Mother-to-infant transmission of multiple blood-borne viral infections from multi-infected mothers

Infants born from mothers with multiple blood-borne viral infections are at risk of multiple transmissions. Whether the risk of transmission of multiple infections increases with the number of viruses infecting the mother is still unknown. The aim of this study was to describe the risk of mother-to-infant transmission of multiple infections from multi-infected mothers. Sixty-four pregnant women infected by at least two viruses among human immunodeficiency virus-type 1 (HIV-1), hepatitis C virus, TT virus, and GB virus type C, together with their 64 infants, were studied. Maternal blood samples were collected in the third trimester of pregnancy and all infants were prospectively followed for evaluation of transmission within 3 months after birth and two times in the subsequent 24 months. Transmission of single and of dual infection from mothers infected by two viruses was, respectively, 10/40 (25%) and 5/40 (12.5%) and from mothers infected by three viruses 9/20 (45%) and 2/20 (10%). One (25%) infant infected by one virus was born from the four mothers infected by four viruses. Transmission of single or dual infection was not significantly associated with the number of viruses infecting the mother (P = 0.9) in the linear regression analysis. Present study suggests the absence of a synergistic effect from viral interactions toward mother-to-infant transmission of multiple infections and supports the hypothesis that transmission from multi-infected mothers is the result of the specific interaction between each virus and the host. These observations may be of clinical relevance in perinatal counseling.     

E. coli-expressed recombinant norovirus capsid proteins maintain authentic antigenicity and receptor binding capability

The baculovirus expression system has been widely used to produce the capsid proteins of Norovirus (NV) and the proteins form virus-like particles (VLPs) that are useful in many studies, such as immunology, diagnosis, and host-receptor interaction. We report here the application of the E. coli expression system in the production of recombinant NV capsid proteins. In a direct comparison of a previous well-characterized NV strain (VA387), we have demonstrated that the E. coli-expressed capsid proteins maintain the same antigenicity and receptor binding specificity as that of the baculovirus-expressed capsid, although the E. coli-expressed VA387 proteins did not form VLPs. Using the E. coli-expression system, we characterized the receptor-binding patterns of three additional NV strains (OIF1998, Parris Island and VA115), in which OIF1998 binds to HBGA of nonsecretors but did not bind or binds weakly to the HBGA of secretors, as seen in strain VA207. Parris Island binds to HBGA of types A and B but not type O secretors and nonsecretors. VA115 did not show specific binding to any A, B, O secretor nor nonsecretor, which is also observed when the capsid protein of this strain was expressed in baculovirus. Our data indicate that VLP formation is not required for receptor binding, and that the bacteria expression system offers a simple alternative for large production of NV capsid protein for various research purposes, particularly for strains generating low yields in the insect cells.     

Acute West Nile virus neuroinvasive infections: cross-reactivity with dengue virus and tick-borne encephalitis virus

Cross-reactions in serology are common among flaviviruses. During the outbreak of West Nile virus (WNV) infections in Greece in 2010, WNV IgM-positive serum and cerebrospinal fluid samples were tested for the presence of IgM and IgG antibodies against Dengue virus (DENV) and tick-borne encephalitis virus. Higher cross-reactivity was observed in IgM antibodies between WNV and DENV; however, the index of the WNV antibodies was in all cases higher than that of the DENV antibodies. There is a need for caution when evaluating serologic results of flaviviral infections, while efforts have to be focused on the development of diagnostic assays with increased specificity.     

Viral etiology of sporadic cases of parotitis among children in Korea during 2013‐2014

Recent years have seen a high incidence of mumps, which is generally diagnosed based on clinical features, especially parotitis, without laboratory confirmation in Korea. To better understand the epidemiology of mumps in Korean children, we investigated sporadic suspected mumps cases with parotitis. In total, 237 buccal swabs or throat swabs collected from children with parotitis who had been clinically diagnosed with mumps were tested using real‐time PCR for the detection of six viruses (Epstein‐Barr virus, Human herpesvirus 6, Mumps virus, Human parainfluenza virus‐1, ‐2, ‐3, Human adenovirus, Human bocavirus). Among 237 parotitis cases, 87 (36.7%) were positive for at least one virus; a single infection was observed in 73 (83.9%) cases, and co‐infections were detected in 14 (16.1%) cases. Epstein‐Barr virus was most frequent (20.7%), followed by human herpesvirus 6 (8.0%), mumps virus (5.5%), human parainfluenza virus‐3 (4.6%), human adenovirus (4.2%), and human bocavirus (0.4%). These data suggested that the sporadic suspected mumps in the children might be related to other respiratory viruses rather than to the mumps virus. Our findings also indicate the limitation of clinical diagnosis without laboratory confirmation for mumps and thus highlight the importance of laboratory testing in suspected mumps cases.     

Viral etiology,clinical and laboratory features of adult hemophagocytic lymphohistiocytosis

Secondary hemophagocytic lymphohistiocytosis (SHLH) is a potentially fatal hyperinflammatory syndrome with a heterogeneous etiology and has nonspecific clinical and laboratory findings. The diagnosis and treatment of adult SHLH is challenging because the etiology of the disease is difficult to identify, and the majority of reported cases are pediatric patients. The aim of this study was to describe the etiology, clinical characteristics, and outcomes of adult SHLH. Fifty‐four adult patients who fulfilled the criteria of SHLH were enrolled in the study. Viral etiology, blood biomarkers, and clinical manifestations of SHLH were analyzed in these patients. Twenty‐four SHLH patients had viraemia, whereas 30 SHLH patients were secondary to other diseases. Epstein‐Barr virus (EBV) was the most common virus that associated SHLH among all viruses studied. Severe SHLH patients with EBV‐viraemia presented significantly high levels of ferritin, lactate dehydrogenase, aspartate transaminase (AST), and alanine transaminase (ALT). Positively relationships existed between EBV DNA titers and levels of AST and ALT (P < 0.05). The prognosis of SHLH patients with EBV viraemia was worse than that of non‐EBV SHLH and non‐viral SHLH. Our data reveal that EBV is the major pathogen in virus‐associated SHLH, and EBV load influence disease development in SHLH patients with EBV infection that prognosis is worse than other viruses associated SHLH. J. Med. Virol. 88:541–549, 2016. © 2015 Wiley Periodicals, Inc.

     

Increased detection of HBV DNA in HBsAg‐positive and HBsAg‐negative South African HIV/AIDS patients enrolling for highly active antiretroviral therapy at a Tertiary Hospital

This retrospective study investigated the prevalence of hepatitis B virus (HBV) in 192 stored sera from human immunodeficiency virus (HIV) positive South African patients initiating antiretroviral therapy (ART), and explored the implications of HBV–HIV co‐infection on laboratory diagnosis of HBV. HBV serology (HBsAg, anti‐HBs and anti‐HBc) and nested HBV PCR assays targeting the HBV polymerase gene were performed, with HBV DNA positive samples being quantified with Cobas Taqman HBV test 48 assay (Roche Diagnostics). The study found that 63% (121/192) of patients had past or present HBV infection, and 40.6% (78/192) had detectable HBV DNA. Also, 22.9% (44/192) of patients were HBsAg positive and HBV DNA positive, while 23% (34/148) of HBsAG negatives had occult HBV infections. Of the 78 HBV DNA positive samples, 62.8% had viral loads ranging from 10² to ≥10⁸ IU/ml, and 37.2% had HBV viral loads <200 IU/ml. There was a statistically significant positive association between HBsAg‐positivity and high viral loads, with 27% (12/44) of HBsAg positives having HBV viral loads between 10⁴ and ≥10⁸ IU/ml, compared to only 5.9% (2/34) of HBsAg negatives (relative risk: 4.64; 95% confidence interval: 1.11, 19.35; chi‐square P‐value = 0.015). The study shows that the majority of HIV/AIDS patients initiating ART have either acute or chronic HBV infections, and further confirms that HIV remains a risk factor for occult HBV infections in South African patients as previously shown. The findings strongly support HBV screening in all HIV‐positive patients initiating ART in South Africa, considering that current ART regimens include drugs with anti‐HBV activity (e.g., lamivudine). J. Med. Virol. 81:406–412, 2009. © 2009 Wiley‐Liss, Inc.     

Development and evaluation of one‐step multiplex real‐time RT‐PCR assay for simultaneous detection of Zika virus and Chikungunya virus

Zika virus (ZIKV) and chikungunya virus (CHIKV) are important human pathogens and mosquito‐borne arboviruses, which have resembling history, common vectors, circulating regions, and indistinguishable clinical symptoms. Wide geographical range that is suitable for ZIKV and CHIKV transmission underlines the concern about the impact of epidemic and endemic infections on burden of public health. In the present study, a highly sensitive and specific one‐step multiplex real‐time RT‐PCR assay was developed and evaluated for simultaneous detection and quantification of ZIKV and CHIKV. The single reaction assay employs two pairs of primers and two TaqMan probes that differentiate ZIKV and CHIKV infections. The entire viral genomic RNA in vitro transcribed from full‐length infectious clones were used to generate the standard curves for absolute quantification in subsequent tests. The detection limit of the one‐step multiplex assay was 1 and 0.5 PFU for infectious ZIKV and CHIKV, respectively. The assessment of specificity indicated this assay is highly specific to targeted viruses showing no amplification of a variety of other flaviviruses. Our assay was able to detect geographically separated and phylogenetically diverse strains of ZIKV and CHIKV. On the applicability of monitoring viral multiplication in cells and testing clinical samples, the one‐step multiplex assay provided efficient and accurate determination. The one‐step multiplex real‐time RT‐PCR assay offers a valuable tool for detection of ZIKV and CHIKV and potentially contributes to general surveillance and clinical treatment.

     

Circulating microRNA‐122 levels are important predictor of hepatitis B virus surface antigen seroclearance

It is currently unclear what impact serum microRNA‐122 (miR‐122) levels have on clearance of hepatitis B virus (HBV) surface antigen (HBsAg) in HBV‐infected patients who had not received antiviral therapy. The current study evaluated the impact of serum miR‐122 levels on HBsAg seroclearance in 367 consecutive HBV‐infected patients who had not received antiviral therapy between their initial and last visit, and investigated the predictive factors of HBsAg seroclearance. Cumulative HBsAg seroclearance rates were 13.5%, 32.0%, and 37.4% after 10, 20, and 30 years, respectively. The yearly incidence of HBsAg seroclearance over the investigated 30‐year period was 1.25%. A significant and strong correlation was observed between serum miR‐122 and HBsAg levels. Moreover, there was a significant correlation between serum miR‐122 levels and the levels of HBV DNA, hepatitis B e‐antigen, and HBV core‐related antigen. The HBsAg seroclearance rate in patients with a <1.0‐fold change of serum miR‐122 levels was significantly higher than in those with a ≥1.0‐fold change. Multivariate analysis identified age (≥30 years), HBV DNA levels (<2.2 log U/mL), HBV genotype (non‐C), and serum miR‐122 levels (<1.0‐fold change) as significant predictors of HBsAg seroclearance. Our results indicated that serum miR‐122 level is an important predictor of HBsAg seroclearance in Japanese patients who do not receive antiviral therapy. Understanding the complexity of the interactions among various virus‐related and host‐related factors could potentially help in the design of new therapies that enhance HBsAg seroclearance.     

Interference of replication between hepatitis B and C viruses in patients infected with HIV

The clinical and cellular interactions between hepatitis B virus (HBV) and hepatitis C virus (HCV) were investigated in patients co-infected with the human immunodeficiency virus (HIV). One hundred ninety-nine patients followed for 6 years were evaluated to compare the level of HBV DNA and HCV RNA in patients co-infected with HIV and HBV, and patients co-infected with HIV, HBV, and HCV. A full-length HBV genome and HCV JFH1 RNA were co-transfected into HuH-7.5.1 cells in vitro to examine the impact of co-infection and dependence on the HBV PreC mutant for replication interference. Before 2',3'-dideoxy-3'-thiacytidine (3TC)-based antiretroviral therapy (ART) was initiated, HBV DNA was found in 56/123 (45.4%) patients co-infected with HIV and HBV, and in 19/76 (25.0%) patients co-infected with HIV, HBV, and HCV. After 3TC-based ART was initiated, detectable HBV DNA decreased to 7/76 (9.2%) in patients co-infected with HIV, HBV, and HCV, but HCV RNA increased from 43/76 (56.6%) to 60/76 (78.9%) (P = 0.003). In vitro HBV and HCV co-infection led to decreased replication of both viruses. The primary factors that influenced the decreased replication were the order of the HBV and HCV infection and the HBV PreC mutation.     

Control of murine gammaherpesvirus infection is independent of NK cells

Numerous studies have shown that NK cells are important in controlling the early stages of infection with alpha- or betaherpesviruses. In contrast, little is known about the impact of NK cells on gammaherpesvirus infections. We tested mice with defects in NK cells for their ability to resist murine gammaherpesvirus (MHV-68) infection. The depletion of NK cells had no effect on the control of the acute or latent stages of the infection. In addition, transgenic mice deficient in NK cells controlled the infection in a comparable manner to wild-type mice. We also showed that the antiviral CD8 T cell response was unaffected by the presence or absence NK cells. We conclude that NK cells contribute little to the control of MHV-68 infection, and therefore, NK cells are not essential for controlling all herpesvirus infections.     

Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and varicella zoster virus encephalitis during treatment of medulloblastoma

The case of a 14-year-old girl who developed Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and Varicella zoster virus encephalitis during treatment for medulloblastoma is described. The patient was diagnosed with a cerebral medulloblastoma and treated with systemic chemotherapy, intrathecal chemotherapy, and radiotherapy. Six months later, she developed persistent low-grade fever, abdominal pain, and vomiting. Several mucosal or ulcerated lesions of the stomach and colon were found on fiberscopy. The infiltrating cells were positive for CD20 and EBER1, and the diagnosis of lymphoproliferative disorder was made. CMV antigen was found in the peripheral lymphocytes at that time. At the same time, it was noted that the patient's language was inappropriate for her age, and a facial and abdominal rash, as well as a right facial palsy, had developed. She was then diagnosed as having VZV encephalitis, because VZV was detected in the CSF. She was treated subsequently with acyclovir and oral steroid, and the VZV encephalitis resolved. The lymphoproliferative disorder improved gradually with rituximab, ganciclovir, and total nutritional support. At the time of the development of the lymphoproliferative disorder and VZV encephalitis, the patient had severe lymphopenia and this may have caused these rare phenomena in a non-transplant setting.     

Current weight of evidence of viruses associated with peri‐implantitis and peri‐implant health: A systematic review and meta‐analysis

The pathological role of human herpesviruses (HHVs) (Epstein‐Barr virus [EBV], Human cytomegalovirus [CMV], and Herpes simplex virus [HSV]) in peri‐implant health needs clarification quantitatively. To determine the weight of evidence for HHVs in patients with peri‐implantitis (PI) and substantiate the significance of HHVs in peri‐implant inflammation, electronic databases including EMBASE, MEDLINE, Cochrane Oral Health Group Trials Register, and Cochrane Central Register of Controlled Trials were searched from 1964 up to and including November 2018. Meta‐analyses were conducted for prevalence of HHVs in PI and healthy controls. Forest plots were generated that recorded risk difference (RD) of outcomes and 95% confidence intervals (CI). Five clinical studies were considered and included. Four clinical studies reported data on EBV while three clinical studies reported data on CMV. Considering the risk of these viruses in PI, significant heterogeneity for CMV (χ² = 53.37, p < 0.0001, I² = 96.25%) and EBV (χ² = 14.14, p = 0.002, I² = 78.79%) prevalence was noticed between PI and healthy control sites. The overall RD for only EBV (RD = 0.20, 95% CI, 0.01‐0.40, p = 0.03) was statistically significant between both groups. Frequencies of the viruses were increased in patients with PI compared with healthy nondiseased sites. However, the findings of the present study should be interpreted with caution because of significant heterogeneity and small number of included studies.     

Production of interleukin-18 and interleukin-12 in patients suffering from chronic hepatitis C virus infection before antiviral therapy

Interleukin-12 and -18 (IL-12 and IL-18) are known to enhance the cytotoxic T-lymphocyte response synergistically, but their precise involvement in hepatitis C virus (HCV) infection is not well known, especially for IL-18. Enzyme-linked immunosorbent assay (ELISA) was used to study the production of these cytokines in plasma and peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) of patients infected chronically with HCV before initiation of antiviral therapy. Fifty-six patients and 40 healthy controls were evaluated. Patients infected with genotype 1 or with genotype other than genotype 1 HCV had significantly a high production of plasma IL-12 compared with controls (P < 0.05). However, patients infected with genotype 1 HCV had lower levels of PBMC IL-18 than were founded in the controls (P < 0.05); plasma IL-18 also tended to be lower in this group of patients than in the controls, although nonsignificantly. Plasma IL-18 was related to hepatic histological activity (P < 0.05). The data suggest a relationship between these two cytokines and some features of HCV infection, so that their respective production in relation to the outcome of the infection deserves further study.     

Novel TTV variants isolated in an epidemic of hepatitis of unknown etiology

TT virus (TTV) is a recently discovered single-stranded DNA virus that has been reported to be associated with elevated transminase levels in the patients with posttransfusion hepatitis of unknown etiology. TTV prevalence is very high in the common population and its pathogenicity remains unclear. In this study, we performed an epidemiological study to investigate the infection rate of TTV and its role in an epidemic of unknown-etiology hepatitis. Moreover, two TTV isolates named L01 and L02 were cloned from the serum of a patient with unknown-etiology hepatitis. Eighty-one subjects were included in the study and were divided into two groups: 18 in the case group and 63 in the control group. TTVDNA was detected by nested PCR from sera samples. The infection rates of TTV in case and control groups were 33.3 and 38.9%, respectively. There was no significant difference between the two groups. Homology analysis showed that L01 had a very poor homology with other TTV isolates and L02, and L02 was 75.5% identical to JA10. The result does not support TTV as a causative agent in this epidemic. The genetic divergence between L01 and other TTV isolates beyond genotype, so it represents a new genotype of TTV.     

Primary pleural effusion posttransplant lymphoproliferative disorder: Distinction from secondary involvement and effusion lymphoma

Pleural effusion presentation of posttransplant lymphoproliferative disorder (PTLD) is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement, and are associated with an aggressive clinical course. We report on a case of primary effusion PTLD in a 70-yr-old male liver transplant recipient with a history of hepatitis B infection. Cytomorphologically, the pleural fluid specimen showed a monomorphous population of intermediate to large-sized transformed lymphoid cells, with irregular multilobated nuclear contours and readily identifiable mitotic figures. Flow cytometric immunophenotypic studies revealed a CD5-negative, CD10-negative, lambda immunoglobulin light chain-positive, monoclonal B-lymphocyte (CD19-positive/CD20-positive) population. The immunocytochemical stain for CD30 antigen was negative. In situ hybridization study for Epstein-Barr virus (EBV) early RNA (EBER) and Southern blot analysis for EBV terminal repeat sequences were both positive. Southern blot analysis for human herpes virus-8 (HHV-8) was negative. No solid-organ PTLD was identified, and the cytologic results supported the diagnosis of primary effusion PTLD. Immunosuppression was decreased, and 8 mo following the diagnosis of pleural fluid PTLD, the patient was stable and his pleural effusion had markedly diminished. Recognition of primary effusion PTLD and its distinction from PTLD secondarily involving the body fluids and from other lymphomas is important, since the behavior and prognosis appear different.