RESUMO
Covid-19 in West Africa masked outbreaks of vaccine-preventable diseases such as the measles epidemic in children in Guinea in 2021-2022 characterized by a lack of confirmation of suspected clinical cases. During weeks 13-22 of 2022, saliva samples were collected from 213 children (3-60 months old) with measles-like symptoms within the St Gabriel dispensary in Conakry. Samples were processed in Virus Transport Medium (VTM) and tested on the same day by triplex reverse transcriptase -real-time polymerase chain reaction for Measles, Rubella and RNaseP. Samples were also tested for HHV6 and Parvovirus B19, viruses causing clinical signs similar to measles. We confirmed 146 (68.5%) measles cases, 27 (12.7%) rubella, 5 (2.3%) double-positive measles-rubella, 35 (16.4%) HHV-6 and 8 (3.75%) Parvovirus B19. To test the assay's robustness, 27 samples were kept at 26-30°C. Measles and rubella were still detected after 7 days at 26-30°C, and after 21 days measles and rubella were still detectable in all samples but one. Sequencing indicated the circulation of the B3 measles genotype, as expected in West Africa. This study highlights the robustness of the measles/rubella diagnostic test on saliva samples stored in VTM. The high level of rubella detection questioned the single valence measles vaccination strategy.
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COVID-19 , Exantema , Herpesvirus Humano 6 , Sarampo , Parvovirus B19 Humano , Rubéola (Sarampo Alemão) , Criança , Humanos , Lactente , Pré-Escolar , Papua Nova Guiné , Anticorpos Antivirais , Imunoglobulina M , COVID-19/epidemiologia , COVID-19/complicações , Guiné , Vírus do Sarampo/genética , Parvovirus B19 Humano/genéticaRESUMO
BACKGROUND: Viruses, which are transmitted mainly via the digestive tract, are responsible for the high morbidity and mortality of diseases, particularly in low-income countries. Although several studies have established the prevalence and characterization of various enteric viruses in Burkina Faso, to date, no aggregate data have been released. OBJECTIVE: Our objective was to describe the available data on the prevalence and circulating genotypes of enteric pathogen viruses responsible for human infections in Burkina Faso by carrying out a systematic review and meta-analysis. METHODS: Potentially relevant studies were identified by a search of PubMed, ScienceDirect, Google Scholar, university libraries and by a manual search of the reference lists of identified studies. The search with no restrictions on language or age was limited to studies conducted only in Burkina. Study selection, data extraction, and methodological quality of the included studies were performed independently by two investigators. Heterogeneity between studies was assessed using the Cochrane Q test and I2 test statistics based on the random effects model. Comprehensive meta-analysis (CMA 3.7) was employed to compute the pooled prevalence of pathogens identified in the studies. RESULTS: Forty-three (43) studies reporting 4,214 diagnosed cases in all aged human populations were selected. Overall, 72.6% of the pathogens diagnosed were gastroenteritis, and 27.2% were entero-transmissible hepatitis viruses. Rotavirus was the most common cause of human viral gastroenteritis, accounting for 27.7% (95% CI: 20.9 - 35.8) of the cases, followed by norovirus (16% (95% CI: 12.25 - 20.6)) and sapovirus (11.2% (95% CI: 6.2 - 19.4)). In terms of human entero-transmissible infections, hepatitis A virus (HAV) was the most prevalent (52% [95% CI: 14.2-87.7] of total antibodies), followed by hepatitis E virus (HEV) (28.3% [95% CI: 17.7-42]). CONCLUSIONS: This study highlights the substantial burden of viral enteric infections and highlights the need for more molecular epidemiological studies to improve preventive measures against these viruses.
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Gastroenterite , Burkina Faso/epidemiologia , Humanos , Prevalência , Gastroenterite/epidemiologia , Gastroenterite/virologia , Genótipo , Vírus/classificação , Vírus/isolamento & purificação , Vírus/genética , Rotavirus/genética , Rotavirus/isolamento & purificaçãoRESUMO
The emerging coronavirus called SARS-CoV-2 has spread rapidly around the world. Responsible for severe pneumonitis (Covid-19), there are also doubts concerning a possible mother-to-fetal transmission of this virus. Current data are patchy and obtained from small groups of patients. They tend to support the idea that the mother-to-fetal transmission of SARS-CoV-2 is very rare, but the period between infection and childbirth was often very short and may not allow sufficient replication to consider transplacental passage. Here, we reviewed the existing virological data and those remaining to explore. Thus, the natural history of SARS-CoV-2 infection in pregnant women and the risk of transmission in utero is not yet fully understood and defined. Four months from the emergence of this virus, it is therefore reasonable to wait for the results of specific studies on larger cohorts which, to be conclusive, must meet the best scientific criteria.
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Betacoronavirus , Infecções por Coronavirus/transmissão , Transmissão Vertical de Doenças Infecciosas , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/virologia , Feminino , Doenças Fetais/virologia , Humanos , Recém-Nascido , Pandemias , Placenta/virologia , Pneumonia Viral/virologia , Gravidez , SARS-CoV-2 , Carga Viral , Tropismo ViralRESUMO
OBJECTIVES: Various rheumatoid arthritis (RA) HLA-DRB-1 risk haplotypes have been regrouped under the shared epitope (SE) in position 70-74. The presence of Valine in position 11 (Val11) and phenylalanine in position 13 (Phe13) are also associated with RA, but it is impossible to differentiate their role compared with the SE since they are in strong linkage disequilibrium (LD) in humans. Similar to humans, certain macaques express the SE (H6). We analysed the effect of various DRB1 haplotypes on T-cell response to citrullinated peptides (Cit-P) in macaques. METHODS: Six H6 and six non-H6 macaques were immunized with four Cit-P. T-cell response was assessed using Interferon γ enzyme-linked immunospot. RESULTS: Animals developed a specific anti-Cit-P T-cell response. Surprisingly, H6 animals had a significantly lower T-cell response than non-H6. In macaques, the 70-74 SE and the Val11 are on separate haplotypes. Presence of Val11 was strongly associated with the anti-Cit-P T-cell response, whatever the 70-74 sequence was. This response was amplified in case of presence of Phe13. CONCLUSION: The absence of LD between Val11 and SE in macaques allowed us to demonstrate that the most important HLA positions to induce a T-cell response against Cit-P were Val11 and Phe13 and not the 70-74 SE.
Assuntos
Cadeias HLA-DRB1/genética , Peptídeos Cíclicos/imunologia , Fenilalanina/imunologia , Linfócitos T/imunologia , Valina/imunologia , Animais , Artrite Reumatoide/imunologia , Epitopos , Cadeias HLA-DRB1/imunologia , Haplótipos , Ativação Linfocitária/imunologia , MacacaRESUMO
Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent. Although day 2, 7 and 30 represent distinct stages of infection and disease, there was a pronounced overlap in up-regulated host genes and pathways. Type I interferon response genes (IRGs) represented up to ≈50% of up-regulated genes, even after loss of type I interferon induction on days 7 and 30. Bioinformatic analyses suggested a number of interferon response factors were primarily responsible for maintaining type I IRG induction. A group of genes prominent in the RNA-Seq analysis and hitherto unexplored in viral arthropathies were granzymes A, B and K. Granzyme A-/- and to a lesser extent granzyme K-/-, but not granzyme B-/-, mice showed a pronounced reduction in foot swelling and arthritis, with analysis of granzyme A-/- mice showing no reductions in viral loads but reduced NK and T cell infiltrates post CHIKV infection. Treatment with Serpinb6b, a granzyme A inhibitor, also reduced arthritic inflammation in wild-type mice. In non-human primates circulating granzyme A levels were elevated after CHIKV infection, with the increase correlating with viral load. Elevated granzyme A levels were also seen in a small cohort of human CHIKV patients. Taken together these results suggest granzyme A is an important driver of arthritic inflammation and a potential target for therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00281294.
Assuntos
Artrite/virologia , Febre de Chikungunya/genética , Febre de Chikungunya/imunologia , Granzimas/imunologia , Inflamação/virologia , Animais , Vírus Chikungunya , Modelos Animais de Doenças , Granzimas/análise , Granzimas/biossíntese , Humanos , Imuno-Histoquímica , Macaca fascicularis , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/análise , TranscriptomaRESUMO
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.
Assuntos
Células Dendríticas/metabolismo , Infecções por HIV/imunologia , HIV-1 , Antígenos de Histocompatibilidade Classe I/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Adulto , Animais , Células Cultivadas , Células Dendríticas/imunologia , Feminino , Infecções por HIV/metabolismo , Humanos , Macaca fascicularis , Masculino , Pessoa de Meia-Idade , Síndrome de Imunodeficiência Adquirida dos Símios/metabolismo , Vírus da Imunodeficiência Símia , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation. METHODS: We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi. We investigated the effect of a single course of MTX during the first exposure to TNFi. Wild-type (WT) and BAFFtg mice were compared for B-Cell surface markers involved in MTX-related purinergic metabolism, adenosine production and regulatory B-cells (Bregs).We translated the study to macaques and patients with rheumatoid arthritis from the ABIRISK cohort to determine if there was an interaction between serum BAFF levels and MTX that prevented immuniation. RESULTS: In BAFFtg but not in WT mice or macaques, a single course of MTX prevented immunisation against TNFi and maintained drug concentration for over 52 weeks. BAFFtg mice B-cells expressed more CD73 and CD39 compared to WT mice. MTX induced adenosine release from B cells and increased Bregs and precursors. Use of CD73 blocking antibodies reversed MTX-induced tolerance. In patients from the ABIRISK cohort treated with TNFi for chronic inflammatory diseases, high BAFF serum level correlated with absence of ADA to TNFi only in patients cotreated with MTX but not in patients on TNFi monotherapy. CONCLUSION: MTX and BAFF interact in mice where CD73, adenosine and regulatory B cells were identified as key actors in this phenomenon. MTX and BAFF also interact in patients to prevent ADA formation.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Fator Ativador de Células B/imunologia , Resistência a Medicamentos/imunologia , Metotrexato/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , 5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Animais , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , Antígenos CD/metabolismo , Apirase/metabolismo , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Fator Ativador de Células B/efeitos dos fármacos , Linfócitos B/metabolismo , Modelos Animais de Doenças , Humanos , Imunização , Macaca , Camundongos , Camundongos Transgênicos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.
Assuntos
Quimiocina CXCL10/metabolismo , Infecções por HIV/imunologia , Intestino Delgado/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Separação Celular , Progressão da Doença , Citometria de Fluxo , HIV-1/imunologia , Humanos , Imuno-Histoquímica , Macaca , Reação em Cadeia da Polimerase , Vírus da Imunodeficiência Símia/imunologia , Carga Viral/imunologia , Viremia/imunologiaRESUMO
Infections with the human hepatitis B virus (HBV) and hepatitis D virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide (hNTCP). Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV, indicating the requirement of additional HBV-specific factors. As an essential premise toward the establishment of an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals. Primary hepatocytes from mice, rats, dogs, pigs, rhesus macaques, and cynomolgus macaques were transduced with adeno-associated viral vectors encoding hNTCP and subsequently infected with HBV. Cells were analyzed for Myrcludex B binding, taurocholate uptake, HBV covalently closed circular DNA formation, and expression of all HBV markers. Sodium taurocholate cotransporting polypeptide (Ntcp) from the respective species was cloned and analyzed for HBV and HDV receptor activity in a permissive hepatoma cell line. Expression of hNTCP in mouse, rat, and dog hepatocytes permits HDV infection but does not allow establishment of HBV infection. Contrarily, hepatocytes from cynomolgus macaques, rhesus macaques, and pigs became fully susceptible to HBV upon hNTCP expression with efficiencies comparable to human hepatocytes. Analysis of cloned Ntcp from all species revealed a pronounced role of the human homologue to support HBV and HDV infection. CONCLUSION: Ntcp is the key host factor limiting HBV infection in cynomolgus and rhesus macaques and in pigs. In rodents (mouse, rat) and dogs, transfer of hNTCP supports viral entry but additional host factors are required for the establishment of HBV infection. This finding paves the way for the development of macaques and pigs as immunocompetent animal models to study HBV infection in vivo, immunological responses against the virus and viral pathogenesis. (Hepatology 2017;66:703-716).
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Regulação Viral da Expressão Gênica , Vírus da Hepatite B/genética , Fator Proteico 1 do Hospedeiro/metabolismo , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Simportadores/genética , Ácido Taurocólico/metabolismo , Replicação Viral/genética , Animais , Células Cultivadas , Modelos Animais de Doenças , Cães , Hepatite B/genética , Hepatite B/fisiopatologia , Hepatócitos/metabolismo , Hepatócitos/virologia , Macaca mulatta , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores Virais/metabolismo , Transdução de Sinais , Especificidade da Espécie , Suínos , TransfecçãoAssuntos
Vírus Chikungunya , Testosterona , Humanos , Masculino , Testículo , Congêneres da TestosteronaRESUMO
UNLABELLED: Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates. IMPORTANCE: As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.
Assuntos
Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Imunização/métodos , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Febre de Chikungunya/imunologia , Modelos Animais de Doenças , Feminino , Leucócitos Mononucleares/imunologia , Camundongos Endogâmicos C57BL , Análise de Sobrevida , Vacinas de DNA/administração & dosagem , Vacinas Virais/administração & dosagemRESUMO
UNLABELLED: Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that has caused severe epidemics in Africa and Asia and occasionally in Europe. As of today, there is no licensed vaccine available to prevent CHIKV infection. Here we describe the development and evaluation of novel CHIKV vaccine candidates that were attenuated by deleting a large part of the gene encoding nsP3 or the entire gene encoding 6K and were administered as viral particles or infectious genomes launched by DNA. The resulting attenuated mutants were genetically stable and elicited high magnitudes of binding and neutralizing antibodies as well as strong T cell responses after a single immunization in C57BL/6 mice. Subsequent challenge with a high dose of CHIKV demonstrated that the induced antibody responses protected the animals from viremia and joint swelling. The protective antibody response was long-lived, and a second homologous immunization further enhanced immune responses. In summary, this report demonstrates a straightforward means of constructing stable and efficient attenuated CHIKV vaccine candidates that can be administered either as viral particles or as infectious genomes launched by DNA. IMPORTANCE: Similar to other infectious diseases, the best means of preventing CHIKV infection would be by vaccination using an attenuated vaccine platform which preferably raises protective immunity after a single immunization. However, the attenuated CHIKV vaccine candidates developed to date rely on a small number of attenuating point mutations and are at risk of being unstable or even sensitive to reversion. We report here the construction and preclinical evaluation of novel CHIKV vaccine candidates that have been attenuated by introducing large deletions. The resulting mutants proved to be genetically stable, attenuated, highly immunogenic, and able to confer durable immunity after a single immunization. Moreover, these mutants can be administered either as viral particles or as DNA-launched infectious genomes, enabling evaluation of the most feasible vaccine modality for a certain setting. These CHIKV mutants could represent stable and efficient vaccine candidates against CHIKV.
Assuntos
Infecções por Alphavirus/imunologia , Vírus Chikungunya/imunologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Infecções por Alphavirus/prevenção & controle , Infecções por Alphavirus/virologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya , Vírus Chikungunya/genética , Feminino , Ordem dos Genes , Genoma Viral , Imunidade Celular , Imunização , Imunização Secundária , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genéticaRESUMO
UNLABELLED: Despite a high prevalence of hepatitis B virus (HBV) infection in endangered apes, no HBV infection has been reported in small, old-world monkeys. In search for a small, nonhuman primate model, we investigated the prevalence of HBV infection in 260 macaque (Cercopithecidae) sera of various geographical origins (i.e., Morocco, Mauritius Island, and Asia). HBV-positive markers were detected in cynomolgus macaques (Macaca fascicularis) from Mauritius Island only, and, remarkably, HBV DNA was positive in 25.8% (31 of 120) and 42% (21 of 50) of serum and liver samples, respectively. Strong liver expression of hepatitis B surface antigen and hepatitis B core antigen was detected in approximately 20%-30% of hepatocytes. Furthermore, chronic infection with persisting HBV DNA was documented in all 6 infected macaques during an 8-month follow-up period. Whole HBV genome-sequencing data revealed that it was genotype D subtype ayw3 carrying substitution in position 67 of preS1. To confirm infectivity of this isolate, 3 Macaca sylvanus were inoculated with a pool of M. fascicularis serum and developed an acute HBV infection with 100% sequence homology, compared with HBV inoculum. We demonstrated the presence of a chronic HBV infection in M. fascicularis from Mauritius Island. This closely human-related HBV might have been transmitted from humans, because the initial breeding colony originated from very few ancestors 300 years ago when it was implemented by Portuguese who imported a handful of macaques from Java to Mauritius Island. CONCLUSION: This report on natural, persisting HBV infection among cynomolgus macaques provides the first evidence for the existence of a novel, small simian model of chronic HBV infection, immunologically close to humans, that should be most valuable for the study of immunotherapeutic approaches against chronic hepatitis B.
Assuntos
Hepatite B Crônica/veterinária , Doenças dos Macacos/transmissão , Alanina Transaminase/sangue , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Genótipo , Hepatite B Crônica/transmissão , Macaca fascicularis , Maurício , Dados de Sequência Molecular , FilogeniaRESUMO
Salmonella is one of the world's leading causes of zoonotic and foodborne illnesses. Recently, antimicrobial resistance (AMR) has become one of the most critical challenges to public health and food safety. Herein, we employed a meta-analysis to determine the pooled prevalence and spatiotemporal distribution of serovars and antimicrobial resistance in NTS in Burkina Faso. To find eligible articles, a comprehensive literature search of PubMed, African Journals Online, ScienceDirect, Google Scholar, and the gray literature (university libraries) in Burkina was conducted for the period from 2008 to 2020. Studies meeting the inclusion criteria were selected and assessed for risk of bias. To assess the temporal and spatial relationships between serotypes and resistant strains from humans, animals, food, and the environment, a random-effects statistical model meta-analysis was carried out using the Comprehensive Meta-Analysis Version 3.0 program. The NTS prevalence rates were 4.6% (95% CI: 3-7) and 20.1% (95% CI: 6.6-47.4) in humans and animals, respectively, and 16.8% (95% CI: 10.5-25.8) and 15.6% (95% CI: 8.2-27.5) in food and the environment, respectively. Most NTS serovars were S. Derby, reported both in food and animals, and S. Typhimurium, reported in humans, while S. Croft II, S. Jodpur II, and S. Kentucky were the most prevalent in the environment. NTS isolates were highly resistant to erythromycin, amoxicillin, cefixime, and cephalothin, with a pooled prevalence of multidrug resistance of 29% (95% CI: 14.5-49.5). The results of this review show a high diversity of Salmonella serotypes, as well as high antibiotic resistance in Salmonella isolates from animal, human, food, and environmental samples in Burkina, calling for a consolidated "One Health" approach to better understand the drivers of pathogen emergence, spread, and antimicrobial resistance, as well as the formulation of intervention measures needed to limit the risk associated with the disease.
RESUMO
Background: Hepatitis E virus (HEV) is transmitted by the fecal route, usually through contaminated water in humans and/or infected animals, especially pigs. The objective of this study was to evaluate the level of anti-HEV antibodies in a panel of pig sera and to identify HEV in pig feces in farms. Methodology: The presence of HEV antibodies was tested by an in-house ELISA and a commercial ELISA IDvet. HEV genome was assessed by nested RT-PCR, and then, genotype was identified by sequencing (MinION Nanopore technology). Results: In 2017-2019, the 43% seroprevalence found in Forest Guinea was significantly higher than the 7% found in the Lower region (p < 0.01). Presence of HEV genotype 3c was demonstrated during a secondary study in the Lower region (Conakry) in 2022. Conclusion: The presence of HEV-3c in pigs calls for an evaluation of seroprevalence in human populations and for a HEV genotype human circulation check. Contribution Heading: This study is the first report, to our knowledge, of seroprevalence and characterization of HEV infection in pigs in Guinea.
Assuntos
Vírus da Hepatite E , Hepatite E , Filogenia , Doenças dos Suínos , Animais , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Vírus da Hepatite E/classificação , Vírus da Hepatite E/imunologia , Estudos Soroepidemiológicos , Hepatite E/epidemiologia , Hepatite E/veterinária , Hepatite E/virologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Cobaias , Guiné/epidemiologia , Fezes/virologia , Anticorpos Anti-Hepatite/sangue , GenótipoRESUMO
The pandemic linked to SARS-CoV-2 has profoundly disrupted the health systems and many studies have led to a better understanding of this virus, which is responsible for severe disease, particularly during pregnancy. Pregnancy is a risk factor for severe COVID-19. Term of pregnancy and vaccination status is the main risk factor in addition to classic comorbidities like general population. COVID-19 during pregnancy is responsible for more maternal death, stillbirth, pre-eclampsia spontaneous and induced prematurity. Vaccination is therefore strongly recommended for pregnant patients. In addition, the COVID-19 pandemic has highlighted a psychological and social dimension that should not be neglected in the management of a pregnant patient. Correlation between immunological changes and clinical impact are described in this review. Many conclusions can now be made and are summarized in this article in order to discuss possible future research.
Assuntos
COVID-19 , Obstetrícia , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Gravidez , Humanos , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Complicações Infecciosas na Gravidez/epidemiologia , Gestantes , Nascimento Prematuro/epidemiologia , Resultado da GravidezRESUMO
Background and aims: Hepatitis B virus (HBV) infection affects 300 million individuals worldwide, representing a major factor for the development of hepatic complications. Although existing antivirals are effective in suppressing replication, eradication of HBV is not achieved. Therefore, a multi-faceted approach involving antivirals and immunomodulatory agents is required. Non-human primates are widely used in pre-clinical studies due to their close evolutionary relationship to humans. Nonetheless, it is fundamental to identify the differences in immune response between humans and these models. Thus, we performed a transcriptomic characterization and interspecies comparison of the early immune responses to HBV in human and cynomolgus macaques. Methods: We characterized early transcriptomic changes in human and cynomolgus B cells, T cells, myeloid and plasmacytoid dendritic cells (pDC) exposed to HBV ex vivo for 2 hours. Differentially-expressed genes were further compared to the profiles of HBV-infected patients using publicly-available single-cell data. Results: HBV induced a wide variety of transcriptional changes in all cell types, with common genes between species representing only a small proportion. In particular, interferon gamma signaling was repressed in human pDCs. At the gene level, interferon gamma inducible protein 16 (IFI16) was upregulated in macaque pDCs, while downregulated in humans. Moreover, IFI16 expression in pDCs from chronic HBV-infected patients anti-paralleled serum HBsAg levels. Conclusion: Our characterization of early transcriptomic changes induced by HBV in humans and cynomolgus macaques represents a useful resource for the identification of shared and divergent host responses, as well as potential immune targets against HBV.
Assuntos
Hepatite B , Transcriptoma , Animais , Humanos , Vírus da Hepatite B/genética , Interferon gama , Antivirais , Macaca fascicularis , Hepatite B/genéticaRESUMO
Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP) natural hosts is usually nonpathogenic, despite high levels of virus replication. We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and African green monkeys (AGMs) is associated with low levels of immune activation and bystander T cell apoptosis. To compare these features with those observed in another natural host, the mandrill (MND), we conducted a cross-sectional survey of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of mandrills available worldwide. Viral loads (VLs) were determined and phenotypic and functional analysis of peripheral blood- and lymph node-derived lymphocytes was performed. We found that mandrills chronically infected with SIVmnd-1 or SIVmnd-2 have similar levels of viral replication, and we observed a trend toward lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1-infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected MNDs could be established. Of note, the levels of T cell activation, proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2-infected MNDs and to those observed in uninfected animals, with the only exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous observations in SIV-infected SMs and AGMs and lend further evidence to the hypothesis that low levels of immune activation protect natural SIV hosts from disease progression.
Assuntos
Mandrillus/imunologia , Mandrillus/virologia , Doenças dos Primatas/imunologia , Doenças dos Primatas/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/isolamento & purificação , Animais , Apoptose , Sangue/imunologia , Contagem de Linfócito CD4 , Proliferação de Células , Estudos Transversais , Linfonodos/imunologia , Ativação Linfocitária , Linfócitos/imunologia , Vírus da Imunodeficiência Símia/classificação , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Carga ViralRESUMO
Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus responsible for numerous outbreaks. Chikungunya can cause debilitating acute and chronic disease. Thus, the development of a safe and effective CHIKV vaccine is an urgent global health priority. This study evaluated the effectiveness of the live-attenuated CHIKV vaccine VLA1553 against WT CHIKV infection by using passive transfer of sera from vaccinated volunteers to nonhuman primates (NHP) subsequently exposed to WT CHIKV and established a serological surrogate of protection. We demonstrated that human VLA1553 sera transferred to NHPs conferred complete protection from CHIKV viremia and fever after challenge with homologous WT CHIKV. In addition, serum transfer protected animals from other CHIKV-associated clinical symptoms and from CHIKV persistence in tissue. Based on this passive transfer study, a 50% micro-plaque reduction neutralization test titer of ≥ 150 was determined as a surrogate of protection, which was supported by analysis of samples from a seroepidemiological study. In conclusion, considering the unfeasibility of an efficacy trial due to the unpredictability and explosive, rapidly moving nature of chikungunya outbreaks, the definition of a surrogate of protection for VLA1553 is an important step toward vaccine licensure to reduce the medical burden caused by chikungunya.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Animais , Anticorpos Antivirais , Febre de Chikungunya/prevenção & controle , Humanos , Estudos Soroepidemiológicos , Vacinas AtenuadasRESUMO
The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising in vitro results to successful clinical implementation. Among the drugs that have been largely tested in clinical trials but failed so far to bring clear evidence of clinical efficacy is favipiravir, a nucleoside analogue with large spectrum activity against several RNA viruses in vitro and in small animal models. Here, we evaluate the antiviral activity of favipiravir against Zika or SARS-CoV-2 virus in cynomolgus macaques. In both models, high doses of favipiravir are initiated before infection and viral kinetics are evaluated during 7 to 15 days after infection. Favipiravir leads to a statistically significant reduction in plasma Zika viral load compared to untreated animals. However, favipiravir has no effects on SARS-CoV-2 viral kinetics, and 4 treated animals have to be euthanized due to rapid clinical deterioration, suggesting a potential role of favipiravir in disease worsening in SARS-CoV-2 infected animals. To summarize, favipiravir has an antiviral activity against Zika virus but not against SARS-CoV-2 infection in the cynomolgus macaque model. Our results support the clinical evaluation of favipiravir against Zika virus but they advocate against its use against SARS-CoV-2 infection.