4-2.0, p < 0.001) vs. non-infectious and 1.3 (95% CI 1.1-1.6, p = 0.002) vs. infectious disease controls. 33 cases (27%), 35 non-infectious (12%) and 57 (18%) infectious disease controls presented more than three times due to an infectious disease (p = 0.01, and p = 0.02, respectively). This results in a relative risk of more than three repeat visits due to an infection for measles cases of 1.8 (95% CI 1.3-2.4, p = 0.01), and 1.4 (95% CI 1.0-1.9, p = 0.04), respectively. Conclusion: Our study demonstrates for the first time in a high-resource setting, that increased post-measles susceptibility to subsequent infections in children is measles-specific-even compared to controls with previous non-measles infections.

13.
Curr Res Chem Biol ; 2: 100021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35815068

RESUMO

Viral diseases are prominent among the widely spread infections threatening human well-being. Real-life clinical successes of the few available therapeutics are challenged by pathogenic resistance and suboptimal delivery to target sites. Nanotechnology has aided the design of functionalised and non-functionalised Au and Ag nanobiomaterials through physical, chemical and biological (green synthesis) methods with improved antiviral efficacy and delivery. In this review, innovative designs as well as interesting antiviral activities of the nanotechnology-inclined biomaterials of Au and Ag, reported in the last 5 years were critically overviewed against several viral diseases affecting man. These include influenza, respiratory syncytial, adenovirus, severe acute respiratory syndromes (SARS), rotavirus, norovirus, measles, chikungunya, HIV, herpes simplex virus, dengue, polio, enterovirus and rift valley fever virus. Notably identified among the nanotechnologically designed promising antiviral agents include AuNP-M2e peptide vaccine, AgNP of cinnamon bark extract and AgNP of oseltamivir for influenza, PVP coated AgNP for RSV, PVP-AgNPs for SARS-CoV-2, AuNRs of a peptide pregnancy-induce d hypertension and AuNP nanocarriers of antigen for MERS-CoV and SARS-CoV respectively. Others are AgNPs of collagen and Bacillus subtilis for rotavirus, AgNPs labelled Ag30-SiO 2 for murine norovirus in water, AuNPs of Allium sativum and AgNPs of ribavirin for measles, AgNPs of Citrus limetta and Andrographis Paniculata for Chikungunya, AuNPs of efavirenz and stavudine, and AgNPs-curcumin for HIV, NPAuG3-S8 for HSV, AgNPs of Moringa oleifera and Bruguiera cylindrica for dengue while AgNPs of polyethyleneimine and siRNA analogues displayed potency against enterovirus. The highlighted candidates are recommended for further translational studies towards antiviral therapeutic designs.

14.
EClinicalMedicine ; 50: 101500, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35784436

RESUMO

Background: Cost-effective demand-side interventions are needed to increase childhood immunization. Multiple studies find tying income support programs (≥USD 50 per year) to immunization raises coverage. Research on maximizing impact from small mobile-based conditional cash transfers (mCCTs) (≤USD 15 per fully immunized child) delivered in lower-income settings remains sparse. Methods: Participants in Karachi, Pakistan, were individually randomized into a seven arm, factorial open label study with five mCCT arms, one reminder (SMS) only arm, and one control arm. The mCCT arms varied by amount (high ∼USD 15 per fully immunized child versus low ∼USD 5 per fully immunized child), schedule (flat versus rising payments over the schedule), design (certain versus lottery payments), and payment method (airtime or mobile money). Children were enrolled at BCG, pentavalent-1 (penta-1) or pentavalent-2 (penta-2) vaccination and followed until at least 18 months of age. A serosurvey in 15% sub-sample validated reported study coverage. The full immunization coverage (FIC) at 12 months (primary outcome) was analyzed using logit regression. ClinicalTrials.gov (NCT03355989), 3ie registry (58f6ee7725fc1), and AEA RCT Registry (AEARCTR-0001953). Findings: Between November 6, 2017, and October 10, 2018, a total of 11,197 caregiver-child pairs were enrolled, with 1598-1600 caregiver-child pairs per arm. FIC at 12 months was statistically significantly higher for any mCCT versus SMS (OR:1.18, 95% CI: 1.05-1.33; p = 0.005). Within the mCCT arms, FIC was statistically significantly higher for high versus low amount (OR: 1.16, 95% CI: 1.04-1.29; p = 0.007), certain versus lottery payment (OR: 1.30, 95% CI: 1.17-1.45; p < 0.001) and airtime versus mobile money (OR: 1.17, 95% CI:1.01-1.36; p = 0.043). There was no statistically significant difference between a flat and increasing schedule (OR: 1.03, 95% CI: 0.93-1.15; p = 0.550). SMS had a marginally statistically significant impact on FIC versus control (OR: 1.16, 95% CI: 1.00-1.35; p = 0.046). Findings were similar for up-to-date coverage of penta-3, measles-1 and measles-2 at 18 months. Interpretation: Small mCCTs (USD 0.8-2.4 per immunization visit) can increase FIC at 12 months and up-to-date coverage at 18 months at USD 23 per additional fully immunized child, in resource-constrained settings like Pakistan. Design details (certainty, schedule and delivery method of mCCTs) matter as much as the size of payments. Funding: Global Innovation Fund, GiveWell.

15.
J Pediatr Nurs ; 66: 191-195, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35835017

RESUMO

OBJECTIVES: The objective was to analyze in silico public search interest during the COVID-19 pandemic for some classic infectious childhood diseases, e.g., measles, mumps, chickenpox, scarlet fever, and inflammatory diseases like Kawasaki disease and the pediatric inflammatory multisystem syndrome (PIMS). STUDY DESIGN: In this study, a comparison of five childhood diseases in public search trends with the pediatric inflammatory multisystem syndrome was performed. METHODS: Google Trends data for the period of five years for six childhood diseases were used. We used topics coverings all languages worldwide and all connected search queries. RESULTS: Public search interest decreased during the COVID-19 pandemic for some classic infectious childhood diseases. Search interest for the pediatric inflammatory multisystem syndrome, despite strong indication of a connection with COVID-19, remained relatively low compared to Kawasaki disease. PRACTICE IMPLICATIONS: Better understanding of Google Trends can map public awareness of childhood diseases in terms of time course and search intensity. CONCLUSIONS: Public interest during the pandemic was generated for diseases with suspected connection to COVID-19, presumably due to media triggers.

16.
Sci Prog ; 105(2): 368504221105172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35848578

RESUMO

Despite the development and deployment of effective COVID-19 vaccines, many regions remain poorly covered. Seeking alternative tools for achieving immunity against COVID-19 remains to be of high importance. "Trained immunity" is the nonspecific immune response usually established through administering live attenuated vaccines and is a potential preventive tool against unrelated infections. Evidence regarding a possible protective role for certain live attenuated vaccines against COVID-19 has emerged mainly for those administered as part of childhood vaccination protocols. This review summarizes the relevant literature about the potential impact of Bacille Calmette-Guérin (BCG) and measles, mumps and rubella (MMR) vaccines on COVID-19. Existing available data suggest a potential role for BCG and MMR in reducing COVID-19 casualties and burden. However, more investigation and comparative studies are required for a better understanding of their impact on COVID-19 outcomes.


Assuntos
COVID-19 , Caxumba , Rubéola (Sarampo Alemão) , Vacina BCG/uso terapêutico , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Humanos , Vacina contra Sarampo-Caxumba-Rubéola/uso terapêutico , Caxumba/epidemiologia , Caxumba/prevenção & controle , Rubéola (Sarampo Alemão)/prevenção & controle , Vacinação , Vacinas Atenuadas/uso terapêutico
17.
Autophagy ; 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35900944

RESUMO

Although it is admitted that secondary infection can complicate viral diseases, the consequences of viral infection on cell susceptibility to other infections remain underexplored at the cellular level. We though to examine whether the sustained macroautophagy/autophagy associated with measles virus (MeV) infection could help cells oppose invasion by Salmonella Typhimurium, a bacterium sensitive to autophagic restriction. We report here the unexpected finding that Salmonella markedly replicated in MeV-infected cultures due to selective growth within multinucleated cells. Hyper-replicating Salmonella localized outside of LAMP1-positive compartments to an extent that equaled that of the predominantly cytosolic sifA mutant Salmonella. Bacteria were subjected to effective ubiquitination but failed to be targeted by LC3 despite an ongoing productive autophagy. Such a phenotype could not be further aggravated upon silencing of the selective autophagy regulator TBK1 or core autophagy factors ATG5 or ATG7. MeV infection also conditioned primary human epithelial cells for augmented Salmonella replication. The analysis of selective autophagy receptors able to target Salmonella revealed that a lowered expression level of SQSTM1/p62 and TAX1BP1/T6BP autophagy receptors prevented effective anti-Salmonella autophagy in MeV-induced syncytia. Conversely, as SQSTM1/p62 is promoting the cytosolic growth of Shigella flexneri, MeV infection led to reduced Shigella replication. The results indicate that the rarefaction of dedicated autophagy receptors associated with MeV infection differentially affects the outcome of bacterial coinfection depending on the nature of the functional relationship between bacteria and such receptors. Thus, virus-imposed reconfiguration of the autophagy machinery can be instrumental in determining the fate of bacterial coinfection.

18.
Vaccine X ; 11: 100190, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35899104

RESUMO

Background: The combination of whole-cell pertussis (wP) antigens with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens provides a high-quality DTwP-IPV-HB-PRP∼T vaccine. This study evaluated a DTwP-IPV-HB-PRP∼T booster coadministered with measles, mumps, and rubella (MMR) vaccine. Methods: Phase II, open-label, randomized study. Healthy toddlers who had previously completed a DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV primary vaccination series received a DTwP-IPV-HB-PRP∼T booster vaccine at 12-24 months of age. All participants had also received 1 or 2 doses of measles-containing vaccine between primary vaccination and enrolment (N = 100 and N = 6, respectively). Those who had received 1 prior measles-containing vaccine received an MMR dose either concomitantly (N = 50) or 28 days after (N = 50) the DTwP-IPV-HB-PRP∼T booster. Immunogenicity was evaluated using validated assays and safety by parental reports. Results: Pre-booster vaccination, 100.0% participants showed antibody persistence after DTwP-IPV-HB-PRP∼T or DTwP-HB-PRP∼T and IPV for anti-T (≥0.01 IU/mL), anti-Hib (≥0.15 µg/mL), and anti-polio 3 (≥8 1/dil) and at least 95.8% of participants for anti-D (≥0.01 IU/mL), anti-HB (≥10 mIU/mL), and anti-polio 1 and 2 (≥8 1/dil). For the pertussis antigens, pre-booster antibody persistence (≥2 EU/mL) ranged from 88.6 to 88.7% (anti-PT), 91.4-98.6% (anti-FHA), 69.0-74.3% (anti-PRN), and 97.1-97.2% (anti-FIM). For the booster response, seroprotection based on either the primary series or measles-containing vaccination regimen was 100.0% for anti-D and anti-T (≥0.01 IU/mL and ≥0.10 IU/mL), anti-HB (≥10 mIU/mL and ≥100 mIU/mL), anti-Hib (≥0.15 µg/mL and ≥1 µg/mL) and anti-polio 1, 2, and 3 (≥8 1/dil), and for the pertussis antigens booster response ranged from 88.6 to 91.8% (anti-PT), 91.1-95.9% (anti-FHA), 88.6-93.9% (anti-PRN), and 95.9-98.6% (anti-FIM). There were no safety concerns in any group. Conclusions: This study showed good antibody persistence of the DTwP-IPV-HB-PRP∼T vaccine and good immunogenicity and safety of a booster dose given with MMR in the second year of life.Clinical Trials Registry India Number: CTRI/2018/04/013375.

19.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(7): 994-1003, 2022 Jul 06.
Artigo em Chinês | MEDLINE | ID: mdl-35899355

RESUMO

Objective: To systematically analyze the IgG seroprevalence of mumps virus (MuV) in Chinese healthy population, and evaluate the immune effect based on the immunization strategy and the incidence of mumps in China. Methods: The databases of Wanfang data knowledge service platform, China National Knowledge Infrastructure, SinoMed, PubMed, and Web of Science were searched to retrieve literature about the level of MuV IgG antibody in Chinese healthy population from January 1, 2000, to March 31, 2022. The quality of eligible papers was appraised by using the cross-sectional study evaluation tool from Joanna Briggs Institute. Data analysis, including the stratified analysis of the IgG seroprevalence in different generations, regions, gender, immunization status, and age groups, was performed using R 4.1.2 and Stata 16.0. Results: A total of 69 papers (66 in Chinese and 3 in English) were included, involving 97 034 people in 26 administrative regions across China. The results showed that the MuV IgG seroprevalence in Chinese healthy population was 74.87% (95%CI: 71.41%-78.17%) and increased over time according to the cumulative Meta-analysis. The geometric mean concentration of antibody was 177.83 U/ml. The subgroup analysis showed that the positive rate of MuV IgG antibody increased with the age and vaccination doses. The positive rate of antibody in children aged from 0 to 17 months was only 32.42% (95%CI: 25.96%-38.88%). The highest positive rate was reported in North China, about 81.45% (95%CI: 75.76%-87.14%). In addition, the positive rate of MuV IgG antibody in urban population was higher than that in rural population (P<0.01) and the positive rate of MuV IgG antibody in women was higher than that in men (P<0.01). Conclusion: Since the vaccine was included in the expanded immunization program, the positive rate of mumps antibody in China has increased, and the antibody level varies in different regions and populations. It is still necessary to improve the MuV antibody level in Chinese healthy population, so as to better prevent and control the mumps epidemic in the future.


Assuntos
Vírus da Caxumba , Caxumba , Anticorpos Antivirais , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Imunoglobulina G , Masculino , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/epidemiologia , Caxumba/prevenção & controle , Estudos Soroepidemiológicos , Vacinação
20.
Nat Commun ; 13(1): 4064, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831325

RESUMO

Here, we study the gamete fusogen HAP2 from Cyanidioschyzon merolae (Cyani), an extremophile red algae that grows at acidic pH at 45 °C. HAP2 has a trimeric postfusion structure with similarity to viral class II fusion proteins, but its prefusion structure has been elusive. The crystal structure of a monomeric prefusion state of Cyani HAP2 shows it is highly extended with three domains in the order D2, D1, and D3. Three hydrophobic fusion loops at the tip of D2 are each required for postfusion state formation. We followed by negative stain electron microscopy steps in the process of detergent micelle-stimulated postfusion state formation. In an intermediate state, two or three linear HAP2 monomers associate at the end of D2 bearing its fusion loops. Subsequently, D2 and D1 line the core of a trimer and D3 folds back over the exterior of D1 and D2. D3 is not required for formation of intermediate or postfusion-like states.


Assuntos
Extremófilos , Proteínas do Envelope Viral , Extremófilos/metabolismo , Células Germinativas/metabolismo , Conformação Proteica , Proteínas do Envelope Viral/metabolismo , Proteínas Virais de Fusão/metabolismo
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