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[Discovery of a chronic HVC infection without seroconversion in a blood donor in France during 28 months].

The HCV-RNA screening technique developed by the French Fractionation and Biotechnology Laboratory singled out in March 1998 a case of positive HCV-RNA viremia in a blood donor without any anti-HCV antibody. That donor was a 46-year-old woman who had made 54 donations of blood products from 1988 to 1997. She had no history of blood transfusion, no history of hepatitis and no life-style risk factor. Clinical examination was normal. Liver tests (serum alanine amino transferases, gamma glutamyl transpeptidase , alkaline phosphatase, bilirubin , prothrombin and albumin) were normal. Total blood count was normal. Lymphocyte count was normal as well as in vitro functional analysis of lymphocytes (stimulation with different antigens). All screening HCV Elisa tests and immunoblot System available on the French market were unable to detect anti-HCV antibodies. Quantification of serum HCV-RNA (Amplicor Monitor Roche) showed 294,000 copies/mL and HCV genotype 1b determination was performed using Innolipa assay. Further examination of the HCV genotype by direct sequencing of the PCR product showed a classical 1b genotype sequence. The hemovigilance inquiry identified 25 labile products distributed since 1988. Analyzing the records of the recipients that have so far been traced and identified revealed three periods: 1997 to 1995: three recipients were found to be positive for anti-HCV antibodies; two are now cured of hepatitis C. In one recipient, direct sequencing after specific PCR of the hypervariable region coding for the envelope domain showed 100% homology with the donor; 1993 to 1990: four recipients were identified and traced without contamination; in 1988: three of four blood product recipients were anti-HCV negative without HCV-RNA viremia. The forth carried anti-HCV antibodies and genotype 1b HCV-RNA but had a history of multiple surgery. Alter et al. [4] and Bush et al. [5] have previously suggested the possibility of a chronic, immunologically silent state of infection. The case described herein, is the first evidence for this hypothesis. Indeed, the donor has not yet seroconverted 28 months after viremia was discovered. This blood donor was identified by HCV-RNA screening of plasma products. The identification of the same sequence in a recipient of blood from this donor clearly establishes the transmission of the virus by transfusion. The prevalence of such cases of infectious silent chronic HCV carriers has to be determined and the mechanisms responsible for the absence of antibody production need to be clarified.

Amino Acid Sequence↗

The effect of CMV infection on progression of human immunodeficiency virus disease is a cohort of haemophilic men followed for up to 13 years from seroconversion.

The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years follow-up. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0.05 x 10(9)/l were 2.28, 2.42 and 2.34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1.89, 1.82 and 1.93 respectively and were marginally non-significant (P = 0.05, 0.08 and 0.08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a 'co-factor' effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses.

Acquired Immunodeficiency Syndrome↗

Seroconversion after influenza vaccination in patients with lung cancer.

There are no data in the literature about the efficacy of influenza vaccination in lung cancer patients. Paired sera were available from 59 patients who received Fluvirin (Evans Medical). Of 41 patients susceptible to one or more influenza strains, 78% responded fully to vaccination. This response rate is comparable to that obtained from healthy volunteers.

Aged↗

Hepatitis G: viroprevalence and seroconversion in a high-risk group of children.

Hepatitis G virus (HGV), a recently discovered flavivirus, is parenterally transmitted and significantly associated with hepatitis C viraemia. Data on the viroprevalence of this agent in children is scant and its seroprevalence is unknown. The aim of this study was to determine the viroprevalence and seroprevalence of HGV in paediatric patients at risk of parenterally transmitted virus infection. Sera from 35 patients, previously tested for hepatitis C virus (HCV) infection, were analysed for the presence of HGV RNA by reverse transcription-polymerase chain reaction (RT-PCR) and for antibody to the E2 envelope protein (anti-E2) of HGV using the HGV-env kit. The mean age of the patients was 9.4 years (range 1-17 years), and risk factors included multiple transfusions and maternal HCV infection. Co-infection with HCV and HGV was a relatively common occurrence (31%). The prevalence of anti-E2, a marker of recovery from infection, was low (5%) when compared with overall viroprevalence (20%). This study highlights the significant association of HGV with HCV in children. The novel finding of a low ratio of anti-E2:HGV RNA contrasts with the pattern seen in adults and may reflect a higher risk of long-term carriage with acquisition of HGV infection at an early age.

Adolescent↗

Rapid seroconversion to Treponema pallidum and HIV positivity in a patient with retinal vasculitis.

A patient with idiopathic retinal vasculitis was found to have rapid conversion of serological tests for Treponema pallidum and HIV. The diagnosis was confirmed by Venereal Disease Research Laboratory (VDRL) testing and dark ground illumination for T. pallidum, and enzyme-linked immunosorbent assay (ELISA) and Western blot assay tests for HIV. Following treatment with intravenous penicillin, the fundus lesions resolved and visual acuity recovered from inaccurate light projection to 6/24 in the right eye and from counting fingers close to face to 2/60 in the left eye. Serological tests for T. pallidum in patients with concurrent HIV infection may be unpredictable. Hence, it is important to repeat these tests even in the early treatment phase of patients with retinal vasculitis who have shown initial seronegativity. This enables earlier diagnosis and initiation of specific treatment.

Adult↗

An unusual case of anti-Borrelia burgdorferi immunoglobulin G seroconversion caused by administration of intravenous gammaglobulins.

Administration of gammaglobulins to individuals without specific anti-Borrelia burgdorferi antibodies may lead to immunoglobulin G (IgG) conversion as detected by enzyme-linked immunosorbent assay (ELISA). In some cases however, complementary techniques such as Western blot or avidity will be of prime importance in distinguishing the start of an infection from the passive immunization induced by the gammaglobulins. In all cases, the key element before reaching conclusions in relation to any of these investigations remains the confrontation between the clinical context and the biological findings. This is the scenario that has been followed in our observation.

Antibodies, Bacterial↗

Pneumococcal polysaccharide revaccination: immunoglobulin g seroconversion, persistence, and safety in frail, chronically ill older subjects.

OBJECTIVES: To determine the 1-month postpneumococcal polysaccharide-revaccination immunoglobulin G (IgG) antibody response, its persistence at 1 year, and tolerability of revaccination in frail, chronically ill older nursing facility residents. DESIGN: Prospective study conducted between December 1998 and July 2000. SETTING: Six skilled nursing facilities in the Minneapolis-St. Paul, Minnesota, metropolitan area. PARTICIPANTS: Sixty-seven subjects aged 65 and older having received primary vaccination with pneumococcal polysaccharide vaccine (PPV) at least 5 years before enrollment. INTERVENTION: Revaccination with one dose of 23-valent PPV. MEASUREMENTS: Adverse events and concentrations of seven individual pneumococcal polysaccharide type-specific IgG antibodies (against serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) and their aggregate before and 1 and 12 months after revaccination. RESULTS: A significant increase in all individual and aggregate median antibody concentrations over baseline was observed 1 month after revaccination. However, after 1 year, the increase remained significant only for serotypes 6B and 18C and the aggregate parameter. One month after revaccination, the mean increase in antibody concentration over baseline was significantly greater than 1.4-fold for six of the seven serotypes and the aggregate. However, the increase was not significantly greater than 1.4 at 1 year for any of the serotypes or the aggregate. Minor, self-limited localized adverse reactions and systemic reactions occurred in 11.3% of the subjects. CONCLUSIONS: In frail, chronically ill older nursing facility residents, revaccination with 23-valent PPV at least 5 years after primary vaccination (whether primary vaccination occurred before or after age 65) is associated with a significant, albeit brief, immunological response for most of the serotypes tested. Revaccination was well tolerated.

Aged↗

Seroconversion to human immunodeficiency virus (HIV) in hemophiliacs. Relation to lymphadenopathy.

The authors studied the natural history of human immunodeficiency virus (HIV) exposure in 187 hemophiliacs followed for an average of 45 months. Overall, 55 percent developed antibody specific for HIV and 21 percent developed persistent generalized lymphadenopathy. Most patients seroconverted sometime between early 1982 and the end of 1984. Four patients developed acquired immune deficiency syndrome (AIDS) and four seropositive patients developed idiopathic thrombocytopenia (ITP). One of the four patients who developed AIDS and three of the four with ITP had preexisting lymphadenopathy. None of the 10 patients with lymphadenopathy or the 20 asymptomatic patients was seropositive for human T-lymphotropic virus, type I. Although seropositivity and lymphadenopathy have been found in many of the authors' patients, few have developed clinical disease that can be related to HIV infection.

AIDS-Related Complex↗

Duration of time from onset of human immunodeficiency virus type 1 infectiousness to development of detectable antibody. The HIV Seroconversion Study Group.

BACKGROUND: For persons newly infected with the human immunodeficiency virus type 1 (HIV-1), the time from the onset of infectivity to the development of detectable HIV-1 antibody is unknown. Persons who donate blood during this period account for nearly all instances of HIV-1 transmission from HIV-1 antibody-screened blood transfusions. STUDY DESIGN AND METHODS: To estimate the window period from infectivity to HIV-1 antibody positivity, 701 HIV-1-seropositive blood donors who made a previous seronegative donation at 40 United States blood centers were studied. The HIV-1 antibody status was determined for at least one recipient of blood from the seronegative donation preceding the seropositive donation made by 182 of the 701 donors. RESULTS: There were 39 seropositive recipients of blood from these 182 donors. Three donors were excluded from further analysis because the seropositive recipients of their blood had other HIV-1 risk factors or had HIV-1 infection before transfusion. The final study population comprised the remaining 179 donors, of whom 36 (20%) transmitted HIV-1 infection to recipients. When the interval between the seropositive donation and the preceding seronegative donation was less than 180 days, 46 percent of the donors transmitted HIV-1. In contrast, when that interval exceeded 540 days, only 2 percent transmitted HIV-1. A mathematical model was developed to explain the relationship between the probability that the previous seronegative donation occurred during the donor's window period of infectiousness, and hence transmitted HIV-1, as a function of both the window period and the duration between the seropositive and previous seronegative donations. This model indicated that the transmission data were most consistent with an average window period of 45 days. Assuming a log-normal window period distribution, it was estimated with 95 percent certainty that at least 90 percent of persons had a window period of less than 141 days. CONCLUSION: The window period averages 45 days, with few, if any, donors remaining infectious and seronegative for longer than 6 months.

Adolescent↗

Anti-hepatitis C virus (anti-HCV) seroconversion in patients undergoing hemodialysis: comparison of second- and third-generation anti-HCV assays.

BACKGROUND: The results obtained in sequential specimens from recently infected subjects generally provide the best means of comparing the sensitivity of assays. STUDY DESIGN AND METHODS: The sensitivity of second- and third-generation assays for antibody to hepatitis C virus (HCV) was compared on sequential specimens, generally collected at monthly intervals from 45 patients undergoing hemodialysis who seroconverted for HCV between 1980 and 1990. RESULTS: Fifteen patients (33%) were positive earlier in the third-generation enzyme-linked immunosorbent assay (ELISA), with a mean difference of 17 days (range, 7-30) between the last negative and the first positive specimens. At the first rise in alanine aminotransferase, and at its peak, 63 and 91 percent of the patients, respectively, were anti-HCV positive in the third-generation ELISA. Third-generation recombinant immunoblot assay (RIBA) reacted at the same time as third-generation ELISA. Of the first specimens that were positive in second-generation ELISA, 44 percent reacted and 56 percent were indeterminate in third-generation RIBA, while 10 percent reacted, 72 percent were indeterminate, and 18 percent did not react in second-generation RIBA. From the beginning to the end of the follow-up, antibody to c33c was the most prevalent, followed in descending order by antibody to c22-3, antibody to c100-3, and antibody to NS5: 56, 54, 26, and 18 percent, respectively, at time 0, and 100, 86, 83, and 31 percent, respectively, 12 months later. CONCLUSION: Third-generation assays (both ELISA and RIBA) were more sensitive than second-generation assays in the diagnosis of HCV infection, in that positive results were obtained earlier and a higher proportion of specimens were confirmed positive in RIBA testing.

Alanine Transaminase↗