Serum immunoglobulin A antibody to varicella-zoster virus in subjects with primary varicella and herpes zoster infections and in immune subjects.

Immunoglobulin A (IgA) antibodies to varicella-zoster virus (VZV) were measured in sera from subjects with acute varicella and herpes zoster, VZV-immune subjects remote from infection, and recipients of a live attenuated varicella vaccine, using a solid-phase radioimmunoassay. Primary infection with VZV was associated with early production of IgA antibodies. Among 36 subjects with varicella tested 1 to 5 days after onset, 22 had detectable IgA, and all of the negative sera were obtained before day 3 of the varicella exanthem. VZV IgA was detected in one of three sera obtained more than 60 days after onset of the illness. Four of five sera obtained from subjects within 1 week of the onset of herpes zoster had measurable levels of IgA. Between 1 and 4 weeks after onset of zoster, all 10 subjects tested had detectable IgA to VZV. VZV IgA was detected as late as 63 days after the onset of herpes zoster. Of 10 vaccine recipients, 5 developed VZV IgA which was detected as early as 4 weeks and persisted for as long as 16 weeks after vaccination. VZV IgA was not detected in sera from 42 children who had no detectable IgG antibody to VZV. VZV IgA was found on only 3 of 23 sera from adults who had varicella more than 20 years before.     

Virus-specific antibodies in sera from patients with genital herpes simplex virus infection.

Virus-specific antibodies against a number of herpes simplex virus type 2 antigens were determined by radioimmunoprecipitation assays in sequential serum samples obtained from 12 patients with initial genital herpes simplex virus infection. The progressive appearance of antibodies to virus-specific antigens was observed; antibodies against a 130,000-molecular-weight glycoprotein complex appeared first, followed by antibodies against the major nucleocapsid polypeptide and then antibodies against a number of other viral antigens, including a polypeptide with a molecular weight of 62,000. Patients who developed a wide variety of antibodies to viral polypeptides shortly after resolution of their initial episode seemed to experience more severe initial infections and more recurrences than did those who reacted poorly with these virus-specific antigens. This was most apparent with respect to antibodies to virus-specific polypeptides with molecular weights between 30,000 and 43,000. Antibody specificity did not change during the course of follow-up regardless of whether serum samples were taken shortly before, during, or after recurrent episodes. Glycoprotein-specific antibodies were quantitated with the purified 130,000-molecular-weight glycoprotein material. No significant fluctuations in these antibody titers were observed before or after recurrences of the disease.     

Antiviral therapy in children with varicella zoster virus and herpes simplex virus infections

A small number of antiviral drugs are available for the treatment of varicella zoster virus (VZV) and herpes simplex virus (HSV) infections in children. This review presents pharmacokinetic data on the following selected antiviral agents: aciclovir, valaciclovir, famciclovir, cidofovir and foscarnet. Support and current recommendations for the treatment of selected VZV and HSV infections in children will also be reviewed.     

Virus-specific immunoglobulin G subclasses in herpes simplex and varicella-zoster virus infections

The subclass specificities of antiviral immunoglobulin G (IgG) produced in response to herpes simplex and varicella-zoster virus infections were investigated. IgG1 and IgG3 with anti-herpes simplex virus activity were seen in patients with primary and reactivated disease, as well as in healthy seropositive subjects and in immunoglobulin preparations. IgG4 was occasionally seen alone or together with IgG1 and IgG3 in patients. In varicella, IgG3-specific antiviral antibodies were predominant, whereas in zoster, IgG1 was the dominant subclass.     

Distribution of varicella zoster virus and herpes simplex virus in disseminated fatal infections.

AIMS: To study the cutaneous and visceral distribution of herpes simplex virus (HSV) and varicella zoster virus (VZV) in fatal infections. METHODS: Standard histology, immunohistochemistry (monoclonal antibodies VL8 and VL2 and polyclonal antibody IE63 directed against VZV; monoclonal antibodies IBD4 and HH2 and polyclonal antibodies directed against HSVI and HSVII) and in situ hybridisation (anti-HSV and anti-VZV probes) were applied to formalin fixed, paraffin wax sections. RESULTS: On histological examination, Herpesviridae infection was evident in various organs including the lungs, liver and skin. In addition, immunohistochemistry and in situ hybridisation revealed the presence of HSV and VZV antigens and nucleic acids in several cell types and tissues showing no cytopathological alterations suggestive of Herpesviridae infection. The organs with histological evidence of infection also contained VZV or HSV antigens and their genes. CONCLUSIONS: These findings suggest that organ failure in disseminated VZV and HSV infections is primarily caused by HSV or VZV induced cell damage and lysis. They also indicate that immunohistochemistry and in situ hybridisation can provide an accurate, type-specific diagnosis on formalin fixed, paraffin wax embedded tissue even when classic histological and cytological characteristics are lacking.     

Specific IgG and IgA antibodies to herpes simplex virus and varicella zoster virus in acute peripheral facial palsy patients

The role of herpes simplex virus (HSV) and varicella zoster virus (VZV) in acute peripheral facial palsy (APFP) was evaluated in 153 patients. The sera of patients were examined for IgG and IgA antibodies to HSV and VZV by the immunoperoxidase antibody-membrane antigen (IPAMA) technique. The prevalence of IgG and IgA seropositivity to HSV was significantly higher in the APFP patients than in the matched control group. No significant difference was found in the geometric mean titer (GMT) to HSV antibodies in the APFP patients compared to the matched control groups. The prevalence of IgA antibodies to VZV was significantly higher in the APFP patients group than in the matched control group. The GMT for VZV IgG antibodies was significantly higher in the APFP patients than in the matched control group. No significant difference was found in the GMT of VZV IgA antibodies. Eleven of 83 patients for whom paired sera were available had significantly increased or decreased IgG and IgA antibody titers to VZV on subsequent examination. Four of these patients did not show any evidence of zosterian eruption. These studies support the concept that VZV and HSV might have a role in the etiopathogenesis of APFP in some of the patients.     

Circulating immune complexes in patients with acute measles and rubella virus infections

A solid-phase C1q radioimmunoassay was used to test for immune complexes (ICs) in sera obtained longitudinally from patients recovering from acute, uncomplicated measles and rubella virus infections. ICs were detected in 12 (18.5%) of 65 sera from 14 measles patients who did not have prolonged IC formation. Of 12 IC-positive measles sera, 9 were collected 4 weeks or more after rash onset. Transient appearance of detectable circulating ICs occurred sooner in 22 rubella patients who did not have prolonged IC formation. Of 109 rubella sera, 14 (12.8%) were IC-positive, and, of these, 10 were collected within 3 weeks of rash onset. Prolonged IC formation was found for an additional four measles and two rubella virus patients. Fractionation of sera from these six patients revealed that levels of large-sized ICs were highest in the initial 10 days after rash onset. Levels of large-sized ICs then declined to those for medium- and small (approximately immunoglobulin G)-sized ICs. IC-associated virus-specific antigens were detected in some of the sera from the six patients having prolonged IC formation. These results suggest two things: first, measles and rubella virus patients differ in the timing of virus clearance or in the reestablishment of normal immunity after infection; second, virus clearance is prolonged in some measles and rubella virus patients who have seemingly normal recoveries from their infections.     

Reactivity of varicella-zoster virus subunit antigens in enzyme-linked immunosorbent assay to sera from varicella,zoster, and herpes simplex virus infections

Serological responses to varicella-zoster virus (VZV) subunit antigens, such as capsid, envelope, and soluble (S) antigens, in patients with VZV and herpes simplex virus (HSV) infections were studied by comparing with responses to virion (V) antigens using an enzyme-linked immunosorbent assay (ELISA). S antigen, prepared by concentrating supernatant of VZV or HSV type 1 (HSV-1)-infected cell culture fluid, reacted strongly to sera from patients with secondary infection but reacted poorly to those from patients with a primary infection of VZV or HSV. Antibody titers to VZV-S antigen persisted for a long period in patients with VZV infections. Patients infected with VZV showed antibody increase to HSV-1, when tested by complement fixation or complement-enhanced neutralization test, in cases with a history of prior HSV infection. However, such a cross-reaction was only observed to a minor extent in ELISA test using S antigen. S antigen reaction was stronger in secondary infections in tests with various subunit antigens. Almost no cross-reactivity was observed in an immunoblotting test with S antigen. Differentiation between infections with either varicella or zoster or HSV can be made by comparison of antibody responses to V and S antigens.     

Enzyme-immunoassays for antibodies in measles, cytomegalovirus infections and after rubella vaccination.

Enzyme-immunoassays using an indirect method with alkaline phosphatase conjugated antiglobulins were satisfactory for detection of antibody to Measles and Cytomegalovirus. The antigen was passively adsorbed to polystyrene micro-harmagglutination plates for the assays. IgM antibody to Rubella was also detected by enzyme-immunoassay at 7 and 28 days after vaccination in a person who had negative Rubella serology before vaccination. IgG antibody was detected at those times in another patient who had positive Rubella serology prior to vaccination. The enzyme immunoassays appear to have the potential for routine laboratory use for virological diagnosis.     

Dot immunobinding assay for simultaneous detection of specific immunoglobulin G antibodies to measles virus, mumps virus, and rubella virus.

A dot immunobinding assay was used to detect antibodies to measles virus, mumps virus, and rubella virus antigens. Filter paper soaked with serum or whole blood was directly applied to the antigen-coated nitrocellulose sheets. The test was easy to perform, and its results agreed very well with those obtained by standard enzyme immunoassay.     

Multiple sclerosis: subclasses of intrathecally synthesized IgG and measles and varicella zoster virus IgG antibodies

Among 12 cases of chronic T lymphoproliferative disorders we observed, six patients showed an expansion of mononuclear cells with azurophilic granules usually referred to as large granular lymphocytes or LGL. Cells obtained from five patients with these abnormal LGL proliferations were studied with several surface markers including their reactivity with the HNK-1 monoclonal antibody reported to be specific for LGL. Cells in four out of five cases were HNK-1 positive. Whereas normal LGL have been reported to be unreactive with several T cell markers, three cases showed the co-existence of HNK-1 and surface markers expressed by T cells. Two cases were characterized by the proliferation of OKT8 cells. Cells from one patient were HNK-1 positive but did not express T or monocytic antigens. These cells were apparently not completely mature since alpha-naphthyl acetate acid esterase activity was negative. Cells from the remaining case were HNK-1 negative and positive for T and monocytic antigens. An increase of OKT-10 cells was observed in only one patient. Our data indicate that proliferations of LGL represent a remarkable proportion of the rare cases of sheep erythrocyte rosetting chronic lymphocytic leukaemias or lymphomas. Besides the morphology of LGL, the rosetting ability and the negativity for peroxidase, cells from these cases showed a vast heterogeneity of other structural and functional markers, possibly reflecting different stages in the maturation of these cells. The HNK-1 monoclonal antibody proved to be an important marker in the identification of these cases.     

Acute central nervous system complications in varicella zoster virus infections.

BACKGROUND: In a previous multicenter study on central nervous system (CNS) viral infections varicella zoster virus (VZV) appeared the most frequent etiologic agent and appeared often without rash. OBJECTIVE: To evaluate the appearance and diagnostics of VZV in CNS more thoroughly, we studied the cases systematically by using sensitive and specific methods to learn the best diagnostic approach in order to start specific therapy. STUDY DESIGN: We analyzed all serum and cerebrospinal fluid samples of 174 patients, 88 females and 86 males, with acute CNS symptoms associated with VZV infection diagnosed in the multicenter study on viral CNS infections. RESULTS: About 38 patients (22%) had chickenpox, 59 (34%) had shingles, and 77 (44%) had no cutaneous symptoms at all. The mean age of chickenpox patients was 8.6 years, of the others 46.6 and 41.4 years. VZV-specific nucleic acid was detected in the CSF in one fourth of the patients in all groups, primarily during the first week of illness. In serum specimens, specific IgM was present in two thirds of the patients with chickenpox, whereas in the others in one third of the cases. In CSF, specific IgM was present in 15-17% of patients with skin manifestations, compared with 6% of those without rash. CONCLUSIONS: The role of VZV infections in CNS complications seems remarkable, often presenting without rash. Even these cases should be promptly recognized in order to conduct proper antiviral therapy. In children, a combination of PCR and IgM tests is the best approach. In adults, PCR, together with the measurement of intrathecal antibody production yields best results.     

Solid-phase radioimmunoassay of rubella virus immunoglobulin G and immunoglobulin M antibodies.

A solid-phase radioimmunoassay method has been developed for the detection of rubella virus-specific immunoglobulin G (IgG) and IgM antibodies in human serum specimens. Purified rubella virus was adsorbed onto polystyrene balls, and antibodies that attached to the virus-treated balls were detected by subsequent binding of 125I-labeled anti-human gamma or anti-human mu immunoglobulins. A total of 77 serum specimens were tested. Binding ratios between positive and negative sera were as high as 22 in the IgG assay but rarely exceeded 3 in the IgM assay. The sensitivity of the IgG assay was found to be 16 to 256 times higher than that of the rubella virus hemagglutination inhibition test. The IgG radioimmunoassay can be readily adopted for routine diagnostic use. The IgM radioimmunoassay, however, due to its lower sensitivity, must be modified before being routinely applied.     

Virus-specific IgA in serum, saliva, and tears of children with measles.

Measles-specific IgA antibody titres were determined by radioimmunoassay (RIA) for serial serum, saliva and tear samples obtained from 21 children with measles infection, from onset of rash until up to 14 months later. Serum IgA titres rose rapidly after onset of illness and remained detectable throughout the follow-up period. Virus-specific salivary IgA titres peaked at 4 to 7 days after onset of rash and decreased thereafter. Measles-specific lacrimal fluid IgA antibodies remained elevated for long periods of time; however, secretory component-bearing measles-specific antibodies in tears became for the most part undetectable by 1 month after onset of rash. These data raise anew the question of whether some form of viral latency is associated with the presence of virus-specific IgA antibody, or whether such antibody is simply a reflection of immune memory.     

Kawasaki disease onset during concomitant infections with varicella zoster and Epstein-Barr virus

Kawasaki disease is an acute systemic vasculitis that predominantly affects preschool-aged children. It has a predilection to coronary arteries, and its precise etiology is still unknown. Many infectious agents, including viruses and bacteria, have been suggested as potential causes of the disease. Here, we report a patient who met the diagnostic criteria of Kawasaki disease during concomitant Epstein-Barr virus and varicella-zoster virus infections, and we discuss the possible roles of these viruses in etiology.     

Concurrent reactivation of varicella zoster virus and herpes simplex virus in an immunocompetent child

Latency within the nervous system is a characteristic feature of herpesviridae infection. It is reactivated by triggering factors such as UV exposure, stress, and trauma. Simultaneous reactivation of herpes simplex and herpes zoster is uncommon, however, an observation provably explained by differences in the triggering mechanism. Concurrent reactivation of herpes simplex virus (HSV) and varicella zoster virus (VZV) is occasionally encountered in immunosuppressed patients; on the other hand, it is rarely reported in immunocompetent individuals. We present the case of an immunocompetent 8-yr-old female patient with concurrent reactivation of HSV on the face and VZV on the right L2 dermatome.     

Immune response to herpes simplex virus infections: virus-specific antibodies in sera from patients with recurrent facial infections.

Radioimmunoprecipitation assays were used to identify antibodies against a number of herpes simplex virus type 1-specific antigens in serum samples from individuals with recurrent facial herpes virus infections and from seropositive individuals without recurrent infections. Individuals with recurrent infections contributed three sequential serum samples each: immediately after the appearance of lesions, 3 weeks later, and 3 months later. Antibodies against at least 18 viral polypeptides were present in all positive sera: these included antibodies against the major nucleocapsid polypeptide (approximate molecular weight, 150,000) and against two glycopolypeptides with molecular weights of 115,000 to 130,000. No significant differences were observed between the serum samples in regard to their virus-specific antibody composition. The high-molecular-weight glycopolypeptides were partially purified and used in quantitative titration experiments. All sera tested were equally reactive with this material. It was concluded that under the experimental conditions an individual's susceptibility to recurrent herpetic infections could not be correlated with quantitative or qualitative changes in the levels of virus-specific antibodies.     

Age-specific prevalence of antibodies to pyrimidine kinase enzymes of herpes simplex virus types 1 and 2, and of varicella zoster virus

The age-specific prevalence of antibodies to pyrimidine kinase enzymes of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and of varicella zoster virus (VZV) was measured in serum specimens from 360 persons. Specific inhibition of viral enzyme activity by the serum was used as an indication of the presence of antibodies to the enzyme. For HSV-1 and HSV-2 together the overall prevalence of positive sera increased with age and reached about 50% in the older age groups, the major part of the positive sera being HSV-1 positive. Sera inhibitory to the VZV pyrimidine kinase enzyme were detected only sporadically. Six percent of the tested sera repeatedly inhibited the cytosolar corresponding enzyme of uninfected host cells by an unidentified mechanism. The results of the pyrimidine kinase antibody-assay test were compared to those obtained by complement fixation (CF) and enzyme immunoassay (EIA) in a separate set of 50 sera. The correlation between the CF and the EIA tests was good in this selected serum set with CF titres from less than 8 to 64. Twenty-four percent of the CF positive sera were negative by the pyrimidine kinase antibody assay, while all pyrimidine-kinase-antibody-positive sera also had antibodies detectable by the two other methods. These results confirm and extend earlier observations on the occurrence of antibodies in human sera to HSV and VZV pyrimidine kinase enzymes.