Poor seroprotection but allosensitization after adjuvanted pandemic influenza H1N1 vaccine in kidney transplant recipients.

BACKGROUND: Seasonal and pandemic influenza virus infections in renal transplant patients are associated with poor outcomes. During the pandemic of 2009-2010, the AS03-adjuvanted monovalent H1N1 influenza vaccine was recommended for transplant recipients, although its immunogenicity in this population was unknown. We sought to determine the safety and immunogenicity of an adjuvant-containing vaccine against pandemic influenza A H1N1 2009 (pH1N1) administered to kidney transplant recipients. METHODS: We prospectively enrolled 124 adult kidney transplant recipients in the fall of 2009 at two transplant centers. Cohort 1 (n = 42) was assessed before and after pH1N1 immunization, while Cohort 2 (n = 82) was only assessed post immunization. Humoral response was measured by the hemagglutination inhibition assay. Vaccine safety was assessed by adverse event reporting, graft function, and human leukocyte antigen (HLA) alloantibody measurements. RESULTS: Cohort 1 had a low rate of baseline seroprotection to pH1N1 (7%) and a low rate of seroprotection after immunization (31%). No patient <6 months post transplant (n = 5) achieved seroprotection. Seroprotection rate was greater in patients receiving double as compared with triple immunosuppression (80% vs. 24%, P = 0.01). In Cohort 2, post-immunization seroprotection was 35%. In both cohorts, no confirmed cases of pH1N1 infection occurred. No difference was seen in estimated glomerular filtration rate before (54.3 mL/min/1.73 m(2) ) and after (53.8 mL/min/1.73 m(2) ) immunization, and no acute rejections had occurred after immunization at last follow-up. In Cohort 1, 11.9% of patients developed new anti-HLA antibodies. CONCLUSION: An adjuvant-containing vaccine to pH1N1 provided poor seroprotection in renal transplant recipients. Receiving triple immunosuppression was associated with a poor seroresponse. Vaccination appeared safe, but some patients developed new anti-HLA antibodies post vaccination. Alternative strategies to improve vaccine responses are necessary.

The prevalence of herpes simplex virus shedding and infection in the oral cavity of seropositive patients undergoing head and neck radiation therapy.

OBJECTIVE: Herpes viruses are characterized by their ability to establish and maintain a latent infection that can reactivate. Only 2 preliminary studies have examined herpes simplex virus (HSV) reactivation in patients receiving head and neck radiotherapy. The role of radiation therapy in the reactivation of a latent virus has not been established. The purpose of the present study was to evaluate the incidence of HSV reactivation in patients receiving radiation treatment for head and neck malignancies. METHODS: Twenty patients, 19 of whom were HSV seropositive, undergoing head and neck radiation therapy were assessed weekly before and during radiation therapy, and HSV cultures were completed during cancer treatment. RESULTS: Only 3.6% of the cultures were positive for HSV during radiation therapy. HSV was cultured in 4 men receiving a mean of 6,000 cGy to the head and neck area. Recovery from HSV was seen in patients nearing completion of radiation therapy. CONCLUSIONS: The results of this study suggest that HSV reactivation is not common during radiation therapy. Therefore, this study does not support prophylaxis of HSV in patients undergoing head and neck irradiation.

Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection.

BACKGROUND: Beginning in 1994, Vancouver experienced an explosive outbreak of HIV infection among injection drug users (IDUs). The objectives of this study were to measure the prevalence and incidence of hepatitis C virus (HCV) infection in this context and to examine factors associated with HCV seroconversion among IDUs. METHODS: IDUs recruited through a study site and street outreach completed interviewer-administered questionnaires covering subjects' characteristics, behaviour, health status and service utilization and underwent serologic testing for HIV and HCV at baseline and semiannually thereafter. A Cox proportional hazards model was used to identify independent correlates of HCV seroconversion. RESULTS: As of Nov. 30, 1999, 1345 subjects had been recruited into the study cohort. The prevalence of anti-HCV antibodies was 81.6% (95% confidence interval [CI] 79.6% to 83.6%) at enrollment. Sixty-two HCV seroconversions occurred among 155 IDUs who were initially HCV negative and who returned for follow-up, for an overall incidence density rate of 29.1 per 100 person-years (95% CI 22.3 to 37.3). The HCV incidence remained above 16 per 100 person-years over 3 years of observation (December 1996 to November 1999), whereas HIV incidence declined from more than 19 to less than 5 per 100 person-years. Independent correlates of HCV seroconversion included female sex, cocaine use, injecting at least daily and frequent attendance at a needle exchange program. INTERPRETATION: Because of high transmissibility of HCV among those injecting frequently and using cocaine, the harm reduction initiatives deployed in Vancouver during the study period proved insufficient to eliminate hepatitis C transmission in this population.

Can pooling be used for seroprevalence studies of hepatitis C?

Two hepatitis C antibody assays were used to test diluted positive sera. Dilutions of 1 in 5, 1 in 10, and 1 in 20 all resulted in loss of reactivity, with the greatest losses occurring in samples with low and moderate reactivities. These results disqualify pooling as a strategy for seroprevalence studies and screening programs.

De novo acute hepatitis B infection in a previously vaccinated liver transplant recipient due to a strain of HBV with a Met 133 Thr mutation in the "a" determinant.

UNLABELLED: De novo HBV infection post-liver transplantation (LT) from an anti-HBc seropositive donor rarely presents as acute failure. We report a 42-year-old Caucasian female, HBsAg and anti-HBc seronegative, with primary biliary cirrhosis who received an allograft from a HBsAg negative, anti-HBc seropositive donor. The patient, previously vaccinated years pre-LT, was re-vaccinated against HBV and 1 year post-LT had an anti-HBs titre of 256 IU/l. Two years post-LT, elevated serum aminotransferases and worsening liver function with an INR of 2.0 developed. The HBsAg became positive, anti-HBs undetectable and serum HBV-DNA >2000 pg/ml by hybridisation assay. Liver biopsy revealed significant ballooning degeneration, piecemeal necrosis and positive immunostaining for HBsAg. Progressive liver failure developed followed by sepsis and terminal multi-organ failure. Subsequent analysis of the predominant HBV strain revealed mutations in the "a" determinant: Met 133 Thr (codon change ATG to ACG) and Asn 131 Thr. CONCLUSION: ' Acute de novo HBV infection from an anti-HBc sero-positive donor may occur long after LT despite protective anti-HBs titres post-vaccination secondary to the emergence of "a" determinant mutated strains of HBV.

Full suppression of viral load is needed to achieve an optimal CD4 cell count response among patients on triple drug antiretroviral therapy.

OBJECTIVE: To characterize the relationship between plasma viral load (pVL) suppression and triple drug antiretroviral therapy, and the accompanying changes in CD4 cell counts. METHOD: Retrospective study of 465 participants in a HIV/AIDS Treatment Program who initiated triple drug therapy between August 1996 and May 1998. Participants were divided into three groups according to their pVL response: (i) non-responders (NR; n = 112) exhibited pVL persistently > 500 copies/ml over the study period; (ii) partial responders (PR; n = 100) achieved a pVL < 100 copies/ml at least once and subsequently rebounded to > 500 copies/ml; and (iii) full responders (FR; n = 253) achieved a pVL < 500 copies/ml and sustained this level for the remainder of the study period. For each group, the accompanying changes in absolute and fractional CD4 cell counts were evaluated. RESULTS: The median net change in pVL per person from baseline to the end of the observation period was -0.37, -2.27, and -2.56 log10 copies/ml for NR, PR and FR, respectively. During weeks 68-83, the median CD4 cell count (x 10(6) cells/l) was 150 [interquartile range (IQR) 90-370], 380 (IQR 300-480) and 525 (IQR 305-705) for NR, PR and FR, respectively. Median changes in CD4 cells (x 10(6) cells/l) were -20 (IQR -90 to 40), 150 (IQR 30-250) and 240 (IQR 110-365) for NR, PR, and FR, respectively. The net percentage change in CD4 cells per person was 0% (IQR -34-31), 54% (IQR 6-160), and 83% (IQR 39-173) for NR, PR, and FR, respectively. By weeks 68-83, the median fractional CD4 cells was 0.16 (IQR 0.07-0.22), 0.22 (IQR 0.15-0.28), and 0.26 (IQR 0.17-0.34) for NR, PR and FR respectively. CONCLUSIONS: An optimal CD4 cell count response appears to be coupled with continued pVL suppression. Our data indicate that maximal suppression of viral replication should remain the primary goal of therapy.

Suppression of plasma virus load below the detection limit of a human immunodeficiency virus kit is associated with longer virologic response than suppression below the limit of quantitation.

Suppression of human immunodeficiency virus type 1 plasma virus load (PVL) to <20 copies/mL is associated with a longer virologic response after initiation of antiretroviral therapy. The relationship between duration of virologic response and PVL nadir according to a less sensitive assay was explored. When compared with subjects with a PVL nadir >500 copies/mL, the relative risks of PVL rising above 1000 copies/mL for participants in the INCAS trial and the British Columbia Drug Treatment Program with a PVL nadir below the limit of detection (LOD) were 0.04 (95% confidence interval [CI], 0.02-0.09) and 0.06 (95% CI, 0.03-0.12), respectively. The corresponding relative risks for persons with a detectable but not quantifiable PVL nadir were 0.25 (95% CI, 0.13-0.50) and 0.54 (95% CI, 0.25-1.19). The relative risks of virologic failure associated with a PVL nadir detectable but not quantifiable and a PVL nadir below the LOD were statistically different (P<.0001) in both data sets.

Effects of anticoagulant, processing delay, and assay method (branched DNA versus reverse transcriptase PCR) on measurement of human immunodeficiency virus type 1 RNA levels in plasma.

We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.

Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy.

Herpes viruses are characterized by their ability to establish and maintain latent infections that can be reactivated. Several stimuli can trigger the reactivation of herpes viruses, which are perhaps best recognized in the recurrent blisters and ulcers associated with herpes simplex virus. We present two clinical cases of reactivation of herpes simplex virus during radiation therapy for management of cancers of the head and neck. Although the role of ionizing radiation in the reactivation of herpes simplex virus has not been established, we review the viral and host events associated with the establishment of orofacial herpes simplex virus infection, latency, and reactivation of the virus. We discuss current models of viral reactivation and suggest directions for further clinical research into the reactivation of orolabial herpes simplex virus during radiotherapy.

Microscopic polyangiitis after influenza vaccination.

We describe a case of microscopic polyangiitis involving skin and joints after influenza vaccination. Titers of antiinfluenza A antibody were markedly elevated in synovial fluid (SF) relative to those in serum. Antiinfluenza B antibodies were not present in SF but were present in serum, suggesting a reaction specifically involving antiinfluenza A antibodies localized to the affected joint. A review identified 16 other cases of vasculitis after influenza vaccination. The cases reclassified according to the Chapel Hill diagnostic criteria identified multiple forms of vasculitis including 7 other cases of microscopic polyangiitis. Three patients had similar illnesses after previous influenza vaccination or influenza-like illness. As in our case 11 cases resolved without recurrence. While this does not provide conclusive evidence that the vaccination caused the vasculitis, together with the serologic data we present it supports this hypothesis.

Continuing investigation and controversy regarding risk of transmission of infection via dental handpieces.

Current epidemiologic evidence indicates that infectious diseases, specifically blood-borne pathogens such as hepatitis B, hepatitis C and HIV, are not transmitted from patient to patient via dental instruments. However, ongoing laboratory investigations suggest that potential pathogens may be retained within dental handpieces, creating a theoretical risk of cross infection. Controversy regarding certain laboratory study results and the clinical implications of these studies continues. Guidelines and regulations for infection control should be rational, and based on a realistic response to a documented risk. Dental professionals should be aware of continuing research focusing on these issues.

Acyclovir prophylaxis of oral herpes virus during bone marrow transplantation.

Oropharyngeal shedding of herpes viruses (herpes simplex, cytomegalovirus) was assessed in patients on standard acyclovir prophylaxis during bone marrow transplantation (BMT) to determine the frequency of viral shedding and to assess possible oropharyngeal complications that may be associated with viral reactivation in these patients. We conducted a prospective assessment of 83 patients receiving BMT. Patients were evaluated weekly and oral surveillance cultures were completed. Shedding of herpes simplex virus (HSV) was detected in the oropharynx of 2.9% of seropositive patients on prophylactic acyclovir, and only one case of clinical oral herpetic infection was seen. Cytomegalovirus (CMV) was cultured from the oropharynx in 13.3% of CMV seropositive patients provided with prophylactic acyclovir, but no oropharyngeal lesions were attributed to CMV reactivation. No correlation was seen between HSV and CMV pretransplant serology and severity of oral mucositis and acute graft versus host disease. No effect on time to engraftment was detected. This study supports the continuing use of acyclovir prophylaxis in HSV seropositive patients receiving BMT. Acyclovir prophylaxis was effective in preventing viral shedding in all but 2.9% of patients, and only one case of clinical infection was diagnosed. The frequency of CMV shedding was approximately four times that of HSV; however, no oral lesions were attributed to CMV.

Use of pooling and outpatient laboratory specimens in an anonymous seroprevalence survey of HIV infection in British Columbia, Canada.

OBJECTIVE: To conduct an anonymous HIV seroprevalence survey to establish a baseline estimate of HIV seroprevalence in a general population; to evaluate serum pooling and alternative testing strategies as cost-saving measures. DESIGN: Prospective anonymous HIV seroprevalence study using outpatient laboratory specimens. SETTING: Two large non-hospital-associated outpatient chemistry testing laboratories in the major population centers in British Columbia, Canada. PATIENTS AND SERA: Leftover sera received for chemistry screen testing in outpatient laboratories were provided to the study after chemistry testing was completed. Those from patients aged < 15 and > or = 55 years were excluded. METHODS: Patient identifiers were erased from samples. Sera were pooled 10:1 and tested by viral lysate enzyme-linked immunosorbent assay (ELISA). Sera from HIV-positive pools were tested individually. All individual HIV-positive specimens were retested for verification of positivity using a recombinant protein ELISA. MAIN OUTCOME MEASURES: HIV seroprevalence rates were stratified by sex, age group, and geographic area; and costs of pooling and alternative algorithm strategy were compared with those of conventional methods. RESULTS: A total of 80,238 sera were collected from 66,658 individuals (53% women, 47% men). Of these, 276 men (88.3 per 10,000) and 24 women (6.8 per 10,000) were HIV-seropositive. The highest rates were in those aged 30-34 years, for both men and women. Using pooling and non-Western blot verification saved US$2.07 per specimen, or 80% of the cost for conventional testing. CONCLUSIONS: The anonymous outpatient laboratory setting is practicable to obtain a reasonable estimate of HIV seroprevalence rates in a general population. Such studies can be made cost-effective by pooling sera and using alternative confirmatory strategies.

Assessing viral retention and elimination in rotary dental instruments.

The authors of this article used a laboratory model of herpes simplex virus infection to assess the potential for contamination of dental handpieces by a human viral pathogen. They found that although all the handpieces in the study were fitted with anti-retraction valves, it was not until the units were flushed internally and disinfected externally that the pathogens were eliminated.

Hepatitis C: rapid progress in medicine and implications for dentistry.

Recent developments in the recognition and diagnosis of the major infectious cause of posttransfusion hepatitis, hepatitis C virus (HCV), have led to an explosion in research. These developments are of relevance to dental providers. Patients may now present to the dentist with a diagnosis of hepatitis C infection and may be undergoing medical treatment for this disease. The risk for transmission of HCV in the dental setting is minimal. The dentist must understand the implications for the diagnosis of HCV for the patient and for the provision of dental care.

Rotary dental instruments and the potential risk of transmission of infection: herpes simplex virus.

A laboratory model of herpes simplex virus infection was used to assess the potential contamination of dental handpieces. When contaminated instruments were treated with surface disinfection and internal chemical disinfection, viable virus was eliminated in all instruments.

Hairy leukoplakia after bone marrow transplantation.

Hairy leukoplakia in 10 patients after bone marrow transplantation was identified clinically and assessed histologically. In situ hybridization for Epstein-Barr virus and human papilloma virus confirmed Epstein-Barr virus in hairy leukoplakia in two cases, and human papillomavirus in three cases. All cases with clinical follow-up resolved without treatment. These findings suggest that severe immunosuppression after a bone marrow transplantation may result in the development of hairy leukoplakia, and that as the immunosuppression resolves after the transplant the lesions also resolve.

Oral manifestations of cytomegalovirus infection.

Disease caused by cytomegalovirus is reported with increasing frequency. Cytomegalovirus is an important pathogen in immunocompromised and immunosuppressed patients. The most common manifestation of cytomegalovirus infection of the gastrointestinal tract including the oral mucosa is ulceration. The role of cytomegalovirus in xerostomia, Sjögren's syndrome, and Kaposi's sarcoma is continuing to be investigated. This article reviews the oral manifestations of cytomegalovirus, including recently reported oral manifestations.

Seroepidemiology of hepatitis C virus in Beijing, China.

To investigate the seroprevalence of hepatitis C virus (HCV) in China we tested sera from healthy individuals without hepatitis and no history of parenteral blood exposure and from patients admitted to a hepatitis hospital in Beijing. Sera were tested for anti-HCV by first-generation enzyme immunoassay; selected positives were tested with two second-generation EIAs, one utilizing recombinant antigens and the other synthetic peptides. We found anti-HCV with the following frequencies: 10 of 164 (6%) individuals with no disease; 2 of 36 (5.5%) patients with acute non-A non-B hepatitis (NANBH); 26 of 39 (67%) patients with post-transfusion NANBH; 10 of 34 (29%) patients with chronic hepatitis negative for hepatitis B surface antigen (HBsAg); 3 of 30 (10%) patients with chronic HBsAg-positive hepatitis; 0 of 19 patients with acute HBsAg-positive hepatitis. Of 24 repeat-positive sera, 19 were positive by both and 4 by one second-generation tests. We conclude that hepatitis C infection is common in China, that it contributes substantially to the incidence of post-transfusion hepatitis, and that HCV plays a significant role in both acute and chronic hepatitis. Further studies are needed to extend these observations and to define the predominant routes of transmission of HCV in China.