Science.gov

Sample records for acute hbv infection

  1. Occult infection with HBV intergenotypic A2/G recombinant following acute hepatitis B caused by an HBV/A2 isolate.

    PubMed

    de Barros, José Júnior França; Peres, Luciana Rego; de Sousa, Paulo Sérgio Fonseca; do Amaral Mello, Francisco Campello; de Araujo, Natalia Motta; de Andrade Gomes, Selma; Niel, Christian; Lewis-Ximenez, Lia Laura

    2015-06-01

    Viral and host factors leading to occult hepatitis B virus (HBV) infection (OBI) are not fully understood. Whether HBV genotype may influence the occurrence and course of OBIs is unknown. Here, we describe the case of a patient infected with HBV genotype A2 who developed symptomatic acute hepatitis and did not seroconvert after loss of HBsAg and HBeAg. The acute phase of hepatitis B was followed by a period of more than 2 years during which the DNA of an intergenotypic HBV/A2/G recombinant was intermittently detected in serum.

  2. Titration of hepatitis B virus infectivity in the sera of pre-acute and late acute phases of HBV infection: transmission experiments to chimeric mice with human liver repopulated hepatocytes.

    PubMed

    Tabuchi, Ayako; Tanaka, Junko; Katayama, Keiko; Mizui, Masaaki; Matsukura, Harumichi; Yugi, Hisao; Shimada, Takashi; Miyakawa, Yuzo; Yoshizawa, Hiroshi

    2008-12-01

    Studies of hepatitis B virus (HBV) infection in non-human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre-acute phases (i.e., rump-up viremia prior to anti-HBc) and late acute phases (i.e., declining phase of HBsAg and anti-HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 x 10(6) and 2.8 x 10(6) copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 microl of pre-acute serum (equivalent to 10(0) copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 microl of pre-acute serum (equivalent to 10(1) copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 microl of 1:10(4) dilution (equivalent to 10(1) copies of HBV DNA) of late-acute serum was infected, while only one of three chimeric mice inoculated with 100 microl of 1:10(3) dilution (equivalent to 10(2) copies of HBV DNA) of late-acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre-acute phase HBV serum is about 100-times more infectious than late acute phase serum.

  3. Analysis of Hepatitis B Virus Intrahepatic Covalently Closed Circular DNA and Serum Viral Markers in Treatment-Naive Patients with Acute and Chronic HBV Infection

    PubMed Central

    Zou, Zhengsheng; Liu, Yan; Li, Baosen; Sun, Ying; Li, Xiaodong; Liu, Shuhong; Cai, Shaoping; Yao, Weimin; Xin, Shaojie; Lu, Fengmin; Xu, Dongping

    2014-01-01

    Background This study aimed to investigate the relationships of intrahepatic cccDNA with serum HBsAg and with HBV DNA in treatment-naive patients throughout acute and chronic HBV infection. Methods A total of 120 patients who had a liver biopsy were enrolled, including 19 with acute hepatitis B (AHB), and 101 patients with chronic HBV infection (CHB) of whom were 10 in immune-tolerant (IT) phase, 59 in immune-clearance (IC) phase, 8 in low-replicative (LR) phase, and 24 in HBeAg-negative hepatitis (ENH) phase. Intrahepatic cccDNA, serum HBsAg and serum HBV DNA levels were comparatively analyzed. Results The median intrahepatic cccDNA levels were 0.18 4.80, 3.81, 0.22 and 0.97 copies/cell for patients with AHB, CHB-IT, CHB-IC, CHB-LR, and CHB-ENH, respectively. In AHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg (r = 0.665, P = 0.003), as well as serum HBV DNA (r = 0.536, P = 0.022). In CHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg in the IC phase (r = 0.392, P = 0.005), and with serum HBV DNA in the IC phase (r = 0.301, P = 0.036) and ENH phase (r = 0.588, P = 0.013). HBV replicative efficiency, defined as the ratio of serum HBV DNA to intrahepatic cccDNA, was obviously lower in AHB and CHB-LR patients than in CHB-IT, CHB-IC and CHB-ENH patients (0.70 and 0.53 vs. 1.12, 1.09 and 0.99, P<0.001, values were logarithmic transformed for analysis). In CHB-IC patients, HBV replicative efficiency was positively correlated with histological activity index of liver inflammation (r = 0.308, P = 0.009). Conclusion Serum HBsAg and HBV DNA levels may reflect the amount of active intrahepatic cccDNA in treatment-naive AHB and CHB-IC patients. Reduced intrahepatic cccDNA and HBV replicative efficiency may imply effective immune control of HBV infection. PMID:24551214

  4. HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases.

    PubMed

    Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng

    2016-01-01

    Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7-20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular "hump-shape" immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis.

  5. HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases

    PubMed Central

    Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng

    2016-01-01

    Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989

  6. HIV-HBV vaccine escape mutant infection with loss of HBV surface antibody and persistent HBV viremia on tenofovir/emtricitabine without antiviral resistance.

    PubMed

    Schirmer, P; Winters, M; Holodniy, M

    2011-11-01

    We report a case of acute hepatitis B virus genotype A vaccine escape mutant infection with loss of HBV vaccine-induced seropositivity in a HIV-1 infected patient. His HBV is unresponsive to tenofovir/emtricitabine treatment demonstrated by persistent viremia despite lacking known resistance mutations and while having an undetectable HIV-1 viral load. PMID:21840252

  7. Rethinking the pathogenesis of hepatitis B virus (HBV) infection.

    PubMed

    Zhang, Yong-Yuan; Hu, Ke-Qin

    2015-12-01

    Chronic hepatitis B virus (HBV) infection affects approximately 375 million people worldwide. Current antiviral treatment effectively controls, but rarely clears chronic HBV infection. In addition, a significant portion of chronic HBV infected patients are not suitable for currently available antiviral therapy, and still face higher risk for cirrhosis and hepatocellular carcinoma. The poorly understood pathogenesis of HBV infection is the main barrier for developing more effective treatment strategies. HBV has long been viewed as non-cytopathic and the central hypothesis for HBV pathogenesis lies in the belief that hepatitis B is a host specific immunity-mediated liver disease. However, this view has been challenged by the accumulating experimental and clinical data that support a model of cytopathic HBV replication. In this article we systematically review the pathogenic role of HBV replication in hepatitis B and suggest possible HBV replication related mechanisms for HBV-mediated liver injury. We propose that a full understanding of HBV pathogenesis should consider the following elements. I. Liver injury can be caused by high levels of HBV replication and accumulation of viral products in the infected hepatocytes. II. HBV infection can be either directly cytopathic, non-cytopathic, or a mix of both in an individual patient depending upon accumulation levels of viral products that are usually associated with HBV replication activity in individual infected hepatocytes.

  8. Management of HBV infection in Japan.

    PubMed

    Minami, Masahito; Okanoue, Takeshi

    2007-07-01

    Hepatitis B virus (HBV) is usually transmitted from mother to infant, and genotype C is prevalent in Japan. Because of these features, guidelines for HBV treatment from other countries are not directly adaptable to Japanese patients. Age is an important factor in deciding the treatment strategy, because many vertically transmitted HBV carriers naturally show spontaneous remission by the age of 25-30 years. In addition, genotype C is considered more refractory to antiviral therapies than genotypes A and B. Considering these differences, we propose a treatment for HBV in Japanese patients. Although the guidelines indicate who to treat and when therapy should be started, it is unclear for how long patientsshould be treated. This situation arises because current lamivudine and interferon monotherapies are not potent at curing HBV infection. To develop a more efficient treatment, we performed a pilot study of lamivudine/interferon sequential therapy in Japan. The biochemical and virological responses were comparable or superior to lamivudine or interferon monotherapies, and this protocol can be a potent alternative because we can take advantage of both the mild side-effects of lamivudine and finite duration of interferon.

  9. Global strategies are required to cure and eliminate HBV infection.

    PubMed

    Revill, Peter; Testoni, Barbara; Locarnini, Stephen; Zoulim, Fabien

    2016-04-01

    Chronic HBV infection results in >1 million deaths per year from cirrhosis and liver cancer. No known cure for chronic HBV exists, due in part to the continued presence of transcriptionally active DNA in the nucleus that is not directly targeted by current antiviral therapies. A coordinated approach is urgently needed to advance an HBV cure worldwide, such as those established in the HIV field. We propose the establishment of an International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) to facilitate the formation of international working groups on HBV virology, immunology, innovative tools and clinical trials: to promote awareness and education as well as to drive changes in government policy and ensure funds are channelled to HBV cure research and drug development. With the ICE-HBV in place, it should be possible to enable a HBV cure within the next decade. PMID:26907881

  10. Clinical Relevance of HLA Gene Variants in HBV Infection

    PubMed Central

    Wang, Li; Zou, Zhi-Qiang; Wang, Kai

    2016-01-01

    Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection. PMID:27243039

  11. If You Have Chronic Hepatitis B Virus (HBV) Infection

    MedlinePlus

    If you have chronic hepatitis B virus (HBV) infection . . . If you have chronic hepatitis B virus (HBV) infection, you are not alone. Today, approximately one ... receive pneumococcal polysaccharide vac- cine.  Get vaccinated against hepatitis A. Hepati- tis A can further damage your ...

  12. Trained immunity in newborn infants of HBV-infected mothers

    PubMed Central

    Hong, Michelle; Sandalova, Elena; Low, Diana; Gehring, Adam J.; Fieni, Stefania; Amadei, Barbara; Urbani, Simonetta; Chong, Yap-Seng; Guccione, Ernesto; Bertoletti, Antonio

    2015-01-01

    The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero. PMID:25807344

  13. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    PubMed

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

  14. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    PubMed

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity. PMID:22235298

  15. [Control of HCV, HBV and HIV Infections in Hemodialysis].

    PubMed

    Fabrizi, Fabrizio; Martin, Paul; Messa, Piergiorgio

    2013-01-01

    Infections with blood-borne pathogens are still common among patients on maintenance dialysis all over the world. The control of infection due to blood-borne viruses (particularly HBV) within dialysis units has been a major goal in the management of patients with chronic kidney disease in the industrialized world. Standard precautions and specific procedures have been recommended to prevent infections with HBV, HCV and HIV within dialysis units. Isolation of HBsAg positive patients by dialysis rooms, staff and machines continues to be an important step to control HBV infection within dialysis units, according to the CDC and other regulatory agencies. Some prospective observational studies have reported the complete prevention of HCV transmission to hemodialysis patients in the absence of any isolation policy, and the use of dedicated dialysis machines for HCV-infected patients is not recommended by clinical guidelines. Isolation of HCV-infected patients should be considered in special circumstances only. Vaccination is an important tool against transmission of HBV among patients on long-term dialysis even if the immune response towards the hepatitis B vaccine remains unsatisfactory. Hemodialysis is considered a low risk setting for the transmission of human immunodeficiency virus (HIV) infection, providing that standard and specific procedures are carefully observed. HIV-infected patients do not have to be isolated from other patients or dialyzed separately on dedicated machines.

  16. Hepatitis B virus (HBV) X gene diversity and evidence of recombination in HBV/HIV co-infected persons.

    PubMed

    Martin, Christina M; Welge, Jeffrey A; Blackard, Jason T

    2011-07-01

    The high frequency of mutation during hepatitis B virus (HBV) infection has resulted in 8 genotypes (A-H) with varying effects on disease severity and treatment efficacy. However, analysis of intrapatient HBV diversity is limited, especially during HIV co-infection. Therefore, a preliminary study was performed to analyze HBV X gene diversity in 17 HBV/HIV co-infected individuals. Phylogenetic analysis revealed HBV genotype A in 13 individuals (76.5%) or genotype E in 1 individual (5.9%). Additionally, 3 individuals were dually infected with HBV genotypes A and G (17.6%). Overall, higher genetic distance and entropy were observed in the X region and overlapping polymerase (Pol(X)) regions when compared to the PreS, S, and overlapping polymerase (Pol(PS) and Pol(S)) regions analyzed in the same patients as part of a previous study. In addition, multiple viral variants from 2 individuals with dual HBV infection did not group with either genotype A or G by phylogenetic analysis, indicating possible recombination. SimPlot bootscan analysis confirmed recombination breakpoints within the X gene in both individuals. Recombination between HBV genotypes may represent an important evolutionary strategy that enhances overall pathogenic potential and/or alters the downstream effects of the HBV X protein.

  17. Molecular epidemiology of HBV infection in chronic hepatitis B virus infected patients in northeast India.

    PubMed

    Saikia, Anjan; Bose, Moumita; Barman, Narendra Nath; Deka, Manab; Thangkhiew, Rangsan Singh; Bose, Sujoy

    2015-09-01

    The present study aimed to evaluate the molecular epidemiology of HBV in chronic HBV infected cases from northeast India (NEI), since scanty data are available from the region which has a predominant ethnically distinct tribal population. A total of 523 clinically diagnosed index chronic HBV infected cases and 172 asymptomatic patients (based on family screening) were enrolled with informed consent. Patients were stratified based on serology, imaging, pathology, and clinical data and grouped as chronic HBV and cirrhotic cohorts. Analysis for serum HBV DNA levels and HBV genotyping was performed, and was statistically co-related with disease severity. Males were more prone to chronic HBV infection. Majority of the patients who had Chronic HBV infection based on family screening were females (59.88%), majorly wives of index patients. Mean viral load in Chronic HBV patients was almost 4.5-folds higher than cirrhosis patients, and was significantly associated with e-antigen positive status(P < 0.001) in both groups. HBV genotype D was the most prevalent genotype (62.30%) in NEI. Mixed genotype infection of A + D was found from Assam, along with C + D cases (1.29%) cumulatively. There is a high prevalence of HBV genotype C (13.96%) in our studied cohort which was found to be associated with higher viral load(P = 0.018), e-antigen positivity(P = 0.043), and increased cirrhosis risk compared to Chronic HBV cases [OR = 1.670]. Family contacts in NEI are prone to infection with HBV and development of Chronic HBV. Higher presence of e-positive cases and genotype C along with the mixed genotypes in NEI is unique and of significance with reference to predisposition to disease severity and even response to antiviral therapy.

  18. HBV vaccine efficacy and detection and genotyping of vaccineé asymptomatic breakthrough HBV infection in Egypt

    PubMed Central

    Abushady, Eman AE; Gameel, Magda MA; Klena, John D; Ahmed, Salwa F; Abdel-Wahab, Kouka SE; Fahmy, Sanya M

    2011-01-01

    AIM: To evaluate the impact of mass vaccination against the hepatitis B virus (HBV) in Egypt, and to search for vaccinee asymptomatic breakthrough HBV infection and its genotype. METHODS: Seven hundred serum samples from vaccinated children and adults (aged 2-47 years) were used for quantitative and qualitative detection of HBsAb by ELISA. Three hundred and sixty serum samples representing undetectable or low or high HBsAb were screened for markers of active HBV infection (HBsAg, HBcAb (IgG) and HBeAb by ELISA, plus HBsAg by AxSYM) and HBV-DNA genotyping by nested multiplex PCR and by DNA sequencing. RESULTS: It was found that 65% of children aged 2-4 years, and 20.5% aged 4-13 years, as well as 45% adults were good responders to HBV vaccination mounting protective level HBsAb. Poor responders were 28%, 59.5% and 34%, and non-responders were 7%, 20% and 21% respectively, in the three studied groups. Markers of asymptomatic HBV infections were HBsAg detected by ELISA in 2.5% vs 11.39% by AxSYM. Other markers were HBcAb (IgG) in 1.38%, HBeAb in 0.83%, and HBV-DNA in 7.8%. All had HBV genotype E infection. CONCLUSION: It is concluded that HBV vaccine is efficient in controlling HBV infection among children and adults. The vaccine breakthrough infection was by HBV genotype E. A booster dose of vaccine is recommended, probably four years after initial vaccination. PMID:21860674

  19. High Seroprevalence of HBV and HCV Infection in HIV-Infected Adults in Kigali, Rwanda

    PubMed Central

    Rusine, John; Ondoa, Pascale; Asiimwe-Kateera, Brenda; Boer, Kimberly R.; Uwimana, Jean Marie; Mukabayire, Odette; Zaaijer, Hans; Mugabekazi, Julie; Reiss, Peter; van de Wijgert, Janneke H.

    2013-01-01

    Background Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. Methods HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART. Results Baseline prevalence of active HBV infection (HBsAg positive), past or occult HBV infection (anti-HBc positive and HBsAg negative) and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY). In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21–14.47) more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01–1.06). Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04–1.14) while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40–0.98). The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88%) with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. Conclusion HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda. PMID:23717409

  20. A case of Gianotti Crosti syndrome with HBV infection.

    PubMed

    Dikici, B; Uzun, H; Konca, C; Kocamaz, H; Yel, S

    2008-01-01

    Gianotti-Crosti syndrome (papular acrodermatitis of childhood), which was first described in 1955, is a nonspecific rash that usually consists of the abrupt onset of pink flesh coloring, smooth or lichenoid, flat-topped papules. It was first related to hepatitis B virus (HBV) infection; however, cases not associated with HBV infection were reported as well. Although a type of delayed hypersensitivity reaction is speculated as a cause, exact pathogenesis still remains unclear. The prognosis is favorable and successful management relies upon general supportive and symptomatic care. We report a seven-year-old boy diagnosed with Gianotti-Crosti syndrome with monomorphous papules on his cheeks, buttocks and extremities associated with hepatitis B virus infection.

  1. Hepatitis B virus infection in blood donors in Argentina: prevalence of infection, genotype distribution and frequency of occult HBV infection.

    PubMed

    Pisano, María Belén; Blanco, Sebastián; Carrizo, Horacio; Ré, Viviana Elizabeth; Gallego, Sandra

    2016-10-01

    This study describes the prevalence of HBV infection based on detection of HBsAg and HBV-DNA by NAT in 70,102 blood donors in Argentina (Córdoba province) and shows the viral genotype distribution and frequency of occult HBV infection (OBI) in this population. Forty-two donors were confirmed positive for HBV infection (0.06 %), and four had OBI. Genotype F was the most prevalent (71.4 %), followed by A (14.3 %), C (7.1 %) and D (7.1 %). This is the first report of the prevalence of confirmed HBV infection and the high frequency of occult HBV infection in a blood bank in Argentina.

  2. Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy

    PubMed Central

    2011-01-01

    Background Occult hepatitis B virus (HBV) infection (OBI) is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease. Case presentation We report the case of an individual with human immunodeficiency virus (HIV) infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART). HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels. Conclusion This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals. PMID:22054111

  3. Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

    PubMed Central

    Morales-Romero, Jaime; Vargas, Gustavo; García-Román, Rebeca

    2014-01-01

    The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems. PMID:24717680

  4. Regulation of HBV-specific CD8(+) T cell-mediated inflammation is diversified in different clinical presentations of HBV infection.

    PubMed

    Dinney, Colin M; Zhao, Lu-Dong; Conrad, Charles D; Duker, Jay M; Karas, Richard O; Hu, Zhibin; Hamilton, Michele A; Gillis, Thomas R; Parker, Thomas M; Fan, Bing; Advani, Andrew H; Poordad, Fred B; Fauceglia, Paulette L; Kirsch, Kathrin M; Munk, Peter T; Ladanyi, Marc P; Bochner, Bernard A; Bekelman, Justin A; Grandori, Carla M; Olson, James C; Lechan, Ronald D; Abou, Ghassan M A; Goodarzi, Mark A

    2015-10-01

    Chronic HBV infection is the leading cause of liver cirrhosis and hepatic cancer, but the individual responses toward HBV infection are highly variable, ranging from asymptomatic to chronic active hepatitis B inflammation. In this study, we hypothesized that the different individual responses to HBV infection was associated with differences in HBV-specific CD8(+) T cell-mediated inflammation and cytotoxicity. Blood samples were collected from subjects with asymptomatic HBV-infection, subjects undergoing active chronic HBV flares (active CHB), and subjects with HBV-infected hepatocellular carcinoma (HBV-HCC). By tetramer staining, we found that all three groups had similar frequencies of HBVspecific CD8(+) T cells. However, after HBV peptide stimulation, the HBV-specific CD8(+) T cells in asymptomatic subjects had significantly stronger interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a expression than those in active CHB and HBV-HCC patients. Examination of surface marker expression revealed that the PD-1(-)Tim-3(-) double-negative cell population was the main contributor to HBV-specific inflammation. In active CHB patients and HBV-HCC patients, however, the frequencies of activated PD-1(-)Tim-3(-) cells were significantly reduced. Moreover, the serum HBV DNA titer was not correlated with the frequencies of HBV-specific CD8(+) T cells but was inversely correlated with the frequencies of IFN-g-expressing and CD107a-express cells in response to HBV stimulation. Together, our data demonstrated that the status of HBVspecific CD8(+) T cell exhaustion was associated with different clinical outcomes of chronic HBV infection.

  5. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients

    PubMed Central

    Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-01-01

    Background Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown. Principal Findings Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels. Conclusions/Significance Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine. PMID:27348302

  6. Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants.

    PubMed

    Kim, Hong; Kim, Bum-Joon

    2015-06-15

    Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea.

  7. Acute hepatitis B caused by a vaccine-escape HBV strain in vaccinated subject: sequence analysis and therapeutic strategy.

    PubMed

    Luongo, Monica; Critelli, Rosina; Grottola, Antonella; Gitto, Stefano; Bernabucci, Veronica; Bevini, Mirco; Vecchi, Chiara; Montagnani, Giuliano; Villa, Erica

    2015-01-01

    HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source.

  8. Immune mediated crescentic MPGN secondary to HBV infection: A rare presentation for a common infection.

    PubMed

    Mareddy, Aswani Srinivas; Rangaswamy, Dharshan; Vankalakunti, Mahesha; Attur, Ravindra Prabhu; Nagaraju, Shankar Prasad; Koti, Neeraja

    2016-01-01

    Hepatitis B virus (HBV) infection presenting as crescentic glomerulonephritis in the absence of cryoglobulinemia is an extremely rare phenomenon. We report a case of a 44-year-old male with HBV infection, who underwent kidney biopsy for rapidly progressive renal failure and nephrotic range proteinuria. Histopathological evaluation of the kidney biopsy was consistent with immune complex mediated crescentic membranoproliferative glomerulonephritis (MPGN). The patient achieved complete renal and virological remission with steroids, plasmapheresis and antiviral therapy. This case report summarises the importance of early initiation of immunosuppression and plasmapheresis under antiviral coverage for improved clinical outcomes.

  9. Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes

    PubMed Central

    Ancey, Pierre-Benoit; Testoni, Barbara; Gruffaz, Marion; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Durantel, David; Herceg, Zdenko; Hernandez-Vargas, Hector

    2015-01-01

    Viral infections are able to modify the host's cellular programs, with DNA methylation being a biological intermediate in this process. The extent to which viral infections deregulate gene expression and DNA methylation is not fully understood. In the case of Hepatitis B virus (HBV), there is evidence for an interaction between viral proteins and the host DNA methylation machinery. We studied the ability of HBV to modify the host transcriptome and methylome, using naturally infected primary human hepatocytes to better mimic the clinical setting. Gene expression was especially sensitive to culture conditions, independently of HBV infection. However, we identified non-random changes in gene expression and DNA methylation occurring specifically upon HBV infection. There was little correlation between expression and methylation changes, with transcriptome being a more sensitive marker of time-dependent changes induced by HBV. In contrast, a set of differentially methylated sites appeared early and were stable across the time course experiment. Finally, HBV-induced DNA methylation changes were defined by a specific chromatin context characterized by CpG-poor regions outside of gene promoters. These data support the ability of HBV to modulate host cell expression and methylation programs. In addition, it may serve as a reference for studies addressing the genome-wide consequences of HBV infection in human hepatocytes. PMID:26565721

  10. Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes.

    PubMed

    Ancey, Pierre-Benoit; Testoni, Barbara; Gruffaz, Marion; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Durantel, David; Herceg, Zdenko; Hernandez-Vargas, Hector

    2015-12-29

    Viral infections are able to modify the host's cellular programs, with DNA methylation being a biological intermediate in this process. The extent to which viral infections deregulate gene expression and DNA methylation is not fully understood. In the case of Hepatitis B virus (HBV), there is evidence for an interaction between viral proteins and the host DNA methylation machinery. We studied the ability of HBV to modify the host transcriptome and methylome, using naturally infected primary human hepatocytes to better mimic the clinical setting.Gene expression was especially sensitive to culture conditions, independently of HBV infection. However, we identified non-random changes in gene expression and DNA methylation occurring specifically upon HBV infection. There was little correlation between expression and methylation changes, with transcriptome being a more sensitive marker of time-dependent changes induced by HBV. In contrast, a set of differentially methylated sites appeared early and were stable across the time course experiment. Finally, HBV-induced DNA methylation changes were defined by a specific chromatin context characterized by CpG-poor regions outside of gene promoters.These data support the ability of HBV to modulate host cell expression and methylation programs. In addition, it may serve as a reference for studies addressing the genome-wide consequences of HBV infection in human hepatocytes.

  11. Expression quantitative trait loci for TNFRSF10 influence both HBV infection and hepatocellular carcinoma development.

    PubMed

    Wen, Juan; Song, Ci; Liu, Jibin; Chen, Jianguo; Zhai, Xiangjun; Hu, Zhibin

    2016-03-01

    Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) is a death domain-containing receptor for the apoptotic ligand TNFSF10, which involves multiple processes, including hepatocarcinogenesis and immune response against HBV infection. Several single nucleotide polymorphisms (SNPs) were identified as expression quantitative trait loci (eQTLs) for TNFRSF10. To assess the association of TNFRSF10 eQTL SNPs with the risk of hepatocellular carcinoma (HCC) and chronic HBV infection, we designed a case-control study that included 1,300 HBV-related HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance, and then genotyped two TNFRSF10 eQTL SNPs (rs79037040 and rs2055822). We found that rs79037040 GT/TT genotypes were associated with a decreased HCC risk (adjusted odds ratio [OR] = 0.83, 95% confidence intervals [CIs] = 0.71-0.97, P = 0.021) but an increased chronic HBV infection risk of borderline significance (adjusted OR = 1.14, 95%CIs = 0.98-1.33, P = 0.085). In contrast, the rs2055822 G allele was a risk factor for HCC (adjusted OR = 1.12, 95%CIs = 1.00-1.25, P = 0.041) but a protective factor for chronic HBV infection (adjusted OR = 0.89, 95%CIs = 0.80-0.99, P = 0.038). Furthermore, we observed a dose-dependent relationship between the number of alleles (rs79037040-T and rs2055822-A) and the risk of HCC and chronic HBV infection. In comparison with "0" alleles, having "1-4" alleles was significantly associated with decreased HCC risk and increased HBV infection risk. These findings suggest that eQTL SNPs for TNFRSF10 may be susceptibility markers for HCC and chronic HBV infection.

  12. Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

    PubMed Central

    Saha, Debraj; Pal, Ananya; Biswas, Avik; Panigrahi, Rajesh; Sarkar, Neelakshi; Das, Dipanwita; Sarkar, Jayeeta; Guha, Subhasish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

    2014-01-01

    Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant. PMID:24587360

  13. Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B.

    PubMed

    Lee, Jong Ho; Hong, Sun Pyo; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook-Hyang

    2015-06-01

    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations.

  14. Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand

    PubMed Central

    Khamduang, Woottichai; Gaudy-Graffin, Catherine; Ngo-Giang-Huong, Nicole; Jourdain, Gonzague; Moreau, Alain; Luekamlung, Nuananong; Halue, Guttiga; Buranawanitchakorn, Yuwadee; Kunkongkapan, Sura; Buranabanjasatean, Sudanee; Lallemant, Marc; Sirirungsi, Wasna; Goudeau, Alain

    2012-01-01

    Background Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log10 IU/mL and 4.47 log10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for

  15. Chronic hepatitis B infection and HBV DNA-containing capsids: Modeling and analysis

    NASA Astrophysics Data System (ADS)

    Manna, Kalyan; Chakrabarty, Siddhartha P.

    2015-05-01

    We analyze the dynamics of chronic HBV infection taking into account both uninfected and infected hepatocytes along with the intracellular HBV DNA-containing capsids and the virions. While previous HBV models have included either the uninfected hepatocytes or the intracellular HBV DNA-containing capsids, our model accounts for both these two populations. We prove the conditions for local and global stability of both the uninfected and infected steady states in terms of the basic reproduction number. Further, we incorporate a time lag in the model to encompass the intracellular delay in the production of the infected hepatocytes and find that this delay does not affect the overall dynamics of the system. The results for the model and the delay model are finally numerically illustrated.

  16. HBV cure: why, how, when?

    PubMed

    Levrero, Massimo; Testoni, Barbara; Zoulim, Fabien

    2016-06-01

    Current HBV treatments control replication and liver disease progression in the vast majority of treated patients. However, HBV patients often require lifelong therapies due to the persistence of transcriptionally active viral cccDNA mini-chromosome in the nucleus, which is not directly targeted by current antiviral therapies. A true complete cure of HBV would require clearance of intranuclear cccDNA from all infected hepatocytes. An intermediate but still relevant step forward that would allow treatment cessation would be reaching a functional cure, equivalent to resolved acute infection, with a durable HBsAg loss±anti-HBs seroconversion, undetectable serum DNA and persistence of cccDNA in a transcriptionally inactive status. Recent advances in technologies and pharmaceutical sciences, including the cloning of the mayor HBV receptor (i.e. the NTCP transporter) and the development in vitro HBV infection models, have heralded a new horizon of innovative antiviral and immune-therapeutic approaches. PMID:27447092

  17. Is mother-to-infant transmission the most important factor for persistent HBV infection?

    PubMed

    Li, Zixiong; Hou, Xiaomei; Cao, Guangwen

    2015-05-01

    Of the infants born to hepatitis B surface antigen (HBsAg)-positive mothers globally, 42.1% who did not receive hepatitis B virus (HBV) passive-active immunoprophylaxis and 2.9% of infants who received the immunoprophylaxis acquired HBV infection perinatally. Moreover, perinatal infection occurred in 84.2% (18.8%-100%) and 8.7% (0.0-21.0%) of infants born to hepatitis B e-antigen (HBeAg)-positive mothers who did not and did receive immunoprophylaxis, respectively; by contrast, the infection rates were 6.7% (0.0-15.4%) and 0.4% (0.0-2.5%) for infants born to HBeAg-negative-carrier mothers, respectively. The chronicity rates of HBV infection acquired perinatally were 28.2% (17.4%-33.9%) in infants born to HBeAg-negative mothers and 64.5% (53.5%-100%) in infants born to HBeAg-positive mothers. HBV mother-to-child transmission was more frequent in East Asia relative to other areas. In addition to differences in the endemic HBV genotype, the interchange of allelic dominance in genetic polymorphisms in HLA class II and NF-κB between the Chinese and European populations may explain why chronic HBV infection frequently affects the Chinese. The risk of progressing into chronic infection was inversely related to the age of children at the time of horizontal transmission. To further diminish HBV chronic infection, it is necessary to enforce antiviral treatment after the 28th week of gestation for HBeAg-positive mothers and to improve the health habits of carrier mothers and household sanitary conditions. PMID:26060603

  18. HBV and HIV co-infection: Prevalence and clinical outcomes in tertiary care hospital Malaysia.

    PubMed

    Akhtar, Ali; Khan, Amer Hayat; Sulaiman, Syed Azhar Syed; Soo, Chow Ting; Khan, Kashifullah

    2016-03-01

    According to WHO, Malaysia has been classified as a concentrated epidemic country due to progression of HIV infection in the population of injecting drug users. The main objectives of current study are to determine the prevalence of HBV among HIV-positive individuals in a tertiary care hospital of Malaysia and to assess the predictors involved in the outcomes of HIV-HBV co-infected patients. A retrospective, cross-sectional study is conducted at Hospital Palau Pinang, Malaysia. The collection of socio-demographic data as well as clinical data is done with the help of data collection form. Data were analyzed after putting the collected values of required data by using statistical software SPSS version 20.0 and P > 0.05 is considered as significant. Results show that the overall prevalence of HBV was 86 (13%) including 495 (74.5%) males and 169 (25.5%) females among a total of 664 HIV-infected patients. It was observed that there is a high prevalence of HIV-HBV co-infection in males 76 (11.4%) as compared to females 10 (1.5%) (P = 0.002). The median age of the study population was 39 years. The statistical significant risk factors involved in the outcomes of HIV-HBV co-infected patients were observed in the variables of gender, age groups, and injecting drug users. The findings of the present study shows that the prevalence of HBV infection among HIV-positive patients was 13% and the risk factors involved in the outcomes of HIV-HBV co-infected patients were gender, age, and intravenous drug users.

  19. HBV Lamivudine Resistance among Hepatitis B and HIV Co-infected Patients Starting Lamivudine, Stavudine and Nevirapine in Kenya

    PubMed Central

    Nina Kim, H.; Scott, John; Cent, Anne; Cook, Linda; Ashley Morrow, Rhoda; Richardson, Barbra; Tapia, Kenneth; Jerome, Keith R.; Lule, Godfrey; John-Stewart, Grace; Chung, Michael H.

    2011-01-01

    Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV co-infected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly-active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg(+) and anti-HBs negative: 24 were HBeAg-negative, 18 had HBV DNA ≤10,000 IU/ml. Sustained HBV suppression to <100 IU/ml occurred in 89% of 19 evaluable patients. Resistance occurred in only 2 subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV co-infected patients with low baseline HBV DNA levels. PMID:21914062

  20. Peripheral blood dendritic cells are phenotypically and functionally intact in chronic hepatitis B virus (HBV) infection

    PubMed Central

    Tavakoli, S; Mederacke, I; Herzog-Hauff, S; Glebe, D; Grün, S; Strand, D; Urban, S; Gehring, A; Galle, P R; Böcher, W O

    2008-01-01

    Persistence of hepatitis B virus (HBV) infection is associated with reduced anti-viral T cell responses. Impaired dendritic cell (DC) function was suggested as the cause of reduced T cell stimulation in chronic HBV carriers. Thus, we compared myeloid (mDC) and plasmacytoid DC (pDC) from chronic HBV carriers and controls. Frequency and phenotype of isolated DC were analysed by fluorescence activated cell sorter staining, DC function by mixed lymphocyte reaction, cytokine bead array, intracellular cytokine staining, enzyme-linked immunosorbent assay and enzyme-linked immunospot. Expression of HBV DNA and mRNA was studied by polymerase chain reaction (PCR). Circulating total DC, mDC or pDC were not reduced in chronic HBV carriers. Isolated mDC and pDC from chronic HBV carriers exhibited similar expression of co-stimulatory molecules and alloreactive T helper cell stimulation as control DC, whether tested directly ex vivo or after in vitro maturation. Secretion of pro- and anti-inflammatory cytokines by CD40 or Toll-like receptor ligand-stimulated patient DC was intact, as was human leucocyte antigen A2-restricted HBV-specific cytotoxic lymphocyte stimulation. Although both DC populations contained viral DNA, viral mRNA was undetectable by reverse transcription–PCR, arguing against viral replication in DC. We found no quantitative, phenotypic or functional impairment of mDC or pDC in chronic hepatitis B, whether studied ex vivo or after in vitro maturation. PMID:18031557

  1. Active co-infection with HBV and/or HCV in South African HIV positive patients due for cancer therapy.

    PubMed

    Musyoki, Andrew M; Msibi, Thembeni L; Motswaledi, Mojakgomo H; Selabe, Selokela G; Monokoane, Tshweu S; Mphahlele, M Jeffrey

    2015-02-01

    Human immunodeficiency virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) share routes of transmission. There is limited data on the incidence of active co-infection with HBV and/or HCV in cancer patients infected with HIV in Africa. This was a prospective study based on 34 patients with varied cancer diagnosis, infected with HIV and awaiting cancer therapy in South Africa. HIV viral load, CD4+ cell counts, Alanine-aminotransferase and aspartate aminotransferase levels were tested. Exposure to HBV and HCV was assessed serologically using commercial kits. Active HBV and/or HCV co-infection was detected using viral specific nested PCR assays. HCV 5'-UTR PCR products were sequenced to confirm active HCV infection. Active viral infection was detected in 64.7% of patients for HBV, 38.2% for HCV, and 29.4% for both HBV and HCV. Occult HBV infection was observed in 63.6% of the patients, while seronegative HCV infection was found in 30.8% of patients. In addition, CD4+ cell count < 350 cells/µl was not a risk factor for increased active HBV, HCV or both HBV and HCV co-infections. A total of 72.7%, 18.2% and 9.1% of the HCV sequences were assigned genotype 5, 1 and 4 respectively.The study revealed for the first time a high active HBV and/or HCV co-infection rate in cancer patients infected with HIV. The findings call for HBV and HCV testing in such patients, and where feasible, appropriate antiviral treatment be indicated, as chemotherapy or radiotherapy has been associated with reactivation of viral hepatitis and termination of cancer therapy. PMID:25156907

  2. Evolution of Hepatitis B Virus in a Chronic HBV-Infected Patient over 2 Years

    PubMed Central

    Shen, Tao; Yan, Xin-Min; Zhang, Jin-Ping; Wang, Jin-Li; Zuo, Rong-Xia; Li, Li; Wang, Lin-Pin

    2011-01-01

    Mutations in full-length HBV isolates obtained from a chronic HBV-infected patient were evaluated at three time points: 1 day, 6 months, and 31 months. While 5 nucleotides variation, and an 18 bp deletion of preS1 have been kept in during at least the first two years, C339T mutation occurring in the hydrophilic region of HBsAg and T770C that caused polymerase V560A substitution were the new point mutations found existing in sequenced clones of the 3rd time point. Internal deletion of coding region obviously appeared in the 3rd time point. The splicers included two new 5′-splice donors and three new 3′-splice acceptors besides the reported donors and acceptors and may have produced presumptive HBV-spliced proteins or truncated preS proteins. ALT, HBeAg and viral DNA load varied during the follow-up years. These data demonstrated the diversity of genomes in HBV-infected patient during evolution. Combined with clinical data, the HBV variants discovered in this patient may contribute to viral persistence of infection or liver pathogenesis. PMID:21785721

  3. Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia.

    PubMed

    Al-Mughales, Jamil A

    2016-09-01

    To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti-toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895691

  4. Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia.

    PubMed

    Al-Mughales, Jamil A

    2016-09-01

    To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti-toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. © 2016 Wiley Periodicals, Inc.

  5. Association of TIP30 expression and prognosis of hepatocellular carcinoma in patients with HBV infection.

    PubMed

    Zhang, Xia; Lv, Lizhi; Ouyang, Xuenong; Zhang, Shi'an; Fang, Jian; Cai, Lirong; Li, Dongliang

    2016-09-01

    Altered expression of TIP30, a tumor suppressor, has been observed in many cancers. In this study, we have evaluated the expression of TIP30 in the tissues of 209 hepatocellular carcinomas (HCC) and their adjacent tissues by using a high-density tissue microarray, and analyzed its correlation with the clinical pathological parameters of the patients. The results revealed negative or weak expression of TIP30 in 43.5% (91/209) of the HCC tissues, and in only 27% (56/209) of the adjacent tissues. The expression level of TIP30 in HCC was inversely correlated with serum alpha-fetoprotein (AFP) levels, HBV infection, and tumor differentiation. Multivariate analysis for survival indicated that serum HBV infection was the most significant predictor of poor prognosis in HCC (P = 0.0023), and TIP30 expression and tumor differentiation were also independent indicators in this respect (P = 0.0364 and P = 0.0397, respectively). Patients with medium or high expression levels of TIP30 (TIP30(++/+++) ) had a better 5-year overall survival rate than those with low/negative (TIP30(+/-) ) expression (P < 0.001). TIP30(+/-/) HBV(+) patients had the worst 5-year overall survival rate, whereas TIP30(++/+++) /HBV(-) patients had the best. To further explore the correlation between TIP30 and HBV infection in HCC, HBV(+) hepatoblastoma cell-line HepG2 2.2.15 and HCC cell-line Hep3B were used. Upon silencing of HBV, we observed an upregulation of TIP30 and decreased cell proliferation. In the in vivo studies, we found that the mice inoculated with HepG2 2.2.15 cells with HBV silencing had a prolonged tumor latency and a longer life span, as compared to the control mice inoculated with untreated control cells. In conclusion, the results suggest that downregulation of TIP30 may result from HBV infection, and subsequently promotes the progression of HCC.

  6. Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk

    PubMed Central

    Ye, Fei; Fan, Qing-Min; Yu, Guo-Feng; Yu, Dan-Dan; Gao, Lu; Sun, Kai; Han, Zhi-Peng; Li, Rong; Yang, Yang; Zhao, Qiu-Dong; Wu, Meng-Chao; Wang, Hong-Yang; Wei, Li-Xin

    2015-01-01

    Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients. PMID:26515593

  7. Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India

    PubMed Central

    Sarkar, Jayeeta; Saha, Debraj; Bandyopadhyay, Bhaswati; Saha, Bibhuti; Kedia, Deepika; Guha Mazumder, D.N.; Chakravarty, Runu; Guha, Subhasish Kamal

    2016-01-01

    Background & objectives: Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. The present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients. Methods: Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination. Results: HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (P<0.001) and APRI (P<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. Interpretation & conclusions: HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to

  8. Current antiviral practice and course of Hepatitis B virus infection in inflammatory arthritis: a multicentric observational study (A + HBV study)

    PubMed Central

    Kalyoncu, Umut; Emmungil, Hakan; Onat, Ahmet Mesut; Yılmaz, Sedat; Kaşifoglu, Timuçin; Akar, Servet; İnanç, Nevsun; Yıldız, Fatih; Küçükşahin, Orhan; Karadağ, Ömer; Mercan, Rıdvan; Bes, Cemal; Yazısız, Veli; Yılmazer, Barış; Özmen, Mustafa; Erten, Şükran; Şenel, Soner; Yazıcı, Ayten; Taşçılar, Koray; Kalfa, Melike; Kiraz, Sedat; Kısacık, Bünyamin; Pehlivan, Yavuz; Kılıç, Levent; Şimşek, İsmail; Çefle, Ayşe; Akkoç, Nurullah; Direskeneli, Haner; Erken, Eren; Turgay, Murat; Öztürk, Mehmet Akif; Soy, Mehmet; Aksu, Kenan; Dinç, Ayhan; Ertenli, İhsan

    2015-01-01

    Objective The reactivation of hepatitis B virus (HBV) infection is a well-known event in hepatitis B surface antigen (HbsAg)-positive patients receiving immunosuppressive therapy. The objective of this study was to assess the antiviral practice and course of HBV infection in inflammatory arthritis. Material and Methods Nineteen rheumatology centers participated in this retrospective study. HbsAg-positive patients who were taking disease-modifying antirheumatic drugs and who were being tested for HBV viral load at a minimum of two different time points were included. The case report form (CRF) consisted of demographic data, rheumatic diseases, treatment profiles, transaminase levels, viral hepatitis serological markers, and HBV viral load. The reactivation of HBV was defined as the abrupt rise in HBV replication by an increase in serum HBV DNA levels in a patient with a previously inactive HBV infection. Results In total, the data of 101 (female 50.5%) patients were included (76 patients with inactive HBV carriers and 25 patients with chronic HBV infection). The mean age of patients was 44±12 years, and the mean follow-up duration was 31±22 months. Of the 101 patients, 70 (69.3%) received antiviral treatment. HBV reactivation was detected in 13 of 76 (17.1%) patients with inactive HBV carriers. HBV reactivation was observed less frequently, not although significantly, in those patients receiving antiviral prophylaxis compared with those not receiving prophylaxis [5/41 (12.2%) vs. 8/33 (24.2%), p=0.17]. Forty-two patients (31 patients had inactive HBV carriers) were using anti-tumor necrosis factor agents. HBV reactivation was detected in 6 of the 31 (19.3%) patients. Twenty-five patients had chronic hepatitis, and five (20%) of them had not received antiviral prophylaxis. HBV viral loads were persistently elevated in 7 (28%) of 25 patients (three patients under and four patients not under antiviral treatment). Conclusion HBV reactivation was observed in

  9. Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection.

    PubMed

    Troy, S B; Rossheim, A E B; Siik, J; Cunningham, T D; Kerry, J A

    2016-05-01

    Even after CD4 count recovery on antiretroviral therapy, HIV infection is associated with decreased response to most vaccines compared to the general population. Chronic infections with viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which are more prevalent in HIV-infected populations, have been linked to immune dysfunction and decreased vaccine response in the general population. However, whether co-infection with these other viruses contributes to the decreased vaccine response seen in adults with well-controlled HIV infection is unknown. We conducted a secondary analysis of data and serum from adults with well-controlled HIV infection from an inactivated polio vaccine trial (224 subjects) and a pneumococcal conjugate vaccine study (128 subjects). We evaluated the association of CMV, HBV, or HCV co-infection with post-vaccination antibody levels using both univariate and multivariate analyses, controlling for factors such as age, race, CD4 count, comorbidities, smoking status, and baseline antibody levels. Ninety-three percent, 7%, and 14% of subjects were co-infected with CMV, HBV, and HCV respectively. On both univariate and multivariate analysis, neither CMV nor HCV co-infection were significantly associated with post-vaccination antibody levels to either vaccine. HBV co-infection was significantly associated with post-vaccination antibody concentrations for pneumococcal serotype 7F on univariate analysis and 6A on multivariate analysis, but the association was with higher antibody concentrations. In conclusion, co-infection with CMV, HBV, or HCV does not appear to contribute to the decreased vaccine response seen in adults with well-controlled HIV infection.

  10. Clearance of HBV DNA in immunized children born to HBsAg-positive mothers, years after being diagnosed with occult HBV infection.

    PubMed

    Sadeghi, A; Yahyapour, Y; Poortahmasebi, V; Shahmoradi, S; Roggendorf, M; Karimzadeh, H; Alavian, S M; Jazayeri, S M

    2016-04-01

    In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended.

  11. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  12. HBV and HAV infection in chronic hepatitis in Argentina.

    PubMed

    Tanno, H; Fay, O H; Roncoroni, M; Palazzi, J

    1981-01-01

    Sera of 155 chronic hepatitis (CH) patients in Argentina were tested for the presence of HBsAg, anti-HBs, anti-HBc, and anti-HAV. Our purpose was to define the role that both virus A and B might play in the etiology and pathogenesis of this condition. The patients were divided into two groups: group I (57) HBsAg-negative; group II (98) HBsAg-positive. The control group consisted of 1,209 healthy blood donors from Banco Central de Sangre de Rosario; 286/1,209 (24%) had viral markers for HBV. In group I, 38/57 (67%) had anti-HBs and/or anti-HBc, but none had anti-HBs alone. Group II showed a higher percentage of males (P less than 0.05). We found similar incidence of anti-HAV among group I, group II, and the control group.

  13. [Present state and the future direction of HBV vaccine].

    PubMed

    Mizokami, Masashi; Sugiyama, Masaya

    2012-06-01

    Hepatitis B virus (HBV) prevention program in Japan is considered one of the most successful and effective public anti-counter programs to HBV infection. However, almost all of population under twenty-five years is extremely susceptibility for HBV infection. HBV genotype A, which was not in Japan and has been from western countries, is increasing in chronic hepatitis B patients in Japan as a consequence of acute hepatitis B spreading in the younger generation through promiscuous sexual transmitted infection and the characteristics of HBV genotype A is a prolonged high HBVDNA viremia compared with other HBV genotypes. These data have strongly indicated that the main transmission route of HBV in Japan has been changed to a horizontal infection with sexual transmitted disease from perinatal transmission from HBsAg positive mothers. Although the HBV vaccine has tipped the balance in our favor, newly issues of HBV vaccine has been arisen such as vaccine escape mutant, efficacy and potency for the prevention of HBV infection, especially different HBV genotypes, HBV reactivation on the patients with HBsAg negative and anti-HBs antibody positive under systemic chemotherapy, and universal vaccination or selective vaccination and so on. PMID:23189826

  14. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc. PMID:26381185

  15. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc.

  16. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  17. Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya

    PubMed Central

    Daw, Mohamed A.; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A.

    2014-01-01

    Background In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. Methods A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. Results A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. Conclusion HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned. PMID:24936655

  18. Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial.

    PubMed

    Pande, C; Sarin, S K; Patra, S; Kumar, A; Mishra, S; Srivastava, S; Bhutia, K; Gupta, E; Mukhopadhyay, C K; Dutta, A K; Trivedi, S S

    2013-11-01

    Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV

  19. IL28B Is Associated with Outcomes of Chronic HBV Infection

    PubMed Central

    Shi, Xiaodong; Chi, Xiumei; Pan, Yu; Gao, Yanhang; Li, Wanyu; Yang, Chen; Zhong, Jin; Xu, Damo; Zhang, Manna; Minuk, Gerald

    2015-01-01

    Purpose The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. Materials and Methods IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. Results Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). Conclusion Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections. PMID:25837166

  20. Liver microRNA hsa-miR-125a-5p in HBV chronic infection: correlation with HBV replication and disease progression.

    PubMed

    Coppola, Nicola; Potenza, Nicoletta; Pisaturo, Mariantonietta; Mosca, Nicola; Tonziello, Gilda; Signoriello, Giuseppe; Messina, Vincenzo; Sagnelli, Caterina; Russo, Aniello; Sagnelli, Evangelista

    2013-01-01

    To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to β-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p<0.0001). Higher liver hsa-miR-125a-5p concentrations were observed in patients with HBV-DNA plasma level >10(3) IU/ml (p<0.02), in those with HAI >6 (p = 0.02) and those with fibrosis score >2 (p<0.02) than in patients with lower scores. Higher HBV-DNA liver concentrations were found in patients with abnormal AST (p = 0.005) and ALT serum levels (p = 0.05), in those with serum HBV DNA higher than 10E3 IU/mL (p = 0.001) and those with fibrosis score >2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R. = 4.21, C.I. 95% = 1.08-16.43, p<0.05, for HAI >6; O.R. = 3.12, C.I. 95% = 1.17-8.27, p<0.05, for fibrosis score >2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression. PMID:23843939

  1. An outbreak of HBV and HCV infection in a paediatric oncology ward: epidemiological investigations and prevention of further spread.

    PubMed

    Dumpis, Uga; Kovalova, Zanna; Jansons, Juris; Cupane, Liene; Sominskaya, Irina; Michailova, Marija; Karayiannis, Peter; Gardovska, Dace; Viazov, Sergey; Ross, Stefan; Roggendorf, Michael; Pumpens, Paul

    2003-03-01

    Hospital-acquired hepatitis B (HBV) and C virus (HCV) infections continue to occur despite increased awareness of this problem among the medical community. One hundred six patients were infected in a haematology oncology ward for children, over the time period 1996 to 2000. Serum samples from 45 such patients and 3 from infected medical personnel were used for nucleic acid amplification. HBV core, as well as HCV core and hypervariable region 1 (HVR1) nucleotide sequences, were analysed by phylogenetic tree analysis, in order to characterise the epidemiological pattern of viral transmission on the ward. Samples from 32 patients were positive for HBV-DNA or HCV-RNA by PCR. Ten patients were positive for both markers. Seventeen out of twenty-three HCV core gene sequences were found to be evolutionarily related and clustered separately from other local sequences in the phylogenetic tree, indicating nosocomial transmission. This was confirmed by analysis of HVR1 gene sequences. One nurse and one physician from the ward were HCV RNA positive, but their HCV sequences were not related evolutionarily to those of the patient cluster. Fifteen out of nineteen HBV core gene sequences were also clustered together and were positioned separately in the relevant tree. Epidemiological investigation excluded a common source infection and indicated that spread of infection was most likely due to inappropriate infection control measures on the ward. No obvious risk factors for transmission were identified during the retrospective survey in patients with related sequences, except use of multidose vials for saline and poor staff compliance with routine hand hygiene procedures. The preventive measures that were introduced reduced the incidence of infection significantly. No new cases of HBV infection and only three anti-HCV seroconversions occurred over a period of 19 months. The introduction and maintenance of strict prevention measures over a 2 year period, combined with HBV vaccination

  2. Unique impacts of HBV co-infection on clinical and laboratory findings in a recent dengue outbreak in China.

    PubMed

    Tang, Yangbo; Kou, Zhihua; Tang, Xiaoping; Zhang, Fuchun; Yao, Xian; Liu, Shengyong; Jin, Xia

    2008-08-01

    High prevalence of hepatitis B virus (HBV) infection in China offers a unique setting to examine HBV's influence on the presentation of dengue fever. In 398 patients admitted for suspected dengue fever, 89% (353/398) were positive for dengue IgM antibodies. Among dengue-infected patients, 8% (29/353) had chronic HBV co-infection. Only dengue virus serotype 1 was identified by virus isolation and reverse transcriptase-polymerase chain reaction assays. No case of dengue hemorrhagic fever/dengue shock syndrome was diagnosed. In addition to routine clinical tests, interleukin 2 (IL-2), IL-4, IL-6, IL-10, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) levels were measured in the sera of 95% (334/353) of dengue-infected subjects as well as controls. Surprisingly, HBV/dengue co-infected patients made less IL-6 (P < 0.05) and TNFalpha (P < 0.05) than patients with only dengue infection. Similar levels of IL-4, IL-10, and IFNgamma were found in both groups. Thus, HBV co-infection seems to alter the cytokine production pattern when patients contract dengue infection.

  3. Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection.

    PubMed

    Wei, Mei-Juan; Pan, Xing-Nan; Wei, Kai-Peng; Li, Xu-Hong; Liu, Xiao-Long; Zhang, Xiao-Man; Jiang, Ya-Ling; Zhang, Chun-Yu; Shen, Jian-Kun

    2015-08-01

    Dendritic cells (DCs) are multifunctional cells that initiate adaptive immune responses. Patients with chronic hepatitis B virus (HBV) infection have reduced numbers of DCs which may be functionally impaired, a defect that may contribute to viral persistence. Autologous DC-based immunotherapy is considered to be a treatment option for chronic HBV infection (CHB). We evaluated the therapeutic efficacy of HBV-pulsed DCs in combination with the antiviral drug entecavir in patients with CHB. Eighty patients were divided into four groups: HBV-pulsed DCs only, HBV-pulsed DCs plus entecavir, entecavir only, and an untreated control group. Patients on combination therapy exhibited greater antiviral responses than patients on either monotherapy. The combination of HBV-pulsed DCs and entecavir resulted in the largest reduction in serum viral DNA levels and the highest percentage of virologic response. In addition, combination therapy resulted in viral e antigen (HBeAg) loss and seroconversion. These results suggest that the combination of HBV-pulsed autologous DCs and entecavir could be therapeutically advantageous for patients with CHB.

  4. [Effect of IL-28B polymorphisms on the natural course of HBV infection].

    PubMed

    Demirtürk, Neşe; Aykın, Nevil; Çevik, Figen; Koca, Buğra; Doğan, Nurhan; Köken, Tülay

    2016-01-01

    The prediction of the consequences of disease is important to determine the therapy approaches and prevention of the chronical state in patients infected with hepatitis B virus (HBV). In recent years various studies are carried on to investigate the effect of IL-28B gene polymorphisms on the clinical course or therapy response in patients with chronic hepatitis B infection. The aim of the study was to evaluate the influence of IL-28B rs12979860 polymorphisms on the natural course of HBV infection. The study was designed prospectively, and the subjects were randomly selected among patients admitted to infectious disease outpatient clinics of Kocatepe University Medical School Hospital and Yunus Emre State Hospital located at provinces in Central Anatolia, Turkey. A total of 99 cases were included in the study and evaluated into three groups, namely, chronic hepatitis B patients (group 1, n= 43); inactive HBV carriers (group 2, n= 34) and subjects with acquired immunity after native infection (group 3, n= 22). There were no significant differences regarding the age and gender distribution between the groups (p> 0.05). All subjects were investigated for the IL-28B promoter single nucleotide polymorphism rs12979860 at position 3176 C/T, by real-time polymerase chain reaction (RT-PCR). Evaluation of the range of IL-28B rs12979860 C/T polymorphisms observed in the study groups showed that, the frequency of CC, CT and TT allels were as follows; 34.9%, 48.8% and 16.3 % in group 1; 47.1%, 35.3% and 17.6% in group 2; 63.6%, 27.7% and 13.6% in group 3, respectively. No significant differences were observed between the groups in terms of C/T allel distriubution (p> 0.05). However, in spite of statistical insignificance, the rate of CC allel in IL-28B rs12979860 gene was the highest in immune subjects (63.6%), while it was the lowest in chronic hepatitis B patients (34.9%). According to our data, IL-28B rs12979860 gene polymorphisms were not effective on the clinical course of

  5. Host Genetic Factors and Vaccine-Induced Immunity to HBV Infection: Haplotype Analysis

    PubMed Central

    Ryckman, Kelli K.; Fielding, Katherine; Hill, Adrian V.; Mendy, Maimuna; Rayco-Solon, Pura; Sirugo, Giorgio; van der Sande, Marianne A.; Waight, Pauline; Whittle, Hilton C.; Hall, Andrew J.; Williams, Scott M.; Hennig, Branwen J.

    2010-01-01

    Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1×10−5 for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes. PMID:20806065

  6. Acute upper airway infections.

    PubMed

    West, J V

    2002-01-01

    Upper respiratory tract infections are common and important. Although rarely fatal, they are a source of significant morbidity and carry a considerable economic burden. Numerous therapies for the common cold have no effect on symptoms or outcome. Complications such as cough are not improved by over-the-counter preparations, while labelling cough alone as a symptom of asthma may result in unnecessary use of inhaled steroid treatment. Clinical presentation of sore throat does not accurately predict whether the infection is viral or bacterial, while throat culture and rapid antigen tests do not significantly change prescribing practice. Antibiotics have only a limited place in the management of recurrent sore throat due to group A beta-haemolytic streptococcal infection. Routine use of antibiotics in upper respiratory infection enhances parent belief in their effectiveness and increases the likelihood of future consultation in primary care for minor self-limiting illness. Respiratory viruses play a major role in the aetiology of acute otitis media (AOM); prevention includes the use of influenza or RSV vaccination, in addition to reducing other risk factors such as early exposure to respiratory viruses in day-care settings and to environmental tobacco smoke. The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children. New conjugate pneumococcal vaccines appear safe in young children and prevent 6-7% of clinically diagnosed AOM.

  7. PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study

    PubMed Central

    Anwar, Muhammad Ayaz; Raheel, Ummar; Badshah, Yasmeen; Akhtar, Hashaam; Tamanna, Kosar; Tahir, Muhammad; Sadaf Zaidi, Najam us Sahar

    2016-01-01

    Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was “reuse of syringes” while in triple infection it was “intravenous drug users” (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration. PMID:27366331

  8. Characterization of Treatment-Naive HIV/HBV Co-Infected Patients Attending ART Clinic of a Tertiary Healthcare Centre in Eastern India

    PubMed Central

    Biswas, Avik; Panigrahi, Rajesh; Sarkar, Neelakshi; Sarkar, Jayeeta; Pal, Manisha; Guha, Subhasish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

    2013-01-01

    Objective The study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile. Methods Pool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance. Results The prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ≥20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p = <0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ≥2,000 IU/ml of which 37.0% had HBV DNA ≥20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients. Conclusion The prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation. PMID:24023688

  9. Association of TNF-α Promoter Polymorphism with HBV Associated Disease Outcome Among HBV Infected Patients from Orissa, Southern Part of East India

    PubMed Central

    Panigrahi, Rajesh; Sarkar, Neelakshi; Biswas, Avik; Pal, Ananya; Saha, Debraj; Singh, Shivaram P.; Panigrahi, Manas K.; Bandopadhyay, Manikanana; Chakrabarti, Sekhar; Chakravarty, Runu

    2014-01-01

    Background TNF-α promoter polymorphism has been known to be a potential predictive factor in patients with HBV infection. We therefore tried to investigate whether the TNF-α promoter polymorphism at position −238, −857 and −863 was associated with the outcome of HBV infection in a population from Orissa, southern part of East India. Methods A total of 195 patients recruited for the study were classified into 85 controls and 110 HBV infected cases, which included 34 IC, 30 CLD, 32 LC and 14 HCC patients. The polymorphisms at the respective sites were detected by a PCR-RFLP followed by statistical analysis. Results The frequency of the genotype −238 GG and the allele −238G in the cases (89.0% and 92.7% respectively) was significantly higher than that in the controls (68.2% and 82.2% respectively) (P < 0.001, OR = 3.8 and P = 0.001, OR = 2.73). Whereas the −238 GA genotype was significantly high in the control group (28.2%) when compared to the cases (7.2%) (P < 0.001, OR = 0.2). Similarly, the frequency of −863CC and the allele −863C was significantly higher among the cases (24.5% and 49.5%) compared to controls (1.17% and 34.7%), (P < 0.001, OR = 27.32 and P = 0.003, OR = 1.85), whereas the −863CA genotype was significantly high in the controls (67.0%) when compared to the cases (50.0%) (P = 0.01, OR = 0.49). Haplotype −863C/−857C/−238G in cases was significantly higher than controls (P = 0.002). Multivariate logistic regression analysis indicates that the genotype −863CC bears a negative association with liver disease progression. Conclusion The present study established an association of polymorphisms at site −238 and −863 of the TNF-α promoter with the outcome HBV infection and disease progression. PMID:25755561

  10. [HORIZONTAL TRANSMISSION OF HBV INFECTION IN MIGRANTSFROM A HYPERENDEMIC AREA TO THEIR CONTACTS IN A LOW ENDEMICITY AREA IN PERU

    PubMed

    Cabezas, César; Anaya, Elizabeth; Bartalesi, Filippo; Sánchez, Jaime

    1997-01-01

    Migration of inhabitants from high endemicity to low endemicity areas, where the majority of population is susceptible, implies a risk of transmission. This factor suggested the study of the presence of HBV infection on migrants from Huanta and in their host communities in Lima.MATERIAL AND METHODS: Forty families from a human settlement in the District of San Juan de Lurigancho, Lima, were chosen at random. This sample included migrant families and people who had born in Lima.The members of these families were subjected to a survey to obtain demographic data and possible risk factor for HBV infection, and venous blood sample was obtained to determine HBV serological markers by ELIZA techniques.RESULTS: A total of 215 people were evaluated, 130 (60,5%) were female, and 85 (39,5%) were male. There were 9 (4,2%) HbsAg carriers; 4 (1,9%) of them were born in Huanta; the other 5 (2,3%) were born in Lima, and had never been to Huanta. They were under 20 years of age. No significant association was found between the presence of HbsAg and the use of injectables, blood transfusions, tatoos, previous surgery, dental extractions or sexual relations.CONCLUSION: The presence of HbsAg carrier on people born in Lima, with no "classical" risk factor for HBV infection, could be associated with carriers migrating from a hyperendemic HBV area, suggesting a mechanism of horizontal transmission. PMID:12219100

  11. Association of Periodontal Diseases and Liver Fibrosis in Patients With HCV and/or HBV infection

    PubMed Central

    Nagao, Yumiko; Kawahigashi, Yuji; Sata, Michio

    2014-01-01

    Background: Periodontal disease and systemic health are closely associated. However, there is no data supporting the association between periodontal disease and patients with liver diseases associated with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection. Objectives: The aim of this study was to evaluate the association between periodontitis and progression of liver diseases in patients with HCV and/or HBV infection. Patients and Methods: In this retrospective study, 351 patients with HCV- and/or HBV-related liver diseases underwent screening for periodontal disease using the Salivaster® salivary occult blood test from February 2010 to June 2014. Furthermore, we examined the prevalence of fimbrillin (fimA) genotype of Porphyromonas gingivalis (P. gingivalis) in 28 HCV-infected patients visited at our hospital between January 2013 and June 2014. P. gingivalis with fimA genotype with types I to V was further detected using a PCR method. Results: Of 351 patients, 76 patients (group 1) had a strong positive result for salivary occult blood test and 275 patients (group 2) had weak positive or negative test results. Significant factors between the groups were obesity, level of AST, ALT, LDH, ALP, Alb, D.Bil, T.cho, AFP, platelets (Plt), IRI, HOMA-IR, current interferon (IFN) treatment and the daily frequency of tooth brushing. Between-groups analysis indicated that total protein (T.pro) level and liver fibrosis were significant factors. According to multivariate analysis, five factors were associated with periodontal disease as Plt count below 80000, brushing teeth only once a day, current IFN treatment, aged 65 years or older and obesity. The adjusted odds ratios for these five factors were 5.80, 3.46, 2.87, 2.50 and 2.33, respectively, and each was statistically significant. Twenty-eight saliva specimens had positive results for P. gingivalis with fimA genotype types I to V. The prevalence of fimA genotype II was higher in 14 patients with liver

  12. [Prevalence change of HGV(GBV-C) infection and its coinfection with HBV a HCV infections in haemodialysis patients].

    PubMed

    Klusonová, Hana; Stepánová, Vlasta; Plísková, Lenka; Stilec, Roman

    2003-01-01

    Prevalence of HGV(GBV-C) infection and its coinfection with HBV a HCV infections were studied in group of 82 haemodialysis patients. This study was realized 20 months latter again -- 16 patients from 82 were running in dialysis, 17 patients were transplanted and 49 patients died (non of this viruses was cause of their death). HGV(GBV-C) RNA was detected in serum of 22 patients, 20 months latter it was detected in serum of 3 patients; one positive was new. 20 months latter any HGV(GBV-C) RNA was not detected in serum of 4 originally positive patients. Three of ten HBsAg positive patients were coinfected by HGV(GBV-C) RNA; 20 months latter any coinfection was found. In the first we found HGV(GBV-C) RNA in serum of 5 anti-HCV positive patients and in serum of 1 HCV RNA positive patient; 20 months latter it was in serum of 1 and 1 respectively. Elevation of ALT and AST levels were found in serum of 3 from 82 patients; two patients were coinfected with HBV or HCV. Any from 2 running dialysis patients with elevation of ALT and AST levels was not HGV(GBV-C) RNA positive. This virus is not probably frequent cause of liver disease in dialysis patients and it is not necessary to routinely screen for HGV(GBV-C) infection in this group of patients. PMID:19569590

  13. Patient with hepatocellular carcinoma related to prior acute arsenic intoxication and occult HBV: epidemiological, clinical and therapeutic results after 14 years of follow-up.

    PubMed

    Casanovas-Taltavull, Teresa; Ribes, Josepa; Berrozpe, Ana; Jordan, Sara; Casanova, Aurora; Sancho, Concha; Valls, Carles; Bosch, F Xavier

    2006-03-28

    Little is known about the long-term survivors of acute arsenic intoxication. We present here a clinical case report of a man with chronic hepatitis B virus (HBV) infection who developed hepatocellular carcinoma four years after acute arsenic poisoning. HBsAg was detected in serum in 1990 when he voluntarily donated blood. In 1991, the patient suffered from severe psychological depression that led him to attempt suicide by massive ingestion of an arsenic-containing rodenticide. He survived with polyneuropathy and paralysis of the lower limbs, and has been wheelchair-bound since then. During participation in a follow-up study conducted among HBV carriers, abdominal ultrasound detected a two-centimeter liver mass consistent with hepatocellular carcinoma. The tumor was confirmed by computed tomography (CT) and magnetic resonance image (MRI). Because of his significant comorbidity, the patient received palliative treatment with transarterial lipiodol chemoembolization (TACE) on three occasions (1996, 1997 and 1999). At his most recent visit in May 2005, the patient was asymptomatic, liver enzymes were normal and the tumor was in remission on ultrasound.

  14. Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada

    PubMed Central

    Osiowy, Carla; Giles, Elizabeth; Trubnikov, Max; Choudhri, Yogesh; Andonov, Anton

    2015-01-01

    Objective The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk. Methods HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV. Results Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections. Conclusion Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection. PMID:26406309

  15. Toll-Like Receptor 3 is Associated With the Risk of HCV Infection and HBV-Related Diseases

    PubMed Central

    Geng, Pei-Liang; Song, Li-Xue; An, Huaijie; Huang, Jing-Yu; Li, Sheng; Zeng, Xian-Tao

    2016-01-01

    Abstract There are inconsistent data on the association of risk of hepatitis virus infection and hepatitis virus-related diseases with the toll-like receptor 3 (TLR3) gene. Several common polymorphism sites were targeted to assess the risk of HBV infection, HCV infection, and HBV-related diseases. Meta-analysis combining data for 3547 cases and 2797 controls from 8 studies was performed in this study. Pooled ORs were calculated to measure the risk of hepatitis virus infection and hepatitis virus-related diseases. Fixed-effects pooled ORs were calculated using the Mantel-Haenszel method. The TLR3 gene was associated with a significantly increased risk of HBV-related diseases among 1355 patients and 1130 controls ([pooled OR, [95%CI]: 1.30, [1.15–1.48] for dominant; 1.77, [1.35–2.31] for recessive; 1.28 [1.16–1.41] for allele frequency). Subgroup analyses by a polymorphism site indicated an increased risk of HCV infection in relation to the TT/CT genotypes of rs3775291 (1.50 [1.11–2.01]), and a decreased risk ascribed to the T allele (0.20 [0.16–0.25]). We also noted an association between rs3775291 and significantly increased risk of HBV-related diseases (2.23 [1.55–3.21]). No significant inter-study heterogeneity or publication bias was detected in the analyses. These data suggest a likely effect on the risk to infect HCV and develop HBV-related diseases for the TLR3 gene. Large-scale studies with racially diverse populations are required to validate these findings. PMID:27227908

  16. A new multiparameter integrated MELD model for prognosis of HBV-related acute-on-chronic liver failure.

    PubMed

    Luo, Yue; Xu, Yun; Li, Mingming; Xie, Ya; Gong, Guozhong

    2016-08-01

    Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is one of the most deadly diseases. Many models have been proposed to evaluate the prognosis of it. However, these models are still controversial. In this study, we aimed to incorporate some characters into model for end-stage liver disease (MELD) to establish a new reliable and feasible model for the prognosis of HBV-ACLF.A total of 530 HBV-ACLF patients who had received antiviral therapy were enrolled into a retrospective study and divided into the training cohort (300) and validation cohort (230). Logistic regression analysis was used to establish a model to predict the 3-month mortality from the patients in the training cohort, and then, the new model was evaluated in the validation cohort.Except for MELD score, 4 other independent factors, namely degree of hepatic encephalopathy (HE), alpha-fetoprotein (AFP), white blood cell (WBC) count, and age, were important for the new model called HBV-ACLF MELD (HAM) model: R = 0.174 × MELD + 1.106 × HE - (0.003 × AFP) + (0.237 × WBC) + (0.103 × Age) - 11.388. The areas under receiver-operating characteristic curve of HAM in the training and validation cohort were 0.894 and 0.868, respectively, which were significantly higher than those of other 7 models. With the best cut-off value of -1.191, HAM achieved higher sensitivity and negative predictive value.We developed a new model that has a great prognostic value of the 3-month mortality of patients with HBV-ACLF. PMID:27559979

  17. HBV culture and infectious systems.

    PubMed

    Hayes, C Nelson; Chayama, Kazuaki

    2016-07-01

    While an effective vaccine against hepatitis B virus (HBV) has long been available, chronic HBV infection remains a severe global public health concern. Current treatment options have limited effectiveness, and long-term therapy is required to suppress HBV replication; however, complete elimination of the virus is rare. The lack of suitable animal models and infection systems has hindered efforts to unravel the HBV life cycle, particularly the early events in HBV entry, which appear to be highly species- and tissue-specific. Human primary hepatocytes remain the gold standard for HBV replication studies but are limited by availability and variability. While the HepaRG cell line is permissive for HBV replication, other hepatoma cell lines such as HepG2 do not support HBV replication. The recent discovery of sodium taurocholate transporting peptide (NTCP) as a primary receptor for HBV binding has led to the development of replication-competent cell lines such as HepG2-NTCP. Human hepatocytes grown in chimeric mice have provided another approach that allows primary human hepatocytes to be used while overcoming many of their limitations. Although the difficulty in developing HBV infection systems has hindered development of effective treatments, the variability and limited replication efficiency among cell lines point to additional liver-specific factors involved in HBV infection. It is hoped that HBV infection studies will lead to novel drug targets and therapeutic options for the treatment of chronic HBV infection.

  18. Khmer American Mothers’ Knowledge about HPV and HBV Infection and Their Perceptions of Parenting: My English Speaking Daughter Knows More

    PubMed Central

    Lee, Haeok; Kiang, Peter; Tang, Shirely S.; Chea, Phala; Peou, Sonith; Semino-Asaro, Semira; Grigg-Saito, Dorcas C.

    2016-01-01

    SUMMARY Purpose The purpose of this study is to explore and describe Khmer mothers’ understanding of HBV and HPV prevention as well as their perception of parenting on health and health education of their daughters in the US. Methods The qualitative pilot study guided by the revised Network Episode Model and informed by ethnographic analysis and community-based purposive sampling method were used. Face-to-face audiotaped interviews with eight Khmer mothers were conducted by bilingual female middle-aged community health leaders who spoke Khmer. Results The findings revealed that Khmer mothers clearly lacked knowledge about HBV and HPV infection prevention and had difficulty understanding and educating their daughters about health behavior, especially on sex-related topics. The findings showed that histo-sociocultural factors are integrated with the individual factor, and these factors influenced the HBV and HPV knowledge and perspective of Khmer mothers’ parenting. Conclusion The study suggests that situation-specific conceptual and methodological approaches that take into account the uniqueness of the sociocultural context of CAs is a novel method for identifying factors that are significant in shaping the perception of Khmer mothers’ health education related to HBV and HPV prevention among their daughters. The communication between mother and daughter about sex and the risk involved in contracting HBV and HPV has been limited, partly because it is seen as a “taboo subject” and partly because mothers think that schools educate their children regarding sexuality and health. PMID:26160247

  19. Noninvasive diagnosis of liver fibrosis in patients with HIV infection and HCV/HBV co-infection.

    PubMed

    Moreno, S; García-Samaniego, J; Moreno, A; Ortega, E; Pineda, J A; del Romero, J; Tural, C; von Wichmann, M A; Berenguer, J; Castro, A; Espacio, R

    2009-04-01

    The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.

  20. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    CMV mononucleosis; Cytomegalovirus (CMV) ... Infection with cytomegalovirus (CMV) is very common. The infection is spread by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact ...

  1. Association Between IL-10 Gene Promoter Polymorphisms (-592 A/C, -819 T/C, -1082 A/G) and Susceptibility to HBV Infection in an Iranian Population

    PubMed Central

    Moudi, Bita; Heidari, Zahra; Mahmoudzadeh-Sagheb, Hamidreza; Hashemi, Mohammad; Metanat, Malihe; Khosravi, Soheila; Farrokh, Parisa

    2016-01-01

    Background IL-10 can play a vital role in immune response against HBV. Three biallelic SNPs from the transcription start site control the transcription of the IL-10 gene. An association between susceptibility to HBV and IL-10 polymorphisms has been suggested in patients with HBV infection. Objectives The present study was designed to study the association between polymorphisms in interleukin-10 (-1082 A/G, -819 T/C and -592 A/C) promoter gene and chronic hepatitis B virus (HBV) infection. Patients and Methods 221 chronically infected patients and 200 healthy control subjects were enrolled in the study. Three biallelic (-1082 A/G, -819 T/C and -592 A/C) polymorphisms in the IL-10 promoter gene were determined by PCR-RFLP method. Results Persistent HBV infection was associated with IL-10-1082 AG (P = 0.001) and GG (P = 0.004) genotypes and G (P = 0.000) allele. IL-10-819 T/C and -592 A/C genotype and allele frequencies did not show any correlation with the risk of chronic hepatitis B infection. Conclusions These results suggest that polymorphisms in interleukin-10 gene promoter influence clinical outcome of HBV infection and susceptibility to HBV infection. PMID:27148384

  2. Continuous up to 4 Years Entecavir Treatment of HBV-Infected Adolescents – A Longitudinal Study in Real Life

    PubMed Central

    Pawłowska, Małgorzata; Smok, Beata; Rajewski, Paweł; Wietlicka-Piszcz, Magdalena; Halota, Waldemar; Tretyn, Andrzej

    2016-01-01

    This study evaluated the long-term (up to 4 years) efficacy and safety of entecavir ETV treatment and analysed the significance of baseline and on-treatment factors in long-term ETV outcomes in adolescents with chronic hepatitis B (CHB). We determined the cumulative virological and serological outcomes of 44 adolescents with CHB receiving ETV for up to 4 years. To investigate the dynamics of HBV DNA, ALT activity and hepatitis B e antigen (HBeAg) seroconversion over time and their associations with the considered factors, generalized estimating equation (GEE) models were used. The cumulative rates of undetectable HBV DNA (<20 IU/ml) and HBeAg seroconversion after 4 years were 89.7% and 55.4%, respectively. In the study group, we showed that having undetectable HBV DNA at the 6th or 12th month of therapy predicted the achievement of a sustained response rate (SRR, defined as the loss of HBV DNA, loss of HBeAg and ALT normalization) at year 3 of ETV therapy (P = 0.048, OR = 5.83; P = 0.012; OR = 14.57, respectively). The GEE analysis indicated that of the different factors, the duration of ETV therapy had a strong impact on the achievement of virological suppression, HBeAg seroconversion and SRR in adolescents. Each month after the initiation of therapy, the odds of loss of HBV DNA increased by approximately 5% (OR = 1.05, P<0.0001), on average. Additionally, the GEE analysis revealed that adolescents with an age at infection of ≥10 years had 3 times higher odds of achieving undetectable HBV DNA than patients with a younger infection age (OR = 3.67, P = 0.028). None of the ETV-treated patients reported significant adverse effects. ETV is an effective and safe treatment option for adolescents with CHB. Undetectable HBV DNA in the 6th and/or 12th month of ETV treatment and older age at infection could predict maintained virological suppression. PMID:27685782

  3. Chronic HBV infection in pregnant immigrants: a multicenter study of the Italian Society of Infectious and Tropical Diseases.

    PubMed

    Sagnelli, Evangelista; Taliani, Gloria; Castelli, Francesco; Bartolozzi, Dario; Cacopardo, Bruno; Armignacco, Orlando; Scotto, Gaetano; Coppola, Nicola; Stroffolini, Tommaso; Sagnelli, Caterina

    2016-04-01

    The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012-2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0±12.1 years and the length of stay in Italy 5.0±4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA ≥2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT ≥1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population. PMID:27196549

  4. Chronic HBV infection in pregnant immigrants: a multicenter study of the Italian Society of Infectious and Tropical Diseases.

    PubMed

    Sagnelli, Evangelista; Taliani, Gloria; Castelli, Francesco; Bartolozzi, Dario; Cacopardo, Bruno; Armignacco, Orlando; Scotto, Gaetano; Coppola, Nicola; Stroffolini, Tommaso; Sagnelli, Caterina

    2016-04-01

    The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012-2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0±12.1 years and the length of stay in Italy 5.0±4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA ≥2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT ≥1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population.

  5. Lower than expected hepatitis B virus infection prevalence among first generation Koreans in the U.S.: results of HBV screening in the Southern California Inland Empire

    PubMed Central

    2014-01-01

    Background Hepatitis B virus (HBV) infection is prevalent in Asian immigrants in the USA. California’s Inland Empire region has a population of approximately four million, including an estimated 19,000 first generation Koreans. Our aim was to screen these adult individuals to establish HBV serological diagnoses, educate, and establish linkage to care. Methods A community-based program was conducted in Korean churches from 11/2009 to 2/2010. Subjects were asked to complete a HBV background related questionnaire, provided with HBV education, and tested for serum HBsAg, HBsAb and HBcAb. HBsAg positive subjects were tested for HBV quantitative DNA, HBeAg and HBeAb, counseled and directed to healthcare providers. Subjects unexposed to HBV were invited to attend a HBV vaccination clinic. Results A total of 973 first generation Koreans were screened, aged 52.3y (18-93y), M/F: 384/589. Most (75%) had a higher than high school education and were from Seoul (62.2%). By questionnaire, 24.7% stated they had been vaccinated against HBV. The serological diagnoses were: HBV infected (3.0%), immune due to natural infection (35.7%), susceptible (20.1%), immune due to vaccination (40.3%), and other (0.9%). Men had a higher infection prevalence (4.9% vs. 1.7%, p = 0.004) and a lower vaccination rate (34.6% vs. 44.0%, p = 0.004) compared to women. Self-reports of immunization status were incorrect for 35.1% of subjects. Conclusions This large screening study in first generation Koreans in Southern California demonstrates: 1) a lower than expected HBV prevalence (3%), 2) a continued need for vaccination, and 3) a need for screening despite a reported history of vaccination. PMID:24884673

  6. Interleukin-22 Promotes Proliferation of Liver Stem/Progenitor Cells in Mice and Patients with Chronic HBV Infection

    PubMed Central

    Feng, Dechun; Kong, Xiaoni; Weng, Honglei; Park, Ogyi; Wang, Hua; Dooley, Steven; Gershwin, M. Eric; Gao, Bin

    2012-01-01

    Background & Aims Proliferation of liver stem/progenitor cells (LPCs), which can differentiate into hepatocytes or biliary epithelial cells, is often observed in chronically inflamed regions of liver in patients. We investigated how inflammation might promote proliferation of LPCs. Methods We examined the role of interleukin (IL)-22, a survival factor for hepatocytes, on proliferation of LPCs in patients with chronic hepatitis B virus (HBV) infection and in mice. Proliferation of LPCs in mice was induced by feeding a diet that contained 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Results Hepatic expression of IL-22 was increased in patients with HBV and correlated with the grade of inflammation and proliferation of LPCs. Mice on the DDC diet that overexpressed an IL-22 transgene specifically in liver (IL-22TG), or that were infected with an IL-22–expressing adenovirus, had increased proliferation of LPCs. Signal transducer and activator of transcription (STAT) 3, a component of the IL-22 signaling pathway, was activated in LPCs isolated from DDC-fed IL-22TG mice. Deletion of STAT3 from livers of IL-22TG mice reduced proliferation of LPCs. Moreover, the receptors IL-22R1 and IL-10R2 were detected on EpCAM+CD45– LPCs isolated from DDC-fed wild-type mice. Culture of these cells with IL-22 activated STAT3 and led to cell proliferation, but IL-22 had no effect on proliferation of STAT3-deficient EpCAM+CD45– LPCs. IL-22 also activated STAT3 and promoted proliferation of cultured BMOL cells (a mouse LPC line). Conclusion In livers of mice and patients with chronic HBV infection, inflammatory cells produce IL-22, which promotes proliferation of LPCs via STAT3. These findings link inflammation with proliferation of LPCs in patients with HBV infection. PMID:22484119

  7. Sorafenib Combined With Transarterial Chemoembolization in Treating HBV-infected Patients With Intermediate Hepatocellular Carcinoma

    ClinicalTrials.gov

    2012-04-24

    PHENYTOIN/SORAFENIB [VA Drug Interaction]; Liver Neoplasms; Carcinoma, Hepatocellular; Digestive System Neoplasms; Neoplasms by Site; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; DOXORUBICIN/TRASTUZUMAB [VA Drug Interaction]; HBV

  8. Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and officers in Ghana: A national multicenter study

    PubMed Central

    Adjei, Andrew A; Armah, Henry B; Gbagbo, Foster; Ampofo, William K; Boamah, Isaac; Adu-Gyamfi, Clement; Asare, Isaac; Hesse, Ian FA; Mensah, George

    2008-01-01

    Background Prisons are known to be high-risk environments for the spread of bloodborne and sexually transmitted infections. Prison officers are considered to have an intermittent exposure potential to bloodborne infectious diseases on the job, however there has been no studies on the prevalence of these infections in prison officers in Ghana. Methods A national multicenter cross-sectional study was undertaken on correlates of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis infections in sample of prison inmates and officers from eight of ten regional central prisons in Ghana. A total of 1366 inmates and 445 officers were enrolled between May 2004 and December 2005. Subjects completed personal risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV and Treponema pallidum; and surface antigen of HBV (HBsAg). These data were analyzed using both univariate and multivariate techniques. Results Almost 18% (1336) of 7652 eligible inmates and 21% (445) of 2139 eligible officers in eight study prisons took part. Median ages of inmates and officers were 36.5 years (range 16–84) and 38.1 years (range 25–59), respectively. Among inmates, HIV seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg. Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%, syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants for HIV, HBV and syphilis infections among inmates were age between 17–46, being unmarried, being illiterate, female gender, being incarcerated for longer than median time served of 36 months, history of homosexuality, history of intravenous drug use, history of sharing syringes and drug paraphernalia, history of participation in paid sexual activity, and history of sexually transmitted diseases. Independent determinants for HIV, HBV, HCV and syphilis infections among officers

  9. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their

  10. Relationship Between Hepatic Steatosis and the Elevation of Aminotransferases in HBV-Infected Patients With HBe-Antigen Negativity and a Low Viral Load

    PubMed Central

    Enomoto, Hirayuki; Aizawa, Nobuhiro; Nishikawa, Hiroki; Ikeda, Naoto; Sakai, Yoshiyuki; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Iwata, Yoshinori; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Abstract Nonalcoholic fatty liver disease has been suggested to be associated with alanine aminotransferase (ALT) elevation in hepatitis B virus (HBV)-infected patients with HBe antigen (HBeAg)-negativity and a low HBV-DNA level. However, few studies have evaluated the association according to histological findings of the liver. Among a total of 198 HBV-infected patients who received a percutaneous liver biopsy, we studied the histological and laboratory findings of HBeAg-negative patients without receiving nucleoside/nucleotide analogues treatment (N = 70) in order to evaluate whether hepatic steatosis and its related metabolic disorders were associated with an elevation in ALT levels in HBeAg-negative patients. In HBeAg-negative patients with a high serum HBV-DNA level (≥2000 IU/mL), the level of HBV-DNA was the only significant factor related to ALT elevation. However, in HBeAg-negative patients with a low HBV-DNA level, the serum ferritin level, and histologically observed hepatic steatosis were significantly associated factors with ALT elevation. When we evaluated 2 metabolic variables (serum ferritin and fasting insulin) that are suggested to be relevant to the presence of progressive disease in Japanese patients, we found that the rate of metabolic disorders was significantly higher among patients with a high ALT level and a low HBV-DNA level than it was among those with other conditions. The triglyceride level and the frequency of moderate or severe hepatic steatosis were significantly higher in patients with a low HBV-DNA level than in those with a high HBV-DNA level. Histologically proven hepatic steatosis and its related metabolic disorders are suggested to be involved in the elevation of aminotransferases of HBeAg-negative patients, particularly those with low HBV-DNA levels. PMID:27124068

  11. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  12. The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis

    PubMed Central

    Yang, Jiao; Sun, Hang; Liu, Qi

    2016-01-01

    Background. Currently, both of entecavir and lamivudine are effective for patients with HBV-associated acute-on-chronic liver failure (ACLF). However, there is no consensus on the efficacy of entecavir versus lamivudine for patients with HBV-associated ACLF. The aim of the study was to compare the efficacy and safety of entecavir with that of lamivudine for HBV-associated ACLF patients. Methods. Publications on entecavir versus lamivudine in HBV-associated ACLF patients were comprehensively identified. Odds ratio and mean difference were used to measure the effect. Results. Ten studies, totaling 1254 patients, were eligible. No significant differences between the two drugs presented in the 1-, 2-, 3-, or 6-month survival rates. However, after 12 months of treatment, patients prescribed entecavir had a statistically higher survival rate (p = 0.008) and lower total bilirubin (p < 0.0001) and alanine aminotransferase (p = 0.04) levels compared to patients prescribed lamivudine. More patients achieved HBV negative levels when taking entecavir as measured at 1-, 3-, and 12-month time points and had a lower rate of HBV recurrence. Conclusion. While entecavir and lamivudine are both relatively safe and well tolerated, entecavir was more efficacious in terms of survival rate and clinical improvement in long-term treatment. Further prospective randomized controlled trials are needed to validate these results. PMID:27148364

  13. Recognition of core-derived epitopes from a novel HBV-targeted immunotherapeutic by T-cells from patients infected by different viral genotypes.

    PubMed

    Godon, Ophelie; Evlachev, Alexei; Bourgine, Maryline; Meritet, Jean-François; Martin, Perrine; Inchauspe, Genevieve; Michel, Marie-Louise

    2015-08-26

    Hepatitis B virus (HBV) infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular carcinoma. Current therapies based on nucleos(t)ide analogs or pegylated-interferon-α lead to control of viral replication in most patients but rarely achieve cure. A potential strategy to control chronic hepatitis B is to restore or induce functional anti-HBV T-cell immune responses using HBV-specific immunotherapeutics. However, viral diversity is a challenge to the development of this class of products as HBV genotypes display a sequence diversity of up to 8%. We have developed a novel HBV-targeted immunotherapeutic, TG1050, based on a non-replicative Adenovirus vector encoding a unique and large fusion protein composed of multiple antigenic regions derived from a HBV genotype D sequence. Using peripheral blood mononuclear cells from 23 patients chronically infected by five distinct genotypes (gt A, B, C, D and E) and various sets of peptides encompassing conserved versus divergent regions of HBV core we have measured ability of TG1050 genotype D core-derived peptides to be recognized by T-cells from patients infected by various genotypes. Overall, PBMCs from 78% of genotype B or C- and 100% genotype A or E-infected patients lead to detection of HBV core-specific T-cells recognizing genotype D antigenic domains located both in conserved and variable regions. This proof-of-concept study supports the clinical development of TG1050 in large patient populations independently of infecting genotypes.

  14. Seroprevalence of HIV, HBV, HCV and syphilis infections among blood donors at Gondar University Teaching Hospital, Northwest Ethiopia: declining trends over a period of five years

    PubMed Central

    2010-01-01

    Background Transfusion-transmissible infectious agents such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis are among the greatest threats to blood safety for the recipient. This study aimed to determine the seroprevalence, risk factors and trends of HIV, HBV, HCV and syphilis infections among blood donors over a period of five years at Gondar University Teaching Hospital, Northwest Ethiopia. Methods A retrospective analysis of consecutive blood donors' records covering the period between January 2003 and December 2007 was conducted. Logistic regression analysis was used to determine risk factors associated with HIV, HBV, HCV and syphilis infections. Results From the total of 6361 consecutive blood donors, 607 (9.5%) had serological evidence of infection with at least one pathogen and 50 (0.8%) had multiple infections. The overall seroprevalence of HIV, HBV, HCV and syphilis was 3.8%, 4.7%, 0.7%, and 1.3% respectively. Among those with multiple infections, the most common combinations were HIV - syphilis 19 (38%) and HIV - HBV 17 (34%). The seropositivity of HIV was significantly increased among female blood donors, first time donors, housewives, merchants, soldiers, drivers and construction workers. Significantly increased HBV seropositivity was observed among farmers, first time donors and age groups of 26 - 35 and 36 - 45 years. Similarly, the seroprevalence of syphilis was significantly increased among daily labourers and construction workers. Statistically significant association was observed between syphilis and HIV infections, and HCV and HIV infections. Moreover, significantly declining trends of HIV, HCV and syphilis seropositivity were observed over the study period. Conclusions A substantial percentage of the blood donors harbour HIV, HBV, HCV and syphilis infections. Strict selection of blood donors and comprehensive screening of donors' blood using standard methods are highly recommended to ensure

  15. HIV, HBV, and HCV infections among drug-involved, inner-city, street sex workers in Miami, Florida.

    PubMed

    Inciardi, James A; Surratt, Hilary L; Kurtz, Steven P

    2006-03-01

    This study describes the rates of HIV, HBV, and HCV seropositivity among drug-involved, female street sex workers in low-income, inner-city sections of Miami, Florida; further, their sociodemographic characteristics, drug use, and sexual risk behaviors were assessed; and predictors of infection were reported. A sample of 586 sex workers was recruited through targeted sampling methods, interviewed, and counseled and tested for the presence of antibody to HIV, HBV, and HCV. Respondents' median age was 38 years, median time in sex work was 14 years, all were heavily involved in the use of alcohol and drugs, and 42% were homeless. More than half (51.0%) had engaged in unprotected vaginal sex in the past month. Prevalences were HIV, 22.4%; HBV, 53.4%; HCV, 29.7%. A multidimensional public health program must address not only issues related to unsafe sex, but also the problems of drug abuse, homelessness, and other lifestyle factors that contribute to risk behaviors. PMID:16378168

  16. The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi

    PubMed Central

    2014-01-01

    Background Coinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response. Methods Women were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm3 continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity. Results A total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm3 (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery. Conclusions In this cohort of nevirapine-treated women the presence of

  17. Rather than Rs1800796 polymorphism, expression of interleukin-6 is associated with disease progression of chronic HBV infection in a Chinese Han population.

    PubMed

    Tang, Shengli; Liu, Zhisu; Zhang, Yongxi; He, Yueming; Pan, Dingyu; Liu, Yuanyuan; Liu, Quanyan; Zhang, Zhonglin; Yuan, Yufeng

    2013-01-01

    Interleukin-6 plays an important role in chronic inflammation as well as tumor growth and progression. Here, a case-control study was undertaken to investigate the association of rs1800796 polymorphism of IL-6 gene and serum levels with disease progression of chronic HBV infection. Rs1800796 polymorphism was genotyped in 641 Chinese Han patients with chronic HBV infection, including 23 IT, 25 IC, 292 CHB, 153 LC, and 148 HCC patients and 265 healthy controls. Serum IL-6 levels were measured in 23 IT, 25 IC, 47 CHB, 41 LC, and 49 HCC patients and 45 healthy controls, and the classifications of HCC were accorded to BCLC staging system. We found no significant association between rs1800796 polymorphism and disease progression of chronic HBV infection; however, serum IL-6 levels showed significant statistical differences between patients with CHB, LC, and HCC. Moreover, statistical differences can be observed in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. Our findings suggest that rs1800796 polymorphism unlikely contribute significantly to affect the progression of chronic HBV infection, and serum IL-6 levels can act as a useful indicator for disease progression and severity of chronic HBV infection.

  18. Epidemiology, Risk Factors and Genotypes of HBV in HIV-Infected Patients in the Northeast Region of Colombia: High Prevalence of Occult Hepatitis B and F3 Subgenotype Dominance

    PubMed Central

    Bautista-Amorocho, Henry; Castellanos-Domínguez, Yeny Zulay; Rodríguez-Villamizar, Laura Andrea; Velandia-Cruz, Sindi Alejandra; Becerra-Peña, Jeysson Andrey; Farfán-García, Ana Elvira

    2014-01-01

    Introduction Chronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission. Objectives Our aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city. Methods A cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 2009–2010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection. Results Participants were on average 37±11 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.4–16.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI. Conclusions The present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients. PMID:25462190

  19. Hepatitis B and human immunodeficiency virus co-infection

    PubMed Central

    Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

    2014-01-01

    Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

  20. Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection

    PubMed Central

    Said, Elias A.; Al-Reesi, Iman; Al-Riyami, Marwa; Al-Naamani, Khalid; Al-Sinawi, Shadia; Al-Balushi, Mohammed S.; Koh, Crystal Y.; Al-Busaidi, Juma Z.; Idris, Mohamed A.; Al-Jabri, Ali A.

    2016-01-01

    Background The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers. Methods Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. Results Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade. Conclusion The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis. PMID:27348308

  1. Intrahepatic Toll-Like Receptor 3 in Chronic HBV Infection Subjects: Asymptomatic Carriers, Active Chronic Hepatitis, Cirrhosis, and Hepatocellular Carcinoma

    PubMed Central

    Yin, Jia Wen; Ping Huang, Mao; Zhong, Bei

    2016-01-01

    Background The entire disease spectrum of chronic HBV infection (CHB) includes asymptomatic carriers (AC), active chronic hepatitis (ACH), cirrhosis (Cir), and hepatocellular carcinoma (HCC). Previous study have demonstrated that the costimulation profiles from the livers of patients influenced immune responses and played various immunological roles in AC, ACH, Cir, and HCC. In addition, activation of TLR3 signaling in the liver may contribute to HBV clearance, although some HBV components are able to block TLR3 signaling and counteract HBV clearance through positive or negative feedback loops. Previous clinical studies have demonstrated that different TLR3 expressions are present in ACH patients, but no studies investigated the expression of TLR3 proteins in the livers of patients with AC, Cir, or HCC. Objectives This study investigated intrahepatic TLR3 expression throughout the entire disease spectrum of CHB patients and assessed the interrelations between TLR3 and costimulation proteins. Patients and Methods Patients with ACH, Cir, HCC, and AC and healthy donors (HD) were recruited. TLR3 expression in the livers of patients were investigated using western blot analysis and immunohistochemistry. Correlations between TLR3 and costimulation proteins, including CD80, CD86, CD83, CD28, CTLA-4, CD40, and ICAM-1, were assessed. Results The TLR3 protein in the ACH group tended toward reduction although the P Value of the comparison between the ACH group and HD group was not statistically significant. The TLR3 levels in the HCC, AC, and Cir groups were higher than those in the HD and ACH groups. TLR3 was not interrelated with all costimulation proteins in the DCs and T cells in all five groups. No group presented any interrelation between TLR3 and CD40, except the AC group. Conclusions The AC, HCC, and Cir patients displayed increased levels of the intrahepatic TLR3 protein compared to the HD and AC patients. Both activation of TLR3/INF-β signaling and inhibition of

  2. Complement Factor 3 Could Be an Independent Risk Factor for Mortality in Patients with HBV Related Acute-on-Chronic Liver Failure

    PubMed Central

    Zhang, Geng-lin; Zhang, Ting; Ye, Yi-nong; Liu, Jing; Zhang, Xiao-hong; Xie, Chan; Peng, Liang; Gao, Zhi-liang

    2016-01-01

    The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Serum levels of the third and fourth complement components (C3, C4) and complement function (CH50) were examined in this prospective, observational study. Associations between their expression and disease activity were analyzed. Survival was analyzed by Kaplan-Meier curves. Predictors of clinical outcome were determined by Cox regression analysis. C3, C4, and CH50 levels were significantly lower in HBV-ACLF patients compared to controls. C3, C4, and CH50 levels were negatively correlated with Tbil levels but positively associated with PTA levels. C3 levels were negatively associated with MELD-Na. C3 levels were significantly lower in HBV-ACLF patients who died compared to patients who survived. In a median hospital stay of 39 days, mortality occurred in 41 patients with a progressive increase based on C3 grade (P = 0.008). The actuarial probability of developing mortality was significantly higher in patients with low C3 grade compared to those with high C3 grade (P < 0.001). Multivariate Cox regression analysis showed that C3 levels were an independent predictor of mortality. Complement played a pathogenic role in HBV-ACLF patients and C3 was an independent predictor of mortality. PMID:27144164

  3. Phylogenetic analysis of torque teno virus genome from Pakistani isolate and incidence of co-infection among HBV/HCV infected patients

    PubMed Central

    2012-01-01

    Background Torque Teno Virus (TTV) was the first single stranded circular DNA virus to be discovered that infects humans. Although there have been numerous reports regarding the prevalence of TTV from other countries of South Asia, there is severe lack of information regarding its prevalence in Pakistan. Thus the present study compiles the first indigenous report to comprehensively illustrate the incidence of the virus in uninfected and hepatitis infected population from Pakistan. Another aim of the study was to present the sequence of full length TTV genome from a local isolate and compare it with the already reported genome sequences from other parts of the world. Methods TTV DNA was screened in the serum of 116, 100 and 40 HBV infected, HCV infected and uninfected individuals respectively. Nearly full length genome of TTV was cloned from a HBV patient. The genome sequence was subjected to in-silico analysis using CLC Workbench, ClustalW, ClustalX and TreeView. Statistical analysis was carried out in SPSS v17.0. Results Our results report that 89.7%, 90.0% and 92.5% of HBV, HCV patients and healthy control population were positive for TTV infection. TTV genome of 3603 bp was also cloned from a local isolate and given the identity of TPK01. The TTV genome sequence mentioned in this paper is submitted in the GenBank/EMBL/DDBJ under the accession number JN980171. Phylogenetic analysis of TPK01 revealed that the Pakistani isolate has sequence similarities with genotype 23 and 22 (Genogroup 2). Conclusion The results of the current study indicate that the high frequency of TTV viremia in Pakistan conforms to the reports from other areas of the world, wherever screening of TTV DNA was performed against 5′-UTR of the genome. The high sequence diversity among TTV genome sequences and the high frequency of prevalence makes it harder to study this virus in cellular systems. PMID:23270330

  4. HIV-1, HBV, HCV, HTLV, HPV-16/18, and Treponema pallidum Infections in a Sample of Brazilian Men Who Have Sex with Men

    PubMed Central

    Soares, Caroline C.; Georg, Ingebourg; Lampe, Elisabeth; Lewis, Lia; Morgado, Mariza G.; Nicol, Alcina F.; Pinho, Adriana A.; Salles, Regina C. S.; Teixeira, Sylvia L. M.; Vicente, Ana Carolina P.; Viscidi, Raphael P.; Gomes, Selma A.

    2014-01-01

    Background Men who have sex with men (MSM) are more vulnerable to blood-borne infections and/or sexually-transmitted infections (STI). This study was conducted to estimate the prevalences of mono and co-infections of HIV-1 and other blood-borne/STIs in a sample of MSM in Campinas, Brazil. Methods Responding Driven Sampling (RDS) was used for recruitment of MSM. Serum samples collected from 558 MSM were analyzed for the presence of serological markers for HIV-1, HBV, HCV, HTLV, HPV-16/18, and T. pallidum infections. Results The highest prevalences of infection in serum samples were found for HPV-16 and 18 (31.9% and 20.3%, respectively). Approximately 8% of the study population showed infection with HIV-1, and within that group, 27.5% had recently become infected with HIV-1. HBV infection and syphilis were detected in 11.4% and 10% of the study population, respectively, and the rates of HTLV and HCV infection were 1.5% and 1%, respectively. With the exception of HTLV, all other studied infections were usually found as co-infections rather then mono-infections. The rates of co-infection for HCV, HPV-18, and HIV-1 were the highest among the studied infections (100%, 83%, and 85%, respectively). Interestingly, HTLV infection was usually found as a mono-infection in the study group, whereas HCV was found only as a co-infection. Conclusions The present findings highlight the need to educate the MSM population concerning their risk for STIs infections and methods of prevention. Campaigns to encourage vaccination against HBV and HPV could decrease the rates of these infections in MSM. PMID:25083768

  5. A comprehensive validation of HBV-related acute-on-chronic liver failure models to assist decision-making in targeted therapeutics

    PubMed Central

    Shen, Yi; Wang, Xulin; Zhang, Sheng; Qin, Gang; Liu, Yanmei; Lu, Yihua; Liang, Feng; Zhuang, Xun

    2016-01-01

    This research utilized an external longitudinal dataset of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) to compare and validate various predictive models that support the current recommendations to select the most effective predictive risk models to estimate short- and long-term mortality and facilitate decision-making about preferable therapeutics for HBV-ACLF patients. Twelve ACLF prognostic models were developed after a systematic literature search using the longitudinal data of 232 HBV-ACLF patients on the waiting list for liver transplantation (LT). Four statistical measures, the constant (A) and slope (B) of the fitted line, the area under the curve (C) and the net benefit (D), were calculated to assess and compare the calibration, discrimination and clinical usefulness of the 12 predictive models. According to the model calibration and discrimination, the logistic regression models (LRM2) and the United Kingdom model of end-stage liver disease(UKELD) were selected as the best predictive models for both 3-month and 5-year outcomes. The decision curve summarizes the benefits of intervention relative to the costs of unnecessary treatment. After the comprehensive validation and comparison of the currently used models, LRM2 was confirmed as a markedly effective prognostic model for LT-free HBV-ACLF patients for assisting targeted and standardized therapeutic decisions. PMID:27633520

  6. A comprehensive validation of HBV-related acute-on-chronic liver failure models to assist decision-making in targeted therapeutics.

    PubMed

    Shen, Yi; Wang, Xulin; Zhang, Sheng; Qin, Gang; Liu, Yanmei; Lu, Yihua; Liang, Feng; Zhuang, Xun

    2016-01-01

    This research utilized an external longitudinal dataset of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) to compare and validate various predictive models that support the current recommendations to select the most effective predictive risk models to estimate short- and long-term mortality and facilitate decision-making about preferable therapeutics for HBV-ACLF patients. Twelve ACLF prognostic models were developed after a systematic literature search using the longitudinal data of 232 HBV-ACLF patients on the waiting list for liver transplantation (LT). Four statistical measures, the constant (A) and slope (B) of the fitted line, the area under the curve (C) and the net benefit (D), were calculated to assess and compare the calibration, discrimination and clinical usefulness of the 12 predictive models. According to the model calibration and discrimination, the logistic regression models (LRM2) and the United Kingdom model of end-stage liver disease(UKELD) were selected as the best predictive models for both 3-month and 5-year outcomes. The decision curve summarizes the benefits of intervention relative to the costs of unnecessary treatment. After the comprehensive validation and comparison of the currently used models, LRM2 was confirmed as a markedly effective prognostic model for LT-free HBV-ACLF patients for assisting targeted and standardized therapeutic decisions. PMID:27633520

  7. HBV and liver cancer.

    PubMed

    Leung, Nancy

    2005-07-01

    The association of hepatitis B virus (HBV) infection and liver cancer is well documented in epidemiological study. Patients with chronic hepatitis B have increased risk of hepatocelluar carcinoma (HCC), in particular those with active liver disease and cirrhosis. The incidence of HCC increases with age and is more common among male patients. The introduction of universal HBV vaccination program for the newborn in endemic regions has started to show beneficial impact. Taiwan introduced this program two decades ago and the incidence of liver cancer among infants and young children have declined significantly. The carcinogenic events leading to HCC are under intense research. A number of hypotheses have been proposed. HBV is not directly hepatotoxic but its interaction with the host immune system creates opportunity for HBV DNA integration into the host genome. One of the main foci of research is the HBX-encoded X protein. Its integration and protein expression impose alteration in cell proliferation cycle and apoptosis process. Many other factors may be involved including viral-induced alterations in p53 and telemerase, HBV genotypes, co-infection with HCV or delta agents, patient's lifestyle such as smoking, alcohol excesses, and genetic factors of the host patient. The processes of necroinflammation, cell proliferation and fibrosis facilitate the initial carcinogenic development. HCC surveillance with tumor markers such as alpha-foetal protein, decarboxylated prothrombin, in conjunction with imaging techniques has identified early small HCC that is amenable to curative therapy. Viral load has been correlated with increase risk of HCC. The available anti-viral agents have demonstrated clinical benefit among those with maintained and sustained response. Interferon and lamivudine therapy have demonstrated reduction of HCC among responders. However, they only constitute a minority proportion of treated patients. The mainstay of prevention should lie in prevention of

  8. Across-sectional study on anxiety and stress in pregnant women with chronic HBV infection in the People’s Republic of China

    PubMed Central

    Zhou, Fen; Li, Jianju; Lin, Keke; Ji, Ping; Sun, Yumei

    2015-01-01

    Purpose To investigate the anxiety and pregnancy-associated stress of pregnant women with chronic hepatitis B virus (HBV) infection in the People’s Republic of China and analyze the relationship between anxiety and pregnancy-associated stress in the hope of finding ways to reduce the stress or improve the coping skills for these mothers-to-be during pregnancy. Methods A cross-sectional study was conducted. One hundred and sixty chronic HBV-infected pregnant women (HBV group) and 160 healthy pregnant women (control group) selected from three Peking University-affiliated hospitals participated in the study, and completed the State-Trait Anxiety Inventory (STAI) and Pregnancy Stress Rating Scale (PSRS) survey. Results The mean scores of STAI and PSRS for the HBV group were higher than for the control group. Factor 2 of PSRS (stress caused by worrying about mother and child’s health and safety) was the highest, and was significantly higher in the HBV group than in the control group. Correlation analysis showed STAI scores were significantly correlated with economic status and diagnosis, as well as the total score, factor 1 (stress about identifying with the role of mother), and factor 2 of PSRS, but not significantly correlated with factor 3 of PSRS (stress caused by the changes of body shape and physical activity). Conclusion Pregnant women with chronic HBV infection experienced higher levels of anxiety and stress than healthy pregnant women. Their major stress came from concerns for the health and safety of the mother and the child. PMID:26346004

  9. Drug delivery systems and liver targeting for the improved pharmacotherapy of the hepatitis B virus (HBV) infection.

    PubMed

    Cuestas, María L; Mathet, Verónica L; Oubiña, José R; Sosnik, Alejandro

    2010-07-01

    In spite of the progress made in vaccine and antiviral therapy development, hepatitis B virus (HBV) infection is still the most common cause of liver cirrhosis and hepatocellular carcinoma, with more than 400 million people chronically infected worldwide. Antiviral therapy with nucleos(t)ide analogues and/or immunomodulating peptides is the only option to control and prevent the progression of the disease in chronic hepatitis B (CHB)-infected patients. So far, the current antiviral monotherapy remains unsatisfactory because of the low efficacy and the development of drug resistance mutants. Moreover, viral rebound is frequently observed following therapy cessation, since covalent closed circular DNA (cccDNA) is not removed from hepatocytes by antiviral therapy. First, this review describes the current pharmacotherapy for the management of CHB and the new drug candidates being investigated. Then, the challenges in the development of drug delivery systems for the targeting of antiviral drugs to the liver parenchyma are discussed. Finally, perspectives in the design of a more efficient pharmacotherapy to eradicate the virus from the host are addressed.

  10. Drug delivery systems and liver targeting for the improved pharmacotherapy of the hepatitis B virus (HBV) infection.

    PubMed

    Cuestas, María L; Mathet, Verónica L; Oubiña, José R; Sosnik, Alejandro

    2010-07-01

    In spite of the progress made in vaccine and antiviral therapy development, hepatitis B virus (HBV) infection is still the most common cause of liver cirrhosis and hepatocellular carcinoma, with more than 400 million people chronically infected worldwide. Antiviral therapy with nucleos(t)ide analogues and/or immunomodulating peptides is the only option to control and prevent the progression of the disease in chronic hepatitis B (CHB)-infected patients. So far, the current antiviral monotherapy remains unsatisfactory because of the low efficacy and the development of drug resistance mutants. Moreover, viral rebound is frequently observed following therapy cessation, since covalent closed circular DNA (cccDNA) is not removed from hepatocytes by antiviral therapy. First, this review describes the current pharmacotherapy for the management of CHB and the new drug candidates being investigated. Then, the challenges in the development of drug delivery systems for the targeting of antiviral drugs to the liver parenchyma are discussed. Finally, perspectives in the design of a more efficient pharmacotherapy to eradicate the virus from the host are addressed. PMID:20333454

  11. HBV pathogenesis in animal models: recent advances on the role of platelets.

    PubMed

    Iannacone, Matteo; Sitia, Giovanni; Ruggeri, Zaverio M; Guidotti, Luca G

    2007-04-01

    Hepatitis B virus (HBV) causes acute and chronic necroinflammatory liver diseases and hepatocellular carcinoma (HCC). HBV replicates noncytopathically in the hepatocyte, and most of the liver injury associated with this infection reflects the immune response. While the innate immune response may not contribute significantly to the pathogenesis of liver disease or viral clearance, the adaptive immune response, particularly the cytotoxic T lymphocyte (CTL) response, contributes to both. Recent observations also reveal that antigen-nonspecific inflammatory cells enhance CTL-induced liver pathology and, more surprisingly, that platelets facilitate the intrahepatic accumulation of CTLs, suggesting that the host response to HBV infection is a highly complex but coordinated process. The notion that platelets contribute to liver disease and viral clearance by promoting the recruitment of virus-specific CTLs into the liver is a new concept in viral pathogenesis, which may prove useful to implement treatments of chronic HBV infection in man.

  12. Stress and acute respiratory infection

    SciTech Connect

    Graham, N.M.; Douglas, R.M.; Ryan, P.

    1986-09-01

    To examine the relationship between stress and upper respiratory tract infection, 235 adults aged 14-57 years, from 94 families affiliated with three suburban family physicians in Adelaide, South Australia, participated in a six-month prospective study. High and low stress groups were identified by median splits of data collected from the Life Events Inventory, the Daily Hassles Scale, and the General Health Questionnaire, which were administered both before and during the six months of respiratory diary data collection. Using intra-study stress data, the high stress group experienced significantly more episodes (mean of 2.71 vs. 1.56, p less than 0.0005) and symptom days (mean of 29.43 vs. 15.42, p = 0.005) of respiratory illness. The two groups were almost identical with respect to age, sex, occupational status, smoking, passive smoking, exposure to air pollution, family size, and proneness to acute respiratory infection in childhood. In a multivariate model with total respiratory episodes as the dependent variable, 21% of the variance was explained, and two stress variables accounted for 9% of the explained variance. Significant, but less strong relationships were also identified between intra-study stress variables and clinically definite episodes and symptom days in both clinically definite and total respiratory episodes. Pre-study measures of stress emphasized chronic stresses and were less strongly related to measures of respiratory illness than those collected during the study. However, significantly more episodes (mean of 2.50 vs. 1.75, p less than 0.02) and symptom days (mean of 28.00 vs. 17.06, p less than 0.03) were experienced in the high stress group. In the multivariate analyses, pre-study stress remained significantly associated with total respiratory episodes nd symptom days in total and ''definite'' respiratory episodes.

  13. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  14. Anti-HBV Drugs: Progress, Unmet Needs, and New Hope

    PubMed Central

    Kang, Lei; Pan, Jiaqian; Wu, Jiaofen; Hu, Jiali; Sun, Qian; Tang, Jing

    2015-01-01

    Approximately 240 million people worldwide are chronically infected with hepatitis B virus (HBV), which represents a significant challenge to public health. The current goal in treating chronic HBV infection is to block progression of HBV-related liver injury and inflammation to end-stage liver diseases, including cirrhosis and hepatocellular carcinoma, because we are unable to eliminate chronic HBV infection. Available therapies for chronic HBV infection mainly include nucleos/tide analogues (NAs), non-NAs, and immunomodulatory agents. However, none of them is able to clear chronic HBV infection. Thus, a new generation of anti-HBV drugs is urgently needed. Progress has been made in the development and testing of new therapeutics against chronic HBV infection. This review aims to summarize the state of the art in new HBV drug research and development and to forecast research and development trends and directions in the near future. PMID:26389937

  15. Anti-HBV Drugs: Progress, Unmet Needs, and New Hope.

    PubMed

    Kang, Lei; Pan, Jiaqian; Wu, Jiaofen; Hu, Jiali; Sun, Qian; Tang, Jing

    2015-09-15

    Approximately 240 million people worldwide are chronically infected with hepatitis B virus (HBV), which represents a significant challenge to public health. The current goal in treating chronic HBV infection is to block progression of HBV-related liver injury and inflammation to end-stage liver diseases, including cirrhosis and hepatocellular carcinoma, because we are unable to eliminate chronic HBV infection. Available therapies for chronic HBV infection mainly include nucleos/tide analogues (NAs), non-NAs, and immunomodulatory agents. However, none of them is able to clear chronic HBV infection. Thus, a new generation of anti-HBV drugs is urgently needed. Progress has been made in the development and testing of new therapeutics against chronic HBV infection. This review aims to summarize the state of the art in new HBV drug research and development and to forecast research and development trends and directions in the near future.

  16. Current Therapy in Acute Mouth Infections

    ERIC Educational Resources Information Center

    Goldfarb, George; Burnstein, Irwin L.

    1970-01-01

    Until a dental department is added to a college health service, a physician or nurse can give treatment for acute oral infections. Treatment excludes the use of caustic, escharotic chemicals in favor of more benign agents. (Author)

  17. The Diagnostic Accuracy and Clinical Utility of Three Noninvasive Models for Predicting Liver Fibrosis in Patients with HBV Infection

    PubMed Central

    Zhang, Zhiqiao; Wang, Gongsui; Kang, Kaifu; Wu, Guobiao; Wang, Peng

    2016-01-01

    Aim To evaluate the diagnostic accuracy and clinical utility of the fibrosis index based on the four factors (FIB-4), aspartate aminotransferase -to-platelet ratio index (APRI), and aspartate aminotransferase–alanine aminotransferase ratio index (AAR) for predicting liver fibrosis in patients with HBV infection. Methods From January 2006 to December 2010,a total of 1543 consecutive chronic hepatitis B(CHB) patients who underwent liver biopsies were enrolled. FIB-4,APRI, and AAR were calculated.The areas under the receiver-operating characteristic curves (AUROCs) were calculated to assess the diagnostic accuracy of these models.The AUROCs of these models were compared by DeLong’s test.For further comparisons in different studies,the AUROCs were adjusted to conduct Adjusted AUROCs(ADjAUROCs) according to the prevalence of fibrosis stages using the difference between advanced and nonadvanced fibrosis (DANA). Results For prediction of significant fibrosis,severe fibrosis,and cirrhosis,the AUROCs of FIB-4 were 0.646(ADjAUROC 0.717),0.670(ADjAUROC 0.741), and 0.715(ADjAUROC 0.786) respectively;whereas it were 0.656(ADjAUROC 0.727),0.653(ADjAUROC 0.724) and 0.639(ADjAUROC 0.710) for APRI, 0.498(ADjAUROC 0.569),0.548(ADjAUROC 0.619) and 0.573(ADjAUROC 0.644) for AAR. The further comparisons demonstrated that there were no significant differences of AUROCs between FIB-4 and APRI in predicting significant and severe fibrosis(P > 0.05),while FIB-4 was superior to APRI in predicting cirrhosis(P < 0.001). Further subgroup analysis demonstrated that the diagnostic accuracy of FIB-4 and APRI in patients with normal alanine aminotransferase(ALT) were higher than that in patients with elevated ALT. Conclusions The results demonstrated that FIB-4 and APRI are useful for diagnosis of fibrosis. FIB-4 and APRI have similar diagnostic accuracy in predicting significant and severe fibrosis,while FIB-4 is superior to APRI in predicting cirrhosis. The clinical utility of FIB-4 and APRI

  18. Pre-acute hepadnaviral infection is associated with activation-induced apoptotic death of lymphocytes in the woodchuck (Marmota monax) model of hepatitis B.

    PubMed

    Gujar, Shashi A; Jenkins, Adam K M; Macparland, Sonya A; Michalak, Tomasz I

    2010-09-01

    Woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV) represent a highly valuable immunopathogenic model of hepatitis B virus (HBV) infection. Both WHV and HBV are noncytopathic hepadnaviruses which induce a strong but delayed virus-specific cellular immune response believed to be a cause of hepatitis. The reason behind this postponement is not well understood and its dissection in the woodchuck model has been hampered by the lack of appropriate research tools. In this study, we applied an assay for the simultaneous detection of cell apoptosis and proliferation to determine the fate of T lymphocytes after WHV infection leading to acute hepatitis. The results revealed that pre-acute WHV infection is associated with the significantly heightened susceptibility of T lymphocytes to activation-induced apoptotic death. This suggests that T lymphocyte function is compromised very early in the course of hepadnaviral infection and this may directly contribute to the postponement of virus-specific T cell response.

  19. HBX Protein-Induced Downregulation of microRNA-18a is Responsible for Upregulation of Connective Tissue Growth Factor in HBV Infection-Associated Hepatocarcinoma

    PubMed Central

    Liu, Xiaomin; Zhang, Yingjian; Wang, Ping; Wang, Hongyun; Su, Huanhuan; Zhou, Xin; Zhang, Lamei

    2016-01-01

    Background This study was designed to improve our understanding of the role of miR-18a and its target (connective tissue growth factor (CTGF), which are mediators in HBX-induced hepatocellular carcinoma (HCC). Material/Methods We first investigated the expression of several candidate microRNAs (miRNAs) reported to have been aberrantly expressed between HepG2 and HepG2.2.15, which is characterized by stable HBV infection, while the CTGF is identified as a target of miR-18a. Furthermore, the expression of CTGF evaluated in HepG2 was transfected with HBX, while the HepG2.2.15 was transfected with miR-18a and CTGF siRNA. We examined the cell cycle at the same time. Results We found that the expression of miR-18a was abnormally reduced in the HBV-positive HCC tissue samples compared with HBV-negative HCC samples. Through the use of a luciferase reporter system, we also identified CTGF 3′UTR (1046–1052 bp) as the exact binding site for miR-18a. We also observed a clear increase in CTGF mRNA and protein expression levels in HBV-positive HCC human tissue samples in comparison with the HBV-negative controls, indicating a possible negatively associated relationship between miR-18a and CTGF. Furthermore, we investigated the effect of HBX overexpression on miR-18a and CTGF, as well as the viability and cell cycle status of HepG2 cells. In addition, we found that HBX introduction downregulated miR-18a, upregulated CTGF, elevated the viability, and promoted cell cycle progression. We transfected HepG2.2.15 with miR-18a mimics and CTGF siRNA, finding that upregulated miR-18a and downregulated CTGF suppress the viability and cause cell cycle arrest. Conclusions Our study shows the role of the CTGF gene as a target of miR-18a, and identifies the function of HBV/HBX/miR-18a/CTGF as a key signaling pathway mediating HBV infection-induced HCC. PMID:27421245

  20. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

    PubMed Central

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases. PMID:27433800

  1. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

    PubMed

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.

  2. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon

    PubMed Central

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010–2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%–2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%–3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%–7.8%). Sixty-one (8.0%; 95% CI, 6.2%–10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB. PMID:26764909

  3. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

    PubMed

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB. PMID:26764909

  4. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  5. Acute otitis media and respiratory virus infections.

    PubMed

    Ruuskanen, O; Arola, M; Putto-Laurila, A; Mertsola, J; Meurman, O; Viljanen, M K; Halonen, P

    1989-02-01

    We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.

  6. Prevalence of HCV Infections and Co-Infection With HBV and HIV and Associated Risk Factors Among Addicts in Drug Treatment Centers, Lorestan Province, Iran

    PubMed Central

    Norouzian, Hossein; Gholami, Mohammadreza; Shakib, Pegah; Goudarzi, Gholamreza; Ghobadian Diali, Hamze; Rezvani, Azam

    2016-01-01

    Background: Hepatitis C is an infectious disease caused by blood-borne pathogen, hepatitis C virus (HCV). Objectives: The purpose of this study was to investigate the prevalence of HCV infection and associated risk factors among addicts in drug treatment centers in Lorestan Province, Iran. Patients and Methods: A cross-sectional sero-behavioral survey was given to drug addicts in the drug treatment centers of Khorramabad, Lorestan Province, Iran during June 2012 - March 2013. Drug addicts were interviewed using a standard questionnaire including demographic, imprisonment history, and HCV-related risk behavior items. Thereafter, the sera drawn from the participants were tested for anti-HCV antibody (Ab), anti-human immunodeficiency virus (HIV) Ab, and hepatitis B surface antigen (HBsAg). Results: The mean age of the cohorts was 31.7. Up to 60.2% of drug users had educational levels less than high school, 67.5% were self-employed, and 32.5% were office workers. The mean duration of drug injection was 6.8 years. Statistical analyses indicated that the prevalence of HCV among drug addicts was positively associated with age, past incarceration, drug injection history, the duration of drug use, and tattooing. In addition, 16.23% of volunteers were HCV-positive. Of those infected with HCV, 1.10% was co-infected with HBV, 2.95% were positive for HIV, and 0.36% of HCV-positive cases were infected with all three viruses. Conclusions: The high prevalence of HCV infection among this group implies a high rate of transmission and exposure to the risk of serious diseases. It is important that the high prevalence of HCV infection be taken into consideration to control further transmission of this infection. PMID:27162762

  7. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

    PubMed Central

    Zeng, Zhengyang; Han, Shisong; Hong, Wei; Lang, Yange; Li, Fangfang; Liu, Yongxiang; Li, Zeyong; Wu, Yingliang; Li, Wenxin; Zhang, Xianzheng; Cao, Zhijian

    2016-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT) and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC). Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV. PMID:26978579

  8. Hepatitis B virus infection in immigrant populations

    PubMed Central

    Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274

  9. Long-term monitoring drug resistance by ultra-deep pyrosequencing in a chronic hepatitis B virus (HBV)-infected patient exposed to several unsuccessful therapy schemes.

    PubMed

    Sede, M; Ojeda, D; Cassino, L; Westergaard, G; Vazquez, M; Benetti, S; Fay, F; Tanno, H; Quarleri, J

    2012-05-01

    The aim of this study was to analyze the spectrum and dynamics of low-prevalent HBV mutations in the reverse transcriptase (rt) and S antigen by ultra-deep pyrosequencing (UDPS). Samples were obtained from a chronically infected patient who was followed throughout a thirteen-year period. This technology enabled simultaneous analysis of 4084 clonally amplified fragments from the patient allowing detecting low prevalent (<1%) mutations during the follow-up. At baseline, HBV sequences were predominately wild-type. Under sequential HBV monotherapies including lamivudine, adefovir and entecavir, a high frequency of rtM204I mutation was detected initially as unique and then coexisting with rtM204V. Both mutations were statistically associated with rtA200V and rtV207I, respectively. Once the entecavir and tenofovir combined therapy was started, polymerase and consequently envelope gene mutations appeared at several positions at a higher frequency than before, including the entecavir resistance-associated mutation rtT184L.

  10. Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

    PubMed Central

    Vitiello, A; Ishioka, G; Grey, H M; Rose, R; Farness, P; LaFond, R; Yuan, L; Chisari, F V; Furze, J; Bartholomeuz, R

    1995-01-01

    Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) as immunogens for the development of prophylactic and therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our first therapeutic target. Because most CTL peptide epitopes are poor immunogens, we specifically modified them by covalently attaching two additional components: a T helper peptide epitope and two lipid molecules. Using the murine influenza virus CTL epitope NP 147-155 as a model system, we found this construct to be highly immunogenic, and a single injection resulted in memory CTL induction that persisted for > 1 yr. Based on the animal studies, a vaccine was designed and tested for both safety and its ability to induce a primary CTL response in normal subjects. The three vaccine components included HBV core antigen peptide 18-27 as the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500 micrograms) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response. A dose-response curve was observed and five out of five subjects responded to the 500-micrograms dose. PMID:7814635

  11. Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure: A Prospective Study.

    PubMed

    Zheng, Qing-Fen; Zhang, Jing-Yun; Wu, Ju-Shan; Zhang, Ying; Liu, Mei; Bai, Li; Zhang, Jin-Yan; Zhao, Jing; Chen, Yu; Duan, Zhong-Ping; Zheng, Su-Jun

    2016-02-01

    Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, -21, -143, and -200a; downregulated: miRNA-486-5p, -192, -148a, -122, and -194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486-5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV

  12. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

  13. Nosocomial outbreak of hepatitis B virus infection involving two hospitals in the Republic of Ireland.

    PubMed

    Burns, K; Heslin, J; Crowley, B; Thornton, L; Laoi, B Ni; Kelly, E; Ward, E; Doody, B; Hickey, M M

    2011-08-01

    The routes of nosocomial hepatitis B virus (HBV) transmission have changed over the years. Initiatives to prevent transfusion-associated HBV and healthcare worker-to-patient transmission have had a positive impact on these transmission routes. Recent reports of outbreaks of nosocomial HBV have implicated breaches in standard precautions as important causes of HBV transmission. This report describes a nosocomial outbreak of HBV infection in the Republic of Ireland, which occurred between January 2005 and March 2006. The outbreak was detected following identification of a case of acute HBV infection in a patient whose only risk factor was a recent surgical procedure. The extensive multi-agency investigation that followed revealed that the patient was one of five cases of acute HBV infection and that four separate transmission events between infectious cases had occurred in two different hospitals over a 15-month period. A definitive cause for each transmission event was not identified, although lapses in adherence to standard precautions, safe injection and phlebotomy practices could not be ruled out. Two secondary cases of acute HBV infection in community contacts of two of the nosocomial cases were identified. Phylogenetic analysis proved a useful tool in confirming infection with a pre-core HBV mutant and viral transmission between the seven patients. A patient notification exercise involving 1028 potentially exposed patients found no evidence of additional cases of nosocomial HBV infection. These findings highlight the importance of consistent application of standard precautions. PMID:21530000

  14. Peritoneal infection in acute intermittent peritoneal dialysis.

    PubMed

    Sharma, Raj Kumar; Kumar, Jitendra; Gupta, Amit; Gulati, Sanjeev

    2003-11-01

    A prospective study was done to evaluate the incidence and microbiological trend of peritoneal infection in patients undergoing acute intermittent peritoneal dialysis (PD). Complete sterile procedure was ensured and at the completion of the procedure PD fluid was sent for bacteriological culture, sensitivity, and total and differential cell count. During the period September 2000 to February 2001 a total of 100 patients were evaluated. Male female ratio was 72:28. Mean age was 43.17 +/- 17.2 years. In 26 patients cyclers were used. Bacterial culture was positive in total of 30 cases (30%). Gram positive, Gram negative and mixed infection was found in 10%, 15%, and 5% respectively. Number of exchanges (31.61 +/- 7.7 vs. 31.3 +/- 6, p = 0.8) were similar and number of repositioning was significantly more in the infected group (23.3% vs. 11.4%, p < 0.01). Total cell count was significantly higher in infected group (274.3 +/- 502 vs. 31.25 +/- 79.34, p < 0.01). Among Gram +ve organisms Staphylococcus was found in 7, Enterococcus faecalis in 4 and Coryne bacterium sps. in 2 cases. Among Gram -ve organisms, E. coli was found in 4, Enterobacter in 3, Klebsiella 1, Pseudomonas 1, Acinetobacter arinatus 5, Acinetobacter baumani 3, and Citrobacter freundii 3. Mixed flora comprised of Enterococcus faecalis 3, Enterobacter 1, Staphlococcus 1, E. coli 3, Citrobacter 1, Acinobacter baumani 1. Although with the cyclers using collapsible bags, staphylococcus was not isolated, the total incidence of infection (11/26 cases) was not decreased with the use of cyclers. We conclude that in acute intermittent peritoneal dialysis the incidence of bacterial infection is 30% with preponderance of Gram -ve over Gram +ve organisms and organism of fecal origin being commoner than those of skin origin. Use of cycler-assisted over manual PD do not improve the incidence of infection. Repositioning of the stiff catheter significantly increases the incidence of infection.

  15. Comparison of Elastography, Serum Marker Scores, and Histology for the Assessment of Liver Fibrosis in Hepatitis B Virus (HBV)-Infected Patients in Burkina Faso

    PubMed Central

    Bonnard, Philippe; Sombié, Roger; Lescure, Francois-Xavier; Bougouma, Alain; Guiard-Schmid, Jean Baptiste; Poynard, Thierry; Calès, Paul; Housset, Chantal; Callard, Patrice; Pendeven, Catherine Le; Drabo, Joseph; Carrat, Fabrice; Pialoux, Gilles

    2010-01-01

    Liver fibrosis (LF) must be assessed before talking treatment decisions in hepatitis B. In Burkina Faso, liver biopsy (LB) remains the “gold standard” method for this purpose. Access to treatment might be simpler if reliable alternative techniques for LF evaluation were available. The hepatitis B virus (HBV)-infected patients who underwent LB was invited to have liver stiffness measurement (Fibroscan) and serum marker assays. Fifty-nine patients were enrolled. The performance of each technique for distinguishing F0F1 from F2F3F4 was compared. The area under receiver operating characteristic (AUROC) curves was 0.61, 0.71, 0.79, 0.82, and 0.87 for the aspartate transaminase to platelet ratio index (APRI), Fib-4, Fibrotest, Fibrometre, and Fibroscan. Elastometric thresholds were identified for significant fibrosis and cirrhosis. Combined use of Fibroscan and a serum marker could avoid 80% of biopsies. This study shows that the results of alternative methods concord with those of histology in HBV-infected patients in Burkina Faso. These alternative techniques could help physicians to identify patients requiring treatment. PMID:20207872

  16. Frequency and genotypic distribution of GB virus C (GBV-C) among Colombian population with Hepatitis B (HBV) or Hepatitis C (HCV) infection

    PubMed Central

    2011-01-01

    Background GB virus C (GBV-C) is an enveloped positive-sense ssRNA virus belonging to the Flaviviridae family. Studies on the genetic variability of the GBV-C reveals the existence of six genotypes: genotype 1 predominates in West Africa, genotype 2 in Europe and America, genotype 3 in Asia, genotype 4 in Southwest Asia, genotype 5 in South Africa and genotype 6 in Indonesia. The aim of this study was to determine the frequency and genotypic distribution of GBV-C in the Colombian population. Methods Two groups were analyzed: i) 408 Colombian blood donors infected with HCV (n = 250) and HBV (n = 158) from Bogotá and ii) 99 indigenous people with HBV infection from Leticia, Amazonas. A fragment of 344 bp from the 5' untranslated region (5' UTR) was amplified by nested RT PCR. Viral sequences were genotyped by phylogenetic analysis using reference sequences from each genotype obtained from GenBank (n = 160). Bayesian phylogenetic analyses were conducted using Markov chain Monte Carlo (MCMC) approach to obtain the MCC tree using BEAST v.1.5.3. Results Among blood donors, from 158 HBsAg positive samples, eight 5.06% (n = 8) were positive for GBV-C and from 250 anti-HCV positive samples, 3.2%(n = 8) were positive for GBV-C. Also, 7.7% (n = 7) GBV-C positive samples were found among indigenous people from Leticia. A phylogenetic analysis revealed the presence of the following GBV-C genotypes among blood donors: 2a (41.6%), 1 (33.3%), 3 (16.6%) and 2b (8.3%). All genotype 1 sequences were found in co-infection with HBV and 4/5 sequences genotype 2a were found in co-infection with HCV. All sequences from indigenous people from Leticia were classified as genotype 3. The presence of GBV-C infection was not correlated with the sex (p = 0.43), age (p = 0.38) or origin (p = 0.17). Conclusions It was found a high frequency of GBV-C genotype 1 and 2 in blood donors. The presence of genotype 3 in indigenous population was previously reported from Santa Marta region in Colombia and

  17. The presence of HBV mRNA in the fertilized in vitro embryo of HBV patients confirms vertical transmission of HBV via the ovum.

    PubMed

    Ye, F; Jin, Y; Kong, Y; Shi, J Z; Qiu, H T; Zhang, X; Zhang, S L; Lin, S M

    2013-05-01

    This study aimed to confirm that vertical transmission of hepatitis B virus (HBV) can occur via the infected ovum. Specimens studied were obtained from discarded test-tube embryos from mothers with chronic HBV infection who had received in vitro fertilization treatment. Single-cell reverse transcriptase-polymerase chain reaction was used to detect HBV mRNA in the embryos. HBV mRNA was detected in the cleavage embryos of patients with chronic HBV infection, with a detection rate of 13.2% (5/38). The level of serum HBV DNA was not related to the HBV mRNA positivity rates in embryos. In this study, HBV mRNA was detected in test-tube embryos from HBV-infected mothers who had received in vitro fertilization treatment. This confirms the theory of vertical transmission of HBV via the ovum, thereby providing an important theoretical basis for further study on the mechanism of HBV vertical transmission, influencing factors and blocking measures.

  18. Acute focal infections of dental origin.

    PubMed

    Olsen, Ingar; van Winkelhoff, Arie J

    2014-06-01

    This article describes the most important pus-producing acute oral infections (dental infections) that can spread extra-orally. Most of these infections are spread by bacteria entering the bloodstream. However, dental infections have a number of other pathways for dissemination. By forming abscesses or phlegmon they can reach facial spaces that communicate with each other and then spread downwards to the mediastinum or upwards to the brain. In such cases dental infections can become, if not properly treated, life-threatening. It seems that early diagnosis and treatment are imperative, and potentially infectious foci should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental biofilm formation are important measures to reduce the risk of these calamities. The more compromised the host defense is, the more importance should be put on these measures. Although commensal bacteria are often involved in these infections, attention should also be paid to specific periodontal pathogens, and a proper microbial diagnosis, obtained using molecular methods plus bacterial sensitivity testing, can provide the patient with optimal care. Drainage of pus must be established where possible so that the optimal effect of antibiotics can be achieved. Penicillin is still the drug of first choice in settings where suspicion of methicillin-resistant Staphylococcus aureus is low.

  19. Acute focal infections of dental origin.

    PubMed

    Olsen, Ingar; van Winkelhoff, Arie J

    2014-06-01

    This article describes the most important pus-producing acute oral infections (dental infections) that can spread extra-orally. Most of these infections are spread by bacteria entering the bloodstream. However, dental infections have a number of other pathways for dissemination. By forming abscesses or phlegmon they can reach facial spaces that communicate with each other and then spread downwards to the mediastinum or upwards to the brain. In such cases dental infections can become, if not properly treated, life-threatening. It seems that early diagnosis and treatment are imperative, and potentially infectious foci should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental biofilm formation are important measures to reduce the risk of these calamities. The more compromised the host defense is, the more importance should be put on these measures. Although commensal bacteria are often involved in these infections, attention should also be paid to specific periodontal pathogens, and a proper microbial diagnosis, obtained using molecular methods plus bacterial sensitivity testing, can provide the patient with optimal care. Drainage of pus must be established where possible so that the optimal effect of antibiotics can be achieved. Penicillin is still the drug of first choice in settings where suspicion of methicillin-resistant Staphylococcus aureus is low. PMID:24738592

  20. HBV/HIV coinfection is associated with poorer outcomes in hospitalized patients with HBV or HIV.

    PubMed

    Rajbhandari, R; Jun, T; Khalili, H; Chung, R T; Ananthakrishnan, A N

    2016-10-01

    We examined the impact of HBV/HIV coinfection on outcomes in hospitalized patients compared to those with HBV or HIV monoinfection. Using the 2011 US Nationwide Inpatient Sample, we identified patients who had been hospitalized with HBV or HIV monoinfection or HBV/HIV coinfection using ICD-9-CM codes. We compared liver-related admissions between the three groups. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality, length of stay and total charges. A total of 72 584 discharges with HBV monoinfection, 133 880 discharges with HIV monoinfection and 8156 discharges with HBV/HIV coinfection were included. HBV/HIV coinfection was associated with higher mortality compared to HBV monoinfection (OR 1.67, 95% CI 1.30-2.15) but not when compared to HIV monoinfection (OR 1.22, 95% CI 0.96-1.54). However, the presence of HBV along with cirrhosis or complications of portal hypertension was associated with three times greater in-hospital mortality in patients with HIV compared to those without these complications (OR 3.00, 95% CI 1.80-5.02). Length of stay and total hospitalization charges were greater in the HBV-/HIV-coinfected group compared to the HBV monoinfection group (+1.53 days, P < 0.001; $17595, P < 0.001) and the HIV monoinfection group (+0.62 days, P = 0.034; $8840, P = 0.005). In conclusion, HBV/HIV coinfection is a risk factor for in-hospital mortality, particularly in liver-related admissions, compared to HBV monoinfection. Overall healthcare utilization from HBV/HIV coinfection is also higher than for either infection alone and higher than the national average for all hospitalizations, thus emphasizing the healthcare burden from these illnesses.

  1. Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015.

    PubMed

    Mochida, Satoshi; Nakayama, Nobuaki; Ido, Akio; Takikawa, Yasuhiro; Yokosuka, Osamu; Sakaida, Isao; Moriwaki, Hisataka; Genda, Takuya; Takikawa, Hajime

    2016-03-01

    In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.

  2. Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion.

    PubMed

    Bruder Costa, Juliana; Dufeu-Duchesne, Tania; Leroy, Vincent; Bertucci, Inga; Bouvier-Alias, Magali; Pouget, Noelle; Brevot-Lutton, Ophelie; Bourliere, Marc; Zoulim, Fabien; Plumas, Joel; Aspord, Caroline

    2016-01-01

    Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. PMID:27348813

  3. Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion

    PubMed Central

    Bruder Costa, Juliana; Dufeu-Duchesne, Tania; Leroy, Vincent; Bertucci, Inga; Bouvier-Alias, Magali; Pouget, Noelle; Brevot-Lutton, Ophelie; Bourliere, Marc; Zoulim, Fabien

    2016-01-01

    Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. PMID:27348813

  4. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  5. Acute neuromuscular weakness associated with dengue infection

    PubMed Central

    Hira, Harmanjit Singh; Kaur, Amandeep; Shukla, Anuj

    2012-01-01

    Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK) were tested. In addition, two patients underwent nerve conduction velocity (NCV) test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2nd to 4th day of illness in 11 of 12 patients. In one patient, it developed on 10th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients. PMID:22346188

  6. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection.

  7. [Requirement of standardizing anti-HBs assay methods in Japan for HBV infection-preventing strategy--discrepancy of anti-HBs measurements among three different kits widely used in Japan].

    PubMed

    Ogata, Norio

    2006-09-01

    The strategy to eliminate hepatitis B virus (HBV) infection by administrating an HB vaccine is changing worldwide; however, this is not the case in Japan. An important concern about the HBV infection-preventing strategy in Japan may be that the assay methods for the antibody to hepatitis B surface antigen (anti-HBs) are not standardized. The minimum protective anti-HBs titer against HBV infection has been established as 10 mIU/ml by World Health Organization (WHO) -standardized assay methods worldwide, but that is still determined as a "positive" test result by the passive hemagglutination (PHA) method in Japan. We compared anti-HBs measurements in given samples among PHA(Mycell II, Institute of Immunology), chemiluminescent enzyme immunoassay (CLEIA) (Lumipulse, Fujirebio), and chemiluminescent immunoassay (CLIA) (Architect, Abbott), all of which are currently in wide use in Japan. First, anti-HBs measurements in serum from individuals who received a yeast-derived recombinant HB vaccine composed of the major surface protein of either subtype adr or subtype ayw were compared. The results clearly showed that in subtype adr-vaccinees CLIA underestimated the anti-HBs amount compared with CLEIA and PHA, but in ayw-vaccinees, the discordance in the measurements among the three kits was not prominent. Second, anti-HBs measurements in standard or calibration solutions of each assay kit were compared. Surprisingly, CLEIA showed higher measurements in all three kit-associated standard or calibration solutions than CLIA. Thus, the anti-HBs titer of 10 mIU/ml is difficult to introduce in Japan as the minimum protective level against HBV infection. Efforts to standardize anti-HBs assay methods are expected to share international evidence about the HBV infection-preventing strategy.

  8. New horizon for radical cure of chronic hepatitis B virus infection.

    PubMed

    Tajiri, Kazuto; Shimizu, Yukihiro

    2016-07-28

    About 250 to 350 million people worldwide are chronically infected with hepatitis B virus (HBV), and about 700000 patients per year die of HBV-related cirrhosis or hepatocellular carcinoma (HCC). Several anti-viral agents, such as interferon and nucleos(t)ide analogues (NAs), have been used to treat this disease. NAs especially have been shown to strongly suppress HBV replication, slowing the progression to cirrhosis and the development of HCC. However, reactivation of HBV replication often occurs after cessation of treatment, because NAs alone cannot completely remove covalently-closed circular DNA (cccDNA), the template of HBV replication, from the nuclei of hepatocytes. Anti-HBV immune responses, in conjunction with interferon-γ and tumor necrosis factor-α, were found to eliminate cccDNA, but complete eradication of cccDNA by immune response alone is difficult, as shown in patients who recover from acute HBV infection but often show long-term persistence of small amounts of HBV-DNA in the blood. Several new drugs interfering with the life cycle of HBV in hepatocytes have been developed, with drugs targeting cccDNA theoretically the most effective for radical cure of chronic HBV infection. However, the safety of these drugs should be extensively examined before application to patients, and combinations of several approaches may be necessary for radical cure of chronic HBV infection. PMID:27478536

  9. New horizon for radical cure of chronic hepatitis B virus infection

    PubMed Central

    Tajiri, Kazuto; Shimizu, Yukihiro

    2016-01-01

    About 250 to 350 million people worldwide are chronically infected with hepatitis B virus (HBV), and about 700000 patients per year die of HBV-related cirrhosis or hepatocellular carcinoma (HCC). Several anti-viral agents, such as interferon and nucleos(t)ide analogues (NAs), have been used to treat this disease. NAs especially have been shown to strongly suppress HBV replication, slowing the progression to cirrhosis and the development of HCC. However, reactivation of HBV replication often occurs after cessation of treatment, because NAs alone cannot completely remove covalently-closed circular DNA (cccDNA), the template of HBV replication, from the nuclei of hepatocytes. Anti-HBV immune responses, in conjunction with interferon-γ and tumor necrosis factor-α, were found to eliminate cccDNA, but complete eradication of cccDNA by immune response alone is difficult, as shown in patients who recover from acute HBV infection but often show long-term persistence of small amounts of HBV-DNA in the blood. Several new drugs interfering with the life cycle of HBV in hepatocytes have been developed, with drugs targeting cccDNA theoretically the most effective for radical cure of chronic HBV infection. However, the safety of these drugs should be extensively examined before application to patients, and combinations of several approaches may be necessary for radical cure of chronic HBV infection. PMID:27478536

  10. A case of acute hepatitis B in a chronic hepatitis C patient after daclatasvir and asunaprevir combination therapy: hepatitis B virus reactivation or acute self-limited hepatitis?

    PubMed

    Hayashi, Kazuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Nishimura, Daisaku; Goto, Hidemi; Hirooka, Yoshiki

    2016-08-01

    Reactivation of hepatitis B virus (HBV) in HBV surface antigen (HBsAg)-positive patients treated with cytotoxic chemotherapy is well known. HBV reactivation in patients with HBV and hepatitis C virus (HCV) coinfection caused by direct-acting antiviral (DAA) therapy has also recently been reported. We report a case of acute hepatitis B in a patient with HCV infection after DAA therapy. An 83-year-old woman was referred for chronic hepatitis C. She was infected with HCV genotype 1b and negative for HBsAg at baseline. She received daclatasvir and asunaprevir therapy, and HCV became negative at 4 weeks and remained negative until 6 months after the end of DAA therapy. Acute hepatitis B developed 5 months after ending DAA therapy. Genome sequencing revealed the subgenotype as B1, and the serological subtype as adr. T118 K mutation at the S region as an immune escape mutant was identified. These virologic features led to HBV reactivation. The presence of hepatitis B core antibody or HBs antibody was not determined before DAA therapy, so prior HBV infection status was unclear. This case is speculated to represent HBV reactivation in a patient with previously resolved HBV induced by DAA therapy, based on virologic analysis and clinical status. The risk might be very low, but DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. When acute hepatitis emerges in patients who have received DAA therapy for HCV, HBV reactivation should be considered to allow early initiation of anti-HBV therapy. PMID:27329484

  11. Dose Determination for Acute Salmonella Infection in Pigs

    PubMed Central

    Loynachan, A. T.; Harris, D. L.

    2005-01-01

    Pigs were exposed to various levels of Salmonella enterica subsp. enterica serovar Typhimurium by either intranasal inoculation or by subjecting them to a contaminated environment. More than 103 salmonellae were required to induce acute Salmonella infection. These results indicate that intervention against acute Salmonella infection in lairage may be more readily achieved than previously thought. PMID:15870368

  12. Hepatitis B virus infection.

    PubMed

    Chang, Mei-Hwei

    2007-06-01

    Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively

  13. Occupational Risk of HIV, HBV and HSV-2 Infections in Health Care Personnel Caring for AIDS Patients.

    ERIC Educational Resources Information Center

    Kuhls, Thomas L.; And Others

    1987-01-01

    Female health care workers with exposure to AIDS patients were studied. Two of the 246 workers showed evidence of opportunistic infections. This analysis confirms the low risk of occupationally acquired HIV infection when hospital infection control practices are employed around AIDS patients. (Author/VM)

  14. Progress and Prospects of Anti-HBV Gene Therapy Development.

    PubMed

    Maepa, Mohube B; Roelofse, Ilke; Ely, Abdullah; Arbuthnot, Patrick

    2015-07-31

    Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV.

  15. Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment.

    PubMed

    Lin, Xiao-Jun; Lao, Xiang-Ming; Shi, Ming; Li, Sheng-Ping

    2016-09-01

    Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.

  16. Hepatitis B (HBV)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) Print A A A Text Size ... Prevented? How Is It Treated? What Is It? Hepatitis (pronounced: hep-uh-TIE-tiss) is a disease ...

  17. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion.

  18. Acute pancreatitis, ascites, and acute renal failure in Plasmodium vivax malaria infection, a rare complication.

    PubMed

    Lakhotia, Manoj; Pahadiya, Hans Raj; Kumar, Harish; Singh, Jagdish; Sangappa, Jainapur Ravi; Choudhary, Prakash Kumar

    2015-01-01

    A 22-year-old male presented with 6 days history of intermittent fever with chills, 2 days history of upper abdomen pain, distension of abdomen, and decreased urine output. He was diagnosed to have Plasmodium vivax malaria, acute pancreatitis, ascites, and acute renal failure. These constellations of complications in P. vivax infection have never been reported in the past. The patient responded to intravenous chloroquine and supportive treatment. For renal failure, he required hemodialysis. Acute pancreatitis, ascites, and acute renal failure form an unusual combination in P. vivax infection. PMID:26629455

  19. Molecular Evolution and Phylodynamics of Acute Hepatitis B Virus in Japan

    PubMed Central

    Lin, Serena Y. C.; Toyoda, Hidenori; Kumada, Takashi; Liu, Hsin-Fu

    2016-01-01

    Hepatitis B virus (HBV) is prevalent worldwide and causes liver diseases, including acute and chronic hepatitis. Ten HBV genotypes (A–J) with distinct geographic distributions have been reported. Cases of acute HBV infection with genotype A have increased in Japan nationwide since the 1990s, mainly through sexual transmission. To investigate the molecular evolution and phylodynamics of HBV genotypes, we collected acute HBV isolates acquired in Japan from 1992–2002. Full genomes were obtained for comprehensive phylogenetic and phylodynamic analysis, with other Japanese HBV sequences from GenBank that were isolated during 1991–2010. HBV genotypes were classified using the maximum-likelihood and Bayesian methods. The GMRF Bayesian Skyride was used to estimate the evolution and population dynamics of HBV. Four HBV genotypes (A, B, C, and H) were identified, of which C was the major genotype. The phylodynamic results indicated an exponential growth between the 1960s and early 1990s; this was followed by a population bottleneck after 1995, possibly linked with successful implementation of a nationwide vaccination program. However, HBV/A increased from 1990 to 2003–2004, and then started to decrease. The prevalence of genotype A has increased over the past 10 years. Phylodynamic inference clearly demonstrates a steady population growth compatible with an ongoing subepidemic; this might be due to the loss of immunity to HBV in adolescents and people being born before the vaccination program. This is the first phylodynamic study of HBV infection in Japan and will facilitate understanding the molecular epidemiology and long-term evolutionary dynamics of this virus in Japan. PMID:27280441

  20. Acute hemiplegia with lacunar infarct after varicella infection in childhood.

    PubMed

    Eda, I; Takashima, S; Takeshita, K

    1983-01-01

    We report 4 cases of acute hemiplegia and a small low-density lesion on computerized tomography (CT) after varicella infection. In 3 of them, CT in the acute hemiplegic stage, and later, reveals the development of lacunar infarct around the internal capsule. Focal low density may be caused by occlusive vascular lesions of the penetrating arteries. Varicella infection may play an important role as one of the causes of acute hemiplegia in childhood producing lacunar infarct, as well as delayed hemiplegia, reported previously in herpes zoster ophthalmicus. PMID:6660422

  1. Shifting hepatitis B virus genotypes of acute hepatitis B patients in northeast Japan.

    PubMed

    Inoue, Jun; Kondo, Yasuteru; Umetsu, Teruyuki; Yamamoto, Takeshi; Miura, Masahito; Mano, Yutaka; Kobayashi, Tomoo; Obara, Noriyuki; Niitsuma, Hirofumi; Kogure, Takayuki; Nakagome, Yu; Kimura, Osamu; Iwata, Tomoaki; Morosawa, Tatsuki; Fujisaka, Yasuyuki; Shimosegawa, Tooru

    2016-01-01

    It has been reported that acute hepatitis B (AHB) patients with genotype A HBV (HBV/A) have been increasing since the 1990s in metropolitan areas in Japan. However, little is known about the trends of HBV genotypes in AHB patients in northeast Japan where genotype B HBV (HBV/B) prevails more than in other areas. In this study, we aimed to clarify the changes in the HBV genotypes and clinical characteristics of AHB patients in this area. HBV genotypes were determined by direct sequencing (n = 125) or enzyme immunoassay (n = 9) using serum samples from AHB patients including fulminant hepatitis in 1987-2014. Among 134 patients, 26 (19%), 33 (25%), and 75 (56%) patients were infected with HBV of genotypes A, B, and C, respectively. HBV/A emerged from 2001 and the percentage was increased gradually up to 48% in 2010-2014, whereas HBV/B was reduced from 40% in 1987-1994 to 10% in 2010-2014. Phylogenetic analysis showed that three major subgenotype A2 strains had come into this area serially. The levels of HBV DNA and prothrombin time were higher in HBV/A patients than other genotypes. This study could not show significant difference in the HBsAg-positive period among genotypes nor the effect of nucleoside analogues to shorten the HBsAg-positive period. A higher level of initial HBV DNA was associated with late disappearance of HBsAg. In conclusion, the percentage of HBV/A in AHB patients has been increasing in northeast Japan since 2001, which is later than metropolitan areas, whereas that of HBV/B is decreasing.

  2. Hepatocytes proteomic alteration and seroproteome analysis of HBV-transgenic mice.

    PubMed

    Ding, Chen; Wei, Haiming; Sun, Rui; Zhang, Jian; Tian, Zhigang

    2009-01-01

    Hepatitis B is the most common and serious liver disease, especially in developing countries. Although HBV pathogenesis has been extensively investigated, the proteomic alteration of hepatocytes during HBV chronic infection is still unclear. Using the purified hepatocytes, we compared the protein profiles by 2-DE and LC-MS between HBV-transgenic (Tg) and corresponding background mice. Twenty-seven altered proteins were identified in hepatocytes from HBV-Tg mice, among which 13 proteins were involved in mitochondrion metabolism pathway including tricarboxylic acid (TCA) cycle and oxidative response; four proteins (SELENBP, SCP2, RGN and PRDX1) were also dramatically changed in liver samples from HBV-infected patients. Important genes (gpx, sod, ogg et al.) correlated to oxidative damage were up-regulated in the liver of HBV-Tg mice. Reactive oxygen species production was significantly increased while ATP production was decreased in liver mitochondria from HBV-Tg mice. Moreover, hepatocytes of HBV-Tg mice were more sensitive to hydrogen peroxide-induced cell death than that of wild-type control. Using 2-D Western blotting analysis, eight hepatocyte proteins were found to react with sera of HBV-Tg mice but not with that of background mice. Interestingly, two (Etfa and Dmgdh) of the eight reactive proteins were overexpressed in HBV-Tg mice. We believe this study is the first proteomic and seroproteome analysis of HBV-infected mammalian hepatocyte and provides insightful links between HBV infection and HBV-induced liver diseases.

  3. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2016-10-14

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  5. Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity

    PubMed Central

    Jiang, Xia; Kanda, Tatsuo; Wu, Shuang; Nakamura, Masato; Miyamura, Tatsuo; Nakamoto, Shingo; Banerjee, Arup; Yokosuka, Osamu

    2014-01-01

    Hepatitis B virus (HBV) chronically infects more than 350 million people worldwide. HBV causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. There exist complex interactions between HBV and the immune system including adaptive and innate immunity. Toll-like receptors (TLRs) and TLR-signaling pathways are important parts of the innate immune response in HBV infections. It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense. Previous immunological studies demonstrated that HBV e antigen (HBeAg) is more efficient at eliciting T-cell tolerance, including production of specific cytokines IL-2 and interferon gamma, than HBV core antigen. HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase. MicroRNAs (miRNAs) are also able to regulate various biological processes such as the innate immune response. When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15, which could produce HBV virion that infects chimpanzees, using real-time RT-PCR, we observed several different expression levels in miRNAs related to TLRs. Although we and others have shown that HBV modulates the host immune response, several of the miRNAs seem to be involved in the TLR signaling pathways. The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered. This article is intended to comprehensively review the association between HBV and innate immunity, and to discuss the role of miRNAs in the innate immune response to HBV infection. PMID:24966589

  6. Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity.

    PubMed

    Jiang, Xia; Kanda, Tatsuo; Wu, Shuang; Nakamura, Masato; Miyamura, Tatsuo; Nakamoto, Shingo; Banerjee, Arup; Yokosuka, Osamu

    2014-06-21

    Hepatitis B virus (HBV) chronically infects more than 350 million people worldwide. HBV causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. There exist complex interactions between HBV and the immune system including adaptive and innate immunity. Toll-like receptors (TLRs) and TLR-signaling pathways are important parts of the innate immune response in HBV infections. It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense. Previous immunological studies demonstrated that HBV e antigen (HBeAg) is more efficient at eliciting T-cell tolerance, including production of specific cytokines IL-2 and interferon gamma, than HBV core antigen. HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase. MicroRNAs (miRNAs) are also able to regulate various biological processes such as the innate immune response. When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15, which could produce HBV virion that infects chimpanzees, using real-time RT-PCR, we observed several different expression levels in miRNAs related to TLRs. Although we and others have shown that HBV modulates the host immune response, several of the miRNAs seem to be involved in the TLR signaling pathways. The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered. This article is intended to comprehensively review the association between HBV and innate immunity, and to discuss the role of miRNAs in the innate immune response to HBV infection. PMID:24966589

  7. Clinical role of respiratory virus infection in acute otitis media.

    PubMed

    Arola, M; Ruuskanen, O; Ziegler, T; Mertsola, J; Näntö-Salonen, K; Putto-Laurila, A; Viljanen, M K; Halonen, P

    1990-12-01

    The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.

  8. Prevention of hepatitis B virus infection: from the past to the future.

    PubMed

    Orlando, R; Foggia, M; Maraolo, A E; Mascolo, S; Palmiero, G; Tambaro, O; Tosone, G

    2015-06-01

    About 3-5 % of the world's population is chronically infected by hepatitis B virus (HBV) and is at risk of developing liver cirrhosis or hepatocellular carcinoma. The risk of dying prematurely because of chronic HBV infection is higher in younger people. The current strategies to prevent HBV infection involve immunization (active and/or passive) and antiviral chemoprophylaxis. The vaccines available for active immunization, containing hepatitis B surface antigen, are safe and confer long-term immunity in most healthy subjects. Since the vaccination is unsatisfactory in some patients, e.g., those with chronic kidney disease, human immunodeficiency virus infection, type I diabetes mellitus, and celiac disease, new strategies of vaccination are required. The neonatal, infant, and adolescent routine program vaccination in about 180 countries has greatly decreased the disease burden. Passive immunization with specific HBV immunoglobulins is recommended after single acute exposure, in infants born to infected mothers, and in HBV-infected patients undergoing liver transplantation combined with nucleoside/nucleotide analogues (chemoprophylaxis). Chemoprophylaxis is also indicated in HBV carrier candidates for immunosuppressive treatment and in patients with occult B infection undergoing immunosuppressive therapy or hematopoietic stem cell transplantation. Since HBV is not eradicable by an immune response or by antiviral drugs developed so far, the only preventive strategy remains global neonatal vaccination in all countries, firstly in HBV-endemic countries. PMID:25678010

  9. Viral antibodies in the CSF after acute CNS infections.

    PubMed

    Cappel, R; Thiry, L; Clinet, G

    1975-09-01

    Viral antibodies were measured in the cerebrospinal fluid (CSF) and serum from 25 patients having acute viral central nervous system (CNS) infections, and from 39 control patients. The results, collected two weeks after the clinical onset, revealed the presence of antibodies in nine of 13 (69%) CSF specimens from patients suffering from encephalitis of myelitis, and in only one of nine (11%) of the CSF samples of those presenting a viral meningitis infection. This difference was statistically significant and suggests that the titration of viral antibodies in the CSF can be helpful in establishing the diagnosis of viral CNS infection. Our data also suggest that localized production of antibodies occurs during the course of acute CNS infections, and that the respiratory syncytial virus can be associated with CNS infections in man.

  10. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection

    PubMed Central

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  11. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection.

    PubMed

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  12. Role of dystrophin in acute Trypanosoma cruzi infection.

    PubMed

    Malvestio, Lygia M; Celes, Mara R N; Milanezi, Cristiane; Silva, João S; Jelicks, Linda A; Tanowitz, Herbert B; Rossi, Marcos A; Prado, Cibele M

    2014-09-01

    Previous studies have demonstrated loss/reduction of dystrophin in cardiomyocytes in both acute and chronic stages of experimental Trypanosoma cruzi (T. cruzi) infection in mice. The mechanisms responsible for dystrophin disruption in the hearts of mice acutely infected with T. cruzi are not completely understood. The present in vivo and in vitro studies were undertaken to evaluate the role of inflammation in dystrophin disruption and its correlation with the high mortality rate during acute infection. C57BL/6 mice were infected with T. cruzi and killed 14, 20 and 26 days post infection (dpi). The intensity of inflammation, cardiac expression of dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability were evaluated. Cultured neonatal murine cardiomyocytes were incubated with serum, collected at the peak of cytokine production and free of parasites, from T. cruzi-infected mice and dystrophin, calpain-1, and NF-κB expression analyzed. Dystrophin disruption occurs at the peak of mortality and inflammation and is associated with increased expression of calpain-1, TNF-α, NF-κB, and increased sarcolemmal permeability in the heart of T. cruzi-infected mice at 20 dpi confirmed by in vitro studies. The peak of mortality occurred only when significant loss of dystrophin in the hearts of infected animals occurred, highlighting the correlation between inflammation, dystrophin loss and mortality.

  13. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed.

  14. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  15. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  16. New HBV subgenotype D9, a novel D/C recombinant, identified in patients with chronic HBeAg-negative infection in Eastern India.

    PubMed

    Ghosh, S; Banerjee, P; Deny, P; Mondal, R K; Nandi, M; Roychoudhury, A; Das, K; Banerjee, S; Santra, A; Zoulim, F; Chowdhury, A; Datta, S

    2013-03-01

    Genome diversity is a hallmark of hepatitis B virus (HBV), which allowed its classification into 10 genotypes (A-J) and numerous subgenotypes. Among them, Genotype D is currently segregated into eight subgenotypes (D1-D8). Here, we report the identification and characterization of a novel subgenotype within genotype D of HBV from chronic hepatitis B e antigen (HBeAg)-negative patients of Eastern India. Phylogenetic tree analysis based on complete genome sequences revealed that six of 39 HBV/D isolates formed a distinct cluster supported by high bootstrap value and had nucleotide divergence >4% relative to the known D subgenotypes (D1-D8), justifying their assignment into a new subgenotype (D9). By comparing the amino acid sequences of the four ORFs of HBV/D9 with D1-D8, 36 specific residues, including a unique one (E(112) in the core region), were identified that could be considered as a signature of D9. Further analysis by Simplot, BootScan and jpHMM demonstrated that D9 resulted from a discrete recombination with genotype C over the precore-core region. This type of recombination has not been described previously as all C/D recombinants reported so far possessed genotype C backbones with mosaic fragments derived from HBV/D. Interestingly, compared to other subgenotypes of HBV/D, D9 isolates had a higher frequency of mutations (A1762T and G1764A) in the basal core promoter region that had been implicated in the development of hepatocellular carcinoma. Further investigations are needed to determine the overall prevalence and clinical significance of these newly characterized D9 strains and to assess the impact of inter-genotypic recombination on viral properties.

  17. HBV endemicity in Mexico is associated with HBV genotypes H and G

    PubMed Central

    Roman, Sonia; Panduro, Arturo

    2013-01-01

    Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics, progression, severity of disease and antiviral response. Herein, we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is predominant among the Mexican population, but not in Central America. Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence, apparently due to a rapid resolution of the infection, low viral loads and a high prevalence of occult B infection. During chronic infections, genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low. Thus, antiviral therapy may differ significantly from the standard guidelines established worldwide. The high prevalence of HBV genotype G in the Americas, especially among the Mexican population, raises new questions regarding its geographic origin that will require further investigation. PMID:24023487

  18. HBV endemicity in Mexico is associated with HBV genotypes H and G.

    PubMed

    Roman, Sonia; Panduro, Arturo

    2013-09-01

    Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics, progression, severity of disease and antiviral response. Herein, we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is predominant among the Mexican population, but not in Central America. Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence, apparently due to a rapid resolution of the infection, low viral loads and a high prevalence of occult B infection. During chronic infections, genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low. Thus, antiviral therapy may differ significantly from the standard guidelines established worldwide. The high prevalence of HBV genotype G in the Americas, especially among the Mexican population, raises new questions regarding its geographic origin that will require further investigation.

  19. Pathophysiology of Clinical Symptoms in Acute Viral Respiratory Tract Infections.

    PubMed

    Kuchar, E; Miśkiewicz, K; Nitsch-Osuch, Aneta; Szenborn, L

    2015-01-01

    In this article we discuss the pathophysiology of common symptoms of acute viral respiratory infections (e.g., sneezing, nasal discharge, sore throat, cough, muscle pains, malaise, and mood changes). Since clinical symptoms are not sufficient to determine the etiology of viral respiratory tract infections, we believe that the host defense mechanisms are critical for the symptomatology. Consequently, this review of literature is focused on the pathophysiology of respiratory symptoms regardless of their etiology. We assume that despite a high prevalence of symptoms of respiratory infection, their pathogenesis is not widely known. A better understanding of the symptoms' pathogenesis could improve the quality of care for patients with respiratory tract infections.

  20. HBV: Do I treat my immunotolerant patients?

    PubMed

    Vlachogiannakos, Jiannis; Papatheodoridis, George V

    2016-01-01

    Immunotolerant patients with chronic hepatitis B virus (HBV) infection are characterized by positive HBeAg, high viral replication, persistently normal ALT and no or minimal liver damage. Since the risk of the progression of liver disease and the chance of a sustained response with existing anti-HBV agents are low, current guidelines do not recommend treatment but close monitoring with serial alanine aminotransferase (ALT) and HBV DNA measurements instead. However, not treating all these patients is a concern because advanced histological lesions have been reported in certain cases who are usually older (>30-40 years old), and continued high HBV replication could increase the risk of hepatocellular carcinoma (HCC). Thus, the optimal management of immunotolerant patients is often individualised according to age, which is associated with histological severity and patient outcome. In particular, immunotolerant patients <30 years old can be monitored for ALT and HBV DNA, while treatment is often recommended in the few patients over 40. A liver biopsy and/or non-invasive assessment of fibrosis may be helpful to determine the therapeutic strategy in patients between 30 and 40 years old. Moreover, there are three specific subgroups of immunotolerant patients who often require treatment with oral anti-HBV agents: patients who will receive immunosuppressive treatment or chemotherapy, women with serum HBV DNA >10(6-7) IU/ml during the last trimester of pregnancy and certain healthcare professionals with high viraemia levels. More studies are needed to further clarify the natural history for the optimal timing of treatment in this setting.

  1. Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

    PubMed Central

    Flieger, Robert Rainer; Mankertz, Annette; Yilmaz, Kadir; Roepke, Torsten Kai

    2016-01-01

    Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade.

  2. Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

    SciTech Connect

    Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin; Zheng, Shusen

    2015-06-05

    Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

  3. HBx M130K and V131I (T-A) mutations in HBV genotype F during a follow-up study in chronic carriers

    PubMed Central

    León, Bernal; Taylor, Lizeth; Vargas, Minor; Luftig, Ronald B; Albertazzi, Federico; Herrero, Libia; Visona, Kirsten

    2005-01-01

    Background Around 400 million people worldwide are chronically infected with Hepatitis B virus (HBV). An estimated 10% of these chronic patients develop progressive liver damage including cirrhosis and Hepatocellular Carcinoma (HCC). The HBx gene encodes a protein of 154 amino acids which is a transactivator and has been associated with HBV pathogenesis. A change in the amino acid sequences at positions 130 and 131 in the HBV-X protein (M130K and V131I) produced by T-A point mutations at the nucleic acids level has been associated with severe liver damage and HCC in patients from China and Africa. Further, such changes have been proposed as a prognostic marker for progressive liver damage and HCC. The purpose of this study was to determine if T-A mutations are present in HBV chronic carriers with genotype F (the major genotype in Costa Rica) and further, if these mutations are associated with HBV disease progression in Costa Rica HBV patients from 1972 to 1985. Results Serum samples from 50 HBV positive individuals were amplified and directly sequenced, 48 belonged to genotype F, 1 from genotype D and another was classified as D or E. T-;A mutations were absent in 17 acute patients who recovered, but was present in 12 of 29 chronic carrier samples (42.8%), in one sample the T-A mutations were detected as early as 29 days after clinical onset of disease. In 17 carriers with available liver biopsies, T-;A mutations were found in 8 sera of 13 (61.5%) classified as moderate or severe, and none in 4 biopsies with mild liver damage. However, it was not possible to demonstrate a statistical association between the presence of T-A mutations and moderate/severe liver damage, using a Fischer exact test, 1 tail, p = 0.05. In 4 patients HCC was diagnosed, and 2 of them presented the T-A mutations in their sera. Conclusion T-A mutations were found in HBV genotype F in chronic carriers but not in patients who recovered from acute infection. These mutations could be developing

  4. Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development

    PubMed Central

    Mina, Thomas; Amini-Bavil-Olyaee, Samad; Tacke, Frank; Maes, Piet; Van Ranst, Marc; Pourkarim, Mahmoud Reza

    2015-01-01

    Context: After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%. Evidence Acquisition: All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection. Results: The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence. Conclusions: Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity. PMID:26288637

  5. Hepatitis B virus (HBV) and autoimmune disease.

    PubMed

    Maya, Ram; Gershwin, M Eric; Shoenfeld, Yehuda

    2008-02-01

    The etiology and pathogenesis of autoimmune diseases have long been an enigmatic subject that have involved genetic and environmental factors. Recent intriguing data has contributed to the mechanisms involved, including the relationship of infectious agents and loss of tolerance. This loss of tolerance is illustrated by the data on the immune response to Hepatitis B virus such as the molecular mimicry between HBV antigens and self proteins, the generation of immune complexes between HBV antigens and antibodies, and apoptosis/tissue damage resulting in the exposure of intracellular antigens to the immune system. In this paper, we review the current database related to HBV infection and a variety of autoimmune conditions, including autoimmune hepatitis, systemic lupus erythematosus, aplastic anemia, antiphospholipid syndrome, polyarteritis nodosa, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, thyroid disease and uveitis. PMID:18270862

  6. Characterization of acute rat parvovirus infection by in situ hybridization.

    PubMed

    Gaertner, D J; Jacoby, R O; Johnson, E A; Paturzo, F X; Smith, A L; Brandsma, J L

    1993-04-01

    In situ hybridization and virus titration were used to characterize early stages of rat virus (RV) infection of rat pups after oronasal inoculation. Results suggest that virus enters through the lung and that early viremia leads rapidly to pantropic infection. Cells derived from all three germ layers were infected with RV, but those of endodermal and mesodermal origin were the predominant targets. Infection of vascular endothelium was widespread and was associated with hemorrhage and infarction in the brain. Convalescence from acute infection was accompanied by mononuclear cell infiltrates at sites containing RV DNA. Viral DNA was also detected in endothelium, fibroblasts and smooth muscle myofibers four weeks after inoculation. Further examination of these cells as potential sites of persistent infection is warranted.

  7. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa

    PubMed Central

    Lemoine, Maud; Shimakawa, Yusuke; Nayagam, Shevanthi; Khalil, Mustapha; Suso, Penda; Lloyd, Jo; Goldin, Robert; Njai, Harr-Freeya; Ndow, Gibril; Taal, Makie; Cooke, Graham; D'Alessandro, Umberto; Vray, Muriel; Mbaye, Papa Saliou; Njie, Ramou; Mallet, Vincent; Thursz, Mark

    2016-01-01

    Background Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. Methods Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). Results Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. Conclusions The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa. PMID:26109530

  8. Emergency Department Management Of Acute Infective Endocarditis.

    PubMed

    Schauer, Steven G; Pfaff, James A; Cuenca, Peter John

    2014-11-01

    Infective endocarditis has a high rate of mortality, and most patients suspected of having the disease will require hospital admission. This review examines the literature as it pertains specifically to emergency clinicians who must maintain vigilance for risk factors and obtain a thorough history, including use of intravenous drugs, in order to guide the workup and treatment. Properly obtained cultures are critical during the evaluation, as they direct the course of antibiotic therapy. Although transthoracic echocardiography is widely available in United States emergency departments, it is not sensitive or specific enough to rule out a diagnosis of infective endocarditis. In high-risk patients, transesophageal echocardiography should be considered.

  9. Predicting development of infected necrosis in acute necrotizing pancreatitis.

    PubMed

    Dambrauskas, Zilvinas; Pundzius, Juozas; Barauskas, Giedrius

    2006-01-01

    The incidence of severe acute pancreatitis is about 30 cases per 100,000 inhabitants, and it carries an overall mortality rate of 10-15%. Infection of pancreatic necrosis occurs in 20-30% of patients with severe acute pancreatitis and triples the mortality rate. Therefore, early prediction and diagnosis of infection in necrotizing pancreatitis are extremely important. The aim of the studies included in this review was to investigate the potential of specific prognostic factors to predict the development of secondary pancreatic infection in severe acute pancreatitis. This is seen as an important tool allowing to perform a computed tomography- or ultrasound-guided fine needle aspiration for bacteriological sampling at the right moment, to confirm the diagnosis, and, finally, to select the subgroup of patients who would benefit from the antibiotic prophylaxis. Precise patients' selection could possibly result in more rational use of antibiotics in patients with acute necrotizing pancreatitis and reduction of multi-resistant bacteria. Recent studies show that C-reactive protein is an important prognostic marker of pancreatic necrosis with the highest sensitivity and negative prognostic value in this respect. Procalcitonin alone or in combination with interleukin-6 best identifies patients not at risk for infection. However, a review of the clinical studies suggests that we still do not have an optimal model, thus there is a need for new more reliable biochemical and/or clinical predictive systems.

  10. Acute Borrelia infection inducing an APMPPE-like picture.

    PubMed

    Al Mousa, Munjid; Koch, Frank

    2016-12-01

    Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon disorder of unknown etiology affecting the retina, the retinal pigment epithelium, and the choroid. Although several etiological factors have been suggested, none has been confirmed. We report a case of APMPPE associated with acute infection of Borreliosis. A 30-year-old man presented with a decrease in vision in the right eye of about 1-week duration. His visual acuity in the right eye was 6/36. Fundus exam revealed the presence of multiple placoid creamy retinal/subretinal lesions in the right eye. Fundus fluorescein angiography supported the diagnosis of APMPPE. Blood tests revealed the presence of concomitant acute Borreliosis infection, as confirmed by IgM. The patient received oral prednisone therapy and amoxicillin. Six weeks later, the visual acuity returned to 6/6, and the patient was symptom free. Borreliosis can have several manifestations in the eye. One of the less common presentations is an APMPPE-like picture. The clinician should suspect acute Borreliosis infection in patients presenting with APMPPE, especially when there is a history of a tick bite, when the patient has systemic symptoms, or when living in/visiting endemic areas. This may help in the prompt management of APMPPE, avoiding complications due to the condition itself, or systemic involvement secondary to the Borreliosis infection. PMID:27294731

  11. Immunochromatography-based Diagnosis of Rotavirus Infection in Acute Diarrhea.

    PubMed

    Vashishtha, Vipin M; Thacker, Sandeep; Namjoshi, Gajanan Sudhir

    2016-07-01

    Documentation of rotavirus diarrhea in a rural, resource-poor setting is a difficult task. We analyzed stool samples of 103 children admitted for acute diarrhea in a pediatric hospital in Bijnor, UP, India, using a simple bedside immunochromatography kit. Rotavirus infection was detected in 47 out of total of 103 children (45.6%). PMID:27508549

  12. Uncommon illness from common infections.

    PubMed Central

    Christian, C. L.

    1988-01-01

    Individual common infectious agents such as EBV, CMV and HBV have well characterized relationships to a variety of acute and chronic disease states; the host and/or environment variables underlying this clinical heterogeneity are not known. Given the high frequency of these viral infections in the general population, there should be a cautious interpretation of antiviral serological data. PMID:3332514

  13. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  14. Sentinel Surveillance of HIV-1 Transmitted Drug Resistance, Acute Infection and Recent Infection

    PubMed Central

    Truong, Hong-Ha M.; Kellogg, Timothy A.; McFarland, Willi; Louie, Brian; Klausner, Jeffrey D.; Philip, Susan S.; Grant, Robert M.

    2011-01-01

    Background HIV-1 acute infection, recent infection and transmitted drug resistance screening was integrated into voluntary HIV counseling and testing (VCT) services to enhance the existing surveillance program in San Francisco. This study describes newly-diagnosed HIV cases and characterizes correlates associated with infection. Methodology/Principal Findings A consecutive sample of persons presenting for HIV VCT at the municipal sexually transmitted infections (STI) clinic from 2004 to 2006 (N = 9,868) were evaluated by standard enzyme-linked immunoassays (EIA). HIV antibody-positive specimens were characterized as recent infections using a less-sensitive EIA. HIV-RNA pooled testing was performed on HIV antibody-negative specimens to identify acute infections. HIV antibody-positive and acute infection specimens were evaluated for drug resistance by sequence analysis. Multivariable logistic regression was performed to evaluate associations. The 380 newly-diagnosed HIV cases included 29 acute infections, 128 recent infections, and 47 drug-resistant cases, with no significant increases or decreases in prevalence over the three years studied. HIV-1 transmitted drug resistance prevalence was 11.0% in 2004, 13.4% in 2005 and 14.9% in 2006 (p = 0.36). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) was the most common pattern detected, present in 28 cases of resistance (59.6%). Among MSM, recent infection was associated with amphetamine use (AOR = 2.67; p<0.001), unprotected anal intercourse (AOR = 2.27; p<0.001), sex with a known HIV-infected partner (AOR = 1.64; p = 0.02), and history of gonorrhea (AOR = 1.62; p = 0.03). Conclusions New HIV diagnoses, recent infections, acute infections and transmitted drug resistance prevalence remained stable between 2004 and 2006. Resistance to NNRTI comprised more than half of the drug-resistant cases, a worrisome finding given its role as the backbone of first

  15. Human bocavirus infection in young children with acute respiratory tract infection in Lanzhou, China.

    PubMed

    Zheng, Li-shu; Yuan, Xin-hui; Xie, Zhi-ping; Jin, Yu; Gao, Han-chun; Song, Jing-rong; Zhang, Rong-fang; Xu, Zi-qian; Hou, Yun-de; Duan, Zhao-jun

    2010-02-01

    Human bocavirus (HBoV) is a recognized human parvovirus associated with acute respiratory tract infection. However, HBoV has yet to be established as a causative agent of respiratory disease. In this study, the epidemiological and virological characteristics of HBoV infection were studied in children with acute respiratory tract infection in China. In total, 406 children younger than 14 years of age with acute respiratory tract infection were included in this prospective 1-year study. HBoV was detected in 29 (7.1%) of the 406 children. No clear seasonal fluctuation was observed in infection rates of HBoV. Of the 29 children infected with HBoV, 16 (55.2%) were coinfected with other respiratory viruses, most commonly respiratory syncytial virus (RSV). Viral coinfection with HBoV did not affect the severity of the respiratory disease (P = 0.291). The number of HBoV genome copies ranged from 5.80 x 10(2) to 9.72 x 10(8) copies/ml in nasopharyngeal aspirates among HBoV-positive specimens by real-time PCR, and neither coinfection nor the severity of disease correlated with the viral load (P = 0.148, P = 0.354, respectively). The most common clinical features were cough and acute upper respiratory infection, and acute bronchopneumonia. Additionally, the NP-1 gene of HBoV showed minimal sequence variation. These data suggest that HBoV is frequent in young children with acute respiratory tract infection in Lanzhou, China, and RSV is the most common coinfecting virus. There was no apparent association between the viral load of HBoV and coinfection or disease severity. The NP-1 gene was highly conserved in HBoV. PMID:20029808

  16. Nematode infection: A rare mimic of acute appendicitis

    PubMed Central

    Hotchen, Andrew; Chin, Kian; Raja, Mahzar

    2014-01-01

    INTRODUCTION Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures. PRESENTATION OF CASE A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved. DISCUSSION Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided. CONCLUSION This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix. PMID:25024022

  17. A real-time quantitative assay for hepatitis B DNA virus (HBV) developed to detect all HBV genotypes.

    PubMed

    Sitnik, Roberta; Paes, Angela; Mangueira, Cristovão Pitangueira; Pinho, João Renato Rebello

    2010-01-01

    Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. Besides genotype, quantitative analysis of HBV infection is extensively used for monitoring disease progression and treatment. Affordable viral load monitoring is desirable in resource-limited settings and it has been already shown to be useful in developing countries for other viruses such as Hepatitis C virus (HCV) and HIV. In this paper, we describe the validation of a real-time PCR assay for HBV DNA quantification with TaqMan chemistry and MGB probes. Primers and probes were designed using an alignment of sequences from all HBV genotypes in order to equally amplify all of them. The assay is internally controlled and was standardized with an international HBV panel. Its efficacy was evaluated comparing the results with two other methods: Versant HBV DNA Assay 3.0 (bDNA, Siemens, NY, USA) and another real-time PCR from a reference laboratory. Intra-assay and inter-assay reproducibilities were determined and the mean of CV values obtained were 0.12 and 0.09, respectively. The assay was validated with a broad dynamic range and is efficient for amplifying all HBV genotypes, providing a good option to quantify HBV DNA as a routine procedure, with a cheap and reliable protocol. PMID:20602019

  18. Modeling inoculum dose dependent patterns of acute virus infections.

    PubMed

    Li, Yan; Handel, Andreas

    2014-04-21

    Inoculum dose, i.e. the number of pathogens at the beginning of an infection, often affects key aspects of pathogen and immune response dynamics. These in turn determine clinically relevant outcomes, such as morbidity and mortality. Despite the general recognition that inoculum dose is an important component of infection outcomes, we currently do not understand its impact in much detail. This study is intended to start filling this knowledge gap by analyzing inoculum dependent patterns of viral load dynamics in acute infections. Using experimental data for adenovirus and infectious bronchitis virus infections as examples, we demonstrate inoculum dose dependent patterns of virus dynamics. We analyze the data with the help of mathematical models to investigate what mechanisms can reproduce the patterns observed in experimental data. We find that models including components of both the innate and adaptive immune response are needed to reproduce the patterns found in the data. We further analyze which types of innate or adaptive immune response models agree with observed data. One interesting finding is that only models for the adaptive immune response that contain growth terms partially independent of viral load can properly reproduce observed patterns. This agrees with the idea that an antigen-independent, programmed response is part of the adaptive response. Our analysis provides useful insights into the types of model structures that are required to properly reproduce observed virus dynamics for varying inoculum doses. We suggest that such models should be taken as basis for future models of acute viral infections.

  19. Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection.

    PubMed

    Shinoda, Koji; Asahara, Hideaki; Uehara, Taira; Miyoshi, Katsue; Suzuki, Satoshi O; Iwaki, Toru; Kira, Jun-ichi

    2015-02-01

    We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus.

  20. Detection of Acute HIV-1 Infection by RT-LAMP.

    PubMed

    Rudolph, Donna L; Sullivan, Vickie; Owen, S Michele; Curtis, Kelly A

    2015-01-01

    A rapid, cost-effective diagnostic test for the detection of acute HIV-1 infection is highly desired. Isothermal amplification techniques, such as reverse-transcription loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for the development of a rapid nucleic acid amplification test (NAAT) because they are quick, easy to perform and do not require complex, dedicated equipment and laboratory space. In this study, we assessed the ability of the HIV-1 RT-LAMP assay to detect acute HIV infection as compared to a representative rapid antibody test and several FDA-approved laboratory-based assays. The HIV-1 RT-LAMP assay detected seroconverting individuals one to three weeks earlier than a rapid HIV antibody test and up to two weeks earlier than a lab-based antigen/antibody (Ag/Ab) combo enzyme immunoassay (EIA). RT-LAMP was not as sensitive as a lab-based qualitative RNA assay, which could be attributed to the significantly smaller nucleic acid input volume. To our knowledge, this is the first demonstration of detecting acute HIV infection using the RT-LAMP assay. The availability of a rapid NAAT, such as the HIV-1 RT-LAMP assay, at the point of care (POC) or in laboratories that do not have access to large platform NAAT could increase the percentage of individuals who receive an acute HIV infection status or confirmation of their HIV status, while immediately linking them to counseling and medical care. In addition, early knowledge of HIV status could lead to reduced high-risk behavior at a time when individuals are at a higher risk for transmitting the virus. PMID:25993381

  1. Hepatitis B Virus Genotype Distribution and Genotype-Specific BCP/preCore Substitutions in Acute and Chronic Infections in Argentina

    PubMed Central

    González López Ledesma, María Mora; Mojsiejczuk, Laura Noelia; Rodrigo, Belén; Sevic, Ina; Mammana, Lilia; Galdame, Omar; Gadano, Adrian; Fainboim, Hugo; Campos, Rodolfo; Flichman, Diego

    2015-01-01

    Aim In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections). Results Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896. Discussion HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying

  2. Pteropine orthoreovirus infection among out-patients with acute upper respiratory tract infection in Malaysia.

    PubMed

    Voon, Kenny; Tan, Yeh Fong; Leong, Pooi Pooi; Teng, Cheong Lieng; Gunnasekaran, Rajasekaran; Ujang, Kamsiah; Chua, Kaw Bing; Wang, Lin-Fa

    2015-12-01

    This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co-infection with other pathogens may potentially lead to different clinical outcomes.

  3. Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

    PubMed

    Hahn, D M; Schimpff, S C; Fortner, C L; Smyth, A C; Young, V M; Wiernik, P H

    1978-06-01

    During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections. PMID:98107

  4. A Golden Hamster Model for Human Acute Nipah Virus Infection

    PubMed Central

    Wong, K. Thong; Grosjean, Isabelle; Brisson, Christine; Blanquier, Barissa; Fevre-Montange, Michelle; Bernard, Arlette; Loth, Philippe; Georges-Courbot, Marie-Claude; Chevallier, Michelle; Akaoka, Hideo; Marianneau, Philippe; Lam, Sai Kit; Wild, T. Fabian; Deubel, Vincent

    2003-01-01

    A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153–2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection. PMID:14578210

  5. TLR3 Plays Significant Roles against HBV-Associated HCC

    PubMed Central

    Chen, Xiao-lan; Xu, Yu-yin; Chen, Li; Wang, Gui-lan; Shen, Yin

    2015-01-01

    Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. PMID:25983748

  6. Acute haematogenous infection of a closed vertebral fracture.

    PubMed

    Marshman, Laurence A G; Allison, Dale; Molloy, Cynthia J

    2009-12-01

    Acute haematogenous infection of a closed fractures is rare. A 68-year-old diabetic male sustained a burst fracture of a lumbar vertebra (L2) after a fall onto his back. After 5 days of conservative management, he developed a chest infection and amoxicillin was commenced empirically. However, after 6 days his previously moderate focal L2 back pain had become more severe. Pyrexia and systemic inflammatory markers continued to rise despite administration of antibiotics. Blood cultures and a CT-guided biopsy of L2 both revealed Staphylococcus aureus which was sensitive to flucloxacillin. The patient's symptoms and signs gradually normalised following administration of flucloxacillin for 6 weeks, and the use of a cast brace. We conclude that haematogenous infection can be successfully managed non-operatively.

  7. Telaprevir in the Treatment of Acute Hepatitis C Virus Infection in HIV-Infected Men

    PubMed Central

    Fierer, Daniel S.; Dieterich, Douglas T.; Mullen, Michael P.; Branch, Andrea D.; Uriel, Alison J.; Carriero, Damaris C.; van Seggelen, Wouter O.; Hijdra, Rosanne M.; Cassagnol, David G.; Akil, Bisher; Bailey, Juan; Bellman, Paul; Bowers, Daniel; Bungay, Krisczar; Burger, Susanne; Carpenter, Ward; Chavez, Robert; Chow, Rita; Cohen, Robert; Dalton, Patrick; Dellosso, John; Demidont, Adrian; Dillon, Stephen; Donlon, Eileen; Farrow, Terry; Gardenier, Donald; Guadron, Rodolfo; Haber, Stuart; Higgins, Lawrence; Hitzeman, Lawrence; Hsu, Ricky; Huprikar, Shirish; Inada, Victor; Jacob, Sneha; Johnson, Livette; Johnston, Barbara; Kaminsky, Donald; Klein, Oscar; Kwong, Jeffrey; Lares-Guia, Jose; Leach, Eric; Levine, Randy; Linetskaya, Irina; Litvinova, Larisa; Malhotra, Amisha; Mandell, William; Markowitz, Martin; Mayer, Gal; Meraz, Eddie; Mortensen, Erik; Ng, Michel; Olivieri, Joseph; Paolino, Charles; Photangtham, Punyadech; Psevdos, George; Radix, Anita; Rapaport, Steven; Rodriguez-Caprio, Gabriela; Shay, William; Somasundaram, Nirupama; Sorra, Lembitu; Stivala, Alicia; Tran, Richie; Urbina, Antonio; Vail, Rona; Wallach, Francis; Wang, Wen; Weiss, Susan; Wiener, Melissa

    2014-01-01

    Background. There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)–infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. Methods. We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. Results. In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. Conclusions. Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic. PMID:24336914

  8. ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE

    PubMed Central

    Bradley, G. Mary; Spink, Wesley W.

    1959-01-01

    When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed. PMID:13803714

  9. Human Bocavirus: Passenger or Pathogen in Acute Respiratory Tract Infections?

    PubMed Central

    Schildgen, Oliver; Müller, Andreas; Allander, Tobias; Mackay, Ian M.; Völz, Sebastian; Kupfer, Bernd; Simon, Arne

    2008-01-01

    Summary: Human bocavirus (HBoV) is a newly identified virus tentatively assigned to the family Parvoviridae, subfamily Parvovirinae, genus Bocavirus. HBoV was first described in 2005 and has since been detected in respiratory tract secretions worldwide. Herein we review the literature on HBoV and discuss the biology and potential clinical impact of this virus. Most studies have been PCR based and performed on patients with acute respiratory symptoms, from whom HBoV was detected in 2 to 19% of the samples. HBoV-positive samples have been derived mainly from infants and young children. HBoV DNA has also been detected in the blood of patients with respiratory tract infection and in fecal samples of patients with diarrhea with or without concomitant respiratory symptoms. A characteristic feature of HBoV studies is the high frequency of coinciding detections, or codetections, with other viruses. Available data nevertheless indicate a statistical association between HBoV and acute respiratory tract disease. We present a model incorporating these somewhat contradictory findings and suggest that primary HBoV infection causes respiratory tract symptoms which can be followed by prolonged low-level virus shedding in the respiratory tract. Detection of the virus in this phase will be facilitated by other infections, either simply via increased sample cell count or via reactivation of HBoV, leading to an increased detection frequency of HBoV during other virus infections. We conclude that the majority of available HBoV studies are limited by the sole use of PCR diagnostics on respiratory tract secretions, addressing virus prevalence but not disease association. The ability to detect primary infection through the development of improved diagnostic methods will be of great importance for future studies seeking to assign a role for HBoV in causing respiratory illnesses. PMID:18400798

  10. Actinomyces infection causing acute right iliac fossa pain

    PubMed Central

    Govindarajah, Narendranath; Hameed, Waseem; Middleton, Simon; Booth, Michael

    2014-01-01

    This is a case of a 75-year-old man being admitted to the on-call surgical department with acute abdominal pain. On arrival he was clinically dehydrated and shocked with localised pain over McBurney's point and examination findings were suggestive of appendiceal or other colonic pathology. Full blood testing revealed a white cell count of 38×109/L and a C reactive protein (CRP) of 278 mg/L. A CT scan revealed a gallbladder empyema that extended into the right iliac fossa. This case highlights the potential for a hyperdistended gallbladder empyema to present as acute right iliac fossa pain with blood tests suggestive of complicated disease. Further analysis confirmed Actinomyces infection as the underlying aetiology prior to a laparoscopic subtotal cholecystectomy. This case serves to remind clinicians of this as a rare potential cause of atypical gallbladder pathology. PMID:24872493

  11. The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

    PubMed Central

    Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

    2015-01-01

    Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

  12. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection.

    PubMed

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets.

  13. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection

    PubMed Central

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M.; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  14. [Nosocomial transfer of HBV and HCV by public health workers].

    PubMed

    Fischer, F; Nauert, T

    2003-04-01

    Transmission of HBV and HCV from people who work in medical professions to their patients is still an unsolved hygienic and legal problem. In Germany, cases of nosocomial hepatitis virus infection in health care units have received great public interest. Medical examinations of the employees according to occupational safety regulations aim at the employees only. Legal regulations including regulations of the European Union limit the purpose of these examinations on safety and health of the employees. These examinations do not serve the safety of patients. Protection against infections is regulated by the relevant German public health law, however regulations--especially those that concern the protection of the public--are incomplete. In Germany it is mandatory to inform the public health departments only in cases of acute hepatitis. Doctors do not need to give information about chronic liver infections. This may lead to the situation that a health care worker is unaware of a chronic, potentially infectious condition and his immunological status may remain unknown for a long period. Examinations in occupational medicine cannot solve this problem. In order to improve the protection of the public, there is a need to extend the regulations concerning the notification of chronic hepatitis and to implement solutions for this difficult and sensible problem in Germany. PMID:12751011

  15. [Risk Management of HBV Reactivation: Construction of Check System].

    PubMed

    Tanaka, Yasuhito

    2015-09-01

    In recent years, reactivation of HBV in patients receiving cancer chemotherapy or immunosuppressive therapy has been a problem. Generally, HBV-DNA levels are elevated prior to HBsAg concentration, and then hepatic dysfunction is observed in the process of hepatitis by HBV reactivation. Therefore, the monitoring of HBV-DNA is useful for the prediction of hepatic dysfunction, and nucleoside/nucleoside analogue (NA) administration is able to prevent this HBV reactivation. According to these facts, "Guidelines for the Prevention of HBV Reactivation in Patients Receiving Immunosuppressive Therapy or Chemotherapy", 2009 (revised as "JSH Guidelines for the Management of Hepatitis B Virus Infection", 2013) is established, and the diagnostic algorithm of HBsAg, anti-HBc, anti-HBs, and HBV-DNA has relevant descriptions. Combination therapy with rituximab and steroid for malignant lymphoma has a high risk of leading to fulminant hepatitis and, consequently, the guidelines are widely followed in such cases. We introduced the improvement of electronic medical recording and ordering systems in collaboration with hepatologists, and such a system has been widely used. Although the monitoring of HBV-DNA levels is required every 1-3 months, the guidelines are not followed strictly in cases such as rheumatoid disease and solid tumors only with chemotherapy or steroid treatment. Since a DNA assay is complicated and expensive, cost-effective, time-saving, and highly sensitive/specific measurements are required as well. Therefore, Lumipulse HBsAg-HQ (CLIA method) with high sensitivity is expected to be used for the monitoring of HBV reactivation.

  16. Hepatitis B and hepatitis delta virus infection in South America.

    PubMed Central

    Torres, J R

    1996-01-01

    About 100,000 cases of acute hepatitis B virus (HBV) infection occur annually in South America. The overall prevalence of HBV infection in low risk populations ranges from 6.7% to 41%, while hepatitis B surface antigen (HBsAg) rates range from 0.4% to 13%. In high endemicity aboriginal or rural populations, perinatal transmission may play a major part in the spread of HBV. In urban populations, however, horizontal transmission, probably by sexual contact, is the predominant mode of spread, with higher rates of HBV positivity in lower socioeconomic groups. High risk populations such as health care workers and haemodialysis patients show higher rates of HBV infection than comparable populations elsewhere. The risk of posttransfusion hepatitis B remains high in some areas. Concomitant HBV infection may accelerate the chronic liver disease seen in decompensated hepatosplenic schistosomiasis. In the north, the prevalence of hepatitis delta virus (HDV) infection ranks among the highest in the world. In the south, the problem appears negligible although it is increasing within high risk urban communities. HDV superinfection has been the cause of large outbreaks of fulminant hepatitis. The cost of comprehensive or mass vaccination programmes remains unaffordable for most South American countries. Less expensive alternatives such as low dose intradermal schedules of immunisation have been used with success in selected adult subjects. PMID:8786054

  17. HIV/HBV coinfection in children and antiviral therapy

    PubMed Central

    Healy, Sara A; Gupta, Sonia; Melvin, Ann J

    2016-01-01

    Small cohort studies from countries where both HIV and HBV are endemic demonstrate prevalence rates of chronic hepatitis B in HIV-infected children of between 1 and 49%. While data on coinfected children are limited, results from studies in adults with HIV/HBV coinfection raise the concern that coinfected children may be at a higher risk of liver disease, hepatic fibrosis and cirrhosis. With the scale-up of combination antiretroviral therapy worldwide, of which lamivudine is included in most first-line regimens, coinfected children treated with lamivudine risk development of HBV resistance mutations. This article summarizes the current literature relevant to HIV/HBV coinfection in children, the options for treatment and highlights priorities for future research. PMID:23458766

  18. Primary and secondary prevention of liver cancer caused by HBV

    PubMed Central

    Blumberg, Baruch S.

    2010-01-01

    Primary cancer of the liver (hepatocellular carcinoma, HCC) is one of the most common cancers worldwide; HBV is the major cause of HCC. A vaccine that protects against HBV infection was invented in 1969 and is now one of the most commonly used vaccines. National vaccination programs have dramatically reduced the prevalence of HBV infection and carriers, with a concomitant decrease in the incidence of HCC in the vaccine-impacted populations. HBV vaccine is the first widely used cancer prevention vaccine; a second that protects against papilloma virus and cancer of the cervix has recently been introduced. Appropriate treatment of HBV carriers with antivirals can reduce the titers of HBV in their blood and thereby greatly reduce the risk of HCC and chronic liver disease. Further data are required to establish criterion for treatment to enable protocols for medical and prevention programs. There are other viral caused cancers and an understanding of their pathogenesis is an important future direction for research to reduce the human burden of cancer. PMID:20036981

  19. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  20. Central venous catheter infection in adults in acute hospital settings.

    PubMed

    Jones, Clare A

    As well as the human cost, central venous catheter (CVC)-related bloodstream infections significantly inflate hospital costs, mainly through increased length of stay in hospital, particularly in intensive care. This literature review appraises recent research on measures used to minimize CVC-related infection and compares it with current best practice. Randomized controlled trials and systematic reviews published on the subject between 2000 and 2005 were reviewed, concentrating on non-tunnelled, short-term CVCs in the acute hospital setting. The new evidence mainly backs up current best practice. However, skin disinfection could be improved by using alcoholic chlorhexidine followed by aqueous povidone-iodine before CVC insertion. Also, alcoholic chlorhexidine is the preferred solution for cleaning the hubs/connectors before accessing the CVC. Good hand hygiene and quality control and education programmes are vital to improve patient care. More research is needed to clarify the effectiveness of certain interventions and technologies, such as antimicrobial CVCs.

  1. Antibiotic use in acute upper respiratory tract infections.

    PubMed

    Zoorob, Roger; Sidani, Mohamad A; Fremont, Richard D; Kihlberg, Courtney

    2012-11-01

    Upper respiratory tract infections account for millions of visits to family physicians each year in the United States. Although warranted in some cases, antibiotics are greatly overused. This article outlines the guidelines and indications for appropriate antibiotic use for common upper respiratory infections. Early antibiotic treatment may be indicated in patients with acute otitis media, group A beta-hemolytic streptococcal pharyngitis, epiglottitis, or bronchitis caused by pertussis. Persistent cases of rhinosinusitis may necessitate the use of antibiotics if symptoms persist beyond a period of observation. Antibiotics should not be considered in patients with the common cold or laryngitis. Judicious, evidence-based use of antibiotics will help contain costs and prevent adverse effects and drug resistance.

  2. [HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study].

    PubMed

    Cañero-Velasco, M C; Mutti, J E; Gonzalez, J E; Alonso, A; Otegui, L; Adragna, M; Antonuccio, M; Laso, M; Montenegro, M; Repetto, L; Brandi, M; Canepa, J; Baimberg, E

    1998-01-01

    Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children. PMID:9773156

  3. Nutritional Predictors of Acute Respiratory Infections Among Children Born to HIV-Infected Women in Tanzania

    PubMed Central

    Spiegelman, Donna; Hertzmark, Ellen; Duggan, Christopher; Msamanga, Gernard; Aboud, Said; Fawzi, Wafaie

    2013-01-01

    We prospectively determined the association between undernutrition and incidence of acute respiratory infections (ARIs) among 711 children born to HIV-infected women. Overall, underweight was associated with a 58% increased risk of ARI. Similarly, wasting (54%), very low birth weight (88%) and child HIV infection (62%) were significantly associated with increased risk of ARI during the first 2 years. Breastfeeding was associated with 52% reduction in risk of ARI only during the first 12 months of life. Among HIV-exposed, but uninfected, children, underweight, wasting and stunting were associated with 73%, 61% and 33% increased risk of ARI, respectively. Very low birthweight and advanced maternal disease stage were also associated with increased risk of ARI. Similar results were observed among HIV-infected children, except for stunting and very low birth weight. Prevention of child undernutrition could have major impact in reducing child ARI morbidity in settings of high HIV prevalence. PMID:23400399

  4. Comparison of the effects of formaldehyde and gaseous ozone on HBV-contaminated hospital quilts

    PubMed Central

    Guo, Dan; Li, Ziqiong; Jia, Bei; Che, Xiaoqiong; Song, Tianshuang; Huang, Wenxiang

    2015-01-01

    Background: Besides being highly infectious, Hepatitis B virus (HBV) is a major cause of liver disease worldwide. In hospital settings, it is easy for the environment and quilts to be contaminated by HBV patient blood and body fluids. Therefore, HBV can be transmitted to other patients via contaminated environmental surfaces or quilts, resulting in an HBV nosocomial infection. Formaldehyde and ozone are commonly used disinfectants that may influence this infectious situation. Objective: To investigate the clinical effectiveness of formaldehyde and gaseous ozone for the terminal cleaning of hospital quilts contaminated by HBV. Methods: Thin cloth and thick cotton soaked with the serum from high HBV copy number patients were prepared and disinfected using formaldehyde fumigation and gaseous ozone at different times. The copy numbers of HBV DNA in the HBV-contaminated cloth and cotton samples were measured quantitatively with fluorescent quantitative polymerase chain reaction (PCR). Results: When gaseous ozone was used to disinfect HBV-contaminated quilts for 23 minutes (min), 36 min, 49 min, and 90 min, the HBV DNA copy number displayed no significant decrease compared with the copy number before disinfection (P > 0.05). In comparison, the copy number of the HBV DNA in the cloth group decreased significantly (P < 0.05) after formaldehyde fumigation disinfection for 1 hour (h), and there was no difference when longer times and increased concentrations were used. In the thick cotton group, there was also a significant decrease (P < 0.05) of the HBV DNA copy numbers, but the decrease was not as dramatic. In addition, in this group, the disinfection effect observed at 4 h was the strongest. Conclusions: The application of ozone to disinfect HBV-contaminated hospital quilts possibly has no effect, whereas, formaldehyde oxide fumigation effectively reduced HBV copy numbers. PMID:26770591

  5. CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade

    PubMed Central

    Tang, Zong-Sheng; Hao, You-Hua; Zhang, E-Juan; Xu, Chun-Li; Zhou, Yun; Zheng, Xin; Yang, Dong-Liang

    2016-01-01

    The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 and B- and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD-1 blockade on the receptor expression profiles, T-cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD-1 blockade on the receptor expression profiles and the levels of interferon (IFN)-γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T-box 21 (T-bet) and GATA binding protein 3 (GATA-3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB. The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics, for example levels of PD-1 and CTLA-4 on CD4 T cells and ICOS, PD-1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals. A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD-1 on CD8+ T cells with the highest expression of PD-1 corresponding to viral levels >106 IU/ml. A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml. PD-1 blockade altered the expression profiles of CD28 family receptors in the T cells of patients with CHB, partly enhanced T cell function and increased the ratio of T-bet/GATA-3 mRNA in PBMCs. Thus, CD28 family receptors are potential clinical indicators for the rapid

  6. Prevalence of occult hepatitis B virus infection in hemodialysis patients in Isfahan, Iran

    PubMed Central

    Kalantari, Hamid; Ferdowsi, Faezeh; Yaran, Majid

    2016-01-01

    Background: The absence of a detectable hepatitis B surface antigen (HBsAg) with or without hepatitis B core antibody (anti-HBc) or hepatitis B surface antibody (anti-HBs) in the presence of hepatitis B virus-DNA (HBV-DNA) is defined as occult HBV infection. This study was aimed to evaluate the prevalence of occult HBV infection in patients receiving hemodialysis (HD) in Isfahan, Iran. Materials and Methods: This cross sectional study was done on 400 patients without acute or chronic HBV infection with end-stage renal disease undergoing regular HD. Blood samples were collected prior to the HD session, and serological markers of viral hepatitis B included HBsAg, anti-HBs and anti-HBc were measured using standard third generation commercially available enzyme immunoassays kit, then samples of positive anti-HBc and negative anti-HBs were tested for HBV DNA using quantitative real-time polymerase chain reaction techniques. Data were analyzed by SPSS using t-test and Chi-square test. Results: The mean age of patients was 51.6 ± 11.2 years. Anti-HBc positive was observed in 32 (8%) of 400 studied patients with negative HBsAg. Of 32 patients with anti-HBc positive, 15 were males and 17 were females with mean age of 49.7 ± 12.6 years. Among 32 patients with anti-HBc positive, 10 patients were negative for anti-HBs. All of 10 patients were negative for HBV DNA. The prevalence of occult HBV infection was 0%. Conclusions: The prevalence of occult HBV infection in HBsAg negative patients undergoing HD was 0% and look to be among the lowest worldwide. So, occult HBV infection is not a significant health problem in HD patients in this region. PMID:27713872

  7. Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

    PubMed

    Laaribi, A B; Zidi, I; Hannachi, N; Ben Yahia, H; Chaouch, H; Bortolotti, D; Zidi, N; Letaief, A; Yacoub, S; Boudabous, A; Rizzo, R; Boukadida, J

    2015-10-01

    Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation.

  8. Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

    PubMed

    Laaribi, A B; Zidi, I; Hannachi, N; Ben Yahia, H; Chaouch, H; Bortolotti, D; Zidi, N; Letaief, A; Yacoub, S; Boudabous, A; Rizzo, R; Boukadida, J

    2015-10-01

    Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation. PMID:25619305

  9. Acute Arboviral Infections in Guinea, West Africa, 2006

    PubMed Central

    Jentes, Emily S.; Robinson, Jaimie; Johnson, Barbara W.; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M. Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G.

    2010-01-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region. PMID:20682888

  10. Acute arboviral infections in Guinea, West Africa, 2006.

    PubMed

    Jentes, Emily S; Robinson, Jaimie; Johnson, Barbara W; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G; Bryan, Juliet

    2010-08-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region.

  11. Differential regulation of host genes including hepatic fatty acid synthase in HBV-transgenic mice.

    PubMed

    Zhang, Hongmin; Li, Hong; Yang, Yixuan; Li, Sanglin; Ren, Hong; Zhang, Dazhi; Hu, Huaidong

    2013-06-01

    Hepatitis B virus (HBV) is the most common of the hepatitis viruses that cause chronic liver infections in humans, and it is considered to be a major global health problem. To gain a better understanding of HBV pathogenesis, and identify novel putative targets for anti-HBV therapy, this study was designed to elucidate the differential expression of host proteins in liver tissue from HBV-transgenic mice. Liver samples from two groups, (1) HBV-transgenic (Tg) mice, (2) corresponding background normal mice, wild-type (WT) mice, were collected and subjected to iTRAQ and mass spectrometry analysis. In total, 1950 unique proteins were identified, and 68 proteins were found to be differentially expressed in HBV-Tg mice as compared with that in WT mice. Several differentially expressed proteins were further validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analysis. Furthermore, the association of HBV replication with fatty acid synthase (FASN), one of the highly expressed proteins in HBV-Tg mice, was verified. Silencing of FASN expression in HepG2.2.15 cells suppressed viral replication through the IFN signaling pathway, and some downstream antiviral effectors. The implicated role of FASN in HBV replication provides an opportunity to test existing compounds against FASN for adjuvant therapy and/or treatment of HBV replication. PMID:23675653

  12. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  13. Airway microbiota and acute respiratory infection in children

    PubMed Central

    Hasegawa, Kohei; Camargo, Carlos A.

    2016-01-01

    Summary Acute respiratory infection (ARI), such as bronchiolitis and pneumonia, is the leading cause of hospitalization for U.S. infants. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a “risk and resilience” model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity, and thereby decrease ARI incidence and severity in children. PMID:25961472

  14. The prognosis and management of inactive HBV carriers.

    PubMed

    Invernizzi, Federica; Viganò, Mauro; Grossi, Glenda; Lampertico, Pietro

    2016-01-01

    Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1 year, while a single-point detection of combined HBsAg <1000 IU/ml and HBV DNA <2000 IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5 kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12 months with periodic measurement of serum HBsAg levels to identify viral clearance. PMID:26725905

  15. Exposure to cold and acute upper respiratory tract infection.

    PubMed

    Eccles, R; Wilkinson, J E

    2015-06-01

    The incidence of acute upper respiratory tract viral infections (URTI) is directly correlated to air temperature with most URTI occurring seasonally in cold weather. This review looks at four types of cold exposure and examines the evidence and possible mechanisms for any relationship to URTI. The effects of cold are discussed as: 1) Chilling of the nose and upper respiratory tract by breathing cold air, 2) Chilling of the mouth and upper digestive tract by ingestion of cold drinks and food, 3) Acute chilling of the body surface, and, 4) Chilling of the body as a whole with a fall in body temperature, hypothermia. Some studies were found to support a relationship between breathing cold air and chilling the body surface with the development of URTI, although this area is controversial. No evidence was found in the literature to support any relationship between ingestion of cold drinks and food and URTI, and similarly no evidence was found to link hypothermia and URTI. PMID:26030031

  16. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  17. Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBsAg-transgenic mice.

    PubMed

    Gao, Wenjuan; Sun, Yuhan; Chen, Shiwen; Zhang, Jingyao; Kang, Jingjing; Wang, Yongqiang; Wang, Hexiang; Xia, Guoliang; Liu, Qinghong; Kang, Youmin

    2013-04-26

    DNA vaccination is a promising strategy for activating immune responses against hepatitis B virus (HBV) infection. However, the accumulated data have shown that DNA vaccination alone generates weak immune responses. To enhance the immunogenicity of HBV DNA vaccine, lectin purified from pleurotus ostreatus (POL) was used as adjuvant of HBV DNA vaccine for C57BL/6 and HBV surface antigen transgenic (HBVsAg-Tg) mice. Our data demonstrate that low dose of POL (1 μg/mouse) in conjunction with HBV DNA vaccine stimulated stronger HBV-specific delayed-type hypersensitivity (DTH) responses and higher HBV-specific IgG level than that in high dose of POL groups (5 μg/mouse and 10 μg/mouse). POL activated strong Th2 and Tc1 cell responses in immunized C57BL/6 and HBVsAg-Tg mice. POL as adjuvant of HBV DNA vaccine effectively enhanced HBV surface protein antibody (HBVsAb) and decreased HBVsAg level for HBV Tg mice treatment. Furthermore, POL infiltrated more lymphocytes excluding Th1, Th2 and Tc1 cell subtypes to liver of HBVsAg-Tg mice. Together, these results suggest that POL as adjuvant enhanced immunogenicity of HBV DNA vaccination and effectively stimulated immune reaponse for HBsAg-Tg mice treatment. Our findings implicate the potential of mushroom lectin as adjuvant of HBV DNA vaccine.

  18. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  19. Hepatitis-B virus infection in anaesthetists.

    PubMed

    Carstens, J; Macnab, G M; Kew, M C

    1977-09-01

    To determine whether anaesthetists are at risk from developing hepatitis-B virus (HBV) infection from their patients, 95 anaesthetists working with black South Africans (who have a high prevalence of hepatitis-B antigenaemia) were questioned about attacks of viral hepatitis and their blood was tested for hepatitis-B (surface) antigen (HBsAg) and antibody (Anti-HBs). Anti-HBs was detected in the serum of 17.9% of the anaesthetists, but none was a chronic carrier of HBsAg. Two anaesthetists had suffered from acute viral hepatitis during their careers, one of whom is now positive for Anti-HBs. Forty-five of the anaesthetists (47.4%) were known to have anaesthetized patients with HBs antigenaemia, and of these seven were Anti-HBs-positive. Anaesthetists working with a population having a high carrier rate of HBV appear to be more at risk from HBV infection than the general population. PMID:911589

  20. Primary Epstein-Barr-virus infections in acute neurologic diseases.

    PubMed

    Grose, C; Henle, W; Henle, G; Feorino, P M

    1975-02-20

    Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

  1. Surveillance for hospitalized acute respiratory infection in Guatemala.

    PubMed

    Verani, Jennifer R; McCracken, John; Arvelo, Wences; Estevez, Alejandra; Lopez, Maria Renee; Reyes, Lissette; Moir, Juan Carlos; Bernart, Chris; Moscoso, Fabiola; Gray, Jennifer; Olsen, Sonja J; Lindblade, Kim A

    2013-01-01

    Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to

  2. Surveillance for Hospitalized Acute Respiratory Infection in Guatemala

    PubMed Central

    Verani, Jennifer R.; McCracken, John; Arvelo, Wences; Estevez, Alejandra; Lopez, Maria Renee; Reyes, Lissette; Moir, Juan Carlos; Bernart, Chris; Moscoso, Fabiola; Gray, Jennifer; Olsen, Sonja J.; Lindblade, Kim A.

    2013-01-01

    Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to

  3. Role of Tim-3 in hepatitis B virus infection: An overview.

    PubMed

    Liu, Yuan; Gao, Li-Fen; Liang, Xiao-Hong; Ma, Chun-Hong

    2016-02-21

    Hepatitis B virus (HBV) infection has received increasing public attention. HBV is the prototypical member of hepadnaviruses, which naturally infect only humans and great apes and induce the acute and persistent chronic infection of hepatocytes. A large body of evidence has demonstrated that dysfunction of the host anti-viral immune response is responsible for persistent HBV replication, unresolved inflammation and disease progression. Many regulatory factors are involved in immune dysfunction. Among these, T cell immunoglobulin domain and mucin domain-3 (Tim-3), one of the immune checkpoint proteins, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In chronic HBV infection, Tim-3 expression is elevated in many types of immune cells, such as T helper cells, cytotoxic T lymphocytes, dendritic cells, macrophages and natural killer cells. Tim-3 over-expression is often accompanied by impaired function of the above-mentioned immunocytes, and Tim-3 inhibition can at least partially rescue impaired immune function and thus promote viral clearance. A better understanding of the regulatory role of Tim-3 in host immunity during HBV infection will shed new light on the mechanisms of HBV-related liver disease and suggest new therapeutic methods for intervention.

  4. Role of Tim-3 in hepatitis B virus infection: An overview

    PubMed Central

    Liu, Yuan; Gao, Li-Fen; Liang, Xiao-Hong; Ma, Chun-Hong

    2016-01-01

    Hepatitis B virus (HBV) infection has received increasing public attention. HBV is the prototypical member of hepadnaviruses, which naturally infect only humans and great apes and induce the acute and persistent chronic infection of hepatocytes. A large body of evidence has demonstrated that dysfunction of the host anti-viral immune response is responsible for persistent HBV replication, unresolved inflammation and disease progression. Many regulatory factors are involved in immune dysfunction. Among these, T cell immunoglobulin domain and mucin domain-3 (Tim-3), one of the immune checkpoint proteins, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In chronic HBV infection, Tim-3 expression is elevated in many types of immune cells, such as T helper cells, cytotoxic T lymphocytes, dendritic cells, macrophages and natural killer cells. Tim-3 over-expression is often accompanied by impaired function of the above-mentioned immunocytes, and Tim-3 inhibition can at least partially rescue impaired immune function and thus promote viral clearance. A better understanding of the regulatory role of Tim-3 in host immunity during HBV infection will shed new light on the mechanisms of HBV-related liver disease and suggest new therapeutic methods for intervention. PMID:26900291

  5. Occult HBV reactivation induced by ibrutinib treatment: a case report.

    PubMed

    de Jésus Ngoma, Patrick; Kabamba, Benoît; Dahlqvist, Geraldine; Sempoux, Christine; Lanthier, Nicolas; Shindano, Tony; Van Den Neste, Eric; Horsmans, Yves

    2015-12-01

    Ibrutinib is a small molecule that has been recently developped for the treatment of B cell malignancies. Common side effects are diarrhoea, nausea, fatigue, infections, neutropenia and thrombocytopenia. Here we report the first case of Hepatitis B virus reactivation in a 80 years old chronic lymphocytic leukaemia patient receiving ibrutinib, suggesting that such treatment must be associated with HBV screening. PMID:26712054

  6. HBV Genotypic Variability in Cuba

    PubMed Central

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  7. HBV genotypic variability in Cuba.

    PubMed

    Loureiro, Carmen L; Aguilar, Julio C; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions.

  8. Prevention of acute otitis media by prophylaxis and treatment of influenza virus infections.

    PubMed

    Glezen, W P

    2000-12-01

    Human experimental challenge studies with influenza virus infection and controlled intervention trials have demonstrated beyond doubt the role of influenza virus infection in the pathogenesis of acute otitis media. Influenza virus infections not only disrupt eustachian tube function, but also impair recovery from infection and facilitate attachment of bacterial pathogens to respiratory epithelial cells. Immunization of young children with either inactivated or live, attenuated influenza vaccine will significantly reduce the incidence of acute otitis media. Early treatment of influenza with antiviral medication will reduce eustachian tube dysfunction that results from influenza virus infection. Influenza produces high morbidity in children that could be averted by universal immunization with attenuated nasal spray vaccine.

  9. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

    PubMed Central

    Messacar, Kevin; Pastula, Daniel M.; Robinson, Christine C.; Leshem, Eyal; Sejvar, James J.; Nix, W. Allan; Oberste, M. Steven; Feikin, Daniel R.; Dominguez, Samuel R.

    2016-01-01

    During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  10. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

    PubMed

    Aliabadi, Negar; Messacar, Kevin; Pastula, Daniel M; Robinson, Christine C; Leshem, Eyal; Sejvar, James J; Nix, W Allan; Oberste, M Steven; Feikin, Daniel R; Dominguez, Samuel R

    2016-08-01

    During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  11. Acute middle East respiratory syndrome coronavirus infection in livestock Dromedaries, Dubai, 2014.

    PubMed

    Wernery, Ulrich; Corman, Victor M; Wong, Emily Y M; Tsang, Alan K L; Muth, Doreen; Lau, Susanna K P; Khazanehdari, Kamal; Zirkel, Florian; Ali, Mansoor; Nagy, Peter; Juhasz, Jutka; Wernery, Renate; Joseph, Sunitha; Syriac, Ginu; Elizabeth, Shyna K; Patteril, Nissy Annie Georgy; Woo, Patrick C Y; Drosten, Christian

    2015-06-01

    Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother-calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.

  12. Should teeth be extracted immediately in the presence of acute infection?

    PubMed

    Johri, Ankur; Piecuch, Joseph F

    2011-11-01

    Immediate extraction of teeth in the setting of an acute infection has shown to be beneficial for many reasons. It results in faster resolution of the infection, decreased pain, and earlier return of function and oral intake. The risk of seeding the infection into deeper spaces by performing immediate extraction is low.

  13. Three atypical lethal cases associated with acute Zika virus infection in Suriname.

    PubMed

    Zonneveld, Rens; Roosblad, Jimmy; Staveren, Jan Willem van; Wilschut, Jan C; Vreden, Stephen G S; Codrington, John

    2016-01-01

    Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks.

  14. Three atypical lethal cases associated with acute Zika virus infection in Suriname.

    PubMed

    Zonneveld, Rens; Roosblad, Jimmy; Staveren, Jan Willem van; Wilschut, Jan C; Vreden, Stephen G S; Codrington, John

    2016-01-01

    Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks. PMID:27630820

  15. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication.

    PubMed

    Murphy, Christopher M; Xu, Yanping; Li, Feng; Nio, Kouki; Reszka-Blanco, Natalia; Li, Xiaodong; Wu, Yaxu; Yu, Yanbao; Xiong, Yue; Su, Lishan

    2016-09-13

    The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome. Using a minicircle HBV (mcHBV) reporter system with HBx-dependent activity, we demonstrate that SMC5/6 knockdown, or inhibition with a dominant-negative SMC6, enhance HBx null mcHBV-Gluc gene expression. Furthermore, SMC5/6 knockdown rescued HBx-deficient HBV replication in human hepatocytes. These results indicate that a primary function of HBx is to degrade SMC5/6, which restricts HBV replication by inhibiting HBV gene expression. PMID:27626656

  16. Hepatitis B virus (HBV) X protein-mediated regulation of hepatocyte metabolic pathways affects viral replication.

    PubMed

    Bagga, Sumedha; Rawat, Siddhartha; Ajenjo, Marcia; Bouchard, Michael J

    2016-11-01

    Chronic HBV infection is a risk factor for hepatocellular carcinoma (HCC). The HBV HBx protein stimulates HBV replication and likely influences the development of HBV-associated HCC. Whether HBx affects regulators of metabolism in normal hepatocytes has not been addressed. We used an ex vivo, cultured primary rat hepatocyte system to assess the interplay between HBV replication and mechanistic target of rapamycin complex 1 (mTORC1) signaling. HBx activated mTORC1 signaling; however, inhibition of mTORC1 enhanced HBV replication. HBx also decreased ATP levels and activated the energy-sensing factor AMP-activated protein kinase (AMPK). Inhibition of AMPK decreased HBV replication. Inhibition of AMPK activates mTORC1, and we showed that activated mTORC1 is one factor that reduces HBV replication when AMPK is inhibited. HBx activation of both AMPK and mTORC1 suggests that these activities could provide a balancing mechanism to facilitate persistent HBV replication. HBx activation of mTORC1 and AMPK could also influence HCC development.

  17. ZEB2 inhibits HBV transcription and replication by targeting its core promoter.

    PubMed

    He, Qiao; Li, Wanyu; Ren, Jihua; Huang, Yecai; Huang, Ying; Hu, Qin; Chen, Juan; Chen, Weixian

    2016-03-29

    Hepatitis B virus (HBV) infection is a major cause of liver diseases, especially liver cirrhosis and hepatocellular carcinoma. However, the interaction between host and HBV has not been fully elucidated. ZEB2 is a Smad-interacting, multi-zinc finger protein that acts as a transcription factor or repressor for several signaling pathways. This study found that the expression of ZEB2 was decreased in HBV-expressing cells. Overexpression of ZEB2 inhibited HBV DNA replicative intermediates, 3.5kb mRNA, core protein level, and the secretion of HBsAg and HBeAg. In contrast, ZEB2 knockdown promoted HBV replication. Furthermore, ZEB2 could bind to HBV core promoter and inhibit its promoter activity. Mutation at the ZEB2 binding site in HBV core promoter eradicated ZEB2-mediated inhibition of HBV replication. This study identifies ZEB2 as a novel host restriction factor that inhibits HBV replication in hepatocytes. These data may shed light on development of new antiviral strategies.

  18. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  19. Occult hepatitis B virus infection

    PubMed Central

    Kwak, Min-Sun; Kim, Yoon Jun

    2014-01-01

    Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI. PMID:25544873

  20. Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection

    PubMed Central

    Reynolds, Tracy D.; Buonocore, Linda; Rose, Nina F.; Rose, John K.

    2015-01-01

    -term control of infection. Recently, a virus-based vector system that combines the nonstructural proteins of Semliki Forest virus with the VSV glycoprotein has been described. In this study, we used this system to construct a novel HBV vaccine and demonstrated that the vaccine is capable of inducing virus-specific immune responses in mouse models of acute and chronic HBV replication. These findings highlight the potential of this new vaccine system and support the idea that highly immunogenic vaccines, such as viral vectors, may be useful in the treatment of chronic hepatitis B. PMID:26246574

  1. Acute respiratory infections in Pakistan: have we made any progress?

    PubMed

    Khan, Tauseef Ahmad; Madni, Syed Ali; Zaidi, Anita K M

    2004-07-01

    Acute respiratory infections (ARI) are the leading cause of death in young children in Pakistan, responsible for 20-30% of all child deaths under age 5 years. This paper summarizes the research and technical development efforts over the last 15 years which have contributed to improving the effectiveness of the case management strategy to reduce mortality from pneumonia in children in Pakistan. Community intervention is viable, effective and practical. Rising antimicrobial resistance among commonly used and low-cost oral agents is of significant concern. Appropriate monitoring and evaluation of the impact of the ARI control programme is lacking. Lack of funding for programmatic activities, lack of coordination with other child survival programs, inadequate training for community health workers and general practitioners in the private sector, lack of public awareness about seeking timely and appropriate care, and insufficient planning and support for ARI programmatic activities at provincial and district levels are major hindrances in decreasing the burden of ARI in the country. The recent introduction of the community-based Lady Health Worker (LHW) Programme and WHO and UNICEF-sponsored integrated management of childhood illness initiative present ideal opportunities for re-emphasizing early case detection and appropriate case management of ARI. Ultimately, focusing on preventive strategies such as improving nutrition, reducing indoor pollution, improving mass vaccination, as well as introduction of new vaccines effective against important respiratory pathogens will likely have the most impact on reducing severe ARI and deaths from severe disease. PMID:15279753

  2. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice.

    PubMed

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-01-01

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the "PICKY" software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients.

  3. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation.

    PubMed

    Tropberger, Philipp; Mercier, Alexandre; Robinson, Margaret; Zhong, Weidong; Ganem, Don E; Holdorf, Meghan

    2015-10-20

    Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection.

  4. Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

    PubMed

    Su, Feifei; Dai, Jianyi; Yang, Shoufeng; Jiang, Xiangao; Cui, Xiaoya; Ning, Hongye; Li, Junhua; Huang, Mohe

    2015-09-01

    The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B.

  5. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  6. Acute Necrotizing Pancreatitis Associated with Mycoplasma pneumoniae Infection in a Child.

    PubMed

    Yang, Aram; Kang, Ben; Choi, So Yoon; Cho, Joong Bum; Kim, Yae-Jean; Jeon, Tae Yeon; Choe, Yon Ho

    2015-09-01

    Mycoplasma pneumoniae is responsible for approximately 20% to 30% of community-acquired pneumonia, and is well known for its diverse extrapulmonary manifestations. However, acute necrotizing pancreatits is an extremely rare extrapulmonary manifestation of M. pneumoniae infection. A 6-year-old girl was admitted due to abdominal pain, vomiting, fever, and confused mentality. Acute necrotizing pancreatitis was diagnosed according to symptoms, laboratory test results, and abdominal computed tomography scans. M. pneumoniae infection was diagnosed by a 4-fold increase in antibodies to M. pneumoniae between acute and convalescent sera by particle agglutination antibody assay. No other etiologic factors or pathogens were detected. Despite the occurrence of a large infected pseudocyst during the course, the patient was able to discharge without morbidity by early aggressive supportive care. This is the first case in Korea of a child with acute necrotizing pancreatitis associated with M. pneumoniae infection. PMID:26473143

  7. Enhancing the detection and management of acute hepatitis C virus infection.

    PubMed

    Martinello, Marianne; Matthews, Gail V

    2015-10-01

    Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID. PMID:26254495

  8. Acute respiratory infections: the forgotten pandemic. Communiqué from the International Conference on Acute Respiratory Infections, held in Canberra, Australia, 7-10 July 1997.

    PubMed

    1998-01-01

    Acute respiratory infections kill 4 million children every year in developing countries, and most of these deaths are caused by pneumonia. This huge loss of life goes virtually unnoticed, despite the fact that we have two very effective ways of preventing many of the deaths from pneumonia: Haemophilus influenzae type b vaccine, and standardised antibiotic treatment regimens. Although H. influenzae type b vaccine has virtually eliminated diseases caused by this organism in children in developed countries, failure to appreciate the importance of this organism and the high cost of the vaccine has meant that it has not been used in developing countries; urgent steps need to be taken to ensure that children in developing countries receive H. influenzae vaccine. Streptococcus pneumoniae is a major cause of fatal pneumonia in developing countries. Controlled trials are needed to define the role of unconjugated 23-valent S. pneumoniae vaccine, and the new conjugate vaccine must be made available to children in developing countries soon after it is licensed. The World Health Organization has developed simple and effective guidelines for the treatment of pneumonia which have been incorporated into its Integrated Management of Childhood Illness strategy, and this programme should be strongly supported. In developed countries, acute respiratory infections are the leading cause of morbidity. The cost of these infections is enormous, because of lost earnings and the cost of treatment. There is an urgent need for systematic evaluation of existing knowledge about acute respiratory infections in developed countries, so that this knowledge can be applied to prevention and treatment. Approximately 75% of antibiotics are prescribed for acute respiratory infections, and many of these prescriptions are unnecessary. Unnecessary use of antibiotics is very expensive, and it has contributed to the rapid increase in resistance which has already made some bacteria resistant to all antibiotics

  9. Disseminated fungal infection complicated with pulmonary haemorrhage in a case of acute myeloid leukaemia

    PubMed Central

    Thulkar, S; Sharma, S; Das, P; Kumar, L

    2000-01-01

    Pulmonary haemorrhage is a common necropsy finding in acute leukaemia, however, it is rarely diagnosed during life. A man with acute myeloid leukaemia is reported who presented with disseminated fungal infection, anaemia, thrombocytopenia, and subconjuctival and petechial haemorrhages. During the course of the patient's illness, the chest infection was complicated with bilateral pulmonary haemorrhage. The diagnosis of pulmonary haemorrhage was based on characteristic clinical and radiological findings. The patient improved on treatment.


Keywords: leukaemia; pulmonary infiltrate; haemorrhage PMID:11060145

  10. Lipschütz acute vulval ulcers associated with primary cytomegalovirus infection.

    PubMed

    Martín, José M; Godoy, Rosa; Calduch, Luis; Villalon, Guillermo; Jordá, Esperanza

    2008-01-01

    A previously healthy 16-year-old girl presented with painful acute genital ulcers that appeared in the context of a primary cytomegalovirus infection. Complementary examinations ruled out both venereal disease and other usual causes of genital ulcerations, and the lesions resolved in < 2 weeks with no sequelae or later recurrences. Cytomegalovirus disease should be considered in the screening of acute vulval ulcers.

  11. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

    PubMed Central

    2013-01-01

    Background Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Methods Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient’s condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Results Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. Discussion In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Conclusion Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID:24180319

  12. Therapeutic vaccines in HBV: lessons from HCV.

    PubMed

    Barnes, Eleanor

    2015-02-01

    Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control.

  13. Therapeutic vaccines in HBV: lessons from HCV.

    PubMed

    Barnes, Eleanor

    2015-02-01

    Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control. PMID:25573348

  14. IL-35 inhibits HBV antigen-specific IFN-γ-producing CTLs in vitro.

    PubMed

    Li, Xuefen; Tian, Li; Dong, Yuejiao; Zhu, Qiaoyun; Wang, Yiyin; Han, Wenzheng; Liu, Xia; Ni, Qin; Chen, Yu; Li, Lanjuan

    2015-09-01

    Interleukin (IL)-35 is an inhibitory cytokine consisting of IL-12A and Epstein-Barr virus-induced gene 3 (Ebi3) and is required by regulatory T-cells (Tregs) for maximal activity. During chronic hepatitis B virus (HBV) infection, Tregs have immunosuppressive effects on HBV-specific T helper (Th) cells, yet little is known about the complex regulation of Tregs and their contribution to the inadequate immune system response to the virus. In the present study, we investigated whether IL-35 is involved in HBV-related cellular immune responses. Cluster of differentiation (CD)4(+) T-cells from peripheral blood were derived from healthy volunteers, resolved HBV individuals and chronic active hepatitis B patients and stimulated with CD3/28-conjugated beads. We analysed mRNA and protein levels of IL-35 and assessed the inhibitory effect of IL-35 on HBV core antigen-specific cytotoxic T lymphocytes (CTLs), dendritic cells (DCs) and effector T-cells (Teffs). Correlation analyses between liver inflammation and HBV DNA load were conducted. Results show that chronic HBV patients harbour significantly higher levels of Ebi3 mRNA and protein in CD4(+) T-cells compared with healthy volunteers and resolved HBV individuals. IL-35 suppressed the proliferation of HBV antigen-specific CTLs and interferon (IFN)-γ production in vitro. Ex vivo, IL-35 decreased the proliferation of CD4(+)CD45RA(+) naïve T-cells, especially in CD4(+)CD25(-)CD45RA(+) naïve Teffs. IL-35 inhibited the expansion of CD11c(+) DCs. Our data indicate that IL-35 is highly expressed in chronic HBV CD4(+) T-cells and plays an important role in the inhibition of the cellular immune response in chronic HBV.

  15. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly

    SciTech Connect

    Kim, Yoon Sik Seo, Hyun Wook Jung, Guhung

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H{sub 2}O{sub 2} and GSH modulate HBV capsid assembly. • H{sub 2}O{sub 2} facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H{sub 2}O{sub 2} and GSH induce conformation change of Hsp90.

  16. Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas

    PubMed Central

    Amaddeo, Giuliana; Cao, Qian; Ladeiro, Yannick; Imbeaud, Sandrine; Nault, Jean-Charles; Jaoui, Daphne; Gaston Mathe, Yann; Laurent, Christophe; Laurent, Alexis; Bioulac-Sage, Paulette; Calderaro, Julien; Zucman-Rossi, Jessica

    2015-01-01

    Background and aim Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated with infection compared with non-HBV-related HCC to understand interactions between viral and hepatocyte genomic alterations and their relationships with clinical features. Methods Frozen HBV (n=86) or non-HBV-related (n=90) HCC were collected in two French surgical departments. Viral characterisation was performed by sequencing HBS and HBX genes and quantifying HBV DNA and cccDNA. Nine genes were screened for somatic mutations and expression profiling of 37 genes involved in hepatocarcinogenesis was studied. Results HBX revealed frequent non-sense, frameshift and deletions in tumours, suggesting an HBX inactivation selected in HCC. The number of viral copies was frequently lower in tumour than in non-tumour tissues (p=0.0005) and patients with low HBV copies in the non-tumour liver tissues presented additional risk factor (HCV, alcohol or non-alcoholic steato-hepatitis, p=0.006). P53 was the most frequently altered pathway in HBV-related HCC (47%, p=0.001). Furthermore, TP53 mutations were associated with shorter survival only in HBV-related HCC (p=0.02) whereas R249S mutations were identified exclusively in migrants. Compared with other aetiologies, HBV-HCC were more frequently classified in tumours subgroups with upregulation of genes involved in cell-cycle regulation and a progenitor phenotype. Finally, in HBV-related HCC, transcriptomic profiles were associated with specific gene mutations (HBX, TP53, IRF2, AXIN1 and CTNNB1). Conclusions Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients. PMID:25021421

  17. A qualitative study of patients' perceptions of acute infective conjunctivitis.

    PubMed Central

    Everitt, Hazel; Kumar, Satinder; Little, Paul

    2003-01-01

    BACKGROUND: Acute infective conjunctivitis is a self-limiting condition that commonly presents to primary care. Patients' understanding of conjunctivitis, their reasons for attendance, and their responses to different management strategies, are unknown. AIM: To explore patients' understanding of conjunctivitis and its management. DESIGN OF STUDY: Qualitative study using semi-structured one-to-one interviews. SETTING: Three general practices in Hampshire and Wiltshire. METHOD: Twenty-five patients presenting with conjunctivitis at their general practices were interviewed. Main outcome measures were patients' perceptions of conjunctivities, their experience and knowledge of the disease, beliefs regarding treatment, and their responses to different management strategies and a patient information leaflet. RESULTS: Patients regarded conjunctivitis as a minor illness, although some considered it might become more serious if not treated. Nearly all were confident at recognising conjunctivitis. They stated a preference for not taking medication, but believed that conjunctivitis would not clear up without treatment. However, they were open to alternative management approaches; for example, the delayed prescription approach, because they trusted their general practitioners' (GPs') judgement. Once they were aware of the self-limiting nature of conjunctivitis, patients felt they would prefer to wait a few days to see if the condition improved before seeking medical advice, even if this resulted in a few more days of symptoms. CONCLUSION: Patients who attend their general practices with conjunctivitis present for treatment because they are not aware of its self-limiting nature. Providing patients with this information may enable patients, enhance self-management, and reduce the use of topical antibiotics and the demand for urgent general practice appointments. PMID:12564275

  18. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    PubMed

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. PMID:27434148

  19. [Occult hepatitis B virus infection and hepatocellular carcinoma].

    PubMed

    Lee, Jong Joon; Kwon, Oh Sang

    2013-09-01

    Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.

  20. Cryptosporidiosis in rhesus macaques challenged during acute and chronic phases of SIV infection.

    PubMed

    Singh, Inderpal; Carville, Angela; Tzipori, Saul

    2011-09-01

    The intestinal immune dysfunction due to loss of mucosal and peripheral CD4(+) T cells in individuals with HIV/AIDS is presumably responsible for the establishment of persistent cryptosporidiosis. Simian immunodeficiency virus (SIV)-infected macaques were used to investigate the phase/timing in SIV infection, which permits a self-limiting Cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. Two groups of SIV-infected macaques were challenged with C. parvum; one was challenged during the acute SIV infection phase (2 weeks post-SIV infection) and the second was challenged during the chronic SIV phase (CD4 counts 200-500 cells/μl of blood). Samples (fecal, blood, biopsy, and necropsy) were collected at different time points after infection to correlate the progression of disease with the immune status of the animals. All seven SIV-infected macaques challenged during the acute phase of SIV infection became persistently infected and excreted oocysts for 1-4 months. However, four of the six in the chronic SIV phase became infected with cryptosporidiosis, of which one survived 2 weeks and one became naturally infected. Sequential analysis of CD4(+) in blood and intestines of coinfected macaques exhibited pronounced losses of CD4 T cells during the first 2 weeks after SIV infection, followed by transient rebound of CD4 T cells in the gut after C. parvum infection, and then a gradual loss over subsequent months. Persistent cryptosporidiosis was more consistently induced during the acute SIV phase indicating that profound viral damage to gut lymphoid tissue during the acute phase was more conducive, compared with the chronic phase, to establishing persistent cryptosporidiosis than low circulating CD4 T cells.

  1. 78 FR 63220 - Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... drugs to treat acute bacterial skin and skin structure infections (ABSSSI). This guidance finalizes...

  2. Evolutionary dynamics of HBV-D1 genotype epidemic in Turkey.

    PubMed

    Ciccozzi, Massimo; Ciccaglione, Anna Rita; Lo Presti, Alessandra; Equestre, Michele; Cella, Eleonora; Ebranati, Erika; Gabanelli, Elena; Villano, Umbertina; Bruni, Roberto; Yalcinkaya, Tulay; Tanzi, Elisabetta; Zehender, Gianguglielmo

    2014-01-01

    Hepatitis B virus (HBV), is the leading cause of liver diseases infecting an estimated 240 million persons worldwide. The HBV prevalence rates are variables between different countries, with an high level of endemicity in the south-eastern part of Europe. Seven main HBV-D subgenotypes have been described until now (D1-D7). Turkey, seems to have played an important role in the penetration of HBV-D1 in the Mediterranean area. The importance of Turkey in the European epidemiology of HBV is also suggested by the observation that the highest spread of HBV infection in the Continent are reported in Turkey with Romania, Bulgaria, Greece, Albania and some southern regions of Italy. In this paper the molecular epidemiology and the epidemiological history of HBV-D in Turkey was studied, by characterizing 34 new Turkish isolates and performing a phylogeographic reconstruction. By using a phylodynamic and phylogeographic Bayesian approach, the analysis suggested that HBV-D1 originated in Turkey about in the early 1940s. The large prevalence of D1 in comparison to the other subgenotypes in Turkey confirms the importance of this Country as epidemiological reservoir of HBV-D1 dispersion. The phylogeny suggests that after each initial introduction of the virus in a specific population, separate transmission clusters have been evolving along independent phylogenetic lineages. Better characterization and continuous monitoring of such groups are going to be crucial to understand in detail the epidemiology of HBV-D1 subgenotype in Turkey and to assess the efficacy of prevention, vaccination and therapy in controlling the epidemic.

  3. Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation.

    PubMed

    Serap, Aksoylar; Funda, Ozgenc; Bengu, Kadioglu; Mehmet, Kantar; Nazan, Cetingul; Rasit, Yagci; Savas, Kansoy

    2011-08-01

      We present an 18-yr-old adolescent with acute lymphocytic leukemia, who underwent peripheral blood SCT with serologically and histologically documented chronic hepatitis B infection. Prior and during the transplant process, lamivudine was administered orally and he underwent SCT with a twofold decrease in viral load at the time of transplant from his HLA full matched, HBV natural immune (anti-HBs and anti-HBc positive) donor. Successful engraftment was achieved and three months after SCT, HBV seroconversion was documented accompanied with an ALT flare. Chronic graft-versus-host disease coincided after the transplantation, and he has been on immunosuppressive treatment for 25 months with sustained HBV seroconversion. We assume that adoptive immunity transfer combined with antiviral treatment might also constitute sustained seroconversion in chronic HBV, besides the reported risk of reactivation. PMID:20102530

  4. Chikungunya virus infection amongst the acute encephalitis syndrome cases in West Bengal, India.

    PubMed

    Taraphdar, D; Roy, B K; Chatterjee, S

    2015-02-01

    Chikungunya virus (CHIKV) infection from the acute encephalitis syndrome cases is an uncommon form and has been observed in the year 2010-11 from West Bengal, India. The case-1 and case-2 had the acute encephalitis syndrome; case-3 was of acute disseminated encephalomyelitis whereas the case-4 had the symptoms of meningo-encephalopathy with bulbar involvement. We are reporting four cases with neurological complications involving central nervous system (CNS) due to CHIKV infection from this state for the first time. The virus has spread almost every districts of this state rapidly. At this stage, these cases are public health threat.

  5. Enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis in 7 dogs from Saskatchewan.

    PubMed

    Kjaergaard, Astrid B; Carr, Anthony P; Gaunt, M Casey

    2016-09-01

    Seven dogs diagnosed with enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis are described. Disease severity ranged from mild in adults to fatal disease in young dogs. Enteropathogenic E. coli infection should be considered as a possible differential diagnosis in dogs with diarrhea. PMID:27587889

  6. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  7. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

    PubMed Central

    O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  8. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

    PubMed

    Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  9. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    PubMed

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  10. Hepatitis B Virus (HBV) Virion and Covalently Closed Circular DNA Formation in Primary Tupaia Hepatocytes and Human Hepatoma Cell Lines upon HBV Genome Transduction with Replication-Defective Adenovirus Vectors

    PubMed Central

    Ren, Shaotang; Nassal, Michael

    2001-01-01

    Hepatitis B virus (HBV), the causative agent of B-type hepatitis in humans, is a hepatotropic DNA-containing virus that replicates via reverse transcription. Because of its narrow host range, there is as yet no practical small-animal system for HBV infection. The hosts of the few related animal viruses, including woodchuck hepatitis B virus and duck hepatitis B virus, are either difficult to keep or only distantly related to humans. Some evidence suggests that tree shrews (tupaias) may be susceptible to infection with human HBV, albeit with low efficiency. Infection efficiency depends on interactions of the virus with factors on the surface and inside the host cell. To bypass restrictions during the initial entry phase, we used recombinant replication-defective adenovirus vectors, either with or without a green fluorescent protein marker gene, to deliver complete HBV genomes into primary tupaia hepatocytes. Here we show that these cells, like the human hepatoma cell lines HepG2 and Huh7, are efficiently transduced by the vectors and produce all HBV gene products required to generate the secretory antigens HBsAg and HBeAg, replication-competent nucleocapsids, and enveloped virions. We further demonstrate that covalently closed circular HBV DNA is formed. Therefore, primary tupaia hepatocytes support all steps of HBV replication following deposition of the genome in the nucleus, including the intracellular amplification cycle. These data provide a rational basis for in vivo experiments aimed at developing tupaias into a useful experimental animal system for HBV infection. PMID:11152483

  11. Acute hepatitis C virus infection related to capillary blood glucose meter

    PubMed Central

    Inayat, Faisal; Rai, Aitzaz BinSultan

    2016-01-01

    Hepatitis C virus (HCV) infects an estimated 130-150 million people worldwide, becoming the major cause of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver transplantation. There are various preventable modes of transmission of HCV infection, including needlestick and sharps injuries. However, HCV infection secondary to needlestick injury by a capillary blood glucose meter (CBGM) lancet has not been previously well reported. We describe an unusual case of a 25-year-old male medical student, acquiring acute HCV infection with a lancing device of CBGM. The source patient was a 54-year-old diabetic male with positive anti-HCV test results. In our patient, after 3 months of initial exposure, a standard set of investigations confirmed the diagnosis of acute HCV infection with the same genotype (3a) as the source. The CBGM, as in our case, may have a role in the transmission of HCV infection warranting radical advancements in diabetes screening and monitoring technology. PMID:26739982

  12. Impact of early cART in the gut during acute HIV infection

    PubMed Central

    Deleage, Claire; Schuetz, Alexandra; Alvord, W. Gregory; Johnston, Leslie; Hao, Xing-Pei; Morcock, David R.; Rerknimitr, Rungsun; Fletcher, James L.K.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Dewar, Robin; McCune, Joseph M.; Robb, Merlin; Kim, Jerome H.; Schacker, Timothy W.; Hunt, Peter; Lifson, Jeffrey D.; Ananworanich, Jintanat

    2016-01-01

    Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (Mx1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART. PMID:27446990

  13. Impact of early cART in the gut during acute HIV infection

    PubMed Central

    Deleage, Claire; Schuetz, Alexandra; Alvord, W. Gregory; Johnston, Leslie; Hao, Xing-Pei; Morcock, David R.; Rerknimitr, Rungsun; Fletcher, James L.K.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Dewar, Robin; McCune, Joseph M.; Sereti, Irini; Robb, Merlin; Kim, Jerome H.; Schacker, Timothy W.; Hunt, Peter; Lifson, Jeffrey D.; Ananworanich, Jintanat; Estes, Jacob D.

    2016-01-01

    Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART. PMID:27446990

  14. Routine Laboratory Screening for Acute and Recent HIV Infection in Lima, Peru

    PubMed Central

    Clark, Jesse L.; Segura, Eddy R.; Montano, Silvia M.; Leon, Segundo R.; Kochel, Tadeusz; Salvatierra, Hector J.; Alcantara, Jorge; Cáceres, Carlos F.; Coates, Thomas J.; Klausner, Jeffrey D.

    2011-01-01

    Background Prior to implementing screening programs for acute HIV infection in developing countries, key issues including cost, feasibility, and public health impact must be determined. We compared fourth-generation enzyme immunoassay (EIA) with pooled HIV-1 RNA assays for the detection of acute and early HIV infection in counseling and testing populations in Lima, Peru. Methods Adults presenting for HIV testing at designated clinics in Lima-Callao, Peru were offered additional screening for acute HIV infection. All serum samples were tested with fourth-generation Ag/Ab EIA and confirmed by line immunoassay (LIA). Negative specimens were combined into 50-sample pools for HIV-1 RNA screening by PCR analysis in standard pooling algorithms. RNA-positive samples were re-tested with a third-generation EIA to evaluate the relative sensitivity of standard testing procedures. Results Between 2007 and 2008 we recruited 1,191 participants. The prevalence of HIV infection was 3.2% (38/1191; 2.2-4.2%) overall and 10.6% (25/237; CI=6.6-14.5%) among men who reported sex with men (MSM). The prevalence of acute or recent HIV infection was 0.2% (CI=0-0.4%) overall and 0.8% (CI=0-2.0%) among MSM. Compared with third generation EIA testing, both fourth generation EIA and RNA PCR increased the rate of HIV case identification by 5.6% overall and by 8.0% within the subpopulation of MSM. Conclusions Screening for acute HIV infection within Peru's resource-limited public health system was acceptable and detected a high prevalence of acute and recent HIV infection among MSM. Additional efforts are needed to screen for and prevent transmission of HIV among MSM in Peru during the acute seroconversion stage. PMID:21113069

  15. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    PubMed

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  16. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  17. Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

    PubMed Central

    Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (dacute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0

  18. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection.

    PubMed

    Pettigrew, Melinda M; Gent, Janneane F; Pyles, Richard B; Miller, Aaron L; Nokso-Koivisto, Johanna; Chonmaitree, Tasnee

    2011-11-01

    Acute otitis media (AOM) is a common complication of upper respiratory tract infection whose pathogenesis involves both viruses and bacteria. We examined risks of acute otitis media associated with specific combinations of respiratory viruses and acute otitis media bacterial pathogens. Data were from a prospective study of children ages 6 to 36 months and included viral and bacterial culture and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and human metapneumovirus. Repeated-measure logistic regression was used to assess the relationship between specific viruses, bacteria, and the risk of acute otitis media complicating upper respiratory tract infection. In unadjusted analyses of data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were significantly associated with AOM (P < 0.05 by χ(2) test). Children with high respiratory syncytial virus loads (≥3.16 × 10(7) copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with high RSV viral load with Streptococcus pneumoniae (odds ratio [OR], 4.40; 95% confidence interval [CI], 1.90 and 10.19) and Haemophilus influenzae (OR, 2.04; 95% CI, 1.38 and 3.02). The risk was higher for the presence of bocavirus and H. influenzae together (OR, 3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.

  19. Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

    PubMed Central

    McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

    2011-01-01

    Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

  20. Regulatory T cells are decreased in acute RHDV lethal infection of adult rabbits.

    PubMed

    Teixeira, Luzia; Marques, Raquel M; Aguas, Artur P; Ferreira, Paula G

    2012-08-15

    Rabbit hemorrhagic disease virus (RHDV) is the etiologic agent of rabbit hemorrhagic disease (RHD), an acute lethal infection that kills 90% of adult rabbits due to severe acute liver inflammation. Interestingly, young rabbits are naturally resistant to RHDV infection. Here, we have compared naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) between young and adult rabbits after infection by RHDV. The number and frequency of Tregs was decreased in the spleen of adult rabbits 24h after the RHDV infection; this was in contrast with the unchanged number and frequency of splenic Tregs found in young rabbits after the same infection. Also, serum levels of IL-10 and TGF-β were enhanced in the infected adult rabbits whereas no alteration was observed in infected young rabbits. However, this increase is accompanied by a burst of pro-inflammatory cytokines, but seems not able to prevent the death of the animals with severe acute liver inflammation in few days after infection. Since Tregs downregulate inflammation, we conclude that their decrease may contribute to the natural susceptibility of adult rabbits to RHDV infection.

  1. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  2. CRISPR/Cas9-based tools for targeted genome editing and replication control of HBV.

    PubMed

    Peng, Cheng; Lu, Mengji; Yang, Dongliang

    2015-10-01

    Hepatitis B virus (HBV) infection remains a major global health problem because current therapies rarely eliminate HBV infections to achieve a complete cure. A different treatment paradigm to effectively clear HBV infection and eradicate latent viral reservoirs is urgently required. In recent years, the development of a new RNA-guided gene-editing tool, the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) system, has greatly facilitated site-specific mutagenesis and represents a very promising potential therapeutic tool for diseases, including for eradication of invasive pathogens such as HBV. Here, we review recent advances in the use of CRISPR/Cas9, which is designed to target HBV specific DNA sequences to inhibit HBV replication and to induce viral genome mutation, in cell lines or animal models. Advantages, limitations and possible solutions, and proposed directions for future research are discussed to highlight the opportunities and challenges of CRISPR/Cas9 as a new, potentially curative therapy for chronic hepatitis B infection.

  3. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  4. Severe Plasmodium falciparum infection mimicking acute myocardial infarction.

    PubMed

    Sulaiman, Helmi; Ismail, Muhammad Dzafir; Jalalonmuhali, Maisarah; Atiya, Nadia; Ponnampalavanar, Sasheela

    2014-08-30

    This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.

  5. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    PubMed Central

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection. PMID:27621819

  6. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    PubMed Central

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection.

  7. Respiratory syncytial virus, adenoviruses, and mixed acute lower respiratory infections in children in a developing country.

    PubMed

    Rodríguez-Martínez, Carlos E; Rodríguez, Diego Andrés; Nino, Gustavo

    2015-05-01

    There is growing evidence suggesting greater severity and worse outcomes in children with mixed as compared to single respiratory virus infections. However, studies that assess the risk factors that may predispose a child to a mixture of respiratory syncytial virus (RSV) and adenoviral infections, are scarce. In a retrospective cohort study, the study investigated the epidemiology of RSV and adenovirus infections and predictors of mixed RSV-adenoviral infections in young children hospitalized with acute lower respiratory infection in Bogota, Colombia, South America, over a 2-year period 2009-2011. Of a total of 5,539 children admitted with a diagnosis of acute lower respiratory infection, 2,267 (40.9%) who were positive for RSV and/or adenovirus were selected. Out the total number of cases, 1,416 (62.5%) infections occurred during the 3-month period from March to May, the first rainy season of Bogota, Colombia. After controlling for gender, month when the nasopharyngeal sample was taken, and other pre-existing conditions, it was found that an age greater than 6 months (OR:1.74; CI 95%:1.05-2.89; P = 0.030) and malnutrition as a comorbidity (OR:9.92; CI 95%:1.01-100.9; P = 0.049) were independent predictors of mixed RSV-adenoviral infections in the sample of patients. In conclusion, RSV and adenovirus are significant causes of acute lower respiratory infection in infants and young children in Bogota, Colombia, especially during the first rainy season. The identified predictors of mixed RSV-adenoviral infections should be taken into account when planning intervention, in order to reduce the burden of acute lower respiratory infection in young children living in the country.

  8. The acute phase response in parasite infection. Nippostrongylus brasiliensis in the mouse.

    PubMed Central

    Lamontagne, L R; Gauldie, J; Befus, A D; McAdam, K P; Baltz, M L; Pepys, M B

    1984-01-01

    Systemic inflammatory reactions are a prominent feature of many parasitic infections and the cellular and humoral components of the acute phase reaction may have an impact on the host-parasite relationship. We examined serum changes of four acute phase reactants: alpha 1-proteinase inhibition (alpha 1Pi); complement C3; serum amyloid A protein (SAA); and serum amyloid P component (SAP), in mice undergoing a primary infection with Nippostrongylus brasiliensis. SAA and SAP showed changes within the first 2 days of infection indicating the presence of an acute phase response associated with inflammation in the lung. Alpha 1Pi and C3 serum levels were not altered. However, all four acute phase reactants were synthesized in greater amounts by primary cultures of hepatocytes taken from infected animals at this time. Subsequently, as parasite-mediated inflammatory changes occur in the gut, both serum and hepatocyte cultures demonstrate an acute inflammatory response in all four reactants. It is proposed that the early reaction between parasites and macrophage/monocyte lead to the release of a mediator of inflammation which initiates the hepatocyte response. In this infection, at least one of the APR is shown to localize to the site of inflammation influencing the host-parasite relationship. Images Figure 2 Figure 3 PMID:6204934

  9. Hospital Epidemiology and Infection Control in Acute-Care Settings

    PubMed Central

    Sydnor, Emily R. M.; Perl, Trish M.

    2011-01-01

    Summary: Health care-associated infections (HAIs) have become more common as medical care has grown more complex and patients have become more complicated. HAIs are associated with significant morbidity, mortality, and cost. Growing rates of HAIs alongside evidence suggesting that active surveillance and infection control practices can prevent HAIs led to the development of hospital epidemiology and infection control programs. The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs. In this review, we summarize the history of the development of hospital epidemiology and infection control, common HAIs and the pathogens causing them, and the structure and role of a hospital epidemiology and infection control program. PMID:21233510

  10. Update on occult hepatitis B virus infection

    PubMed Central

    Makvandi, Manoochehr

    2016-01-01

    The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.

  11. Prevalence of antibiotic use for pediatric acute upper respiratory tract infections in Korea.

    PubMed

    Shin, Sun Mi; Shin, Ju-Young; Kim, Mi Hee; Lee, Shin Haeng; Choi, Sohyun; Park, Byung-Joo

    2015-05-01

    This study was conducted to estimate the prevalence of antimicrobial prescribing for acute upper respiratory tract infections (URI) among pediatric outpatients and to identify the national patterns of its use from 2009 to 2011 in Korea. Using National Patients Sample database from 2009 to 2011, we estimated the frequency of antibiotics prescribing for URI in pediatric outpatients with diagnoses of acute nasopharyngitis (common cold), acute sinusitis, acute pharyngitis, acute tonsillitis, acute laryngitis/tracheitis, acute obstructive laryngitis/epiglottitis, and acute upper respiratory infections of multiple and unspecified sites. The proportions of each antibiotic class were calculated by year and absolute and relative differences were estimated. Also, we investigated daily amount of prescribed antibiotics per defined population according to the type of medical care institution, physician specialty, and geographic region. The overall antibiotic prescribing proportion was 58.7% and its annual proportion slightly decreased (55.4% in 2011 vs. 60.5% in 2009; adjusted odds ratio, 0.82; 95% confidence interval, 0.82-0.83). Variations by the type of medical care institution were observed. Tertiary hospitals (45.0%) were less likely to prescribe antibiotics than primary care clinics (59.4%), hospitals (59.0%), and general hospitals (61.2%); they showed different tendencies in choosing antibiotics. Variations by physician specialty and region were also observed. Prevalence of antimicrobial prescribing for pediatric URI is still considered higher than that of western countries and varies by the type of medical care institution, physician specialty, and geographic region.

  12. Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection

    PubMed Central

    2005-01-01

    Background Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection. Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm. Case report We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation. Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids. Conclusion This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis. PMID:16164756

  13. Epidemiology of acute infections among patients with chronic kidney disease.

    PubMed

    Dalrymple, Lorien S; Go, Alan S

    2008-09-01

    The objectives of this review were (1) to review recent literature on the rates, risk factors, and outcomes of infections in patients who had chronic kidney disease (CKD) and did or did not require renal replacement therapy; (2) to review literature on the efficacy and use of selected vaccines for patients with CKD; and (3) to outline a research framework for examining key issues regarding infections in patients with CKD. Infection-related hospitalizations contribute substantially to excess morbidity and mortality in patients with ESRD, and infection is the second leading cause of death in this population. Patients who have CKD and do not require renal replacement therapy seem to be at higher risk for infection compared with patients without CKD; however, data about patients who have CKD and do not require dialysis therapy are very limited. Numerous factors potentially predispose patients with CKD to infection: advanced age, presence of coexisting illnesses, vaccine hyporesponsiveness, immunosuppressive therapy, uremia, dialysis access, and the dialysis procedure. Targeted vaccination seems to have variable efficacy in the setting of CKD and is generally underused in this population. In conclusion, infection is a primary issue when caring for patients who receive maintenance dialysis. Very limited data exist about the rates, risk factors, and outcomes of infection in patients who have CKD and do not require dialysis. Future research is needed to delineate accurately the epidemiology of infections in these populations and to develop effective preventive strategies across the spectrum of CKD severity. PMID:18650409

  14. Neurological complications of acute and persistent Epstein-Barr virus infection in paediatric patients.

    PubMed

    Häusler, Martin; Ramaekers, Vincent Thomas; Doenges, Martin; Schweizer, Klaus; Ritter, Klaus; Schaade, Lars

    2002-10-01

    Neurological complications of Epstein-Barr virus (EBV) have been reported almost exclusively in the course of acute primary infections. The role of EBV in paediatric neurological disease was investigated prospectively over a 2-year period, searching for acute primary, chronic, and reactivated EBV infections. Active EBV infections were diagnosed in 10/48 patients, including two with acute primary EBV infections (cranial neuritis and cerebellitis), one with chronic active infection (T/NK cell lymphoma with cranial neuritis), and seven with reactivated infections. Among these seven patients, three showed "Alice in Wonderland" syndrome, one facial nerve palsy, one progressive macrocephaly, and two prolonged encephalitic illness. The prognosis was good except for the patient with lethal T/NK cell lymphoma and the two girls with encephalitic illness. Despite steroid treatment, these girls suffered prolonged cognitive impairment and epileptic seizures. Both developed left-sided hippocampal atrophy, and one of them hippocampal sclerosis. Like primary infections, reactivated EBV infections cause neurological complications in a considerable number of paediatric patients, lead to serious long-term complications, and may contribute to the pathogenesis of hippocampal lesions. PMID:12210416

  15. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

  16. Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes▿

    PubMed Central

    Sominskaya, Irina; Skrastina, Dace; Dislers, Andris; Vasiljev, Denis; Mihailova, Marija; Ose, Velta; Dreilina, Dzidra; Pumpens, Paul

    2010-01-01

    A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcΔ protein (N-terminal aa 1 to 144 of full-length HBc) were produced in Escherichia coli cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-γ) production profile. PMID:20410327

  17. Endovascular intervention for acute stroke due to infective endocarditis: case report.

    PubMed

    Dababneh, Haitham; Hedna, V Shushrutha; Ford, Jenna; Taimeh, Ziad; Peters, Keith; Mocco, J; Waters, Michael F

    2012-02-01

    The overall incidence of neurological complications due to infective endocarditis is as high as 40%, with embolic infarcts more common than hemorrhagic strokes. The standard of care for typical strokes does not apply to infective endocarditis because there is a substantial risk of hemorrhage with thrombolysis. In the last decade there have been multiple case reports of intravenous and intraarterial thrombolysis with successful outcomes for acute strokes with related infective endocarditis, but successful endovascular interventions for acute strokes associated with infective endocarditis are rarely reported. To the authors' knowledge, this report is the first case in the literature to use a mechanical retrieval device in successful vegetation retrieval in an infective endocarditis acute stroke. Although an interventional approach for treatment of acute stroke related to infective endocarditis is a promising option, it is controversial and a cautious clinical decision should be made on a case-by-case basis. The authors conclude that this approach can be tested in a case series with matched controls, because this condition is rare and a randomized clinical trial is not a realistic option.

  18. Whole-body protein kinetics in marasmus and kwashiorkor during acute infection.

    PubMed

    Manary, M J; Broadhead, R L; Yarasheski, K E

    1998-06-01

    Marasmus and kwashiorkor are clinically distinct manifestations of severe malnutrition. This study tested the hypothesis that rates of whole-body protein synthesis and breakdown are higher in marasmus than in kwashiorkor during acute infection. We measured whole-body protein kinetics using stable isotope tracers in eight children with marasmus and acute infection (pneumonia or malaria) to determine the rate of appearance of urea and leucine in plasma. Serum concentrations of total protein, albumin, and C-reactive protein were also measured. These findings were compared with those reported previously for 13 children with kwashiorkor (including marasmic kwashiorkor) and acute infection who were studied with the same methods. HIV infection was present in 10 of 21 children. Rates of protein breakdown and synthesis were higher in marasmus than in kwashiorkor (227 +/- 59 compared with 103 +/- 30 micromol leucine x kg(-1) x h(-1) and 216 +/- 60 compared with 97 +/- 30 micromol leucine x kg(-1) x h(-1), P < 0.001). The concentration of globulin (total protein minus albumin) was higher in marasmus than kwashiorkor (40 +/- 17 compared with 25 +/- 7 g/L, P < or = 0.01), but C-reactive protein was not different (73 +/- 79 compared with 83 +/- 89 mg/L). HIV infection and body composition did not explain the differences between marasmus and kwashiorkor. The accelerated rate of protein turnover in children with marasmus and acute infection requires further investigation.

  19. Occult hepatitis B virus infection and S gene escape mutants in HIV-infected patients after hepatitis B virus vaccination.

    PubMed

    Aghakhani, Arezoo; Mohraz, Minoo; Aghasadeghi, Mohammad Reza; Banifazl, Mohammad; Vahabpour, Rouhollah; Karami, Afsaneh; Foroughi, Maryam; Ramezani, Amitis

    2016-10-01

    Hepatitis B virus (HBV) vaccination is recommended for HIV patients. Despite the relative success of HBV vaccination, breakthrough infections can occur infrequently in patients, and it can be due to occult HBV infection, vaccine unresponsiveness and/or emergence of escape mutants. This study assessed the presence of occult HBV infection and S gene escape mutants in HIV-positive patients after HBV vaccination. Ninety-two HIV-positive patients were enrolled in this study, including 52 responders to HBV vaccine and 40 non-responders. All of the cases received HBV vaccine according to routine HBV vaccination protocols. The presence of HBV-DNA was determined by real-time polymerase chain reaction (PCR). In HBV-DNA positive samples, the most conserved regions of S gene sequences were amplified by nested PCR and PCR products were sequenced. Occult HBV infection was detected in two cases. Glycine to arginine mutation at residue 145 (G145R) within the 'a' region of the S gene was detected in one of the occult HBV infection cases who was in the non-responder group. This study showed that the prevalence of occult HBV infection and vaccine escape mutants was low in our HBV-vaccinated HIV-positive patients in both responder and non-responder groups, so there was no alarming evidence indicating breakthrough HBV infection in our vaccinated HIV-positive cases.

  20. Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

    PubMed Central

    Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

    2015-01-01

    Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

  1. Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in a male Chinese Han population.

    PubMed

    Tang, Shengli; Yuan, Yufeng; He, Yueming; Pan, Dingyu; Zhang, Yongxi; Liu, Yuanyuan; Liu, Quanyan; Zhang, Zhonglin; Liu, Zhisu

    2014-04-01

    As a multifunctional cytokine, interleukin-6 (IL-6) plays a key role in chronic inflammation as well as tumor growth and progression of hepatitis B virus (HBV) infection. Recent studies have implicated that single nucleotide polymorphism (SNP) -572C>G (rs1800796) located within the promoter region of IL-6 gene was associated with susceptibility to several diseases. Here, a case-control study was undertaken to investigate the association between this polymorphism and HBV-related hepatocellular carcinoma (HCC) susceptibility in a Chinese Han population. A total of 900 patients with chronic HBV infection, including 505 HBV-related HCC patients and 395 HBV infected patients without HCC were enrolled, and rs1800796 polymorphism was genotyped by the TaqMan method and DNA sequencing technology. The results indicated no significant association between rs1800796 polymorphism and the risk of HBV-related HCC in all subjects; however, a significant difference was identified in male subjects. Under the dominant model, male subjects with the G allele (CG/GG) have higher susceptibility to HBV-related HCC than those with CC genotype after adjusting confounding factors (P=0.012, odds ratio [OR] 1.68, 95% confidence interval [95% CI] 1.15-2.42). Our results suggested that rs1800796 polymorphism of IL-6 gene was associated with susceptibility to HBV-related HCC in a male Chinese Han population.

  2. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  3. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

  4. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques

    PubMed Central

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L.; Frank, Daniel N.; Ma, Dongzhu; Policicchio, Benjamin B.; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S.; Trichel, Anita; Ribeiro, Ruy M.; Tracy, Russell; Wilson, Cara; Landay, Alan L.; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  5. The HBV Drugs Work: Now What?

    PubMed

    Pruett, Timothy L

    2016-09-01

    Chemotherapeutic agents for Hepatitis B virus (HBV) suppression work, but only when administered to the patient. They do not appear to promote durable, long-term immunological control. After 3 years of effective anti-HBV therapy, a small percentage of patients maintained good control, manifest by controlled serum liver enzymes, low-level HBV-DNA, and controlled HBsAg concentrations. However, this did not occur in the majority of patients. We need a better understanding of the defects in HBV immunity and how to induce effective reconstitution that will maintain viral suppression, albeit either through innate or adaptive immunity. PMID:27580778

  6. Antihepatitis B virus activity of a protein-enriched fraction from housefly (Musca domestica) in a stable HBV-producing cell line.

    PubMed

    Lu, Xuemei; Jin, Xiaobao; Wang, Jie; Chu, Fujiang; Zhu, Jiayong

    2014-01-01

    Hepatitis B virus (HBV) infection remains a major public health problem. Although several vaccines and therapeutic strategies are currently being implemented to combat HBV virus, effective antiviral therapy against HBV infection has not been fully developed. Alternative strategies and new drugs to combat this disease are urged. Insects and insect derivatives are a large and unexploited source of potentially useful compounds for modern medicine. In the present study, we investigated the first anti-HBV activity of a protein-enriched fraction (PE) from the larvae of the housefly (Musca domestica) in a stable HBV-producing cell line. HBsAg and HBeAg in the culture medium were measured by enzyme-linked immunosorbent assay. HBV-DNA was quantified by fluorescent quantification PCR. HBV core protein was assayed by immunofluorescent staining. Results indicate PE treatment inhibited both HBsAg, HBeAg secretion, and HBV-DNA replication. Furthermore, PE could also suppress HBV core protein expression. PE could be a potential candidate for the development of a novel and effective drug for the treatment of HBV infection.

  7. Synthesis and biological evaluation of nucleoside analogues than contain silatrane on the basis of the structure of acyclovir (ACV) as novel inhibitors of hepatitis B virus (HBV).

    PubMed

    Han, Anyue; Li, Lingna; Qing, Kuiyou; Qi, Xiaolu; Hou, Leping; Luo, Xintong; Shi, Shaohua; Ye, Faqing

    2013-03-01

    Hepatitis B virus (HBV) infection causes major public health problems worldwide. Acyclovir (ACV) is mainly used to inhibit herpes simplex virus (HSV) rather than HBV. In this study, we used the combination principle to design and synthesize nucleoside analogues that contain silatrane on the basis of the structure of ACV. We found that the compounds were effective inhibitors of HBV, both in vitro and in vivo. All of the compounds showed suppressive activity on the expression of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the HepG2.2.15 cell line with low cytotoxicity. One of compounds was studied in HBV transgenic mice model, and the test results showed its ability to reduce the levels of HBsAg, HBeAg and HBV DNA by ELASE and qPCR. Furthermore, significant improvement of T lymphocyte was observed after treatment, as evaluated by flow cytometry (FCM).

  8. [Clinical analysis of acute invasive fungal sinusitis with orbital infection].

    PubMed

    Chen, Feifei; Hu, Haiwen; Li, Jin

    2014-10-01

    The clinical manifestation of acute invasive fungal sinusitis was associated with facial pain,altered sense of smell, blindness and headache. Physical examinations show that dark brown nasal secretions with bone resorption in paranasal sinus. Radiographi parameters showed uneven density in paranasal sinus and intraorbital extension. Fungus smears and pathological examination can make a definitive diagnosis.

  9. Platelets from thrombocytopenic ponies acutely infected with equine infectious anemia virus are activated in vivo and hypofunctional.

    PubMed

    Russell, K E; Perkins, P C; Hoffman, M R; Miller, R T; Walker, K M; Fuller, F J; Sellon, D C

    1999-06-20

    Thrombocytopenia is a consistent finding and one of the earliest hematological abnormalities in horses acutely infected with equine infectious anemia virus (EIAV), a lentivirus closely related to human immunodeficiency virus. Multifactorial mechanisms, including immune-mediated platelet destruction and impaired platelet production, are implicated in the pathogenesis of EIAV-associated thrombocytopenia. This study was undertaken to investigate whether regenerative thrombopoiesis and platelet destruction occurred in ponies acutely infected with EIAV. Circulating large, immature platelets were increased in ponies acutely infected with EIAV late in the infection when platelet count was at a nadir. Morphometric analysis of bone marrow from acutely infected ponies revealed significant increased in megakaryocyte area and megakaryocyte nuclear area. A trend toward increased numbers of megakaryocytes was also observed. Platelets from acutely infected ponies had increased surface-bound fibrinogen and ultrastructural changes consistent with in vivo platelet activation. Platelets also had hypofunctional aggregation responses to three agonists in vitro. We conclude that thrombocytopenia in ponies acutely infected with EIAV is regenerative and suggest that bone marrow platelet production is not severely compromised in these ponies. Our findings reveal that in vivo platelet activation occurs in ponies acutely infected with EIAV, and as a result platelets are hypofunctional in vitro. Activation of platelets in vivo may cause platelet degranulation or formation of platelet aggregates, which would result in removal of these damages platelets from circulation. This may represent a form of nonimmune-mediated platelet destruction in ponies acutely infected with EIAV.

  10. Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

    NASA Astrophysics Data System (ADS)

    Walshe, R.; Ruskin, H. J.; Callaghan, A.

    Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

  11. Viral load and acute otitis media development after human metapneumovirus upper respiratory tract infection.

    PubMed

    Nokso-Koivisto, Johanna; Pyles, Richard B; Miller, Aaron L; Patel, Janak A; Loeffelholz, Michael; Chonmaitree, Tasnee

    2012-07-01

    The role of human metapneumovirus (hMPV) in acute otitis media complicating upper respiratory tract infection (URI) was studied. Nasopharyngeal specimens from 700 URI episodes in 200 children were evaluated; 47 (7%) were positive for hMPV, 25 (3.6%) with hMPV as the only virus. Overall, 24% of URI episodes with hMPV only were complicated by acute otitis media, which was the lowest rate compared with other respiratory viruses. hMPV viral load was significantly higher in children with fever, but there was no difference in viral load in children with hMPV-positive URI with or without acute otitis media complication.

  12. Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana

    PubMed Central

    2012-01-01

    Background Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. Method Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. Results Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. Conclusion The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection. PMID:22490115

  13. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  14. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    PubMed

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P < 0.05) as a consequence of lower iron levels. Ferritin and transferrin levels were higher in both phases (acute and subclinical) of the disease. The AOPP and FRAP levels increased in infected animals on the acute phase; however, the opposite occurred in the subclinical phase. We concluded that dogs naturally infected by E. canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology. PMID:26724737

  15. [Epidemiologic features of acute viral respiratory infections in familial foci].

    PubMed

    Lidina, P V; Mironovskaia, A V

    1977-03-01

    A study was made of the epidemiological peculiarities of viral respiratory infections of various etiology in the familial foci with the use of a methodical approach permitting to detect the true spread of infection in the familial foci, with consideration to the subclinical forme fruste of the disease and "carrier state". It appeared that in the familial foci the infectiousness of the majority of respiratory viral infections was greater than in the closed collective bodies uniting persons of the same age. The age composition of the family influences the manifestness (particularly in parainfluenza infection) and the intensity of the epidemic process characterized by the coefficient of the secondary affections. The type of the apartment, the floor on which it is located, and the number of persons residing in it had no significant influence on the spread of the viral infections in the familial foci. A definite role in this process is played by the level of specific serum antibodies in the members of the family surrounding the patient. The association of morbidity level with the antibody level proved to be the most distinct in children with influenza and adenoviral infection; this association was less significant in adults. PMID:193325

  16. Strategies to Prevent Surgical Site Infections in Acute Care Hospitals: 2014 Update

    PubMed Central

    Anderson, Deverick J.; Podgorny, Kelly; Berríos-Torres, Sandra I.; Bratzler, Dale W.; Dellinger, E. Patchen; Greene, Linda; Nyquist, Ann-Christine; Saiman, Lisa; Yokoe, Deborah S.; Maragakis, Lisa L.; Kaye, Keith S.

    2014-01-01

    PURPOSE Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their surgical site infection (SSI) prevention efforts. This document updates “Strategies to Prevent Surgical Site Infections in Acute Care Hospitals,”1 published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.2 PMID:24799638

  17. Complete Spectrum of CRISPR/Cas9-induced Mutations on HBV cccDNA.

    PubMed

    Seeger, Christoph; Sohn, Ji A

    2016-08-01

    Hepatitis B virus (HBV) causes chronic infections that cannot yet be cured. The virus persists in infected hepatocytes, because covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is stable in nondividing cells. Antiviral therapies with nucleoside analogues inhibit HBV DNA synthesis in capsids in the cytoplasm of infected hepatocytes, but do not destroy nuclear cccDNA. Because over 200 million people are still infected, a cure for chronic hepatitis B (CHB) has become one of the major challenges in antiviral therapy. As a first step toward the development of curative therapies, we previously demonstrated that the CRISPR/Cas9 system can be used to functionally inactivate cccDNA derived from infectious HBV. Moreover, some evidence suggests that certain cytokines might induce an APOBEC-mediated cascade leading to the destruction of cccDNA. In this report we investigated whether a combination of the two mechanisms could act synergistically to inactivate cccDNA. Using next generation sequencing (NGS), we determined the complete spectrum of mutations in cccDNA following Cas9 cleavage and repair by nonhomologous end joining (NHEJ). We found that over 90% of HBV DNA was cleaved by Cas9. In addition our results showed that editing of HBV DNA after Cas9 cleavage is at least 15,000 times more efficient that APOBEC-mediated cytosine deamination following treatment of infected cells with interferon alpha (IFNα). We also found that a previously used method to detect cytosine deaminated DNA, termed 3D-PCR, overestimates the amount and frequency of edited HBV DNA. Taken together, our results demonstrated that the CRISPR/Cas9 system is so far the best method to functionally inactivate HBV cccDNA and provide a cure for CHB. PMID:27203444

  18. Complete Spectrum of CRISPR/Cas9-induced Mutations on HBV cccDNA

    PubMed Central

    Seeger, Christoph; Sohn, Ji A

    2016-01-01

    Hepatitis B virus (HBV) causes chronic infections that cannot yet be cured. The virus persists in infected hepatocytes, because covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is stable in nondividing cells. Antiviral therapies with nucleoside analogues inhibit HBV DNA synthesis in capsids in the cytoplasm of infected hepatocytes, but do not destroy nuclear cccDNA. Because over 200 million people are still infected, a cure for chronic hepatitis B (CHB) has become one of the major challenges in antiviral therapy. As a first step toward the development of curative therapies, we previously demonstrated that the CRISPR/Cas9 system can be used to functionally inactivate cccDNA derived from infectious HBV. Moreover, some evidence suggests that certain cytokines might induce an APOBEC-mediated cascade leading to the destruction of cccDNA. In this report we investigated whether a combination of the two mechanisms could act synergistically to inactivate cccDNA. Using next generation sequencing (NGS), we determined the complete spectrum of mutations in cccDNA following Cas9 cleavage and repair by nonhomologous end joining (NHEJ). We found that over 90% of HBV DNA was cleaved by Cas9. In addition our results showed that editing of HBV DNA after Cas9 cleavage is at least 15,000 times more efficient that APOBEC-mediated cytosine deamination following treatment of infected cells with interferon alpha (IFNα). We also found that a previously used method to detect cytosine deaminated DNA, termed 3D-PCR, overestimates the amount and frequency of edited HBV DNA. Taken together, our results demonstrated that the CRISPR/Cas9 system is so far the best method to functionally inactivate HBV cccDNA and provide a cure for CHB. PMID:27203444

  19. Low-level Circulation of Enterovirus D68–Associated Acute Respiratory Infections, Germany, 2014

    PubMed Central

    Reiche, Janine; Böttcher, Sindy; Diedrich, Sabine; Buchholz, Udo; Buda, Silke; Haas, Walter; Schweiger, Brunhilde

    2015-01-01

    We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August–October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions. PMID:25898320

  20. The association between obesity and outpatient visits for acute respiratory infections in Ontario, Canada

    PubMed Central

    Campitelli, Michael A.; Rosella, Laura C.; Kwong, Jeffrey C.

    2016-01-01

    Objectives Recent evidence suggests that obesity increases the risk of severe outcomes following respiratory infection. It is less clear whether obesity is associated with the risk of being infected with influenza or other respiratory pathogens. Therefore, we examined the association between obesity and outpatient visits for acute respiratory infections. Design We conducted a retrospective cohort study over 13 years on 104,665 individuals in Ontario, Canada who responded to population health surveys and agreed to linkage with health administrative data. Individuals aged 18–64 years who responded to a survey within 5 years prior to the start of an influenza season were included. Poisson regression, with adjustment for relevant confounders, was used to measure the association between self-reported BMI and outpatient visits coded as acute respiratory infection. We conducted numerous sensitivity analyses to assess the robustness of our findings. Results We observed higher rates of outpatient visits for ARI during influenza season periods compared with normal weight individuals for those who were overweight (BMI 25–29.9) (Rate Ratio [RR] 1.10; 95% Confidence Interval [95% CI] 1.07–1.13), obese class I (BMI 30–34.9) (RR 1.17; 95% CI 1.13–1.22), and obese class II or III (BMI ≥35) (RR 1.19; 95% CI 1.12–1.25) Associations of a similar magnitude were observed during non-influenza season periods. Obesity was a greater risk factor for acute respiratory infections managed in emergency departments than physician offices. Conclusions Obese individuals are at an increased risk of outpatient visits for acute respiratory infection during both influenza and non-influenza season periods, suggesting that the effect of obesity on the risk of respiratory infections is not limited to influenza. Interventions designed to reduce the prevalence of obesity may have the added benefit reducing the population burden of respiratory infections. PMID:23670219

  1. West Nile virus infection in a teenage boy with acute lymphocytic leukemia in remission.

    PubMed

    Hindo, Heather; Buescher, E Stephen; Frank, L Matthew; Pettit, Dee; Dory, Christopher; Byrd, Rebecca

    2005-12-01

    West Nile Virus (WNV) infection is an important cause of encephalitis. Although the medical literature contains examples of WNV encephalitis in susceptible, mainly elderly, immunocompromised hosts, few case reports have described pediatric cases. The authors describe an adolescent with acute lymphocytic leukemia and WNV encephalitis. Surveillance studies indicate an increase in WNV activity. Physicians need to be aware of WNV activity in their community and consider WNV as a potential source of infection.

  2. [Gemifloxacin for the treatment of uncomplicated urinary infections (acute cystitis)].

    PubMed

    Blondeau, Joseph M; Tillotson, Glenn S

    2009-12-01

    Uncomplicated urinary infections are a significant and growing cause of morbidity amongst young women. Commonly these infections are caused by Escherichia coil or Staphylococcus saprophyticus. Escherichia coil is resistant to several empirical antibiotics: amoxicilin, trimetoprima-sulfametozaxol and, more recently, to some more old flouroquinolons. Gemifloxacin is a flouroquinolon with an excellent in vitro activity against many community acquired bacteria which cause respiratory or urinary infections. This antibiotic has a very unique and dual action mechanism directed against girasa and topoisomerasa II DNA, which grants minimum low inhibitory concentrations against Escherichia coil, Klebsiella and S. saprophyticus species and others attacking respiratory system. Young women with uncomplicated urinary infections were evaluated in two random clinical studies; they were treated with 320 mg gemifloxacin once a day for three days. Gemifloxacin was compared to ofloxacin or ciprofloxacin in approved doses and durations and it proved to be useful with clinical success rates of 95% or more in both studies. Gemifloxacin showed to be safe and well tolerated. A dose a day is a safe and useful alternative amongst current empirical options to treat patients with uncomplicated urinary infections.

  3. Acute phase proteins: a potential approach for diagnosing chronic infection by Trypanosoma vivax.

    PubMed

    Almeida, Katyane de Sousa; Costa, Alinny Ferreira; Silva, Paulo Cesar da; Fagliari, José Jurandir; Machado, Rosangela Zacarias; Nascimento, Adjair Antonio do

    2012-01-01

    The present study aimed to assess potential changes in acute phase proteins in sheep experimentally infected with Trypanosoma vivax. There were studied eight male sheep, four used as controls and four infected with 10(5) T. vivax trypomastigotes. Blood samples were collected at two points times before infection and then at 5,7, 9, 11, 13, 15, 20, 30, 45, 60, 75, 90, 105 and 120 days post-infection (dpi). Blood samples were centrifuged and allotted, and acute phase proteins were then separated by electrophoresis on acrylamide gel containing sodium dodecyl sulfate. Protein concentrations were determined by computer-assisted densitometry. Total protein was determined by colorimetric biuret method. Trypanosomes were counted daily using a 5 mL aliquot of blood smear on a glass slide under a 22 × 22 mm coverslip. Parasites were counted in 100 microscopic fields (40× magnification), and then multiplied by a correction factor. The results were expressed as parasites per mL of blood. For statistical analyses, we used the Wilcoxon test at 5% significance level. There was found a reduction in several acute phase proteins and increase in antitrypsin and transferrin. This finding can be used for the diagnosis of T. vivax infection, especially in chronic infection.

  4. IL6 Inhibits HBV Transcription by Targeting the Epigenetic Control of the Nuclear cccDNA Minichromosome

    PubMed Central

    Palumbo, Gianna Aurora; Scisciani, Cecilia; Pediconi, Natalia; Lupacchini, Leonardo; Alfalate, Dulce; Guerrieri, Francesca; Calvo, Ludovica; Salerno, Debora; Di Cocco, Silvia; Levrero, Massimo; Belloni, Laura

    2015-01-01

    The HBV covalently closed circular DNA (cccDNA) is organized as a mini-chromosome in the nuclei of infected hepatocytes by histone and non-histone proteins. Transcription from the cccDNA of the RNA replicative intermediate termed pre-genome (pgRNA), is the critical step for genome amplification and ultimately determines the rate of HBV replication. Multiple evidences suggest that cccDNA epigenetic modifications, such as histone modifications and DNA methylation, participate in regulating the transcriptional activity of the HBV cccDNA. Inflammatory cytokines (TNFα, LTβ) and the pleiotropic cytokine interleukin-6 (IL6) inhibit hepatitis B virus (HBV) replication and transcription. Here we show, in HepG2 cells transfected with linear HBV monomers and HBV-infected NTCP-HepG2 cells, that IL6 treatment leads to a reduction of cccDNA-bound histone acetylation paralleled by a rapid decrease in 3.5kb/pgRNA and subgenomic HBV RNAs transcription without affecting cccDNA chromatinization or cccDNA levels. IL6 repressive effect on HBV replication is mediated by a loss of HNF1α and HNF4α binding to the cccDNA and a redistribution of STAT3 binding from the cccDNA to IL6 cellular target genes. PMID:26580974

  5. Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus

    PubMed Central

    Richter, Jan; Panayiotou, Christakis; Tryfonos, Christina; Koptides, Dana; Koliou, Maria; Kalogirou, Nikolas; Georgiou, Eleni; Christodoulou, Christina

    2016-01-01

    In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections. PMID:26761647

  6. Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus.

    PubMed

    Richter, Jan; Panayiotou, Christakis; Tryfonos, Christina; Koptides, Dana; Koliou, Maria; Kalogirou, Nikolas; Georgiou, Eleni; Christodoulou, Christina

    2016-01-01

    In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections. PMID:26761647

  7. TGF-β triggers HBV cccDNA degradation through AID-dependent deamination.

    PubMed

    Qiao, Ying; Han, Xiaoxu; Guan, Gefei; Wu, Na; Sun, Jianbo; Pak, Vladimir; Liang, Guoxin

    2016-02-01

    The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a viral center molecule for HBV infection and persistence. However, the cellular restriction factors of HBV cccDNA are not well understood. Here, we show that TGF-β can induce nuclear viral cccDNA degradation and hypermutation via activation-induced cytidine deaminase (AID) deamination activity in hepatocytes. This suppression by TGF-β is abrogated when AID or the activity of uracil-DNA glycosylase (UNG) is absent, which indicates that AID deamination and the UNG-mediated excision of uracil act in concert to degrade viral cccDNA. Moreover, the HBV core protein promotes the interaction between AID and viral cccDNA. Overall, our results indicate a novel molecular mechanism that allows cytokine TGF-β to restrict viral nuclear cccDNA in innate immunity, thereby suggesting a novel method for potentially eliminating cccDNA.

  8. Risk Factors for the Development of Intra-Abdominal Fungal Infections in Acute Pancreatitis

    PubMed Central

    Schwender, Brian J.; Gordon, Stuart R.; Gardner, Timothy B.

    2015-01-01

    Objectives Intra-abdominal fungal infections (AFI) complicating acute pancreatitis arise in the context of pancreatic necrosis. Our goal was to determine which risk factors contribute to AFI in patients with acute pancreatitis. Methods Records were reviewed from 479 non-transfer patients admitted to our medical center with acute pancreatitis from 1985–2009. Using multivariable regression models, risk factors for AFI were identified. Results Out of 479 patients admitted with acute pancreatitis, 17 patients were subsequently found to have an AFI and 3 of these patients expired. The mean length of stay for patients with an AFI was 24 days and 76% were admitted to the intensive care unit. Patients with AFI were more likely to have received prophylactic antibiotics on admission (OR 1.7, 95% C.I. 1.2–2.3), TPN within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7) or to have necrosis on CT scan within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7). Multivariable regression models identified admission antibiotic use (OR 1.6, 95% C.I. 1.4–1.8) as the strongest predictor of AFI. Conclusion Admission antibiotics are the biggest risk factor for the development of intra-abdominal fungal infections in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis should therefore be discouraged. PMID:25872170

  9. Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

    PubMed

    Wali, R K; Lee, A H; Kam, J C; Jonsson, J; Thatcher, A; Poretz, D; Ambardar, S; Piper, J; Lynch, C; Kulkarni, S; Cochran, J; Djurkovic, S

    2015-12-01

    We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function. PMID:26228743

  10. Knowledge of Acute Human Immnuodeficiency Virus Infection among Gay and Bisexual Male College Students

    ERIC Educational Resources Information Center

    Grin, Benjamin; Chan, Philip A.; Operario, Don

    2013-01-01

    Objective: To examine human immunodeficiency virus (HIV)-related knowledge, attitudes, and behaviors in at-risk college men who have sex with men (MSM), focusing on knowledge about acute HIV infection (AHI). Participants and Methods: A one-time anonymous survey was administered to college students attending a lesbian, gay, bisexual, transgender,…

  11. Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.

    PubMed

    Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

    2011-10-01

    Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

  12. Cutaneous Infection Caused by Macrophomina phaseolina in a Child with Acute Myeloid Leukemia▿

    PubMed Central

    Srinivasan, Ashok; Wickes, Brian L.; Romanelli, Anna M.; Debelenko, Larisa; Rubnitz, Jeffrey E.; Sutton, Deanna A.; Thompson, Elizabeth H.; Fothergill, Annette W.; Rinaldi, Michael G.; Hayden, Randall T.; Shenep, Jerry L.

    2009-01-01

    We report a case of Macrophomina phaseolina skin infection in an immunocompromised child with acute myeloid leukemia, which was treated successfully with posaconazole without recurrence after a hematopoietic stem cell transplant. The fungus was identified by DNA sequencing using both the internal transcribed spacer and D1/D2 region of the 28S ribosomal DNA gene. PMID:19386841

  13. Disseminated Infection Caused by Scedosporium prolificans in a Patient with Acute Multilineal Leukemia

    PubMed Central

    de Batlle, J.; Motjé, M.; Balanzà, R.; Guardia, R.; Ortiz, R.

    2000-01-01

    In this report, we describe a case of disseminated infection caused by Scedosporium prolificans (S. inflatum) in a patient affected by chemotherapy-induced acute multilineal leukemia and neutropenia. For the fungus isolated in four blood cultures, high MICs of currently available antifungal agents were found. Postmortem examination revealed multiorgan involvement. PMID:10747173

  14. Development of Hamster Models for Acute and Chronic Infections with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Golden Syrian hamster is frequently used as a small animal model to study acute leptospirosis. However, use of this small animal model to study Leptospira borgpetersenii serovar Hardjo infections has not been well documented. Cattle are the normal maintenance hosts of L. borgpetersenii serovar...

  15. Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening.

    PubMed

    Hoenigl, Martin; Green, Nella; Camacho, Martha; Gianella, Sara; Mehta, Sanjay R; Smith, Davey M; Little, Susan J

    2016-03-01

    We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program that offered universal HIV-1 nucleic acid amplification testing. Forty-seven (52%) patients reported ongoing signs or symptoms at the time of testing. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing.

  16. Comparative analysis of the acute response of zebrafish Danio rerio skin to two different bacterial infections.

    PubMed

    Lü, Aijun; Hu, Xiucai; Wang, Yi; Shen, Xiaojing; Zhu, Aihua; Shen, Lulu; Ming, Qinglei; Feng, Zhaojun

    2013-12-01

    Skin is an important innate immune organ in fish; however, little is known about the skin's immune response to infectious pathogens. We conducted a comparative analysis of the acute immune response of Zebrafish Danio rerio skin against gram-positive (Staphylococcus chromogenes) and gram-negative (Citrobacter freundii) bacterial infections. Gene expression profiles induced from the two different infections were identified by microarray hybridization, with many genes demonstrating an acute immune response in the skin. Differentially expressed genes were mainly involved in response to stress and stimulus, complement activation, acute-phase response, and defense and immune response. Compared with transcription patterns of skin from the two infections, a similar innate immunity (e.g., transferrin, coagulation factor, complements, and lectins) was observed but with different acute-phase genes (e.g., ceruloplasmin, alpha-1-microglobulin, vitellogenin, and heat shock protein). These results suggest that the skin of fish plays an important role in the innate immune responses to bacterial infection. PMID:24341765

  17. Capgras-like syndrome in a patient with an acute urinary tract infection

    PubMed Central

    Salviati, Massimo; Bersani, Francesco Saverio; Macrì, Francesco; Fojanesi, Marta; Minichino, Amedeo; Gallo, Mariana; De Michele, Francesco; Chiaie, Roberto Delle; Biondi, Massimo

    2013-01-01

    Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%–40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder. PMID:23355784

  18. Infective endocarditis caused by Scedosporium prolificans infection in a patient with acute myeloid leukemia undergoing induction chemotherapy.

    PubMed

    Ochi, Yotaro; Hiramoto, Nobuhiro; Takegawa, Hiroshi; Yonetani, Noboru; Doi, Asako; Ichikawa, Chihiro; Imai, Yukihiro; Ishikawa, Takayuki

    2015-06-01

    Disseminated Scedosporium prolificans infection occurs mainly in immunocompromised patients. The mortality rate is high, as the fungus is resistant to most antifungal agents. Here, we present the case of a 66-year-old female with acute myeloid leukemia who developed infective endocarditis caused by S. prolificans infection during induction chemotherapy. Her 1,3-β-D-glucan levels were elevated and computed tomography revealed bilateral sinusitis and disseminated small nodular masses within the lungs and spleen; it nonetheless took 6 days to identify S. prolificans by blood culture. The patient died of multi-organ failure despite the combined use of voriconazole and terbinafine. Autopsy revealed numerous mycotic emboli within multiple organs (caused by mitral valve vegetation) and endocarditis (caused by S. prolificans). The geographic distribution of this infection is limited to Australia, the United States, and southern Europe, particularly Spain. The first Japanese case was reported in 2011, and four cases have been reported to date, including this one. Recently, the incidence of S. prolificans-disseminated infection in immunocompromised patients has increased in Japan. Therefore, clinicians should consider S. prolificans infection as a differential diagnosis when immunocompromised patients suffer disseminated infections with elevated 1,3-β-D-glucan levels.

  19. Magnetic Resonance Imaging of Acute Head and Neck Infections.

    PubMed

    Thayil, Neil; Chapman, Margaret N; Saito, Naoko; Fujita, Akifumi; Sakai, Osamu

    2016-05-01

    This article discusses the use of MR imaging in various acute infectious diseases of the head and neck, with particular emphasis on situations where MR imaging provides additional information that can significantly impact treatment decisions and outcomes. MR imaging findings of various disease processes are discussed, based on the head and neck compartments from which they originate. Specifically, infectious entities of the orbit, paranasal sinuses, pharynx, oral cavity (including periodontal disease), salivary glands, temporal bone, and lymph nodes are described in detail. PMID:27150323

  20. Apoptosis of Hippocampal Pyramidal Neurons Is Virus Independent in a Mouse Model of Acute Neurovirulent Picornavirus Infection

    PubMed Central

    Buenz, Eric J.; Sauer, Brian M.; LaFrance-Corey, Reghann G.; Deb, Chandra; Denic, Aleksandar; German, Christopher L.; Howe, Charles L.

    2009-01-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler’s murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non–cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  1. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.

    PubMed

    Buenz, Eric J; Sauer, Brian M; Lafrance-Corey, Reghann G; Deb, Chandra; Denic, Aleksandar; German, Christopher L; Howe, Charles L

    2009-08-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  2. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    SciTech Connect

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  3. Serious Infection Following Acute Myocardial Infarction: Incidence, Clinical Features, and Outcomes

    PubMed Central

    Truffa, Adriano A. M.; Granger, Christopher B.; White, Kyle R.; Newby, L. Kristin; Mehta, Rajendra H.; Hochman, Judith S.; Patel, Manesh R.; Pieper, Karen S.; Al-Khalidi, Hussein R.; Armstrong, Paul W.; Lopes, Renato D.

    2013-01-01

    Background Little is known about the incidence, location, etiologic organisms, and outcomes of infection in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Objectives To address this knowledge gap using the database of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. We also assessed the association between serious infections and 90-day death or death/MI. Methods We analyzed data from 5745 STEMI patients enrolled in the APEX-AMI trial. Detailed information on infection was collected on all patients. We describe characteristics of patients according to infection and details of infection. Cox proportional hazards models were used to assess 90-day outcomes among patients with and without infections after adjusting for associated clinical variables and using infection as a time-dependent covariate. Results Overall, 138 patients developed a serious infection (2.4%), most of whom presented with a single-site infection. The median (25th, 75th percentile) time until diagnosis of infection was 3 (1, 6) days. The most commonly identified organism was Staphylococcus aureus, and the main location of infection was the bloodstream. These patients had more comorbidities and lower procedural success at index PCI than those without infections. Serious infection was associated with significantly higher rates of 90-day death (adjusted hazard ratio [HR] 5.6; 95% confidence interval [CI] 3.8-8.4) and death or MI (adjusted HR 4.9; 95% CI 3.4-7.1). Conclusion Infections complicating the course of patients with STEMI are uncommon but associated with markedly worse 90-day clinical outcomes. Mechanisms for early identification of these high-risk patients, as well as design of strategies to reduce their risk of infection, are warranted. PMID:22814783

  4. An examination of co-infection in acute gastroenteritis and histo-blood group antigens leading to viral infection susceptibility

    PubMed Central

    FURUYA, KENTA; NAKAJIMA, HITOSHI; SASAKI, YOUSUKE; URITA, YOSHIHISA

    2016-01-01

    The aim of the present study was to evaluate co-infection in the gastrointestinal tract in terms of viruses, bacteria and the ABO blood group. We hypothesized that a combination of norovirus (NV) and bacteria in the gastrointestinal tract could affect the likelihood of an individual to contracting NV. Histo-blood group antigens (HBGAs) are considered to act as receptors that can lead to NV susceptibility. In addition to genetics, co-infection in the gastrointestinal tract may be associated with this mechanism. A total of 370 patients with acute gastroenteritis presenting with diarrhea (14–89 years) were recruited. The male/female ratio was 20/17. Single infection (bacteria or virus), co-infection with two viruses, and co-infection with one virus and one bacterium were statistically analyzed. In total, 88 of the 376 subjects (23.4%) were positive for one virus, and 50 (13.3%) were positive for one bacterium. Co-transfection with bacteria and a virus were detected in 46 (47.9%) of the 96 bacterial gastroenteritis cases. Statistical analysis revealed that co-infection of bacteria and NV was not significant in all viral infections (P=0.768). In terms of the ABO histo-blood group type and NV infection, the frequency in the O type was not significantly increased (P=0.052). Co-infection of bacteria and a virus occurred frequently in the gastrointestinal tract. The ABO blood phenotype expression was not a significant factor in NV infection in the present case series and the results did not suggest an affinity of NV for specific bacteria. PMID:26998270

  5. Urinary tract infections in patients admitted to rehabilitation from acute care settings: a descriptive research study.

    PubMed

    Romito, Diane; Beaudoin, JoAnn M; Stein, Patricia

    2011-01-01

    The use of an indwelling urinary catheter comes with associated risks. At a hospital in southern California, nurses on the acute rehabilitation unit suspected their patients were arriving from acute care with undiagnosed urinary tract infections (UTIs). This descriptive research study quantified the incidence of UTI on admission to a rehabilitation unit and correlations with catheter use. During the study period, 132 patients were admitted to acute rehabilitation from an acute care setting, and 123 met criteria to participate in the study. Among participants, 12% had a UTI upon admission. Questionnaires examined nursing attitudes toward appropriate urinary catheter use and proactive catheter removal. The data revealed that nurses want to be involved in decisions about urinary catheter use and that medical/surgical and rehabilitation nurses agree strongly about advocating for patients with indwelling urinary catheters.

  6. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

  7. Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

    PubMed

    Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

    2015-09-01

    This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome.

  8. A cluster of acute hepatitis E infection in United Nations Bangladeshi peacekeepers in Haiti.

    PubMed

    Drabick, J J; Gambel, J M; Gouvea, V S; Caudill, J D; Sun, W; Hoke, C H; Innis, B L

    1997-10-01

    In the fall of 1995, within a month of deployment to Haiti for peacekeeping duty, four Bangladeshi soldiers developed acute icteric hepatitis in rapid succession. Hepatitis E virus (HEV) was found to be the etiology by demonstrating HEV genomic sequences in serum samples by the polymerase chain reaction (PCR) and serologically by the detection of elevated IgM titers to HEV. No case had serologic evidence of acute hepatitis A or C infection. The soldiers had probably acquired their infection while living in a cantonment area outside Dhaka, Bangladesh for one month prior to deployment. Cloning and sequencing of amplified PCR products demonstrated a single strain suggestive of a common source of infection. Furthermore, high genomic identity with Asian strains of HEV and dissimilarity with the Mexican strain was demonstrated, verifying that the strain had indeed been imported. Human waste management from the Bangladesh camp in Haiti was strictly controlled and no secondary cases were observed. A convenience sample of 105 (12%) soldiers from the Bangladesh battalion (850 men) revealed anicteric or asymptomatic HEV infection in seven (7%) of 105. This report contains the first demonstration of acute hepatitis E in natives of Bangladesh and demonstrates the power of the PCR in the rapid diagnosis and epidemiologic analysis of HEV infection. More importantly, this cluster demonstrates the importation of an important infectious disease by multinational peacekeepers to a potentially susceptible host country.

  9. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep

    PubMed Central

    2014-01-01

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development. PMID:24475786

  10. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep.

    PubMed

    Castaño, Pablo; Fuertes, Miguel; Ferre, Ignacio; Fernández, Miguel; Ferreras, Maria del Carmen; Moreno-Gonzalo, Javier; González-Lanza, Camino; Katzer, Frank; Regidor-Cerrillo, Javier; Ortega-Mora, Luis Miguel; Pérez, Valentín; Benavides, Julio

    2014-01-29

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development.

  11. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam.

    PubMed

    Phuong, Hoang Lan; Nga, Tran T T; van Doornum, Gerard J; Groen, Jan; Binh, Tran Q; Giao, Phan T; Hung, Le Q; Nams, Nguyen V; Kager, P A; de Vries, Peter J

    2010-09-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control program. Serum was collected on first presentation (t0) and after 3 weeks (t3) for serology. After exclusion of acute dengue infection, acute and convalescent serum samples from 606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM and IgG antibodies against common respiratory viruses. Paired sera showed the following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial virus (HRSV, 0.6%). There was no association between type of infection and age, sex or seasonality; some inter-annual differences were observed for influenza. Antibody prevalence, indicative of previous infections, was relatively low: HPV, 56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%.

  12. Fatal systemic adenoviral infection superimposed on pulmonary mucormycosis in a child with acute leukemia

    PubMed Central

    Seo, Yu Mi; Hwang-Bo, Seok; Kim, Seong koo; Han, Seung Beom; Chung, Nack-Gyun; Kang, Jin Han

    2016-01-01

    Abstract Background: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. Case summary: We report a case of a 15-year-old boy with a fatal systemic ADV infection. He had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia. He complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy. In spite of appropriate antibiotic and antifungal therapy, pneumonia was aggravated and gross hematuria was accompanied. A multiplex polymerase chain reaction test for respiratory viruses was positive for ADV in a blood sample, and a urine culture was positive for ADV. He received oral ribavirin, intravenous immunoglobulin, and intravenous cidofovir therapy; however, he eventually died. Relapsed leukemia, concurrent fungal pneumonia, and delayed cidofovir administration were considered the cause of the grave outcome in this patient. Conclusion: ADV may cause severe infections not only in allogeneic hematopoietic cell transplant recipients, but also in patients undergoing chemotherapy for acute leukemia. The risk factors for severe ADV infection in patients undergoing chemotherapy should be determined in the future studies, and early antiviral therapy should be administered to immune compromised patients with systemic ADV infection. PMID:27749571

  13. New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media

    PubMed Central

    Leino, Tuija; Kilpi, Terhi

    2016-01-01

    For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2–24 months at scheduled visits and at visits during respiratory infection in 1994–97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media. PMID:27257789

  14. Is accounting for acute care beds enough? A proposal for measuring infection prevention personnel resources.

    PubMed

    Gase, Kathleen A; Babcock, Hilary M

    2015-02-01

    There is still little known about how infection prevention (IP) staffing affects patient outcomes across the country. Current evaluations mainly focus on the ratio of IP resources to acute care beds (ACBs) and have not strongly correlated with patient outcomes. The scope of IP and the role of the infection preventionist in health care have expanded and changed dramatically since the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) recommended a 1 IP resource to 250 ACB ration in the 1980s. Without a universally accepted model for accounting for additional IP responsibilities, it is difficult to truly assess IP staffing needs. A previously suggested alternative staffing model was applied to acute care hospitals in our organization to determine its utility.

  15. Pathogenesis of acute murine cytomegalovirus infection in resistant and susceptible strains of mice.

    PubMed

    Mercer, J A; Spector, D H

    1986-02-01

    We have characterized the progress of acute murine cytomegalovirus (MCMV) infection in the spleen, liver, and salivary gland of susceptible (BALB/c) and resistant (C3H) strains of mice after intraperitoneal inoculation. Viral replication was analyzed by virus titration, infectious-center assays, and in situ cytohybridization with cloned subgenomic fragments of the MCMV genome. The most striking differences between strains were observed in the spleen. At 24 h postinfection (p.i.), both strains had a similar number of infected spleen cells. At 48 h p.i., BALB/c mice showed marked dissemination of the splenic infection which continued until 96 h p.i. In contrast, the number of infected C3H spleen cells did not increase from the 24-h level but declined later on. This early block in dissemination of MCMV infection in C3H mouse spleens was not a result of the H-2k haplotype, as BALB.K (H-2k) mice, which show an intermediate level of resistance to MCMV infection, exhibited dissemination of the infection between 24 and 48 h p.i., albeit at a reduced level. However, between 72 and 96 h p.i., we observed a decline in the number of infected spleen cells in BALB.K mice similar to that observed in C3H mice. We also demonstrated by Southern blot analysis of DNA from the infected spleen cells that the termini of the MCMV genome fuse after in vivo infection.

  16. Prevalence of Astrovirus Infection among Chilean Children with Acute Gastroenteritis

    PubMed Central

    Gaggero, Aldo; O’Ryan, Miguel; Noel, Jacqueline S.; Glass, Roger I.; Monroe, Stephan S.; Mamani, Nora; Prado, Valeria; Avendaño, Luis F.

    1998-01-01

    The frequency of astrovirus infection in 456 Chilean children with diarrhea was determined by enzyme-linked immunosorbent assay, reverse transcriptase PCR, and cell culture. Astrovirus was detected in 16.5% of rotavirus-negative and 7% of rotavirus-positive samples obtained from emergency rooms or hospitals and in 11% of samples from day care centers. HAst-1 was the predominant serotype identified. PMID:9817899

  17. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    PubMed Central

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  18. Knowledge and Awareness of Acute Human Immunodeficiency Virus Infection Among Mobile App-Using Men Who Have Sex With Men: A Missed Public Health Opportunity

    PubMed Central

    Siegler, Aaron J.; Sanchez, Travis; Sineath, R. Craig; Grey, Jeremy; Kahle, Erin; Sullivan, Patrick S.

    2015-01-01

    In a national online survey, we assessed awareness and knowledge of acute human immunodeficiency virus (HIV) infection manifestation among 1748 men who have sex with men (MSM). Only 39% of respondents were aware that acute HIV infection may be accompanied by symptoms. Education and increased access to acute HIV testing may facilitate MSM to appropriately seek acute HIV testing. PMID:26034766

  19. HBx truncation mutants differentially modulate SREBP-1a and -1c transcription and HBV replication.

    PubMed

    Wu, Qi; Liu, Qiang

    2015-12-01

    As master transcription factors for lipogenesis, sterol regulatory element-binding protein-1 (SREBP-1) has two isoforms, SREBP-1a and SREBP-1c. Hepatitis B virus X (HBx) can up-regulate the transcription of both SREBP-1a and SREBP-1c. HBx is a small protein consisting of 154 amino acids. Truncated forms of HBx, often found in the tissues after HBV infection, may have a role in the pathogenesis associated with HBV infection. In this study, we examined the effects of two HBx truncation mutants, HBx aa. 1-127 and HBx aa. 43-154, on the transcription of SREBP-1a and SREBP-1c. HBx 1-127 can up-regulate SREBP-1c, but not SREBP-1a transcription, whereas HBx 43-154 can activate SREBP-1a, but not SREBP-1c transcription. We further determined the activities of two HBV enhancers after the expression of the truncated HBx proteins. HBx 1-127 and HBx 43-154 can only up-regulate HBV enhancer I or HBV enhancer II, respectively. Knocking down SREBP-1 abrogates enhancer activation by HBx proteins, suggesting a role of SREBP-1. In addition, using HBV enhancer mutants, we found that the binding sequence for AP-1 on enhancer I is essential for its activation by HBx 1-127, whereas C/EBP and Sp1 sites are required for enhancer II activation by HBx 43-154. Finally, we showed that both HBx 1-127 and HBx 43-154 can increase HBV transcription and HBV replication dependent upon SREBP-1 because knocking down SREBP-1 abrogates the up-regulation. Furthermore, upon ectopic expression of either SREBP-1a or SREBP-1c, we showed that SREBP-1a is involved in HBV transcription and replication up-regulation by HBx 43-154, whereas SREBP-1c is involved in HBV transcription and replication up-regulation by HBx 1-127. Our results should help understand the interactions between HBV and the SREBP-1-mediated lipogenic pathway.

  20. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    PubMed

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed. PMID:27084183

  1. Acute compartment syndrome of the forearm secondary to infection within the space of Parona.

    PubMed

    Jamil, Wiqqas; Khan, Irfan; Robinson, Paul; Thalava, Ramesh

    2011-09-01

    The deep midpalmar space of the hand communicates with the space of Parona in the forearm. Infection of these deep spaces can be difficult to diagnose. This article presents the first reported case of acute compartment syndrome of the forearm secondary to infection within the space of Parona. This article discusses the anatomy of the space of Parona, highlighting its communicating spaces and the importance of recognizing a deep-space infection of the hand as a possible cause of compartment syndrome of the forearm. This article also suggests a method of clinical examination to aid in the diagnosis of infection within the space of Parona to allow more specific planning of surgical intervention through early decompressive surgery, with surgical exploration to exclude and drain infection when no other clear cause for the rise in pressure within the osteofascial compartment is apparent. PMID:21902163

  2. Acute compartment syndrome of the forearm secondary to infection within the space of Parona.

    PubMed

    Jamil, Wiqqas; Khan, Irfan; Robinson, Paul; Thalava, Ramesh

    2011-09-09

    The deep midpalmar space of the hand communicates with the space of Parona in the forearm. Infection of these deep spaces can be difficult to diagnose. This article presents the first reported case of acute compartment syndrome of the forearm secondary to infection within the space of Parona. This article discusses the anatomy of the space of Parona, highlighting its communicating spaces and the importance of recognizing a deep-space infection of the hand as a possible cause of compartment syndrome of the forearm. This article also suggests a method of clinical examination to aid in the diagnosis of infection within the space of Parona to allow more specific planning of surgical intervention through early decompressive surgery, with surgical exploration to exclude and drain infection when no other clear cause for the rise in pressure within the osteofascial compartment is apparent.

  3. Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus

    PubMed Central

    Sakai, Kouji; Singh, Harpal; Himeji, Daisuke; Kikuchi, Ikuo; Ueda, Akira; Yamamoto, Seigo; Miura, Miho; Shioyama, Yoko; Kawano, Kimiko; Nagaishi, Tokiko; Saito, Minako; Minomo, Masumi; Iwamoto, Naoyasu; Hidaka, Yoshio; Sohma, Hirotoshi; Kobayashi, Takeshi; Kanai, Yuta; Kawagishi, Takehiro; Nagata, Noriyo; Fukushi, Shuetsu; Mizutani, Tetsuya; Tani, Hideki; Taniguchi, Satoshi; Fukuma, Aiko; Shimojima, Masayuki; Kurane, Ichiro; Kageyama, Tsutomu; Odagiri, Takato; Saijo, Masayuki; Morikawa, Shigeru

    2014-01-01

    A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low. PMID:24667794

  4. Viral upper respiratory tract infections in young children with emphasis on acute otitis media.

    PubMed

    Nokso-Koivisto, Johanna; Hovi, Tapani; Pitkäranta, Anne

    2006-08-01

    Viral upper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications (e.g. acute otitis media (AOM)) are a burden for children, their families and society. Over the past decade, our knowledge on the significance of respiratory viruses has broadened remarkably. Viruses cause large variety of respiratory diseases and cause alone diseases, which previously have been assumed to be bacterial only (e.g. AOM and pneumonia). Methods for detection analysis of respiratory viruses are developing making both the diagnosis and epidemiological investigations of respiratory infections easier. Accurate diagnosis of respiratory infections and awareness of possible viral etiology could reduce the use of antibiotics. Etiologic studies of viral infections are becoming increasingly important, with the emergence of new antiviral drugs and vaccines.

  5. Establishment of a Persistent Escherichia coli Reservoir during the Acute Phase of a Bladder Infection

    PubMed Central

    Mulvey, Matthew A.; Schilling, Joel D.; Hultgren, Scott J.

    2001-01-01

    The vast majority of urinary tract infections are caused by strains of uropathogenic Escherichia coli that encode filamentous adhesive organelles called type 1 pili. These structures mediate both bacterial attachment to and invasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a urinary tract infection is unknown. Here we show that type 1-piliated uropathogens can invade the superficial epithelial cells that line the lumenal surface of the bladder and subsequently replicate, forming massive foci of intracellular E. coli termed bacterial factories. In response to infection, superficial bladder cells exfoliate and are removed with the flow of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within the bladder mucosa that may serve as a source for recurrent acute infections. These observations suggest that urinary tract infections are more chronic and invasive than generally assumed. PMID:11402001

  6. Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection

    PubMed Central

    Eller, Michael A.; Goonetilleke, Nilu; Tassaneetrithep, Boonrat; Eller, Leigh Anne; Costanzo, Margaret C.; Johnson, Susan; Betts, Michael R.; Krebs, Shelly J.; Slike, Bonnie M.; Nitayaphan, Sorachai; Rono, Kathleen; Tovanabutra, Sodsai; Maganga, Lucas; Kibuuka, Hannah; Jagodzinski, Linda; Peel, Sheila; Rolland, Morgane; Marovich, Mary A.; Kim, Jerome H.; Michael, Nelson L.; Robb, Merlin L.

    2016-01-01

    ABSTRACT Attrition within the CD4+ T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8+ T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8+ T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38+ CD27− CD8+ T cells characterized by the low expression of the CD8 receptor (CD8dim). Interestingly, while high frequencies of HIV-specific CD8+ T cell responses occur within the CD38+ CD27− CD8dim T cell population, the minority populations of CD8bright T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8dim T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8dim T cells, and the size of this population inversely correlates with the acute loss of CD4+ T cells. These data indicate, for the first time, that early CD4+ T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8dim T cell population less efficient in controlling HIV viremia. IMPORTANCE A distinct population of activated CD8+ T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8+ T cell dysfunction during acute infection. PMID:26842474

  7. Knowledge, attitude and practices regarding acute respiratory infections.

    PubMed

    Kapoor, S K; Reddaiah, V P; Murthy, G V

    1990-01-01

    One hundred and six mothers in a rural area were interviewed to determine as to how they recognise pneumonia in children, what therapies they practice with mild acute respiratory illnesses and pneumonias and the feeding practices they adopt. Most mothers recognised pneumonia by noticing fast respiratory rate and difficulty in breathing. More severe cases were recognised by these signs among a higher percentage of mothers. As regards management of mild ARI episodes, more than half the mothers preferred not to give any treatment or use only home remedies. In pneumonias, a majority of them preferred to consult a qualified doctor. Nearly a third of them were of the opinion that they would take the child to hospital if the disease was severe. Regarding feeding practices, most of them stated that they would continue feeding, fluids and breast feeds. Only 10% desired to stop and another 15% would decrease the amounts.

  8. HBV-DNA levels predict overall mortality in HIV/HBV coinfected individuals.

    PubMed

    Nikolopoulos, Georgios K; Paraskevis, Dimitrios; Psichogiou, Mina; Hatzakis, Angelos

    2016-03-01

    The coinfection of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has been associated with increased death rates. However, the relevant research has mostly relied on serologic HBV testing [HBV surface antigen (HBsAg)]. The aim of this work was to explore the relationship of HBV viraemia with overall mortality among HIV/HBV coinfected individuals. The analysis included 1,609 HIV seropositives of a previously described cohort (1984-2003) with limited exposure to tenofovir (12%) and a median follow-up of approximately 5 years. Those with persistent expression of HBsAg were further tested for HBV-DNA. The data were analyzed using Poisson regression models. Totally, 101 participants were chronic carriers of HBsAg (6.28%). Of these, 81 were tested for HBV-DNA. The median HBV-DNA levels were 3.81 log (base-10) International Units (IU)/ml. A third (31%) of those tested for HBV-DNA had received tenofovir. Before developing acquired immune deficiency syndrome (AIDS), the adjusted incidence rate ratio (IRR) for all-cause mortality of coinfected patients with HBV viraemia above the median value versus the HIV monoinfected group was 3.44 [95% confidence interval (CI): 1.05-11.27]. Multivariable regressions in the coinfected group only (n = 81) showed that one log-10 increase in HBV-DNA levels was associated with an elevated risk for death (IRR: 1.24, 95%CI: 1.03-1.49). HBV-DNA levels predict overall mortality in the setting of HIV/HBV coinfection, especially during the period before developing AIDS, and could thus help prioritize needs and determine the frequency of medical monitoring.

  9. Mechanisms of HBV-induced hepatocellular carcinoma.

    PubMed

    Levrero, Massimo; Zucman-Rossi, Jessica

    2016-04-01

    Hepatitis B virus (HBV) contributes to hepatocellular carcinoma (HCC) development through direct and indirect mechanisms. HBV DNA integration into the host genome occurs at early steps of clonal tumor expansion and induces both genomic instability and direct insertional mutagenesis of diverse cancer-related genes. Prolonged expression of the viral regulatory protein HBx and/or altered versions of the preS/S envelope proteins dysregulates cell transcription and proliferation control and sensitizes liver cells to carcinogenic factors. Accumulation of preS1 large envelope proteins and/or preS2/S mutant proteins activates the unfold proteins response, that can contribute to hepatocyte transformation. Epigenetic changes targeting the expression of tumor suppressor genes occur early in the development of HCC. A major role is played by the HBV protein, HBx, which is recruited on cellular chromatin and modulates chromatin dynamics at specific gene loci. Compared with tumors associated with other risk factors, HBV-related tumors have a higher rate of chromosomal alterations, p53 inactivation by mutations and overexpression of fetal liver/hepatic progenitor cells genes. The WNT/β-catenin pathway is also often activated but HBV-related tumors display a low rate of activating β-catenin mutations. HBV-related HCCs may arise on non-cirrhotic livers, further supporting the notion that HBV plays a direct role in liver transformation by triggering both common and etiology specific oncogenic pathways in addition to stimulating the host immune response and driving liver chronic necro-inflammation.

  10. Estimating the impact of vaccination in acute SHIV-SIV infection

    SciTech Connect

    Ribeiro, Ruy

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  11. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.

    PubMed

    Kløverpris, Henrik N; Kazer, Samuel W; Mjösberg, Jenny; Mabuka, Jenniffer M; Wellmann, Amanda; Ndhlovu, Zaza; Yadon, Marisa C; Nhamoyebonde, Shepherd; Muenchhoff, Maximilian; Simoni, Yannick; Andersson, Frank; Kuhn, Warren; Garrett, Nigel; Burgers, Wendy A; Kamya, Philomena; Pretorius, Karyn; Dong, Krista; Moodley, Amber; Newell, Evan W; Kasprowicz, Victoria; Abdool Karim, Salim S; Goulder, Philip; Shalek, Alex K; Walker, Bruce D; Ndung'u, Thumbi; Leslie, Alasdair

    2016-02-16

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction. PMID:26850658

  12. Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection.

    PubMed

    Guglietta, Silvia; Garbuglia, Anna Rosa; Pacciani, Valentina; Scottà, Cristiano; Perrone, Maria Paola; Laurenti, Luca; Spada, Enea; Mele, Alfonso; Capobianchi, Maria Rosaria; Taliani, Gloria; Folgori, Antonella; Vitelli, Alessandra; Ruggeri, Lionello; Nicosia, Alfredo; Piccolella, Enza; Del Porto, Paola

    2005-09-01

    Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8+ T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8+ T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+ T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8+ T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage. PMID:16114108

  13. An unusual case of infective endocarditis presenting as acute myocardial infarction.

    PubMed

    Chen, Zhong; Ng, Francesca; Nageh, Thuraia

    2007-06-01

    A 39-year-old Zimbabwean man presented with a 1 week history of fever, general malaise and acute-onset chest pain. He had a urethral stricture, which had been managed with an indwelling supra-pubic catheter. The electrocardiography on admission showed inferior ST-T segments elevation. His chest pain and electrocardiography changes resolved subsequent to thrombolysis, and he remained haemodynamically stable. The 12-h troponin I was increased at 10.5 microg/l (NR <0.04 microg/l). Echocardiography confirmed severe mitral regurgitation and a flail anterior mitral valve leaflet with an independently oscillating mobile vegetation. Enterococci faecalis were grown on blood cultures. A diagnosis of enterococci infective endocarditis with concomitant acute myocardial infarction due to possible septic emboli was made. Despite the successful outcome from thrombolysis in the setting of acute myocardial infarction with infective endocarditis, the case highlights the current lack of definitive data on the optimal acute management of such an unusual clinical scenario. Although there is serious concern that thrombolytic treatment for myocardial infarction in the setting of infective endocarditis may be associated with higher risk of cerebral haemorrhage, there is little documented evidence supporting the safety of primary percutaneous coronary intervention with these patients. PMID:17513553

  14. Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

    PubMed Central

    Ferrari, T.C.A.; Xavier, M.A.P.; Vidigal, P.V.T.; Amaral, N.S.; Diniz, P.A.; Resende, A.P.; Miranda, D.M.; Faria, A.C.; Lima, A.S.; Faria, L.C.

    2014-01-01

    Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population. PMID:25296362

  15. Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center.

    PubMed

    Ferrari, T C A; Xavier, M A P; Vidigal, P V T; Amaral, N S; Diniz, P A; Resende, A P; Miranda, D M; Faria, A C; Lima, A S; Faria, L C

    2014-11-01

    Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

  16. Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center.

    PubMed

    Ferrari, T C A; Xavier, M A P; Vidigal, P V T; Amaral, N S; Diniz, P A; Resende, A P; Miranda, D M; Faria, A C; Lima, A S; Faria, L C

    2014-08-29

    Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

  17. Acute transverse myelitis and subacute thyroiditis associated with dengue viral infection: A case report and literature review

    PubMed Central

    Mo, Zhiming; Dong, Yaxian; Chen, Xiaolian; Yao, Huiyan; Zhang, Bin

    2016-01-01

    Acute transverse myelitis is a rare manifestation of dengue infection. To the best of our knowledge, only 6 cases of acute transverse myelitis as a manifestation of dengue infection have been reported thus far. The present study described a case of acute transverse myelitis complicated with subacute thyroiditis 6 days after the onset of dengue viral infection. In addition, the available literature was searched to identify similar previous cases. Treatment with intravenous pulse methylprednisolone immunoglobulin plasmapheresis and physiotherapy resulted in partial recovery at 3 months post-infection. In conclusion, the involvement of dengue infection should be considered in patients who develop central nervous system manifestations during or after the recovery period of dengue infection. Furthermore, since methylprednisolone and immunoglobulin are effective during the active phase of the infection, prompt diagnosis and initiation of treatment are crucial. PMID:27703498

  18. Core protein: a pleiotropic keystone in the HBV lifecycle

    PubMed Central

    Zlotnick, Adam; Venkatakrishnan, Balasubramanian; Tan, Zhenning; Lewellyn, Eric; Turner, William; Francis, Samson

    2015-01-01

    Hepatitis B Virus (HBV) is a small virus whose genome has only four open reading frames. We argue that the simplicity of the virion correlates with a complexity of functions for viral proteins. We focus on the HBV core protein (Cp), a small (183 residue) protein that self-assembles to form the viral capsid. However, its functions are a little more complicated than that. In an infected cell Cp modulates every step of the viral lifecycle. Cp is bound to nuclear viral DNA and affects its epigenetics. Cp correlates with RNA specificity. Cp assembles specifically on a reverse transcriptase-viral RNA complex or, apparently, nothing at all. Indeed Cp has been one of the model systems for investigation of virus self-assembly. Cp participates in regulation of reverse transcription. Cp signals completion of reverse transcription to support virus secretion. Cp carries both nuclear localization signals and HBV surface antigen (HBsAg) binding sites; both of these functions appear to be regulated by contents of the capsid. Cp can be targeted by antivirals -- while self-assembly is the most accessible of Cp activities, we argue that it makes sense to engage the broader spectrum of Cp function. This article forms part of a symposium in Antiviral Research on “From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B: an unfinished story.” PMID:26129969

  19. Core protein: A pleiotropic keystone in the HBV lifecycle.

    PubMed

    Zlotnick, Adam; Venkatakrishnan, Balasubramanian; Tan, Zhenning; Lewellyn, Eric; Turner, William; Francis, Samson

    2015-09-01

    Hepatitis B Virus (HBV) is a small virus whose genome has only four open reading frames. We argue that the simplicity of the virion correlates with a complexity of functions for viral proteins. We focus on the HBV core protein (Cp), a small (183 residue) protein that self-assembles to form the viral capsid. However, its functions are a little more complicated than that. In an infected cell Cp modulates almost every step of the viral lifecycle. Cp is bound to nuclear viral DNA and affects its epigenetics. Cp correlates with RNA specificity. Cp assembles specifically on a reverse transcriptase-viral RNA complex or, apparently, nothing at all. Indeed Cp has been one of the model systems for investigation of virus self-assembly. Cp participates in regulation of reverse transcription. Cp signals completion of reverse transcription to support virus secretion. Cp carries both nuclear localization signals and HBV surface antigen (HBsAg) binding sites; both of these functions appear to be regulated by contents of the capsid. Cp can be targeted by antivirals - while self-assembly is the most accessible of Cp activities, we argue that it makes sense to engage the broader spectrum of Cp function. This article forms part of a symposium in Antiviral Research on "From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B: an unfinished story." PMID:26129969

  20. Undernutrition, the Acute Phase Response to Infection, and Its Effects on Micronutrient Status Indicators12

    PubMed Central

    Bresnahan, Kara A.; Tanumihardjo, Sherry A.

    2014-01-01

    Infection and undernutrition are prevalent in developing countries and demonstrate a synergistic relation. Undernutrition increases infection-related morbidity and mortality. The acute phase response (APR) is an innate, systemic inflammatory reaction to a wide array of disruptions in a host’s homeostasis, including infection. Released from immune cells in response to deleterious stimuli, proinflammatory cytokines act on distant tissues to induce behavioral (e.g., anorexia, weakness, and fatigue) and systemic effects of the APR. Cytokines act to increase energy and protein requirements to manifest fever and support hepatic acute phase protein (APP) production. Blood concentrations of glucose and lipid are augmented to provide energy to immune cells in response to cytokines. Additionally, infection decreases intestinal absorption of nutrients and can cause direct loss of micronutrients. Traditional indicators of iron, zinc, and vitamin A status are altered during the APR, leading to inaccurate estimations of deficiency in populations with a high or unknown prevalence of infection. Blood concentrations of APPs can be measured in nutrition interventions to assess the time stage and severity of infection and correct for the APR; however, standardized cutoffs for nutrition applications are needed. Protein-energy malnutrition leads to increased gut permeability to pathogens, abnormal immune cell populations, and impaired APP response. Micronutrient deficiencies cause specific immune impairments that affect both innate and adaptive responses. This review describes the antagonistic interaction between the APR and nutritional status and emphasizes the need for integrated interventions to address undernutrition and to reduce disease burden in developing countries. PMID:25398733

  1. Microorganisms Causing Community-Acquired Acute Bronchitis: The Role of Bacterial Infection

    PubMed Central

    Park, Ji Young; Park, Sunghoon; Lee, Sun Hwa; Lee, Myung Goo; Park, Yong Bum; Oh, Kil Chan; Lee, Jae-Myung; Kim, Do Il; Seo, Ki-Hyun; Shin, Kyeong-Cheol; Yoo, Kwang Ha; Ko, Yongchun; Jang, Seung Hun; Jung, Ki-Suck; Hwang, Yong Il

    2016-01-01

    Background Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness. Methods We performed a prospective study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012. Sputum specimens were collected for polymerase chain reaction (PCR) and culture of microorganisms. Results Of the 811 enrolled patients, 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution. With multiplex PCR testing, viruses were identified in 36.1% (105/291), most commonly rhinovirus (25.8%) and coronavirus (3.8%). Typical bacteria were isolated in 126/291 (43.3%) patients. Among these patients Haemophilus influenzae (n = 39) and Streptococcus pneumoniae (n = 30) were isolated most commonly; atypical bacteria were identified in 44 (15.1%) patients. Bacteria-only, virus-only, and mixed infections (bacteria plus virus) accounted for 36.7% (98/291), 17.2% (50/291), and 18.9% (55/291) of infections, respectively. In particular, 52.4% of patients with viral infection had a concurrent bacterial infection, and rhinovirus was the most common virus in mixed infections (40/55). Additionally, infections with typical bacteria were more common in patients with chronic lung disease (p = 0.029), and typical bacterial infections showed a trend towards a higher prevalence with older age (p = 0.001). Conclusions Bacteria were associated with almost half of community-acquired acute bronchitis cases. Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment. PMID:27788254

  2. One single nucleotide difference alters the differential expression of spliced RNAs between HBV genotypes A and D.

    PubMed

    Huang, Chien-Chiao; Kuo, Tzer-Min; Yeh, Chau-Ting; Hu, Cheng-Po; Chen, Ya-Ling; Tsai, Yue-Lin; Chen, Mong-Liang; Chou, Yu-Chi; Chang, Chungming

    2013-06-01

    Hepatitis B virus (HBV) is generally classified into eight genotypes (A to H) based on genomic sequence divergence. The sequence variation among the different HBV genotypes suggests that the spliced RNAs should be different from genotype to genotype. However, the cis-acting element involved in the modulation of the distinct expression profiles of spliced HBV RNAs remains unidentified. Moreover, the biological role of splicing in the life cycle of HBV is not yet understood. In this study, spliced RNAs generated from genotypes A and D were carefully characterized in transfected HepG2 cells. The species and frequency of the spliced RNAs were dramatically different in the two genotypes. Of note, a population of multiply spliced RNAs with intron 2067-2350 excision was identified in HBV genotype A-transfected HepG2 cells, but not in genotype D transfected HepG2 cells. Further, we found a single nucleotide difference (2335) located within the polypyrimidine tract of the splice acceptor site 2350 between the two genotypes, and a single base substitution at 2335 was able to convert the splicing pattern of genotype D (or genotype A) to that of genotype A (or genotype D). These findings suggest that different unique splice sites may be preferentially used in different HBV genotypes resulting in distinct populations of spliced RNAs. The possible significance of the distinct spliced RNAs generated from the different HBV genotypes in HBV infection is discussed.

  3. A Pediatric Case of Acute Generalized Pustular Eruption without Streptococcal Infection.

    PubMed

    Tabata, Nobuko; Yoshizawa, Hideka

    2016-01-01

    Generalized pustular lesions characterized by acute onset with fever occur in pustulosis acuta generalisata, acute generalized exanthematous pustulosis, and generalized pustular psoriasis. In the present report, we describe a pediatric case of generalized pustular eruption that was not completely consistent with clinical features. Our patient had no evidence of a post-streptococcal infection. We observed scattered symmetric eruption of discrete pustules with an inflammatory halo on normal skin. The eruption was absent on her palms and soles of the feet. To the best of our knowledge, there are no reports in the English literature of cases with clinical features similar to those of our patient. PMID:27462226

  4. Patterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study

    PubMed Central

    Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly; Kim, Arthur Y.; McGovern, Barbara H.; Cox, Andrea L.; Rice, Thomas M.; Sacks-Davis, Rachel; Bruneau, Julie; Morris, Meghan; Amin, Janaki; Schinkel, Janke; Applegate, Tanya; Maher, Lisa; Hellard, Margaret; Lloyd, Andrew R.; Prins, Maria; Dore, Gregory J.; Grebely, Jason

    2015-01-01

    Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex

  5. Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI

    PubMed Central

    Pfeiler, Susanne; Khandagale, Avinash B.; Magenau, Astrid; Nichols, Maryana; Heijnen, Harry F. G.; Rinninger, Franz; Ziegler, Tilman; Seveau, Stephanie; Schubert, Sören; Zahler, Stefan; Verschoor, Admar; Latz, Eicke; Massberg, Steffen; Gaus, Katharina; Engelmann, Bernd

    2016-01-01

    The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of Ly6C+ (inflammatory) macrophages, and prevented hepatocyte necrosis in the core of infectious foci. Perifocal levels of Ly6C+ macrophages and Ly6C− macrophages were unaffected, indicating predominant regulation of the focus core. SR-BI-triggered autophagy promoted co-elimination of apoptotic immune cells and dead bacteria but barely influenced bacterial sequestration and survival or inflammasome activation, thus exclusively counteracting damage inflicted by immune responses. Hence, SR-BI- and autophagy promote a surveillance pathway that partially responds to products of antimicrobial defenses and selectively prevents immunity-induced damage during acute infection. Our findings suggest that control of infection-associated immunopathology can be based on a unified defense operation. PMID:27694929

  6. Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection

    PubMed Central

    Lühn, Kerstin; Simmons, Cameron P.; Moran, Edward; Dung, Nguyen Thi Phuong; Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thao, Le Thi Thu; Van Ngoc, Tran; Dung, Nguyen Minh; Wills, Bridget; Farrar, Jeremy; McMichael, Andrew J.; Dong, Tao; Rowland-Jones, Sarah

    2007-01-01

    Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4+CD25highFoxP3+ T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease. PMID:17452519

  7. HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection.

    PubMed

    Du, Victor Y; Bansal, Anju; Carlson, Jonathan; Salazar-Gonzalez, Jesus F; Salazar, Maria G; Ladell, Kristin; Gras, Stephanie; Josephs, Tracy M; Heath, Sonya L; Price, David A; Rossjohn, Jamie; Hunter, Eric; Goepfert, Paul A

    2016-04-15

    Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen. PMID:26983786

  8. HIV-1-specific CD8 T cells exhibit limited cross-reactivity during acute infection

    PubMed Central

    Du, Victor Y.; Bansal, Anju; Carlson, Jonathan; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Ladell, Kristin; Gras, Stephanie; Josephs, Tracy M.; Heath, Sonya; Price, David A.; Rossjohn, Jamie; Hunter, Eric; Goepfert, Paul A.

    2016-01-01

    Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, the majority of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T-cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T-cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen. PMID:26983786

  9. Enzyme-linked immunosorbent assay for acute adenovirus infection.

    PubMed

    Roggendorf, M; Wigand, R; Deinhardt, F; Frösner, G G

    1982-02-01

    An enzyme-linked immunosorbent assay (ELISA) is described for demonstrating antibodies to the hexone antigen of adenoviruses. The antigen-coated, flat-bottomed microtiter plates are incubated sequentially with dilutions of patients' sera (2 h at 37 degrees C) and peroxidase-coupled anti-human IgG (2 h at 37 degrees C). After a final washing, orthophenylenediamine is added to the plates, and the absorbance (A) measured 30 min later. The ELISA was found to be a hundred-fold more sensitive than complement fixation. An evaluation methods for determining antibody concentration is described which correlates the absorbance of sera diluted 10(-3) to the absorbance of a reference serum containing an arbitrary value (100) of antibody. This methods avoids titration of sera and day-to-day assay variations by different background reactions. A significant increase in antibody concentration of acute-phase serum over that of convalescent phase serum is observed. The ability to test sera in a single dilution and the automatic reading of results and their evaluation by computer make this assay suitable for diagnostic laboratories.

  10. Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children

    PubMed Central

    Moesker, Fleur M.; van Kampen, Jeroen J. A.; van Rossum, Annemarie M. C.; de Hoog, Matthijs; Koopmans, Marion P. G.; Osterhaus, Albert D. M. E.; Fraaij, Pieter L. A.

    2016-01-01

    Background Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. Objective The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Study Design Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. Results We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Conclusion Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified. PMID:26964038

  11. Bone marrow is a major site of long-term antibody production after acute viral infection.

    PubMed Central

    Slifka, M K; Matloubian, M; Ahmed, R

    1995-01-01

    Antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. Despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. As a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. Using the lymphocytic choriomeningitis virus (LCMV) model, we found that after resolution of the acute infection, when antiviral plasma cells in the spleen decline, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production. Following infection of adult mice, LCMV-specific antibody-secreting cells (ASC) peaked in the spleen at 8 days postinfection but were undetectable in the bone marrow at that time. The infection was essentially cleared by 15 days, and the ASC numbers in the spleen rapidly declined while an increasing population of LCMV-specific ASC began to appear in the bone marrow. Compared with the peak response at 8 days postinfection, time points from 30 days to more than 1 year later demonstrated greater-than-10-fold reductions in splenic ASC. In contrast, LCMV-specific plasma cell numbers in the bone marrow remained high and correlated with the high levels of antiviral serum antibody. The presence of LCMV-specific plasma cells in the bone marrow was not due to persistent infection at this site, since the virus was cleared from both the spleen and bone marrow with similar kinetics as determined by infectivity and PCR assays. The immunoglobulin G subclass profile of antibody-secreting cells derived from bone marrow and the spleen correlated with the immunoglobulin G subclass distribution of LCMV-specific antibody in the serum. Upon rechallenge with LCMV, the spleen exhibited a substantial increase in virus-specific plasma cell numbers during the early phase

  12. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy

    PubMed Central

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-01-01

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research. PMID:27468190

  13. Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

    PubMed

    Wiegand, J; Wedemeyer, H; Franke, A; Rößler, S; Zeuzem, S; Teuber, G; Wächtler, M; Römmele, U; Ruf, B; Spengler, U; Trautwein, C; Bock, C T; Fiedler, G M; Thiery, J; Manns, M P; Brosteanu, O; Tillmann, H L

    2014-10-01

    Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 μm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 μm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 μm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

  14. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic

  15. Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

    PubMed Central

    El-Diwany, Ramy; Wasilewski, Lisa N.; Witwer, Kenneth W.; Bailey, Justin R.; Page, Kimberly; Ray, Stuart C.; Cox, Andrea L.; Thomas, David L.

    2015-01-01

    ABSTRACT Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe

  16. Invasive fungal infection of the central nervous system in a patient with acute myeloid leukaemia

    PubMed Central

    Janik-Moszant, Anna; Matyl, Aleksander; Rurańska, Iwona; Machowska-Majchrzak, Agnieszka; Kluczewska, Ewa; Szczepański, Tomasz

    2012-01-01

    Summary Background: Although the new intensive chemotherapeutic programs introduced recently into hematooncological therapies have led to a higher number of recoveries, persistent neutropenia favours the spread of severe infections, frequently fungal infections. Systemic fungal infections in patients treated for proliferative diseases of the hematopoietic system are characterised by a severe, progressing course and high morbidity. Case Reports: We present a case report that demonstrates the diagnostic problem of lesions in the central nervous system which developed following the fourth block of chemotherapy in an eight-year-old boy treated for acute myeloid leukaemia. The risk factors, high values of the inflammatory parameters and imaging results enabled us to diagnose a fungal infection of the central nervous system. Results: A fast improvement in the clinical condition of the patient after the applied antifungal therapy and the regression of lesions in the central nervous system shown in the imaging studies confirmed our final diagnosis. PMID:22802867

  17. Depletion of alveolar macrophages prolongs survival in response to acute pneumovirus infection

    PubMed Central

    Rigaux, Peter; Killoran, Kristin E.; Qiu, Zhijun; Rosenberg, Helene F.

    2011-01-01

    Alveolar macrophages are immunoregulatory effector cells that interact directly with respiratory virus pathogens in vivo. We examined the role of alveolar macrophages in acute infection with pneumonia virus of mice (PVM), a rodent pneumovirus that replicates the clinical sequelae of severe human respiratory syncytial virus disease. We show that PVM replicates in primary mouse macrophage culture, releasing infectious virions and proinflammatory cytokines. Alveolar macrophages isolated from PVM-infected mice express activation markers Clec43 and CD86, cytokines TNFα, IL-1, IL-6, and numerous CC and CXC chemokines. Alveolar macrophage depletion prior to PVM infection results in small but statistically significant increases in virus recovery but paradoxically prolonged survival. In parallel, macrophage depleted PVM-infected mice exhibit enhanced NK cell recruitment and increased production of IFNγ by NK, CD4+ and CD8+ T cells. These results suggest a protective, immunomodulatory role for IFNγ, as overproduction secondary to macrophage depletion may promote survival despite increased virus recovery. PMID:22129848

  18. Analysis of reference gene stability after Israeli acute paralysis virus infection in bumblebees Bombus terrestris.

    PubMed

    Niu, Jinzhi; Cappelle, Kaat; de Miranda, Joachim R; Smagghe, Guy; Meeus, Ivan

    2014-01-01

    To date, there are no validated internal reference genes for the normalization of RT-qPCR data from virus infection experiments with pollinating insects. In this study we evaluated the stability of five candidate internal reference genes: elongation factor-1-alpha (ELF1α), peptidylprolyl isomerase A (PPIA), 60S ribosomal protein L23 (RPL23), TATA-binding protein (TBP) and polyubiquitin (UBI), in relation to Israeli acute paralysis virus (IAPV) infection of Bombus terrestris. We investigated the stability of these genes: in whole bodies and individual body parts, as well as in whole bodies collected at different time intervals after infection with IAPV. Our data identified PPIA as the single, most-optimal internal reference gene and the combination of PPAI-RPL23-UBI as a fully-sufficient multiple internal reference genes set for IAPV infection experiments in B. terrestris.

  19. Anemia and mechanism of erythrocyte destruction in ducks with acute Leucocytozoon infections

    USGS Publications Warehouse

    Kocan, R.M.

    1968-01-01

    In the anemia which accompanies infection by Leucocytozoon simondi in Pekin ducks there was a far greater loss of erythrocytes than could be accounted for as a result of direct physical rupture by the parasite. Erythrocyte loss began at the same time the 1st parasites appeared in the blood and was severest just prior to maximum parasitemia. Blood replacement and parasite loss occurred simultaneously. Examination of the spleen and bone marrow revealed that erythrophagocytosis was not the cause of anemia as reported for infections of Plasmodium, Babesia and Anaplasma. An anti-erythrocyte (A-E) factor was found in the serum of acutely infected ducks which agglutinated and hemolyzed normal untreated duck erythrocytes as well as infected cells. This A-E factor appeared when the 1st red cell loss was detected and reached its maximum titer just prior to the greatest red cell loss. Titers of the A-E factor were determined using normal uninfected erythrocytes at temperatures between 4 and 42 C. Cells agglutinated below 25 C and hemolyzed at 37 and 42 C. These results indicated that the A-E factor could be responsible for loss of cells other than those which were infected and could thus produce an excess loss of red cells. Attempts to implicate the A-E factor as an autoantibody were all negative. The A-E factor was present in the gamma fraction of acute serum but no anamnestic response could be detected when recovered ducks were reinfected. Anemia was never as severe in reinfections as in primary infections. The A-E factor also never reached as high a titer and was removed from the circulation very rapidly in reinfected ducks. It is concluded that red cell loss in ducks with acute Leucocytozoon disease results from intravascular hemolysis rather than erythrophagocytosis. The A-E factor responsible for hemolysis is more likely a parasite product rather than autoantibody.

  20. [Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

    PubMed

    Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

    2009-01-01

    The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic.

  1. Saving the limb in diabetic patients with ischemic foot lesions complicated by acute infection.

    PubMed

    Clerici, Giacomo; Faglia, Ezio

    2014-12-01

    Ischemia and infection are the most important factors affecting the prognosis of foot ulcerations in diabetic patients. To improve the outcome of these patients, it is necessary to aggressively treat 2 important pathologies--namely, occlusive arterial disease affecting the tibial and femoral arteries and infection of the ischemic diabetic foot. Each of these 2 conditions may lead to major limb amputation, and the presence of both critical limb ischemia (CLI) and acute deep infection is a major risk factor for lower-extremity amputation. Thus, the management of diabetic foot ulcers requires specific therapeutic approaches that vary significantly depending on whether foot lesions are complicated by infection and/or ischemia. A multidisciplinary team approach is the key to successful treatment of a diabetic foot ulcer: ischemic diabetic foot ulcers complicated by acute deep infection pose serious treatment challenges because high levels of skill, organization, accuracy, and timing of intervention are required to maximize the chances of limb salvage: these complex issues are better managed by a multidisciplinary clinical group.

  2. Perceived social support among adults seeking care for acute respiratory tract infections in US EDs.

    PubMed

    Levin, Sara K; Metlay, Joshua P; Maselli, Judith H; Kersey, Ayanna S; Camargo, Carlos A; Gonzales, Ralph

    2009-06-01

    Emergency departments (EDs) provide a disproportionate amount of care to disenfranchised and vulnerable populations. We examined social support levels among a diverse population of adults seeking ED care for acute respiratory tract infections. A convenience sample of adults seeking care in 1 of 15 US EDs was telephone interviewed 1 to 6 weeks postvisit. The Multidimensional Scale of Perceived Social Support (7-point Likert) assessed social support across 3 domains: friends, family, and significant others. Higher scores indicate higher support. Of 1104 subjects enrolled, 704 (64%) completed the follow-up interview. Factor analysis yielded 3 factors. Mean social support score was 5.54 (SD 1.04). Female sex, greater household income, and better health status were independently associated with higher levels of social support. Social support levels among adults seeking care in the ED for acute respiratory tract infections are similar to general population cohorts, suggesting that social support is not a strong determinant of health care seeking in EDs.

  3. Influenza Virus-Associated Fatal Acute Necrotizing Encephalopathy: Role of Nonpermissive Viral Infection?

    PubMed Central

    Mungaomklang, Anek; Chomcheoy, Jiraruj; Wacharapluesadee, Supaporn; Joyjinda, Yutthana; Jittmittraphap, Akanitt; Rodpan, Apaporn; Ghai, Siriporn; Saraya, Abhinbhen; Hemachudha, Thiravat

    2016-01-01

    In 2014, two unusual peaks of H1N1 influenza outbreak occurred in Nakhon Ratchasima Province, in Thailand. Among 2,406 cases, one of the 22 deaths in the province included a 6-year-old boy, who initially presented with acute necrotizing encephalopathy. On the other hand, his sibling was mildly affected by the same influenza virus strain, confirmed by whole-genome sequencing, with one silent mutation. Absence of acute necrotizing encephalopathy and other neurological illnesses in the family and the whole province, with near identical whole viral genomic sequences from the two siblings, and an absence of concomitant severe lung infection (cytokine storm) at onset suggest nonpermissive infection as an alternative pathogenetic mechanism of influenza virus. PMID:27812294

  4. Management of acute respiratory infections by community health volunteers: experience of Bangladesh Rural Advancement Committee (BRAC).

    PubMed Central

    Hadi, Abdullahel

    2003-01-01

    OBJECTIVE: To assess the role of management practices for acute respiratory infections (ARIs) in improving the competency of community health volunteers in diagnosing and treating acute respiratory infections among children. METHODS: Data were collected by a group of research physicians who observed the performance of a sample of 120 health volunteers in 10 sub-districts in Bangladesh in which Bangladesh Rural Advancement Committee (BRAC) had run a community-based ARI control programme since mid-1992. Standardized tests were conducted until the 95% interphysician reliability on the observation of clinical examination was achieved. FINDINGS:The sensitivity, specificity, and overall agreement rates in diagnosing and treating ARIs were significantly higher among the health volunteers who had basic training and were supervised routinely than among those who had not. CONCLUSION: Diagnosis and treatment of ARIs at the household level in developing countries are possible if intensive basic training and the close supervision of service providers are ensured. PMID:12764514

  5. The prevalence of molecular and immunologic infective markers of hepatitis viruses in patients with hematological malignancies.

    PubMed

    Mirzaee, Mitra; Yaghobi, Ramin; Ramzi, Mani; Roshan Nia, Mahdi

    2012-02-01

    Acute and chronic viral hepatitis infections are corresponding to increase the risk of different types of hematological malignancies especially with leukemia. In this study the serological and molecular markers of hepatitis viruses were evaluated in patients with different types of leukemia in comparing with control group. In this cross sectional study, 100 EDTA-treated blood samples were collected from leukemia patients and also from healthy control group, respectively. Serological and molecular markers of HBV, HCV and HDV viruses were analyzed for determination of the role of these hepatitis viruses in clinical outcomes of leukemia disorders. Increasing risk factors of leukemia were evaluated statistically in two studied groups by SPSS software. One of molecular and immunological markers of HBV, HDV and HCV was found in 24 of 100 (24%), 22 of 100 (22%), and 1 of 100 (1%) patients with leukemia and in 12 of 100 (12%), 6 of 100 (6%), and 2 of 100 (2%) control patients. Significant differences were detected in detection of HBsAg (P = 0.02), HBeAb (P = 0.009), and HCV-RNA (P = 0.05) between leukemia patients and control group, respectively. The high prevalence of HBV and HCV infective markers were detected in ALL and AML patients. Identification of high prevalence of HBV and HCV infective markers in leukemia patients proposed strong association between hepatitis viral infections and leukemia. Therefore, evaluation of the prevalence of viral hepatitis infections in larger groups of patients with long lasting follow up is suggesting.

  6. Hepatitis B virus infection in Latin America: A genomic medicine approach

    PubMed Central

    Roman, Sonia; Jose-Abrego, Alexis; Fierro, Nora Alma; Escobedo-Melendez, Griselda; Ojeda-Granados, Claudia; Martinez-Lopez, Erika; Panduro, Arturo

    2014-01-01

    Hepatitis B virus (HBV) infection is the leading cause of severe chronic liver disease. This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America. Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection. Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America; these strains have historically circulated among the indigenous population. Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans. In contrast, genotypes F, A and D are common in acute and chronic infections among mestizos with Caucasian ancestry. Hepatocellular carcinoma is rare in Mexicans, but it has been associated with genotype F1b among Argentineans. This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America, which contrast with those reported in other regions of the world. PMID:24966588

  7. Hepatitis B virus infection in Latin America: a genomic medicine approach.

    PubMed

    Roman, Sonia; Jose-Abrego, Alexis; Fierro, Nora Alma; Escobedo-Melendez, Griselda; Ojeda-Granados, Claudia; Martinez-Lopez, Erika; Panduro, Arturo

    2014-06-21

    Hepatitis B virus (HBV) infection is the leading cause of severe chronic liver disease. This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America. Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection. Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America; these strains have historically circulated among the indigenous population. Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans. In contrast, genotypes F, A and D are common in acute and chronic infections among mestizos with Caucasian ancestry. Hepatocellular carcinoma is rare in Mexicans, but it has been associated with genotype F1b among Argentineans. This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America, which contrast with those reported in other regions of the world.

  8. Acute Shunt Malfunction Caused by Percutaneous Endoscopic Gastrostomy without Shunt Infection

    PubMed Central

    Choi, Jingyu; Ki, Seung Seog

    2014-01-01

    Percutaneous endoscopic gastrostomy tube placement is often performed in patients with a ventriculoperitoneal shunt and it has been accepted as a safe procedure. The authors report a case of a 50-year-old male who developed acute exacerbation of the hydrocephalus immediately after the percutaneous endoscopic gastrostomy tube placement without any signs of shunt infection, which has not been reported until now. After revision of the intraperitoneal shunt catheter, the sizes of the intracranial ventricles were normalized. PMID:25371790

  9. Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in Argentine children

    PubMed Central

    Carballal, Guadalupe; Videla, Cristina; Misirlian, Alicia; Requeijo, Paula V; Aguilar, María del Carmen

    2002-01-01

    Background Adenoviruses are the second most prevalent cause of acute lower respiratory infection of viral origin in children under four years of age in Buenos Aires, Argentina. The purpose of this study was to analyze the clinical features and outcome of acute lower respiratory infection associated with different adenovirus genotypes in children. Methods Twenty-four cases of acute lower respiratory infection and adenovirus diagnosis reported in a pediatric unit during a two-year period were retrospectively reviewed. Adenovirus was detected by antigen detection and isolation in HEp-2 cells. Adenovirus DNA from 17 isolates was studied by restriction enzyme analysis with Bam HI and Sma I. Results Subgenus b was found in 82.3% of the cases, and subgenus c in 17.7%. Within subgenus b, only genotype 7 was detected, with genomic variant 7h in 85.7% (12/14) and genomic variant 7i in 14.3% (2/14). Mean age was 8.8 ±; 6 months, and male to female ratio was 3.8: 1. At admission, pneumonia was observed in 71% of the cases and bronchiolitis in 29%. Malnutrition occurred in 37% of the cases; tachypnea in 79%; chest indrawing in 66%; wheezing in 58%; apneas in 16%; and conjunctivitis in 29%. Blood cultures for bacteria and antigen detection of other respiratory viruses were negative. During hospitalization, fatality rate was 16.7% (4 /24). Of the patients who died, three had Ad 7h and one Ad 7i. Thus, fatality rate for adenovirus type 7 reached 28.6% (4/14). Conclusions These results show the predominance of adenovirus 7 and high lethality associated with the genomic variants 7h and 7i in children hospitalized with acute lower respiratory infection. PMID:12184818

  10. Complete Genome Sequence of a Novel Human WU Polyomavirus Isolate Associated with Acute Respiratory Infection

    PubMed Central

    Dehority, Walter N.; Schwalm, Kurt C.; Young, Jesse M.; Gross, Stephen M.; Schroth, Gary P.; Young, Stephen A.

    2016-01-01

    We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, NM040708, collected from a patient with an acute respiratory infection in New Mexico. The double-stranded DNA (dsDNA) genome of NM040708 is 5,229 bp in length and differs from the WUPyV reference with accession no. NC_009539 by 6 nucleotides and 2 amino acids. PMID:27151782

  11. Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

    PubMed Central

    Sun, Hsin-Yun; Sheng, Wang-Huei; Tsai, Mao-Song; Lee, Kuan-Yeh; Chang, Sui-Yuan; Hung, Chien-Ching

    2014-01-01

    Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients. PMID:25356024

  12. HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

    PubMed

    Mamun-Al-Mahtab; Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-02-01

    Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in

  13. Respiratory virus infection as a cause of prolonged symptoms in acute otitis media.

    PubMed

    Arola, M; Ziegler, T; Ruuskanen, O

    1990-05-01

    We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.

  14. Levofloxacin in the treatment of complicated urinary tract infections and acute pyelonephritis

    PubMed Central

    McGregor, Jessina C; Allen, George P; Bearden, David T

    2008-01-01

    Levofloxacin is a widely used fluoroquinolone approved for the treatment of complicated urinary tract infections and acute pyelonephritis. A comprehensive review of the medical literature identified five publications evaluating levofloxacin for the treatment of either complicated urinary tract infections or acute pyelonephritis. All trials, although variable in their inclusion criteria and levofloxacin dosing strategies, reported microbiologic, clinical, and safety-related outcomes. High microbiologic eradication rates, ranging from 79.8% to 95.3%, were observed in all studies. Escherichia coli was the most commonly isolated uropathogen. Data on levofloxacin resistance, both at baseline and after therapy, were limited. Clinical success was observed to range from 82.6% to 93% when measured after the completion of therapy. These clinical and microbiologic results were comparable to the fluoroquinolone comparators in all trials. Insufficient data are available to evaluate the outcomes in any meaningful patient subgroups, including catheterized patients, and those with other specific complicating factors. Levofloxacin was well tolerated in these studies, with headache, gastrointenstinal effects, and dizziness being the most commonly reported adverse events. The published data support the use of levofloxacin in complicated urinary tract infections and acute pyelonephritis. Further trials are necessary to evaluate levofloxacin within specific patient sub-populations. PMID:19209267

  15. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    PubMed Central

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  16. Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

    SciTech Connect

    Sun, Zhen; Xiang, Wenqing; Guo, Yajuan; Chen, Zhi; Liu, Wei; Lu, Daru

    2011-06-10

    Highlights: {yields} LNA-modified oligonucleotides can pass through the plasma membrane of cultured cells even without using transfection machinery. {yields} LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. {yields} LNA-oligonucleotide designed to target nuclear HBV DNA efficiently suppresses HBV replication and transcription in cultured hepatic cells. -- Abstract: Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently, triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry of oligonucleotides and enhancement of their affinity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modified oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more efficiently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modified oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-modified oligonucleotides has strong potential as a new strategy for HBV inhibition.

  17. Rapid Development of gp120-Focused Neutralizing B Cell Responses during Acute Simian Immunodeficiency Virus Infection of African Green Monkeys

    PubMed Central

    Amos, Joshua D.; Himes, Jonathon E.; Armand, Lawrence; Gurley, Thaddeus C.; Martinez, David R.; Colvin, Lisa; Beck, Krista; Overman, R. Glenn; Liao, Hua-Xin; Moody, M. Anthony

    2015-01-01

    ABSTRACT The initial phases of acute human immunodeficiency virus type 1 (HIV-1) infection may be critical for development of effective envelope (Env)-specific antibodies capable of impeding the establishment of the latent pool of HIV-1-infected CD4+ T cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical virus transmission. However, the initial systemic HIV-1 Env-specific antibody response targets gp41 epitopes and fails to control acute-phase viremia. African-origin, natural simian immunodeficiency virus (SIV) hosts do not typically progress to AIDS and rarely postnatally transmit virus to their infants, despite high milk viral loads. Conversely, SIV-infected rhesus macaques (RMs), Asian-origin nonnatural SIV hosts, sustain pathogenic SIV infections and exhibit higher rates of postnatal virus transmission. In this study, of acute SIV infection, we compared the initial systemic Env-specific B cell responses of AGMs and RMs in order to probe potential factors influencing the lack of disease progression observed in AGMs. AGMs developed higher-magnitude plasma gp120-specific IgA and IgG responses than RMs, whereas RMs developed more robust gp140-directed IgG responses. These gp120-focused antibody responses were accompanied by rapid autologous neutralizing responses during acute SIV infection in AGMs compared to RMs. Moreover, acute SIV infection elicited a higher number of circulating Env-specific memory B cells in peripheral blood of AGMs than in the blood of RMs. These findings indicate that AGMs have initial systemic Env-specific B cell responses to SIV infection distinct from those of a nonnatural SIV host, resulting in more functional SIV-specific humoral responses, which may be involved in impairing pathogenic disease progression and minimizing postnatal transmission. IMPORTANCE Due to the worldwide prevalence of HIV-1 infections, development of a vaccine to prevent infection or limit the viral reservoir

  18. Immunoglobulin G antibody response in children and adults with acute dengue 3 infection.

    PubMed

    Vazquez, Susana; Acosta, Nadia; Ruiz, Didye; Calzada, Naifi; Alvarez, Angel M; Guzman, Maria G

    2009-07-01

    Using a serological test, different criteria have been established for classifying a case as primary or secondary dengue virus infection. Considering the dengue epidemiological situation in Cuba, IgG antibody response to dengue virus infection in serum samples from children and adults with a dengue 3 infection, in Havana city during the 2001-2002 epidemic was evaluated. Samples were collected on days 5-7 of fever onset and tested by an ELISA inhibition. A total of 713 serum samples positive for IgM antibody, 93 from children and 620 from adult patients were studied. Serum samples collected from healthy blood donors and patients not infected with dengue were included as controls. An IgG primary infection pattern was observed in sera collected from children, with titers of < or =20 in the 89.3% of the patients, while both, a primary and secondary patterns were observed in sera collected from adult patients with titers of < or =20 (13.4%) and > or =1280 (83.9%), respectively. These results permitted the definition of a primary or secondary case of dengue virus infection in serum samples collected during the acute phase of dengue virus infection.

  19. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.

    PubMed

    Page, Carly; Goicochea, Lindsay; Matthews, Krystal; Zhang, Yong; Klover, Peter; Holtzman, Michael J; Hennighausen, Lothar; Frieman, Matthew

    2012-12-01

    Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(-/-) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(-/-) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA

  20. Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus

    PubMed Central

    2012-01-01

    Background Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer’s Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined. Results Plasma IgA level was reduced by 46% by 28 days post infection (dpi), and no IgA plasma cells were found within germinal centers of Peyer’s Patches and isolated lymphoid follicles. This lack of a T-dependent IgA response occurs although germinal centers remained functional with no sign of follicular damage, while a prolonged survival of follicular CD4+ T-cells and normal generation of IgG plasma cells is observed. Whereas the average plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to 1.9-fold more numerous in the lamina propria, the relative proportion of IgA plasma cells in this effector site was reduced by 19% (duodemun) to 35% (ileum) at 28 dpi. Conclusion Our data provide evidence that SIV is unable to initiate a T-dependent IgA response during the acute phase of infection and favors the production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA plasma cells. Therefore, an early and generalized default in IgA production takes place during the acute of phase of HIV/SIV infection, which might impair not only the virus-specific antibody response but also IgA responses to other pathogens and

  1. Screening, detecting and enhancing the yield of previously undiagnosed hepatitis B and C in patients with acute medical admissions to hospital: A pilot project undertaken at the Vancouver General Hospital

    PubMed Central

    Kapeluto, Jordanna E; Kadatz, Matthew; Wormsbecker, Andrew; Sidhu, Kiran; Yoshida, Eric M

    2014-01-01

    BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent an increasing health burden and morbidity in Canada. Viral hepatitis, specifically HCV, has high prevalence among persons born between 1945 and 1965, with 45% to 85% of infected adults asymptomatic and unaware of their infection. Screening has been shown to be cost effective in the detection and treatment of viral hepatitis. OBJECTIVE: To quantify incidence and identify undocumented HBV and HCV infection in hospitalized patients at a single centre with secondary analysis of risk factors as part of a quality improvement initiative. METHODS: A one-time antibody test was conducted in patients admitted to the acute medicine and gastroenterology services. RESULTS: Over a 12-week period, hospital screening for HBV and HCV was performed in 37.3% of 995 admitted patients. There was identification of 15 previously undiagnosed cases of HCV (4%) and 36 undocumented cases of occult (ie, antihepatitis B core antigen seropositive) or active (ie, hepatitis B surface antigen seropositive) HBV (9.7%). Among patients with positive screens, 60% of seropositive HCV patients had no identifiable risk factors. CONCLUSIONS: The prevalence of HBV and HCV infection among hospitalized patients in Vancouver was higher than that of the general population. Risk factors for contraction are often not identified. These results can be used as part of an ongoing discussion regarding a ‘seek and treat’ approach to the detection and treatment of chronic blood-borne viral illnesses. PMID:24945186

  2. Validating a decision tree for serious infection: diagnostic accuracy in acutely ill children in ambulatory care

    PubMed Central

    Verbakel, Jan Y; Lemiengre, Marieke B; De Burghgraeve, Tine; De Sutter, An; Aertgeerts, Bert; Bullens, Dominique M A; Shinkins, Bethany; Van den Bruel, Ann; Buntinx, Frank

    2015-01-01

    Objective Acute infection is the most common presentation of children in primary care with only few having a serious infection (eg, sepsis, meningitis, pneumonia). To avoid complications or death, early recognition and adequate referral are essential. Clinical prediction rules have the potential to improve diagnostic decision-making for rare but serious conditions. In this study, we aimed to validate a recently developed decision tree in a new but similar population. Design Diagnostic accuracy study validating a clinical prediction rule. Setting and participants Acutely ill children presenting to ambulatory care in Flanders, Belgium, consisting of general practice and paediatric assessment in outpatient clinics or the emergency department. Intervention Physicians were asked to score the decision tree in every child. Primary outcome measures The outcome of interest was hospital admission for at least 24 h with a serious infection within 5 days after initial presentation. We report the diagnostic accuracy of the decision tree in sensitivity, specificity, likelihood ratios and predictive values. Results In total, 8962 acute illness episodes were included, of which 283 lead to admission to hospital with a serious infection. Sensitivity of the decision tree was 100% (95% CI 71.5% to 100%) at a specificity of 83.6% (95% CI 82.3% to 84.9%) in the general practitioner setting with 17% of children testing positive. In the paediatric outpatient and emergency department setting, sensitivities were below 92%, with specificities below 44.8%. Conclusions In an independent validation cohort, this clinical prediction rule has shown to be extremely sensitive to identify children at risk of hospital admission for a serious infection in general practice, making it suitable for ruling out. Trial registration number NCT02024282. PMID:26254472

  3. Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

    PubMed Central

    Coelho, Ana Maria M.; Sampietre, Sandra; Patzina, Rosely; Jukemura, Jose; Cunha, Jose Eduardo M.; Machado, Marcel C.C.

    2007-01-01

    Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy. PMID:18345325

  4. Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1.

    PubMed Central

    Cantin, E M; Hinton, D R; Chen, J; Openshaw, H

    1995-01-01

    This study was initiated to evaluate a role for gamma interferon (IFN-gamma) in herpes simplex virus type 1 (HSV-1) infection. At the acute stage of infection in mice, HSV-1 replication in trigeminal ganglia and brain stem tissue was modestly but consistently enhanced in mice from which IFN-gamma was by ablated monoclonal antibody treatment and in mice genetically lacking the IFN-gamma receptor (Rgko mice). As determined by reverse transcriptase PCR, IFN-gamma and tumor necrosis factor alpha transcripts were present in trigeminal ganglia during both acute and latent HSV-1 infection. CD4+ and CD8+ T cells were detected initially in trigeminal ganglia at day 5 after HSV-1 inoculation, and these cells persisted for 6 months into latency. The T cells were focused around morphologically normal neurons that showed no signs of active infection, but many of which expressed HSV-1 latency-associated transcripts. Secreted IFN-gamma was present up to 6 months into latency in areas of the T-cell infiltration. By 9 months into latency, both the T-cell infiltrate and IFN-gamma expression had cleared, although there remained a slight increase in macrophage levels in trigeminal ganglia. In HSV-1-infected brain stem tissue, T cells and IFN-gamma expression were present at 1 month but were gone by 6 months after infection. Our hypothesis is that the persistence of T cells and the sustained IFN-gamma expression occur in response to an HSV-1 antigen(s) in the nervous system. This hypothesis is consistent with a new model of HSV-1 latency which suggests that limited HSV-1 antigen expression occurs during latency (M. Kosz-Vnenchak, J. Jacobson, D.M. Coen, and D.M. Knipe, J. Virol. 67:5383-5393, 1993). We speculate that prolonged secretion of IFN-gamma during latency may modulate a reactivated HSV-1 infection. PMID:7609058

  5. The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients

    PubMed Central

    Ghorbani, Raheb; Afshar, Reza Kiaee

    2015-01-01

    Background Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. Objectives The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. Materials and Methods In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. Results Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients’ categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). Conclusion Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID:26676277

  6. [Interaction of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus in mammals with mixed infec