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1.
PLoS One ; 16(1): e0245547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444422

RESUMO

Endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are members of the family Coronaviridae. Comparing the findings of the infections caused by these viruses would help reveal the novel characteristics of SARS-CoV-2 and provide insight into the unique pathogenesis of SARS-CoV-2 infection. This study aimed to compare the clinical and radiological characteristics of SARS-CoV-2 and endemic HCoVs infection in adult hospitalized patients with community-acquired pneumonia (CAP). This study was performed at a university-affiliated tertiary hospital in the Republic of Korea, between January 1, 2015, and July 31, 2020. A total of 109 consecutive patients who were over 18 years of age with confirmed SARS-CoV-2 and endemic HCoVs were enrolled. Finally, 19 patients with SARS-CoV-2 CAP were compared to 40 patients with endemic HCoV CAP. Flu-like symptoms such as cough, sore throat, headache, myalgia, and prolonged fever were more common in SARS-CoV-2 CAP, whereas clinical findings suggestive of bacterial pneumonia such as dyspnea, leukocytosis with left shift, and increased C-reactive protein were more common in endemic HCoV CAP. Bilateral peripherally distributed ground-glass opacities (GGOs) were typical radiologic findings in SARS-CoV-2 CAP, whereas mixed patterns of GGOs, consolidations, micronodules, and pleural effusion were observed in endemic HCoV CAP. Coinfection was not observed in patients with SARS-CoV-2 CAP, but was observed in more than half of the patients with endemic HCoV CAP. There were distinctive differences in the clinical and radiologic findings between SARS-CoV-2 and endemic HCoV CAP. Further investigations are required to elucidate the mechanism underlying this difference. Follow-up observations are needed to determine if the presentation of SARS-CoV-2 CAP changes with repeated infection.


Assuntos
/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Idoso , /patologia , Estudos de Coortes , Coinfecção/diagnóstico por imagem , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Infecções Comunitárias Adquiridas , Coronavirus/isolamento & purificação , Doenças Endêmicas , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Radiografia Torácica/métodos , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tórax/diagnóstico por imagem
2.
Pediatr Infect Dis J ; 40(1): e36-e39, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33044434

RESUMO

The clinical presentation of human coronavirus (HCoV) infections in children varies strongly. We show that children with an HCoV-associated lower respiratory tract infection more frequently had respiratory syncytial virus codetected and higher abundance of Haemophilus influenzae/haemolyticus than asymptomatic HCoV carriers as well as children with a non-HCoV-associated lower respiratory tract infection. Viral and bacterial cooccurrence may drive symptomatology of HCoV-associated infections including coronavirus disease 2019.


Assuntos
Coinfecção/microbiologia , Coinfecção/virologia , Infecções por Coronavirus/patologia , Infecções Respiratórias/patologia , Bactérias/classificação , Bactérias/isolamento & purificação , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/patologia , Coronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Feminino , Haemophilus/classificação , Haemophilus/isolamento & purificação , Humanos , Lactente , Masculino , Países Baixos/epidemiologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Estações do Ano , Índice de Gravidade de Doença
3.
Pediatr Infect Dis J ; 40(1): e12-e17, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33165274

RESUMO

BACKGROUND: Human coronaviruses (HCoVs) are a significant cause of acute respiratory illness (ARI) in children; however, the role of HCoVs in ARI among hospitalized children in the Middle East is not well defined. METHODS: Children under 2 years admitted with fever and/or respiratory symptoms were enrolled from 2010 to 2013 in Amman, Jordan. Nasal/throat swabs were collected and stored for testing. Demographic and clinical characteristics were collected through parent/guardian interviews and medical chart abstractions. Prior stored specimens were tested for HCoVs (HKU1, OC43, 229E and NL63) by qRT-PCR. RESULTS: Of the 3168 children enrolled, 6.7% were HCoVs-positive. Among HCoV-positive children, the median age was 3.8 (1.9-8.4) months, 59% were male, 14% were premature, 11% had underlying medical conditions and 76% had viral-codetection. The most common presenting symptoms were cough, fever, wheezing and shortness of breath. HCoVs were detected year-round, peaking in winter-spring months. Overall, 56%, 22%, 13% and 6% were OC43, NL63, HKU1 and 229E, respectively. There was no difference in disease severity between the species, except higher intensive care unit admission frequency in NL63-positive subjects. CONCLUSIONS: HCoVs were detected in around 7% of children enrolled in our study. Despite HCoV detection in children with ARI with highest peaks in respiratory seasons, the actual burden and pathogenic role of HCoVs in ARI merits further evaluation given the high frequency of viral codetection.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavirus/isolamento & purificação , Doença Aguda , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Coronavirus/classificação , Coronavirus/genética , Infecções por Coronavirus/patologia , Feminino , Hospitalização , Humanos , Lactente , Jordânia/epidemiologia , Masculino , Vigilância da População , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Fatores de Risco , Estações do Ano , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificação
4.
Diagn Microbiol Infect Dis ; 98(4): 115199, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979617

RESUMO

COVID-19 positive (194) and negative (212) pneumonia patients were selected to analyze bacterial pathogens coinfection. Results showed that 50% of COVID-19 patients were coinfected or carried bacterial pathogens. Bordetella pertussis infection rate was significantly higher in positive patients. Consequently, preventions should be taken to control bacterial pathogens coinfection in COVID-19 patients.


Assuntos
Coinfecção/epidemiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Infecções por Pseudomonas/epidemiologia , Coqueluche/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Bordetella pertussis/isolamento & purificação , Criança , Pré-Escolar , Coinfecção/microbiologia , Coinfecção/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologia , Adulto Jovem
6.
BMC Infect Dis ; 20(1): 588, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770955

RESUMO

BACKGROUND: Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015-2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling. METHODS: A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall. RESULTS: Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030. CONCLUSION: Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.


Assuntos
Infecções por HIV/patologia , Hepatite C/diagnóstico , Modelos Teóricos , Antivirais/uso terapêutico , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/patologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Estudos Prospectivos , Espanha/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Resposta Viral Sustentada
7.
Allergol Immunopathol (Madr) ; 48(5): 500-506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771236

RESUMO

The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS-CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Adulto , Fatores Etários , Portador Sadio/transmissão , Portador Sadio/virologia , Criança , Coinfecção/epidemiologia , Coinfecção/imunologia , Coinfecção/patologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Humanos , Sistema Imunitário , Estilo de Vida , Melatonina/imunologia , Melatonina/metabolismo , Pandemias , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Vacinas Pneumocócicas/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia
8.
Parasitol Res ; 119(10): 3535-3539, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681193

RESUMO

Parasites co-infecting hosts can interact directly and indirectly to affect parasite growth and disease manifestation. We examined potential interactions between two common parasites of house finches: the bacterium Mycoplasma gallisepticum that causes conjunctivitis and the intestinal coccidian parasite Isospora sp. We quantified coccidia burdens prior to and following experimental infection with M. gallisepticum, exploiting the birds' range of natural coccidia burdens. Birds with greater baseline coccidia burdens developed higher M. gallisepticum loads and longer lasting conjunctivitis following inoculation. However, experimental inoculation with M. gallisepticum did not appear to alter coccidia shedding. Our study suggests that differences in immunocompetence or condition may predispose some finches to more severe infections with both pathogens.


Assuntos
Doenças das Aves/patologia , Tentilhões , Isospora/fisiologia , Infecções por Mycoplasma/veterinária , Mycoplasma gallisepticum/fisiologia , Carga Parasitária/veterinária , Animais , Doenças das Aves/microbiologia , Doenças das Aves/parasitologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/patologia , Coinfecção/veterinária , Conjuntivite Bacteriana/microbiologia , Conjuntivite Bacteriana/parasitologia , Conjuntivite Bacteriana/patologia , Conjuntivite Bacteriana/veterinária , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/parasitologia , Suscetibilidade a Doenças/veterinária , Tentilhões/microbiologia , Tentilhões/parasitologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/parasitologia , Infecções por Mycoplasma/patologia
9.
Jpn J Infect Dis ; 73(5): 377-380, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32475878

RESUMO

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.


Assuntos
Coinfecção/diagnóstico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Infecções Respiratórias/diagnóstico , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , Coinfecção/patologia , Coinfecção/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Japão/epidemiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia
10.
Influenza Other Respir Viruses ; 14(6): 739-746, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32567818

RESUMO

BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the impacts of coinfection on disease severity are less understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in Nepal. Prospective weekly household-based active surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT-PCR. Coinfection was defined as the presence of two or more respiratory viruses detected as part of the same illness episode. RESULTS: Of 1730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected in their primary illness episode. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. The cohort of infants with coinfection had increased occurrence of fever lasting ≥ 4 days (OR 1.4, 95% CI: 1.1, 2.0), and so did the subset of coinfected infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 0.96, 1.6). CONCLUSION: A high proportion of infants had multiple viruses detected. Coinfection was associated with greater odds of fever lasting for four or more days, but not with increased illness severity by other measures.


Assuntos
Coinfecção/epidemiologia , Coinfecção/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Coinfecção/patologia , Febre/epidemiologia , Febre/patologia , Febre/virologia , Humanos , Lactente , Recém-Nascido , Nepal/epidemiologia , Razão de Chances , Estudos Prospectivos , Infecções Respiratórias/patologia , População Rural , Viroses/epidemiologia , Viroses/patologia , Viroses/virologia , Vírus/classificação , Vírus/isolamento & purificação
11.
PLoS Pathog ; 16(5): e1008585, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433713

RESUMO

Mucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use peripheral blood cells. Whether MAIT cells are recruited to Mtb-affected granulomas and lymph nodes (LNs) during early Mtb infection and what purpose they might serve there is less well understood. Furthermore, whether HIV/SIV infection impairs MAIT cell frequency or function at the sites of Mtb replication has not been determined. Using Mauritian cynomolgus macaques (MCM), we phenotyped MAIT cells in the peripheral blood and bronchoalveolar lavage (BAL) before and during infection with SIVmac239. To test the hypothesis that SIV co-infection impairs MAIT cell frequency and function within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb Erdman, and necropsied at 6 weeks post Mtb-challenge. MAIT cell frequency and function were examined within the peripheral blood, BAL, and Mtb-affected lymph nodes (LN) and granulomas. MAIT cells did not express markers indicative of T cell activation in response to Mtb in vivo within granulomas in animals infected with Mtb alone. SIV and Mtb co-infection led to increased expression of the activation/exhaustion markers PD-1 and TIGIT, and decreased ability to secrete TNFα when compared to SIV-naïve MCM. Our study provides evidence that SIV infection does not prohibit the recruitment of MAIT cells to sites of Mtb infection, but does functionally impair those MAIT cells. Their impaired function could have impacts, either direct or indirect, on the long-term containment of TB disease.


Assuntos
Coinfecção/imunologia , Células T Invariáveis Associadas à Mucosa/imunologia , Mycobacterium tuberculosis/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Tuberculose Pulmonar/imunologia , Animais , Coinfecção/patologia , Granuloma/imunologia , Granuloma/patologia , Linfonodos/imunologia , Linfonodos/patologia , Macaca fascicularis , Células T Invariáveis Associadas à Mucosa/patologia , Receptor de Morte Celular Programada 1/imunologia , Receptores Imunológicos/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Tuberculose Pulmonar/patologia
12.
Indian J Gastroenterol ; 39(2): 186-195, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32436176

RESUMO

BACKGROUND: Though a few studies in animal models suggest that intestinal helminths (IH) favorably affect evolution of gastritis associated with Helicobacter pylori (H. pylori) the studies supporting this concept in humans are only a few and are based on serological data. METHODS: To evaluate the possible influence of IH on the human gastric mucosa, three groups of Venezuelan adults with gastropathy (endoscopically diagnosed) were studied: H. pylori-/IH- (n = 17), H. pylori+/IH- (n = 18), and H. pylori+/IH+ (n = 11). Histological analysis (hematoxylin-eosin) and immunohistochemical staining (peroxidase) for cytokines interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin 4 (IL-4) were undertaken in gastric antral biopsies. RESULTS: Expression of the four cytokines was detected in all individuals in varying degrees, but proinflammatory cytokines were expressed in a higher degree in the H. pylori+/IH- group, mainly IL-1ß (Th1-dominant immune response), associated with a higher degree of both histological inflammation and gastric cancer risk index (GCRI), as compared to the H. pylori-/IH- group. In contrast, an increased expression of IL-4 and a reduced expression of proinflammatory cytokines (Th2-dominant response), plus the tendency to a lower degree of mononuclear infiltration, mucosal atrophy in gastric corpus, and GCRI, were evidenced in the coinfected group. CONCLUSIONS: The findings of the present study is perhaps the first histological evidence of a possible modulatory effect of IH on the gastric mucosal inflammatory response due to H. pylori infection in humans.


Assuntos
Coinfecção/metabolismo , Coinfecção/patologia , Citocinas/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter , Helicobacter pylori , Mediadores da Inflamação/metabolismo , Enteropatias Parasitárias/metabolismo , Enteropatias Parasitárias/patologia , Adolescente , Adulto , Atrofia , Coinfecção/imunologia , Feminino , Mucosa Gástrica/imunologia , Gastrite/imunologia , Gastrite/metabolismo , Humanos , Imuno-Histoquímica , Enteropatias Parasitárias/imunologia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Parasit Vectors ; 13(1): 109, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111243

RESUMO

BACKGROUND: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.


Assuntos
Coinfecção/patologia , Coinfecção/veterinária , Hepatopatias Parasitárias/patologia , Hepatopatias Parasitárias/veterinária , Esquistossomose/patologia , Esquistossomose/veterinária , Tricuríase/patologia , Tricuríase/veterinária , Doenças dos Animais/parasitologia , Doenças dos Animais/patologia , Animais , Doença Crônica , Coinfecção/parasitologia , Feminino , Granuloma/patologia , Humanos , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Hepatopatias Parasitárias/parasitologia , Masculino , Papio , Contagem de Ovos de Parasitas , Projetos Piloto , Primatas , Schistosoma mansoni , Esquistossomose/parasitologia , Transcriptoma , Tricuríase/parasitologia , Trichuris
15.
PLoS Pathog ; 16(2): e1008240, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106253

RESUMO

Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen is particularly relevant in HIV+ patients, where it leads to around 200,000 deaths per annum. A key feature of cryptococcal pathogenesis is the ability of the fungus to survive and replicate within the phagosome of macrophages, as well as its ability to be expelled from host cells via a novel non-lytic mechanism known as vomocytosis. Here we show that cryptococcal vomocytosis from macrophages is strongly enhanced by viral coinfection, without altering phagocytosis or intracellular proliferation of the fungus. This effect occurs with distinct, unrelated human viral pathogens and is recapitulated when macrophages are stimulated with the anti-viral cytokines interferon alpha or beta (IFNα or IFNß). Importantly, the effect is abrogated when type-I interferon signalling is blocked, thus underscoring the importance of type-I interferons in this phenomenon. Lastly, our data help resolve previous, contradictory animal studies on the impact of type I interferons on cryptococcal pathogenesis and suggest that secondary viral stimuli may alter patterns of cryptococcal dissemination in the host.


Assuntos
Coinfecção , Criptococose , Cryptococcus neoformans , Infecções por HIV , HIV-1 , Macrófagos , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/patologia , Coinfecção/virologia , Criptococose/imunologia , Criptococose/microbiologia , Criptococose/patologia , Criptococose/virologia , Cryptococcus neoformans/imunologia , Cryptococcus neoformans/patogenicidade , Células HEK293 , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Interferon-alfa/imunologia , Interferon beta/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/virologia , Transdução de Sinais/imunologia
16.
J Immunol ; 204(5): 1274-1286, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953351

RESUMO

Helminth infections are known to influence T and B cell responses in latent tuberculosis infection (LTBI). Whether helminth infections also modulate monocyte responses in helminth-LTBI coinfection has not been fully explored. To this end, we examined the activation, polarization, and function of human monocytes isolated from individuals with LTBI with (n = 25) or without (n = 25) coincident Strongyloides stercoralis infection (S. stercoralis-positive and S. stercoralis-negative respectively). Our data reveal that the presence of S. stercoralis infection is associated with lower frequencies of monocytes expressing CD54, CD80, CD86 at baseline (absence of stimulation) and in response to mycobacterial-Ag stimulation than monocytes from S. stercoralis-negative individuals. In contrast, S. stercoralis infection was associated with higher frequencies of M2-like monocytes, as determined by expression of CD206 and CD163. Monocytes from S. stercoralis-positive individuals had a reduced capacity to phagocytose or exhibit respiratory burst activity following mycobacterial-Ag or LPS stimulation and were less capable of expression of IL-1ß, TNF-α, IL-6, and IL-12 at baseline and/or following Ag stimulation compared with those without S. stercoralis infection. In addition, definitive treatment of S. stercoralis infection resulted in a significant reversal of the altered monocyte function 6 mo after anthelmintic therapy. Finally, T cells from S. stercoralis-positive individuals exhibited significantly lower activation at baseline or following mycobacterial-Ag stimulation. Therefore, our data highlight the induction of dampened monocyte activation, enhanced M2 polarization, and impaired monocyte function in helminth-LTBI coinfection. Our data also reveal a different mechanism by which helminth infection modulates immune function in LTBI.


Assuntos
Coinfecção , Monócitos , Mycobacterium tuberculosis/imunologia , Strongyloides stercoralis/imunologia , Estrongiloidíase , Adulto , Animais , Antígenos CD/imunologia , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/patologia , Citocinas/imunologia , Feminino , Humanos , Tuberculose Latente/imunologia , Tuberculose Latente/parasitologia , Tuberculose Latente/patologia , Masculino , Monócitos/imunologia , Monócitos/patologia , Estrongiloidíase/imunologia , Estrongiloidíase/microbiologia , Estrongiloidíase/patologia
17.
Infect Immun ; 88(4)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31932329

RESUMO

Stenotrophomonas maltophilia is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. S. maltophilia is increasingly observed in patient sputa in cystic fibrosis (CF), and while existing epidemiology indicates that patients with S. maltophilia have poorer diagnoses, its clinical significance remains unclear. Moreover, as multidrug resistance is common among S. maltophilia isolates, treatment options for these infections may be limited. Here, we investigated the pathogenicity of S. maltophilia alone and during polymicrobial infection with Pseudomonas aeruginosa Colonization, persistence, and virulence of S. maltophilia were assessed in experimental respiratory infections of mice. The results of this study indicate that S. maltophilia transiently colonizes the lung accompanied by significant weight loss and immune cell infiltration and the expression of early inflammatory markers, including interleukin 6 (IL-6), IL-1α, and tumor necrosis factor alpha (TNF-α). Importantly, polymicrobial infection with P. aeruginosa elicited significantly higher S. maltophilia counts in bronchoalveolar lavages and lung tissue homogenates. This increase in bacterial load was directly correlated with the density of the P. aeruginosa population and required viable P. aeruginosa bacteria. Microscopic analysis of biofilms formed in vitro revealed that S. maltophilia formed well-integrated biofilms with P. aeruginosa, and these organisms colocalize in the lung during dual-species infection. Based on these results, we conclude that active cellular processes by P. aeruginosa afford a significant benefit to S. maltophilia during polymicrobial infections. Furthermore, these results indicate that S. maltophilia may have clinical significance in respiratory infections.


Assuntos
Coinfecção/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Interações Microbianas , Pneumonia Bacteriana/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Stenotrophomonas maltophilia/crescimento & desenvolvimento , Animais , Carga Bacteriana , Peso Corporal , Líquido da Lavagem Broncoalveolar/microbiologia , Coinfecção/patologia , Modelos Animais de Doenças , Infecções por Bactérias Gram-Negativas/patologia , Imunidade Inata , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Pneumonia Bacteriana/patologia
18.
Cancer ; 126(7): 1470-1479, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31977082

RESUMO

BACKGROUND: Electrocautery ablation (EA) is a common treatment modality for patients with anal high-grade squamous intraepithelial lesions (HSILs), but to the authors' knowledge its effectiveness has been understudied. The objective of the current study was to determine ablation outcomes and to identify clinicopathological factors associated with postablation disease recurrence. METHODS: A total of 330 people living with HIV with de novo intra-anal HSIL who were treated with EA from 2009 to 2016 were studied retrospectively. Using long-term, surveillance high-resolution anoscopy biopsy data, treatment failures were classified as local recurrence (HSIL noted at the treated site at the time of surveillance) or overall recurrence (HSIL noted at treated or untreated sites). The associations between these outcomes and clinical factors were analyzed using Cox proportional hazards models. RESULTS: Approximately 88% of participants were men who have sex with men. The median age of study  participants was 45.5 years (range, 35-51 years) and approximately 49% had multiple index HSILs (range, 2-6 index HSILs). At a median of 12.2 months postablation (range, 6.3-20.9 months postablation), approximately 45% of participants had developed local recurrence whereas 60% had developed overall recurrence. Current cigarette smoking, HIV viremia (HIV-1 RNA ≥100 copies/mL), and multiple index HSILs were found to be predictive of local recurrence. Overall recurrence was more common in current smokers and those with multiple index lesions. In multivariable models that included human papillomavirus (HPV) genotypes, baseline and persistent infections with HPV-16 and/or HPV-18 were found to be significantly associated with both local and overall recurrence. CONCLUSIONS: EA is an effective treatment modality for anal HSIL in people living with HIV, but rates of disease recurrence are substantial. Multiple index HSILs, HIV viremia, current cigarette smoking, and both baseline and persistent infection with HPV-16 and/or HPV-18 appear to negatively impact treatment success. Ongoing surveillance is imperative to capture recurrence early and improve long-term treatment outcomes.


Assuntos
Neoplasias do Ânus/cirurgia , Neoplasias do Ânus/virologia , Lesões Intraepiteliais Escamosas/cirurgia , Lesões Intraepiteliais Escamosas/virologia , Adulto , Neoplasias do Ânus/patologia , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Eletrocoagulação , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Fatores de Risco , Lesões Intraepiteliais Escamosas/patologia , Resultado do Tratamento
19.
BMC Infect Dis ; 20(1): 59, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959123

RESUMO

BACKGROUND: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. METHODS: Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. RESULTS: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), CONCLUSIONS: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/genética , HIV-1 , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/genética , Tuberculose/complicações , Tuberculose/genética , Brasil , Coinfecção/tratamento farmacológico , Coinfecção/genética , Coinfecção/patologia , Feminino , Seguimentos , Frequência do Gene/genética , Marcadores Genéticos , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Síndrome Inflamatória da Reconstituição Imune/patologia , Masculino , Receptores KIR/genética , Fatores Sexuais , Tuberculose/tratamento farmacológico , Tuberculose/patologia
20.
J Biomed Sci ; 27(1): 20, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906962

RESUMO

BACKGROUND: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world's population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20-30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection. METHODS: A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles. RESULTS: Our results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome. CONCLUSIONS: We conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.


Assuntos
Coinfecção/imunologia , Desidroepiandrosterona/análogos & derivados , Infecções por HIV/imunologia , HIV-1/imunologia , Mycobacterium tuberculosis/imunologia , Células Th1/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Doença Crônica , Coinfecção/patologia , Estudos Transversais , Desidroepiandrosterona/imunologia , Desidroepiandrosterona/farmacologia , Feminino , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/patologia , Tuberculose Pulmonar/patologia
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