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1.
Microbiol Spectr ; : e0101721, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787487

RESUMO

A big challenge for the control of COVID-19 pandemic is the emergence of variants of concern (VOCs) or variants of interest (VOIs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may be more transmissible and/or more virulent and could escape immunity obtained through infection or vaccination. A simple and rapid test for SARS-CoV-2 variants is an unmet need and is of great public health importance. In this study, we designed and analytically validated a CRISPR-Cas12a system for direct detection of SARS-CoV-2 VOCs. We further evaluated the combination of ordinary reverse transcription-PCR (RT-PCR) and CRISPR-Cas12a to improve the detection sensitivity and developed a universal system by introducing a protospacer adjacent motif (PAM) near the target mutation sites through PCR primer design to detect mutations without PAM. Our results indicated that the CRISPR-Cas12a assay could readily detect the signature spike protein mutations (K417N/T, L452R/Q, T478K, E484K/Q, N501Y, and D614G) to distinguish alpha, beta, gamma, delta, kappa, lambda, and epsilon variants of SARS-CoV-2. In addition, the open reading frame 8 (ORF8) mutations (T/C substitution at nt28144 and the corresponding change of amino acid L/S) could differentiate L and S lineages of SARS-CoV-2. The low limit of detection could reach 10 copies/reaction. Our assay successfully distinguished 4 SARS-CoV-2 strains of wild type and alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) variants. By testing 32 SARS-CoV-2-positive clinical samples infected with the wild type (n = 5) and alpha (n = 11), beta (n = 8), and delta variants (n = 8), the concordance between our assay and sequencing was 100%. The CRISPR-based approach is rapid and robust and can be adapted for screening the emerging mutations and immediately implemented in laboratories already performing nucleic acid amplification tests or in resource-limited settings. IMPORTANCE We described CRISPR-Cas12-based multiplex allele-specific assay for rapid SARS-CoV-2 variant genotyping. The new system has the potential to be quickly developed, continuously updated, and easily implemented for screening of SARS-CoV-2 variants in resource-limited settings. This approach can be adapted for emerging mutations and implemented in laboratories already conducting SARS-CoV-2 nucleic acid amplification tests using existing resources and extracted nucleic acid.

2.
Front Microbiol ; 12: 729016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650533

RESUMO

A longitudinal serological study to investigate the seropositive frequency, incidence, and antibody dynamics of Chlamydia trachomatis infection in the general population of China is urgently needed in order to optimize the strategies for surveillance and precise prevention of C. trachomatis infection. This longitudinal study enrolled 744 subjects aged 18-65 years from Jidong Community of Northern China from 2014 to 2018. Seropositive frequency, incidence, and reinfection of C. trachomatis were determined by detecting antibody against C. trachomatis Pgp3 using "in-house" luciferase immunosorbent assay (LISA). The dynamic of anti-Pgp3 antibody was analyzed using the Generalized Estimating Equation (GEE) model. The overall Pgp3 seropositive frequency among the 18-65-year-old population was 28.1% (95% CI 24.9-31.5), and significantly increased from 12.0% in those aged 18-29 years to 48.6% in the 60-65 years old. The seropositive frequency was slightly higher in women than in men (31.3% vs. 25.4%) without statistical significance. The C. trachomatis incidence and reinfection rate were 11 and 14 per 1,000 person-years, respectively, and showed no significant difference with respect to age, gender, ethnicity, marital status, and education levels. Furthermore, anti-Pgp3 antibody remained detectable in 93.3% (195/209) of the seropositive subjects during the 5 years of follow-up. The overall decay rate for anti-Pgp3 antibody for CT-infected persons was -0.123 Log2 RLU/year, which was dramatically slower than in CT new infection (-3.34 Log2 RLU/year) or reinfection (-1.1 Log2 RLU/year). In conclusion, at least one quarter of the people aged 18-65 years have been infected with C. trachomatis over their lifetime while all age groups are susceptible to C. trachomatis infection in the community of Northern China. Therefore, comprehensive prevention strategies are urgently needed.

3.
J Invest Dermatol ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662561

RESUMO

Sexually transmitted infections such as Chlamydia trachomatis can enhance HIV-1 infection. However, the molecular mechanisms modulating the enhancement of HIV-1 infectivity and replication during HIV-1/sexually transmitted infections coinfection remain elusive. In this study, we performed an ex vivo infection of HIV-1 in PBMCs of C. trachomatis‒infected patients and observed a significant increase in HIV-1 p24 levels compared with those in cells from healthy donors. Similarly, C. trachomatis‒stimulated PBMCs from healthy donors showed enhanced susceptibility to HIV-1. C. trachomatis‒stimulated CD4 T cells also harbored more HIV-1 copy numbers. RNA sequencing data revealed the upregulation of CCL3L1/CCL3L3, a paralog of CCL3 in C. trachomatis‒stimulated CD4 T cells infected with HIV-1. Furthermore, an increase in CCL3L1/CCL3L3 expression levels correlated with HIV-1 replication in C. trachomatis‒stimulated cells. However, the addition of exogenous CCL3L1 reduces HIV-1 infection of healthy cells, indicating a dual role of CCL3L1 in HIV-1 infection. Further investigation revealed that a knockout of CCL3L1/CCL3L3 in Jurkat T cells rescued the increased susceptibility of C. trachomatis‒stimulated cells to HIV-1 infection. These results reveal a role for CCL3L1/CCL3L3 in enhancing HIV-1 replication and production and highlight a mechanism for the enhanced susceptibility to HIV-1 among C. trachomatis‒infected patients.

4.
Front Cell Infect Microbiol ; 11: 728415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466405

RESUMO

Background: The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms. Methods: Intrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA). Results: Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV. Conclusion: This study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.


Assuntos
Infecções por Flaviviridae , Hepatite C Crônica , Hepatite C , Antivirais , Estudos Transversais , Infecções por Flaviviridae/complicações , Hepacivirus/genética , Hepatite C/complicações , Humanos , Pegivirus , Filogenia , RNA Viral
5.
ChemSusChem ; 14(19): 3981, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34519414

RESUMO

Invited for this month's cover is the collaborative group of Dr. Carol Sze Ki Lin and Dr. Xiang Wang. The image illustrates the biodegradation of plastics and the potential for plastic waste recycling and valorization to address the plastic waste dilemma. The Minireview itself is available at 10.1002/cssc.202100752.

6.
Front Microbiol ; 12: 703145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335535

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuously mutating since its first emergence in early 2020. These alterations have led this virus to gain significant difference in infectivity, pathogenicity, and host immune evasion. We previously found that the open-reading frame 8 (ORF8) of SARS-CoV-2 can inhibit interferon production by decreasing the nuclear translocation of interferon regulatory factor 3 (IRF3). Since several mutations in ORF8 have been observed, therefore, in the present study, we adapted structural and biophysical analysis approaches to explore the impact of various mutations of ORF8, such as S24L, L84S, V62L, and W45L, the recently circulating mutant in Pakistan, on its ability to bind IRF3 and to evade the host immune system. We found that mutations in ORF8 could affect the binding efficiency with IRF3 based on molecular docking analysis, which was further supported by molecular dynamics simulations. Among all the reported mutations, W45L was found to bind most stringently to IRF3. Our analysis revealed that mutations in ORF8 may help the virus evade the immune system by changing its binding affinity with IRF3.

7.
Virus Res ; 303: 198505, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34271038

RESUMO

Human immunodeficiency virus type one (HIV-1) infection is one of the major public health problems worldwide. Effective control of HIV-1 epidemic relies on early diagnosis of HIV-1 infection by using simple, rapid point-of-care test (POCT). An integrated assay was developed and evaluated in this study to combine a real-time isothermal reverse-transcription recombinase-aided amplification (rRT-RAA) and CRISPR Cas12a-mediated detection for HIV-1. The testing results could be directly observed with naked eye using a blue light imager, making it a suitable on-site testing assay. Our preliminary data indicated that the assay was capable of detecting 20 copies of purified HIV-1 DNA or RNA per reaction or as low as 123 copies/ml of HIV-1 viral load in clinical samples. When screening 155 clinical samples with or without HIV-1 infection, the sensitivity and specificity of the rRT-RAA assay were 98.95% (94/95) and 100% (60/60), respectively. The coefficient value was 0.986 when compared with the Chinese FDA approved HIV-1 RT-qPCR assay. Furthermore, the newly developed HIV-1 rRT-RAA assay could detect the major HIV-1 genotypes CRF01_AE, CRF07_BC, CRF08_BC, CRF08_BC and subtype B in China. Our preliminary results indicated that the rRT-RAA assay or its combination with CRISPR Cas12a-mediated detection could serve as a rapid, convenient, and robust assay for HIV-1 detection.

8.
Front Med (Lausanne) ; 8: 662689, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307399

RESUMO

Objectives: The objectives of this study were to distinguish the role of men who have sex with men (MSM) with or without syphilis testing in HIV-1 transmission and to provide molecular evidence of syphilis testing as a proxy marker for identifying the subgroup of MSM. Methods: HIV-1 transmission clusters were constructed by HIV-TRACE and Cluster Picker using HIV-1 pol sequences from 729 newly diagnosed HIV-infected MSM from 2008 to 2012 in Guangzhou, China. The role of MSM in HIV-1 transmission networks was determined by a node influence measurement and centrality analysis. The association between syphilis testing and factors related to HIV-1 transmission and antiretroviral treatment (ART) were analyzed by the Cox regression model. Results: Among HIV-infected MSM, 56.7% did not test for syphilis at the time of HIV-1 diagnosis. MSM without syphilis testing was a specific subgroup of MSM with a larger closeness centrality and clustering coefficient than the recipients of syphilis testing (P < 0.001), indicating their central position in the HIV-1 transmission networks. The median degree and radiality within HIV-1 transmission networks as well as the median K-shell scores were also greater for MSM without syphilis testing (P < 0.001), suggesting their relatively greater contribution in transmitting HIV-1 than the receipts of syphilis testing. MSM with syphilis testing usually did not disclose their occupation or were more likely to be unemployed or to take non-skilled jobs, to have a history of sexually transmitted infections (STIs), and to be AIDS patients when diagnosed with HIV-1 infection (P < 0.05). Multivariable Cox regression analysis indicated that syphilis testing per se did not promote the engagement of ART (P = 0.233) or affect the speed of CD4+ T cell count recovery after treatment (P = 0.256). Conclusions: Our study identifies syphilis testing as a proxy marker of a specific subgroup of HIV-infected MSM who refuse syphilis testing during HIV-1 diagnosis with an important role in HIV-1 transmission. Specific prevention and intervention targeting MSM without syphilis testing during HIV-1 care are urgently needed.

9.
ChemSusChem ; 14(19): 4103-4114, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34137191

RESUMO

Although fossil-based plastic products have many attractive characteristics, their production has led to severe environmental burdens that require immediate solutions. Despite these plastics being non-natural chemical compounds, they can be degraded and metabolized by some microorganisms, which suggests the potential application of biotechnologies based on the mechanism of plastic biodegradation. In this context, microbe-based strategies for the degradation, recycling, and valorization of plastic waste offer a feasible approach for alleviating environmental challenges created by the accumulation of plastic waste. This Minireview highlights recent advances in the biotechnology-based biodegradation of both traditional polymers and bio-based plastics, focusing on the mechanisms of biodegradation. From an application perspective, this Minireview also summarizes recent progress in the recycling and valorization of plastic waste, which are feasible solutions for tackling the plastic waste dilemma.

10.
Infect Genet Evol ; 92: 104870, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33901684

RESUMO

BACKGROUND: Post-migration infection and domestic transmission of HIV-1 between immigrants and local population are critical for the HIV epidemic, but have not been addressed thus far in China. METHODS: Transmission clusters were analyzed with two cluster reconstruction methods, HIV-TRACE and Cluster Picker, using 1695 HIV-1 pol sequences obtained from 139 HIV-infected foreigners and 1556 Chinese natives in Guangzhou, China from 2008 to 2012. The geographic origin of the HIV-1 sequences was further determined by PastML while the factors associated with recent HIV-1 transmission were documented by logistic regression analysis. RESULTS: HIV-1 genotypes that are prevalent in African and East Asian countries were identified in HIV-infected Chinese subjects and vice versa. In addition, more NRTI drug resistance mutations were found in HIV-infected foreigners than in native Chinese (p < 0.001). HIV-1 transmission between HIV-infected foreigners and native Chinese individuals was documented in 12.95% (18/139) of the HIV-infected foreigners. Furthermore, Asian (odds ratio [OR] = 3.45), male (OR = 16.88) and those with known HIV-1 infection routes (OR = 3.23) were more likely associated with recent HIV-1 transmission in China. The Chinese natives linked to recent HIV-1 transmission were more likely to be infected through men who have sex with men (OR = 3.05) or people who inject drugs (OR = 3.05), rather than by heterosexual transmission. CONCLUSION: Our study demonstrates the impact of recent HIV-1 transmission between HIV-infected foreigners and Chinese natives on the HIV-1 epidemic in Guangzhou, China. Moreover, the results highlight the importance of phylogenetic analysis of HIV-1 surveillance data and the need for specific prevention strategies that target the immigrant population.

11.
Front Immunol ; 12: 609421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767695

RESUMO

Chimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.


Assuntos
Antígeno de Maturação de Linfócitos B/imunologia , Quimiocina CCL19/biossíntese , Imunoterapia Adotiva , Interleucina-7/biossíntese , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Idoso , Animais , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Feminino , Ordem dos Genes , Vetores Genéticos/genética , Humanos , Memória Imunológica , Imunofenotipagem , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Camundongos , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Recidiva , Retratamento , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Virol Methods ; 292: 114141, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33753172

RESUMO

In this study, we developed and evaluated a luciferase immunosorbent assay (LISA) for quantitative detection of IgG antibody against SARS-CoV-2 nucleoprotein (NP). Anti-SARS-CoV-2 NP antibody in serum or plasma samples was captured by protein G-coated microtiter plate and detected using the crude cell lysates expressing Nanoluc luciferase (Nluc) enzyme fused with SARS-CoV-2 NP. After the addition of furimazine substrate, the levels of anti-SARS-CoV-2 NP IgG antibody were quantitatively measured as luciferase light units. As expected, SARS-CoV-2 NP showed cross-reactivity with the monoclonal antibodies against SARS-CoV NP, but not MERS-CoV NP-specific monoclonal antibodies or the monoclonal antibodies against SARS-CoV Spike protein. LISA for detecting murine monoclonal antibody against SARS-CoV NP showed a low limit of detection of 0.4 pg/µl and linear detection range from 0.4 pg/µl to 75 pg/µl. Furthermore, LISA had a sensitivity of 71 % when testing COVID-19 patients at the second week post onset and a specificity of 100 % when testing healthy blood donors.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Proteínas do Nucleocapsídeo/imunologia , SARS-CoV-2/imunologia , Anticorpos Monoclonais/imunologia , Reações Cruzadas , Humanos , Luciferases
13.
Virus Res ; 296: 198350, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33626380

RESUMO

The open reading frame 8 (orf8) is an accessory protein of SARS-CoV-2. It has 121 amino acids with two genotypes, orf8L and orf8S. In this study, we overexpressed the orf8L and orf8S of SARS-CoV-2 as well as the orf8b of SARS-CoV to investigate their roles in the regulation of endoplasmic reticulum (ER) stress and the inhibition of interferon beta (IFNß) production. We found that the two genotypes of SARS-CoV-2 orf8 are capable of inducing ER stress without significant difference by triggering the activating transcription factor 6 (ATF6) and inositol-requiring enzymes 1 (IRE1) branches of the ER stress pathway. However, the third branch of ER stress pathway, i.e. the protein kinase-like ER kinase (PERK), was unaffected by the overexpression of SARS-CoV-2 orf8L or orf8S. Moreover, both orf8L and orf8S of SARS-CoV-2 are capable of down regulating the production of IFNß and interferon-stimulated genes (ISG), ISG15 and ISG56 induced by polyinosinic-polycytidylic acid (poly (I:C)). Moreover, we also found decreased nuclear translocation of Interferon regulatory factor 3 (IRF3), after overexpressing orf8L and orf8S induced by poly (I:C). Our data demonstrated that SARS-CoV-2 orf8 protein could induce ER stress by activating the ATF6 and IRE1 pathways, but not the PERK pathway, and functions as an interferon antagonist to inhibit the production of IFNß. However, these functions appeared not to be affected by the genotypes of SARS-CoV-2 orf8L and orf8S.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Evasão da Resposta Imune , Interferon beta/antagonistas & inibidores , Proteínas Virais/fisiologia , Fator 6 Ativador da Transcrição/fisiologia , Endorribonucleases/fisiologia , Células HEK293 , Humanos , Interferon beta/biossíntese , Proteínas Serina-Treonina Quinases/fisiologia , Alinhamento de Sequência , Transdução de Sinais/fisiologia , Resposta a Proteínas não Dobradas , Proteínas Virais/química , Proteína 1 de Ligação a X-Box/fisiologia , eIF-2 Quinase/fisiologia
14.
BMC Microbiol ; 21(1): 3, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397284

RESUMO

BACKGROUND: Chlamydia trachomatis is the most common sexually transmitted infection and the bacterial agent of trachoma globally. C. trachomatis undergoes a biphasic developmental cycle involving an infectious elementary body and a replicative reticulate body. Little is currently known about the gene expression dynamics of host cell mRNAs, lncRNAs, and miRNAs at different stages of C. trachomatis development. RESULTS: Here, we performed RNA-seq and miR-seq on HeLa cells infected with C. trachomatis serovar E at 20 h post-infection (hpi) and 44 hpi with or without IFN-γ treatment. Our study identified and validated differentially expressed host cell mRNAs, lncRNAs, and miRNAs during infection. Host cells at 20 hpi showed the most differential upregulation of both coding and non-coding genes while at 44 hpi in the presence of IFN-γ resulted in a dramatic downregulation of a large proportion of host genes. Using RT-qPCR, we validated the top 5 upregulated mRNAs and miRNAs, which are specific for different stages of C. trachomatis development. One of the commonly expressed miRNAs at all three stages of C. trachomatis development, miR-193b-5p, showed significant expression in clinical serum samples of C. trachomatis-infected patients as compared to sera from healthy controls and HIV-1-infected patients. Furthermore, we observed significant upregulation of antigen processing and presentation, and T helper cell differentiation pathways at 20 hpi whereas T cell receptor, mTOR, and Rap1 pathways were modulated at 44 hpi. Treatment with IFN-γ at 44 hpi showed the upregulation of cytokine-cytokine receptor interaction, FoxO signaling, and Ras signaling pathways. CONCLUSIONS: Our study documented transcriptional manipulation of the host cell genomes and the upregulation of stage-specific signaling pathways necessary for the survival of the pathogen and could serve as potential biomarkers in the diagnosis and management of the disease.


Assuntos
Infecções por Chlamydia/genética , Chlamydia trachomatis/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Transdução de Sinais , Estudos de Casos e Controles , Infecções por Chlamydia/sangue , Chlamydia trachomatis/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/sangue , Infecções por HIV/genética , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Interferon gama/farmacologia , MicroRNAs/sangue , RNA Longo não Codificante/sangue , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
15.
Int J Infect Dis ; 104: 594-600, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33515775

RESUMO

OBJECTIVES: The moving epidemic method (MEM) has been well used for assessing seasonal influenza epidemics in temperate regions. This study used the MEM to establish epidemic threshold for influenza in Guangdong, a subtropical province in China. METHODS: Influenza virology surveillance data from 2011/2012 to 2017/2018 seasons in Guangdong were used with the MEM to calculate the epidemic thresholds and timeously detect the 2018/2019 influenza season epidemic. The weekly positive proportion of influenza A(H1N1)pdm09, A(H3N2), B/Victoria-lineage and B/Yamagata-lineage were separately adapted to calculate the subtype-specific epidemic thresholds. The performance of MEM was evaluated using a cross-validation procedure. RESULTS: For the 2018/2019 influenza season, the epidemic threshold of a weekly positive proportion was 15.08%. Epidemic detection for the 2018/2019 season was 1 week in advance. Influenza A(H1N1)pdm09, B/Yamagata-lineage and B/Victoria-lineage prevailed during winter and spring and their epidemic thresholds were 5.12%, 4.53% and 4.38%, respectively. Influenza A(H3N2) was active in the summer, with an epidemic threshold of 11.99%. CONCLUSIONS: Using influenza virology surveillance data stratified by types of influenza virus, the MEM was effectively used in Guangdong, China. This study provided a practical way for subtropical regions to establish local influenza epidemic thresholds.


Assuntos
Monitoramento Epidemiológico , Influenza Humana/epidemiologia , China/epidemiologia , Epidemias , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Influenza Humana/virologia , Modelos Teóricos , Estações do Ano
16.
Virology ; 551: 26-35, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33011520

RESUMO

BACKGROUND: SARS-CoV-2 is a novel coronavirus and the cause of COVID-19. More than 80% of COVID-19 patients exhibit mild or moderate symptoms. In this study, we investigated the dynamics of viral load and antibodies against SARS-CoV-2 in a longitudinal cohort of COVID-19 patients with severe and mild/moderate diseases. METHODS: Demographic and clinical information were obtained. Serial samples of blood, nasal and pharyngeal and anal swabs were collected at different time points post-onset. SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies were measured by qRT-PCR and immunoassays, respectively. RESULTS: Respiratory SARS-CoV-2 RNA was detectable in 58.0% (58/100) COVID-19 patients upon admission and lasted for a median of 13 days post-onset. In addition, 5.9% (1/17) and 20.2% (19/94) of the blood and anal swab specimens were positive for SARS-CoV-2 RNA, respectively. Anal viral RNA was more frequently detected in the patients who were positive for viral RNA in the respiratory samples upon admission. Specific anti-SARS-CoV-2 antibody developed within two weeks after onset, reached peak approximately 17 days post-onset and then maintained at relatively high level up to 50 days we analyzed in most patients. However, the levels of antibodies were variable among the patients. High titers of antibodies appeared to be associated with the severity of the disease. Furthermore, viral proteins from different sources showed significant difference of serological sensitivity especially during the first week post-onset. CONCLUSIONS: Our results indicate rapid clearance or self-elimination of viral RNA in about half of the COVID-19 patients upon admission. Viral RNA shedding of SARS-CoV-2 occurred in multiple tissues including the respiratory system, blood, and intestine. Variable levels of specific anti-SARS-CoV-2 antibody may be associated with disease severity. These findings have shed light on viral kinetics and antibody response in COVID-19 patients and provide scientific evidence for infection control and patient management.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Humanos , Cinética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , RNA Viral/análise , SARS-CoV-2/isolamento & purificação , Carga Viral , Eliminação de Partículas Virais
17.
Open Forum Infect Dis ; 7(5): ofaa154, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32500089

RESUMO

Background: Men who have sex with men (MSM) are vulnerable risk group for human immunodeficiency virus (HIV)-1 infection. However, some MSM do not disclose their same-sex behavior and could impact the transmission and prevention of HIV-1 infection. Here, we evaluated the role of nondisclosed MSM in HIV-1 transmission in Guangzhou, China. Methods: The HIV-1 pol sequences were obtained from HIV-infected subjects from 2008 to 2015. A transmission network was constructed using HIV TRAnsmission Cluster Engine (HIV-TRACE) at a pairwise genetic distance of 0.5%. The position of nondisclosed MSM in the network was determined by centrality analysis. Results: Nondisclosed MSM were inferred in 9.92% (61 of 615) of slightly older, self-reported non-MSM (P = .006). They were more likely to be married (P = .002) and less educated (P < .001) than the MSM with whom they clustered. Closeness centrality was bigger for nondisclosed MSM than for MSM (P < .001), indicating the central position of nondisclosed MSM in the networks. The average shortest path length was smaller for nondisclosed MSM than for MSM (P < .001), whereas radiality was bigger for nondisclosed MSM than for MSM, suggesting a relatively greater contribution of nondisclosed MSM in transmitting HIV-1 than MSM. Assortativity analysis indicated that nondisclosed MSM were more likely to link each other with coefficient of 0.025. Conclusions: Nondisclosed MSM are a specific group, and they play an important role in HIV-1 transmission. They could be bisexual and might increase the risk of HIV-1 infection to their sex partners. Therefore, specific prevention and intervention targeting nondisclosed MSM are urgently needed.

18.
J Clin Virol ; 128: 104414, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32417676

RESUMO

OBJECTIVE: Antiretroviral therapy (ART) can lead to a decline or absence of anti-HIV antibodies in HIV-infected children or acutely HIV-infected (AHI) subjects. However, the characteristics of anti-HIV antibody response in the subjects who are treated during chronic HIV-1 infection (CHI) have not yet been fully investigated. METHODS: Different anti-HIV antibodies were longitudinally quantified and analyzed in 81 CHI adults under ART. The factors associated with antibody decline were evaluated by binary logistic regression analysis. RESULTS: ART led to 36.0% (27/75) and 52.1% (38/73) of the patients whose anti-HIV levels reduced by more than 75% of the baseline levels at 12 and 24 months post-ART, respectively. The reduction of anti-HIV antibodies correlated with the decline of HIV-1 viral load with correlation coefficients in the range 0.556-0.848 or R2 value of 0.576-0.873 (P < 0.001). However, no negative detection of anti-HIV antibody was observed at 24 months post-ART. The time from HIV-1 diagnosis to ART initiation and the baseline anti-HIV levels were the key factors associated with quick decline of anti-HIV antibodies during ART. CONCLUSIONS: ART-induced kinetics of anti-HIV antibody response was different among the subjects with AHI and CHI. Misdiagnosis of HIV-1 infection may not be a serious issue in HIV-1 chronically infected subjects under ART, and could ideally be avoided by using multiple HIV-1 antigens for screening purposes.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Formação de Anticorpos/efeitos dos fármacos , Anticorpos Anti-HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doença Crônica/terapia , Estudos de Coortes , Feminino , HIV-1 , Humanos , Estudos Longitudinais , Masculino , Carga Viral , Adulto Jovem
19.
Front Microbiol ; 11: 827, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431682

RESUMO

Chlamydia trachomatis and human papillomavirus (HPV) are the most common pathogens of sexually transmitted infections (STIs), which can increase the risk of cervical cancer and infertility. The purpose of this study was to evaluate the prevalence, genotype and risk factors of C. trachomatis and/or HPV infection in women attending the annual physical examination, assistant reproductive treatment and visiting the gynecology clinics from Southern Hunan province in China. Cervical-swab samples were collected from 5006 participants. We found that the overall prevalence of C. trachomatis, HPV infection and C. trachomatis/HPV coinfection was 4.7% (236/5006), 15.5% (778/5006) and 1.2% (59/5006), while the prevalence of asymptomatic infection of that was 3.8% (38/1006), 10.8% (109/1006) and 0.6% (6/1006), respectively. Furthermore, 25.0% (59/236) of C. trachomatis infection and 7.6% (59/778) of HPV infection were attributable to C. trachomatis and HPV coinfection. C. trachomatis and HPV infection were more often observed in young women of less than 25 years (10.4% and 21.3%, respectively) and in the outpatients from gynecology clinics (5.2% and 18.0%, respectively). Of note, a higher prevalence of C. trachomatis infection was observed in HPV-positive women (7.6%) than HPV- negative ones (4.2%), and vice versa. The top three C. trachomatis genotypes were E (1.4%), F (1.1%) and J (0.8%), and the counterparts of HPV genotypes were HPV52 (4.2%), HPV16 (2.3%) and HPV58 (2.2%), respectively. Among the 151 outpatients with colposcopy data, HPV infection was associated with severe cervical lesions with OR of 15.86 (95% CI 3.14-80.0, P < 0.001) while C. trachomatis infection was more likely associated with a low grade colposcopy impression (OR = 3.25, 95% CI: 1.22-8.65, P = 0.018). Our data highlight the high prevalence of asymptomatic C. trachomatis and HPV infection, particularly among women of <25 years. The two pathogens may serve as mutual risk factors to increase the risk of infections and cervical lesions. Widespread implementation of HPV and C. trachomatis screening programs, especially for young women, would be an effective strategy to relieve the burden of sexually transmitted infections.

20.
BMC Infect Dis ; 20(1): 345, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410628

RESUMO

BACKGROUND: The prevalence of HIV/HCV/HBV/ Treponema pallidum is an essential health issue in China. However, there are few studies focused on foreigners living in China. This study aimed to assess the prevalence and socio-demographic distribution of HIV, HBV, HCV, and T. pallidum among foreigners in Guangzhou in the period of 2010-2017. METHODS: A cross-sectional study was conducted to screen serological samples of 40,935 foreigners from 2010 to 2017 at the Guangdong International Travel Health Care Center in Guangzhou. Samples were tested for hepatitis B surface antigen (HBsAg), anti-HCV, syphilis antibody (anti-TPPA) and anti-HIV 1 and 2. We collected secondary data from laboratory records and used multiple logistic regression analyses to verify the association between different factors and the seroprevalence of HIV/HBV/HCV/ T. pallidum. RESULTS: The prevalence of HBV/HCV/HIV/ T. pallidum was 2.30, 0.42, 0.02, and 0.60%, respectively, and fluctuated slightly for 7 years. The results of multiple logistic regression showed that males were less susceptible to HBV than females (odds ratio [OR] = 0.77, 95% CI: 0.67-0.89). Participants under the age of 20 had a lower risk of HBV (OR = 0.25, 95% CI: 0.18-0.35), HCV (OR = 0.06, 95% CI: 0.02-0.18), and T. pallidum (OR = 0. 10, 95% CI: 0.05-0.20) than participants over the age of 50. Participants with an education level below high school were more likely to have HBV (OR = 2.98, 95% CI: 1.89-4.70) than others, and businessmen (OR = 3.02, 95% CI: 2.03-4.49), and designers (OR = 3.83, 95% CI: 2.49-5.90) had a higher risk of T. pallidum than others. Co-infection involved 58 (4.20%) total cases, and the highest co-infection rate was observed for HBV and T. pallidum (2.60%). CONCLUSION: The prevalence of HBV/HCV/HIV/ T. pallidum was low among foreigners in Guangzhou. Region, gender, age, educational level, and occupation were risk factors for positive infection.


Assuntos
Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Doenças Sexualmente Transmissíveis/epidemiologia , Sífilis/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção/epidemiologia , Estudos Transversais , Emigrantes e Imigrantes , Feminino , HIV-1/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Socioeconômicos , Adulto Jovem
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