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This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus of great economic importance due to the million-dollar losses it generates in the pig industry. PEDV has many similarities to the SARS-CoV-2 betacoronavirus that causes COVID-19 disease. This review presents possible scenarios for SARS-CoV-2 based on the collected literature on PEDV and the tools or strategies currently developed for SARS-CoV-2 that would be useful in PEDV research. The speed of the study of SARS-CoV-2 and the generation of strategies to control the pandemic was possible due to the knowledge derived from infections caused by other human coronaviruses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Therefore, from the information obtained from several coronaviruses, the current and future behavior of SARS-CoV-2 could be inferred and, with the large amount of information on the virus that causes COVID-19, the study of PEDV could be improved and probably that of new emerging and re-emerging coronaviruses.
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COVID-19 , Vírus da Diarreia Epidêmica Suína , Humanos , Animais , Suínos , SARS-CoV-2RESUMO
During 2020-2023, Mexico had a large COVID-19 emergency with >331,000 adult deaths and one of the highest excess mortalities worldwide. Age at COVID-19 death has been lower in Mexico than in high-income countries, presumably because of the young demographics and high prevalence of chronic metabolic diseases in young and middle-aged adults. SARS-CoV-2 vaccination covered 85% of adults with at least one dose and 50% with booster(s) up to April 2022. No new vaccination efforts or updated boosters were introduced until October 2023; thus, we explored the public health impact of massive SARS-CoV-2 vaccination against ancestral strains and asked whether their real-world protection has persisted through time. We compared three periods with respect to vaccine roll-outs: before, during and after vaccine introduction in a national retrospective cohort of >7.5 million COVID-19 cases. The main findings were that after vaccination, COVID-19 mortality decreased, age at COVID-19 death increased by 5-10 years, both in populations with and without comorbidities; obesity stopped being a significant risk factor for COVID-19 death and protection against severe disease persisted for a year after boosters, including at ages 60-79 and 80+. Middle-aged adults had the highest protection from vaccines/hybrid immunity and they more than halved their proportions in COVID-19 deaths.
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Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) can be transmitted by blood transfusion. Most transmission occurs during the acute viremic phase (AVP), before antibody development. To reduce transmission risk, individual donor nucleic acid testing (ID-NAT) is used. In Puebla, Mexico, serological tests and ID-NAT have been applied to screen blood donors and detect individuals in AVP. In the present study, 106,125 blood donors' data in two periods (2012-2015 and 2017-2019) were analyzed. The residual risk (RR) values were calculated considering ID-NAT results. The RR for HIV was 14 in 1 million donations or 1 in 71,428, the RR for HVC was 6.8 in 1 million donations or 1 in 147,058 and, for HBV, it was 156 in 1 million donations, or 1 in 6410. Previously, it was predicted that the transmission RR of these viruses would be reduced in Mexico through better screening with NAT. The use of ID-NAT has, indeed, increased the safety of blood reserves for HIV and HCV. However, more research is needed to determine why the residual risk of HBV did not decrease as much over the study period. ID-NAT is an important complementary tool for blood donor screening that should be implemented.
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Infecções por HIV , HIV-1 , Hepatite B , Hepatite C , Humanos , Vírus da Hepatite B/genética , Hepacivirus/genética , Bancos de Sangue , México/epidemiologia , Centros de Atenção Terciária , HIV-1/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Doadores de Sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Viremia/diagnóstico , Doença Iatrogênica , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
Mexico, one of the countries severely affected by COVID-19, accumulated more than 5. 1 all-cause excess deaths/1,000 inhabitants and 2.5 COVID-19 confirmed deaths/1,000 inhabitants, in 2 years. In this scenario of high SARS-CoV-2 circulation, we analyzed the effectiveness of the country's vaccination strategy that used 7 different vaccines from around the world, and focused on vaccinating the oldest population first. We analyzed the national dataset published by Mexican health authorities, as a retrospective cohort, separating cases, hospitalizations, deaths and excess deaths by wave and age group. We explored if the vaccination strategy was effective to limit severe COVID-19 during the active outbreaks caused by Delta and Omicron variants. Vaccination of the eldest third of the population reduced COVID-19 hospitalizations, deaths and excess deaths by 46-55% in the third wave driven by Delta SARS-CoV-2. These adverse outcomes dropped 74-85% by the fourth wave driven by Omicron, when all adults had access to vaccines. Vaccine access for the pregnant resulted in 85-90% decrease in COVID-19 fatalities in pregnant individuals and 80% decrease in infants 0 years old by the Omicron wave. In contrast, in the rest of the pediatric population that did not access vaccination before the period analyzed, COVID-19 hospitalizations increased >40% during the Delta and Omicron waves. Our analysis suggests that the vaccination strategy in Mexico has been successful to limit population mortality and decrease severe COVID-19, but children in Mexico still need access to SARS-CoV-2 vaccines to limit severe COVID-19, in particular those 1-4 years old.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , México/epidemiologia , Estudos Retrospectivos , VacinaçãoRESUMO
Evidence suggests that SARS-CoV-2 entry into the central nervous system can result in neurological and/or neurodegenerative diseases. In this review, routes of SARS-Cov-2 entry into the brain via neuroinvasive pathways such as transcribrial, ocular surface or hematogenous system are discussed. It is argued that SARS-Cov-2-induced cytokine storm, neuroinflammation and oxidative stress increase the risk of developing neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Further studies on the effects of SARS-CoV-2 and its variants on protein aggregation, glia or microglia activation, and blood-brain barrier are warranted.
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BACKGROUND: Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy. METHODS: A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment. RESULTS: SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction. CONCLUSIONS: DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.
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BACKGROUND: Human brucellosis is a global health problem. Mexico is one of the main countries affected; timely diagnosis and serological tests are the basis for detection. AIM: To know the frequency of confirmed cases of brucellosis in different of Family Medicine Units of the Mexican Social Security Institute in the state of Puebla, Mexico. METHODS: Cross-sectional study in patients of both genders, adults and pediatrics, with clinical manifestations suggestive of brucellosis; serological tests were performed for the confirmatory diagnosis. RESULTS: Out of a total of 77 patients, 39 (50.6%) were positive, 21 (27.3%) cases coming out of infection, 9 (11.7%) were negative and 8 (10.4%) were defined with immunological memory; of positive cases, 32 (82.1%) were found in the adult group and 30 (76.9%) were female. CONCLUSION: Around half of samples were confirmed as brucellosis, the clinical manifestations of the patients studied were non-specific, which highlights the importance of laboratory diagnosis.
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Brucella , Brucelose , Adulto , Brucelose/diagnóstico , Brucelose/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , México/epidemiologia , Testes SorológicosRESUMO
The first cases of COVID-19, caused by the virus called SARS-CoV-2, were recorded in Wuhan, China, in December 2019; however, its transmission ability caused for the infection to be practically present throughout the world six months later. The origin of the virus appears to be zoonotic; it has been proposed that it comes from a bat and that it may have had an intermediate host that led to its introduction in the human population. SARS-CoV-2 is an enveloped virus, with a positive single-stranded RNA genome, and it binds to the angiotensin-converting enzyme, present in susceptible cells, to infect the human respiratory system. Although other coronaviruses have been previously known, they have not had the same impact, and, therefore, research on pharmacological treatments is not sufficiently developed to face the current challenge. Almost since the beginning of the epidemic, several molecules have been proposed for the treatment of infection; however, there is not yet a drug available with sufficient effectiveness for treatment. This review describes SARS-CoV-2 main characteristics, its replicative cycle, its possible origin and some advances in the development of antiviral treatments.
Los primeros casos de COVID-19, causada por el virus denominado SARS-CoV-2, se registraron en Wuhan, China, en diciembre de 2019; sin embargo, su capacidad de transmisión ocasionó que seis meses después la infección prácticamente estuviera presente en todo el mundo. El origen del virus parece ser zoonótico; se propone que proviene del murciélago y podría haber tenido un hospedero intermediario que llevó a su introducción en la población humana. SARS-CoV-2 es un virus envuelto, con genoma de ARN de cadena sencilla en sentido positivo y se ancla a la enzima convertidora de angiotensina, presente en las células susceptibles para infectar el sistema respiratorio de los humanos. Aunque previamente se han conocido otros coronavirus, no han tenido el mismo impacto, por lo que la investigación en tratamientos farmacológicos no tiene el desarrollo suficiente para afrontar el reto actual. Casi desde el comienzo de la epidemia se han propuesto moléculas para el tratamiento de la infección, sin embargo, aún no se cuenta con un fármaco con suficiente efectividad terapéutica. En esta revisión se describen las características principales de SARS-CoV-2, su ciclo replicativo, su posible origen y algunos avances en el desarrollo de tratamientos antivirales.
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Tratamento Farmacológico da COVID-19 , COVID-19/virologia , SARS-CoV-2/fisiologia , SARS-CoV-2/ultraestrutura , HumanosRESUMO
INTRODUCCIÓN: La brucelosis humana es un problema zoo-sanitario global. México es uno de los principales países que se ven afectados, el diagnóstico oportuno y las pruebas serológicas confirmatorias son la base para la detección. OBJETIVO: Conocer la frecuencia de casos confirmados de brucelosis en diferentes Unidades de Medicina Familiar del Instituto Mexicano del Seguro Social en el estado de Puebla, México. PACIENTES Y MÉTODOS: Estudio transversal en pacientes de ambos sexos, adultos y pediátricos, con manifestaciones clínicas sugestivas de brucelosis; se realizaron pruebas serológicas para el diagnóstico confirmatorio. RESULTADOS: De un total de 77 pacientes, se obtuvieron 39 (50,6%) casos positivos, 21 (27,3%) casos saliendo de la infección, 9 (11,7%) negativos y 8 (10,4%) con memoria inmunológica; de los casos positivos, 32 (82,1%) eran adultos y 30 (76,9%) fueron del género femenino. CONCLUSIÓN: Del total de muestras, la mitad tuvo diagnóstico de brucelosis, las manifestaciones clínicas de los pacientes estudiados fueron inespecíficas, lo cual resalta la importancia del diagnóstico de laboratorio.
BACKGROUND: Human brucellosis is a global health problem. Mexico is one of the main countries affected; timely diagnosis and serological tests are the basis for detection. AIM: To know the frequency of confirmed cases of brucellosis in different of Family Medicine Units of the Mexican Social Security Institute in the state of Puebla, Mexico. METHODS: Cross-sectional study in patients of both genders, adults and pediatrics, with clinical manifestations suggestive of brucellosis; serological tests were performed for the confirmatory diagnosis. RESULTS: Out of a total of 77 patients, 39 (50.6%) were positive, 21 (27.3%) cases coming out of infection, 9 (11.7%) were negative and 8 (10.4%) were defined with immunological memory; of positive cases, 32 (82.1%) were found in the adult group and 30 (76.9%) were female. CONCLUSION: Around half of samples were confirmed as brucellosis, the clinical manifestations of the patients studied were non-specific, which highlights the importance of laboratory diagnosis.
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Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Brucella , Brucelose/diagnóstico , Brucelose/epidemiologia , Testes Sorológicos , Estudos Transversais , México/epidemiologiaRESUMO
Resumen Los primeros casos de COVID-19, causada por el virus denominado SARS-CoV-2, se registraron en Wuhan, China, en diciembre de 2019; sin embargo, su capacidad de transmisión ocasionó que seis meses después la infección prácticamente estuviera presente en todo el mundo. El origen del virus parece ser zoonótico; se propone que proviene del murciélago y podría haber tenido un hospedero intermediario que llevó a su introducción en la población humana. SARS-CoV-2 es un virus envuelto, con genoma de ARN de cadena sencilla en sentido positivo y se ancla a la enzima convertidora de angiotensina, presente en las células susceptibles para infectar el sistema respiratorio de los humanos. Aunque previamente se han conocido otros coronavirus, no han tenido el mismo impacto, por lo que la investigación en tratamientos farmacológicos no tiene el desarrollo suficiente para afrontar el reto actual. Casi desde el comienzo de la epidemia se han propuesto moléculas para el tratamiento de la infección, sin embargo, aún no se cuenta con un fármaco con suficiente efectividad terapéutica. En esta revisión se describen las características principales de SARS-CoV-2, su ciclo replicativo, su posible origen y algunos avances en el desarrollo de tratamientos antivirales.
Abstract The first cases of COVID-19, caused by the virus called SARS-CoV-2, were recorded in Wuhan, China, in December 2019; however, its transmission ability caused for the infection to be practically present throughout the world six months later. The origin of the virus appears to be zoonotic; it has been proposed that it comes from a bat and that it may have had an intermediate host that led to its introduction in the human population. SARS-CoV-2 is an enveloped virus, with a positive single-stranded RNA genome, and it binds to the angiotensin-converting enzyme, present in susceptible cells, to infect the human respiratory system. Although other coronaviruses have been previously known, they have not had the same impact, and, therefore, research on pharmacological treatments is not sufficiently developed to face the current challenge. Almost since the beginning of the epidemic, several molecules have been proposed for the treatment of infection; however, there is not yet a drug available with sufficient effectiveness for treatment. This review describes SARS-CoV-2 main characteristics, its replicative cycle, its possible origin and some advances in the development of antiviral treatments.
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Humanos , SARS-CoV-2/fisiologia , SARS-CoV-2/ultraestrutura , COVID-19/tratamento farmacológico , COVID-19/virologiaRESUMO
INTRODUCTION AND OBJECTIVES: HCV infection is targeted by the WHO's Global Health Sector Strategy on Viral Hepatitis to be reduced notably by 2030. However, renovated epidemiological data is needed to line up with such goals. Herein, we provide an updated review of incidence, prevalence, genotypes (GTs), and risk factors (RFs) of HCV infection in Mexico to build elimination strategies. MATERIAL AND METHODS: HCV incidence was charted using the cumulative new cases/year at week 52. Prevalence, GTs, and RFs data from low-risk (LR-G) and high-risk (HR-Gs) groups were searched in PubMed/MEDLINE/Medigraphic/Scielo databases from January 2008 to December 2019 as per PRISMA guidelines. Weighted mean prevalence (WMP) was estimated; GTs and RFs were registered. RESULTS: In this study, 25,247 new cases were reported. Ten states accumulated 76.32% of HCV incidence that peaked in men at 50-59 years and women at 60-64 years. Thirty-four studies revealed a WMP between 0.774%-2.5% in LR-Gs and 11.8%-39.6% in HR-Gs that included mainly prison inmates, drug users, and dialyzed patients. GT1 and GT2 were predominant; GT3a emerged. Subtypes 1a and 1b circulate differentially, whereas novel GT2 subtypes appeared. Unsafe blood transfusion was infrequent in younger groups, but parenteral/intravenous transmission through drug-related risk behaviors has arisen. CONCLUSIONS: HCV transmission increased notably among LR-Gs and HR-Gs in Mexico. Novel genotypes/subtypes emerged as well as risky behavioral routes of transmission. A national elimination strategy will require pro-active screening in designated risk groups, research in molecular epidemiology, medical training, robust epidemiological databases, and antiviral treatment available to all eligible HCV-infected patients.
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Hepatite C/epidemiologia , Humanos , Incidência , México/epidemiologia , Prevalência , Fatores de RiscoRESUMO
The altered expression of glycan antigens has been reported during cervix transformation, demonstrating increased mRNA levels of certain glycogenes. Human papillomavirus (HPV) is the aetiological agent of cervical cancer. High risk HPV E5 is considered an oncogene and has been implicated in cell transformation. E6 and E7 HPV oncoproteins modify the expression of certain glycogenes. The role of the E5 HPV protein in glycogene expression changes has not yet been reported. The aim of the present study was to determine the effects of HPV16 E5 oncoprotein on glycogene expression. For these, a microarray assay was performed using the HaCaT cell line and altered glycogenes were identified. The mRNA levels of certain glycogenes were determined via reverse transcriptionquantitative PCR (RTqPCR). Using in silico analysis, the present study identified that glycosylation pathways were altered by E5. Microarray analysis revealed alterations in certain glycogenes, including the upregulation of ST6GAL1, ST3GAL3, CHST2 and MANBA, and the downregulation of UGT2B15, GALNT11, NDST2 and UGT1A10. Increased mRNA levels were confirmed via RTqPCR for sialyltransferases genes. Additionally, in silico analysis was performed to identify glycosylation networks altered in the presence of the E5 oncoprotein. The analysis revealed that E5 could modify glycan sialylation, the Nglycosylation pathway, keratan sulfate and glycosaminoglycan synthesis. To the best of our knowledge, the current study was the first to determine the role of the HPV16 E5 oncoprotein in glycogene expression changes. The results indicated that increased sialyltransferase mRNA levels reported in premalignant and malignant cervical tissues could be the result of E5 oncoprotein expression. The results provide a possible role of HPV infection on glycosylation changes reported during cervix transformation.
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Regulação Viral da Expressão Gênica/genética , Proteínas Oncogênicas Virais/genética , Polissacarídeos/genética , Linhagem Celular Tumoral , Colo do Útero/patologia , Feminino , Expressão Gênica/genética , Glicosilação , Células HaCaT , Papillomavirus Humano 16/genética , Humanos , N-Acetilgalactosaminiltransferases/genética , Proteínas Oncogênicas Virais/metabolismo , Oncogenes , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Polissacarídeos/imunologia , RNA Mensageiro/metabolismo , Transfecção , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologiaRESUMO
Neuraminidase (NA) of influenza viruses enables the virus to access the cell membrane. It degrades the sialic acid contained in extracellular mucin. Later, it is responsible for releasing newly formed virions from the membrane of infected cells. Both processes become key functions within the viral cycle. Therefore, it is a therapeutic target for research of the new antiviral agents. Structure-activity relationships studies have revealed which are the important functional groups for the receptor-ligand interaction. Influenza virus type A NA activity was inhibited by five scaffolds without structural resemblance to sialic acid. Intending small organic compound repositioning along with drug repurposing, this study combined in silico simulations of ligand docking into the known binding site of NA, along with in vitro bioassays. The five proposed scaffolds are N-acetylphenylalanylmethionine, propanoic 3-[(2,5-dimethylphenyl) carbamoyl]-2-(piperazin-1-yl) acid, 3-(propylaminosulfonyl)-4-chlorobenzoic acid, ascorbic acid (vitamin C), and 4-(dipropylsulfamoyl) benzoic acid (probenecid). Their half maximal inhibitory concentration (IC50) was determined through fluorometry. An acidic reagent 2'-O-(4-methylumbelliferyl)-α-dN-acetylneuraminic acid (MUNANA) was used as substrate for viruses of human influenza H1N1 or avian influenza H5N2. Inhibition was observed in millimolar ranges in a concentration-dependent manner. The IC50 values of the five proposed scaffolds ranged from 6.4 to 73 mM. The values reflect a significant affinity difference with respect to the reference drug zanamivir (p < 0.001). Two compounds (N-acetyl dipeptide and 4-substituted benzoic acid) clearly showed competitive mechanisms, whereas ascorbic acid reflected non-competitive kinetics. The five small organic molecules constitute five different scaffolds with moderate NA affinities. They are proposed as lead compounds for developing new NA inhibitors which are not analogous to sialic acid.
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Inibidores Enzimáticos/química , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H5N2/enzimologia , Neuraminidase/antagonistas & inibidores , Antivirais/química , Antivirais/metabolismo , Ácido Benzoico/química , Ácido Benzoico/metabolismo , Sítios de Ligação , Ligação Competitiva , Inibidores Enzimáticos/metabolismo , Humanos , Cinética , Ligantes , Simulação de Acoplamento Molecular , Ácido N-Acetilneuramínico/química , Neuraminidase/metabolismo , Relação Estrutura-Atividade , Zanamivir/química , Zanamivir/metabolismoRESUMO
The ST3GAL4 gene encodes the enzyme Galß1-4GlcNAc α2,3 sialyltransferase (ST3Gal IV). This enzyme participates in the synthesis of the sialyl Lewis x antigen. In different cancer types altered expression of this antigen has been reported. The transcriptional regulation of this gene is very complex, different mRNA variants (V1-V10) have been reported and are originated by the activity of different promoters and alternative splicing. Only the promoter that gives rise to the V3 variant has not been previously reported. The objective of this work was to identify and characterize the V3 promoter of the ST3GAL4 gene. For this, the putative V3 promoter of the ST3GAL4 gene was delimited by in silico analysis. The complete promoter and smaller versions were cloned in a reporter plasmid. The constructs were transfected in the HaCaT cells and the promoter activity was evaluated by luciferase reporter assays. The cloned region showed promoter activity, and the basal activity was not dependent on TATA boxes. However, the GC boxes, an initiator element (Inr) and downstream promoter element (DPE) could contribute to basal activity. The promoter contains several binding sites for the nuclear factor of activated T-cells (NFAT) that could participate in inducible activity during the immune response. The minimal promoter corresponds to a fragment of approximately 300 bp, located in the position -347 b to -40 b. The characterization of the V3 promoter of the ST3GAL4 gene completes the study of the four promoters of this gene, this contributes to the understanding of its complex transcription regulation.
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Regiões Promotoras Genéticas , Sialiltransferases/genética , Transcrição Gênica , Processamento Alternativo , Sítios de Ligação , Linhagem Celular , Clonagem Molecular , Biologia Computacional , Humanos , Isoenzimas/genética , Fatores de Transcrição NFATC/metabolismoRESUMO
Background: Dengue manifestations can range from subclinical to fatal. The study of factors that influence dengue's clinical severity can provide information to potentially limit or predict severe cases. Secondary infection (SI) with a different dengue serotype has been recognized as an important determinant of severity. However, severe dengue (SD) manifestations, including shock, can happen during primary infection (PI) too and the mechanisms involved are less understood. To characterize the severe manifestations associated to PI, we distinguished between primary and secondary dengue cases in hospitalized patients from a region of low and recent dengue incidence in central Mexico. This region can serve as a model for dengue's behavior as it spreads to new areas worldwide. Methods: Dengue-specific immunoglobulin M (IgM) and IgG concentrations were measured in the serum of 78 hospitalized patients with dengue hemorrhagic fever, and their ratios were used to discriminate between PI and SI, as recommended by World Health Organization. Clinical and laboratory manifestations were compared between PI and SI. Results and Conclusions: PI was detected in 23% of hospitalized dengue cases, a proportion similar to that reported in high-incidence regions in Mexico. PI was more frequent in 16- to 40-year-olds, and was absent in patients older than 60 years. Only dengue with warning signs and SD were present in the studied population of hospitalized patients, and case frequency decreased with clinical severity both in PI and SI groups. No significant differences in demographics, laboratory tests, or symptoms were found between PI and SI, which illustrates that cases requiring hospitalization during outbreaks can be severe, even if they are PI. This information can help plan for sanitary contingencies in places where dengue is recently emergent and numerous PI cases are expected. The mechanisms involved in PI clinical severity need to be studied further.
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Dengue/epidemiologia , Dengue/patologia , Adolescente , Adulto , Criança , Surtos de Doenças , Feminino , Hospitalização , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
The participation of proinflammatory cytokines in the progression of Multiple Sclerosis (MS) has been well documented. Cytokines activate the JAK-STAT pathway, in which the suppressors of cytokine signaling (SOCS) exert a negative feedback. This paper analyzes the levels of SOCS5 and SOCS7 transcripts, quantified by RT-qPCR, in MS patients, and the concentrations of proinflammatory cytokines, IFN-γ, IL17, and IL6, determined by ELISA. Samples of peripheral blood were obtained from MS patients in the relapsing-remitting phase, treated with IFN-ß or glatiramer acetate (GA), and from healthy individuals. SOCS7 mRNA was significantly higher in patients treated with GA (1.36 ± 0.23) than in those treated with IFN-ß (0.65 ± 0.1). Regarding gender, the level of SOCS5 and SOCS7 transcripts were similar between MS and healthy females; in MS males, the level of SOCS7 transcripts were significantly lower (0.59 ± 0.03) than in healthy males (1.008 ± 0.05). Plasmatic levels of IFN-γ were significantly higher in MS patients (60 pg/mL, range 0-160) than in healthy subjects (0 range, 0-106). The same pattern was observed in MS patients treated with IFN-ß (68 pg/mL, range 0-160) compared to patients treated with GA (51 pg/mL, range 0-114), and in MS females (64 pg/mL, range 0-161) compared to healthy females (0, range 0-99). We hypothesize that the increase in SOCS7 transcription in patients treated with GA could partially explain the action mechanism of this drug, while the increase in the concentration of IFN-γ in MS patients could help elucidate the immunopathology of the disease.
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Acetato de Glatiramer/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
BACKGROUND: Influenza causes high rates of morbidity and mortality. Genetic variability of influenza viruses generates resistance to antivirals, which are of two types, since they act on two different viral targets: adamantanes, which block the M2 ion channel, and the neuraminidase (NA) inhibitors. METHODS: In Mexico, the available studies on the antiviral resistance of circulating influenza strains are scarce, so this work undertook an analysis of the Mexican sequences reported in public gene banks to perform a systematic analysis of the antiviral resistance markers on both M2 and NA. In all, 284 M2 sequences and 423 NA sequences were retrieved from three genetic databases (sequences from 2000 to 2017 were considered). RESULTS: The resistance markers to M2 blockers were present in 100% of H1N1 pdm2009, 83.6% of H3N2, and 5.8% of seasonal H1N1 sequences. Two resistance markers conferring resistance to NA inhibitors were present in seasonal H1N1 sequences, H275Y (50.0%) and N70S (33.3%). None of these viruses had both resistance markers, which are associated with oseltamivir resistance. The more frequent resistance marker in H1N1 pdm2009 NA sequences was H275Y, present in 3.6%, while S247N was present in 0.30%. Only one of the resistance-associated markers (Q136K) in NA (1.5%) was present in the analyzed H3N2 sequences, while sequences of influenza B virus did not present resistance markers to NA inhibitors. Some influenza A H1N1 pdm2009 sequences (1.8%) presented resistance markers to both M2 and NA. CONCLUSION: Based on the present analysis, 7.1% of the all serotypes of influenza virus A sequences analyzed in Mexico from 2000 to 2017 have mutations conferring resistance to NA inhibitors. Because of this, and the limited availability of influenza drugs, it is necessary to increase the epidemiological surveillance, including molecular analysis, which will provide data such as the presence of changes associated with antiviral resistance.
RESUMO
BACKGROUND: Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HVB) DNA in the liver of HBsAg negative individuals with or without detectable viral DNA in serum. OBI is a diagnostic challenge as it is characterized by a very low viral load, intermittently detectable through time. Individuals with OBI can develop chronic hepatic disease, including liver cirrhosis and hepatocellular carcinoma. The aim of this work was to produce tools to improve OBI detection of the HVB genotypes prevalent in Mexico. METHODS: We designed and tested primers to detect OBI in serum samples by nested and real-time PCR. Conserved sites in the viral genome were determined by alignment of the most frequent HBV genotypes in Mexico (H, G/H, F and D) and primers spanning the entire viral genome were designed for first round and nested PCR. Primers were tested in serum samples of 45 patients not co-infected with hepatitis C virus or with HIV, out of a group of 116 HBsAg (-)/anti-HBc (+) individuals. Primers were also tested in a control group with chronic HBV. Nested PCR products obtained from HBsAg (-)/anti-HBc (+) were sequenced and used to design primers for real-time PCR (SYBR Green). RESULTS: The most effective primer pairs to detect HBV products by nested PCR targeted ORF regions: PreS2/P, S/P, X/PreC, and C; while by real-time PCR they targeted ORF regions PreS2/P, S/P, X, and C. Out of the 45 HBsAg (-)/anti-HBc (+) patients tested, the viral genome was detected in 28 (62.2%) and 34 (75.5%), with nPCR and real-time PCR respectively. CONCLUSION: Primers designed for real-time PCR detected up to 75.5% of suspected OBI Mexican patients, with or without liver disease, which represents an improvement from previous PCR strategies.
Assuntos
DNA Viral/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B/sangue , Fígado/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Hepatite B/epidemiologia , Hepatite B/genética , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Humanos , Fígado/patologia , Fígado/virologia , Masculino , México , Pessoa de Meia-Idade , Carga ViralRESUMO
BACKGROUND: Aberrant glycosylation is a characteristic of tumour cells. The expression of certain glycan structures has been associated with poor prognosis. In cervical carcinoma, changes in the expression levels of some glycogenes have been associated with lymph invasion. Human papillomavirus (HPV) infection is one of the most important factors underlying the development of cervical cancer. The HPV oncoproteins E6 and E7 have been implicated in cervical carcinogenesis and can modify the host gene expression profile. The roles of these oncoproteins in glycosylation changes have not been previously reported. METHODS: To determine the effect of the E6 and E7 oncoproteins on glycogene expression we partially silenced the E6 and E7 oncogenes in HeLa cells, we performed a microarray expression assay to identify altered glycogenes and quantified the mRNA levels of glycogenes by RT-qPCR. A protein-protein interaction network was constructed to identify potentially altered glycosylation pathways. RESULTS: The microarray analysis showed 9 glycogenes that were upregulated and 7 glycogenes that were downregulated in HeLa shE6/E7 cells. Some of these genes participate in glycosylation related to Notch proteins and O-glycans antigens. CONCLUSIONS: Our results support that E6 and E7 oncoproteins could modify glycogene expression the products of which participate in the synthesis of structures implicated in proliferation, adhesion and apoptosis.
RESUMO
ST3GAL4 gene expression is altered in different cancer types, including cervical cancer. Several mRNA transcripts have been reported for this gene; however, their expression levels in cervical cancer have not been analyzed. ST3GAL4 encodes for ßgalactosidase α2,3sialyltransferase 4, involved in the biosynthesis of the tumour antigens sLe(x) and sulfosLe(x). The present study evaluated the presence of three mRNA variants (V1, V2 and V3) in cervical cancer cell lines, detecting the three variants. Additionally, the expression level of the V1 transcript of the ST3GAL4 gene was determined by reverse transcriptionquantitative polymerase chain reaction in cervical cell lines and in normal, premalignant and cervical cancer tissue. The V1 transcript of the ST3GAL4 demonstrated significant decreased expression in premalignant and malignant cervical tissues. The results suggested that deregulation of this gene could occur prior to the presence of cancer and demonstrated the importance of evaluating the expression level of V1, and its association with disease progression.