Parvovirus infection in children with AIDS: high prevalence of B19-specific immunoglobulin M and G antibodies.

OBJECTIVE: Investigation of the prevalence and pathogenic role of parvovirus B19 infection in Italian and Rumanian children with AIDS, compared with age-matched HIV-negative children (controls) with various recurrent infections of unknown aetiology. DESIGN: Detection of B19-specific immunoglobulin (Ig) M and IgG antibodies as the most indicative markers of past or current B19 infection. METHODS: B19 antibodies were detected by two enzyme immunoassays using synthetic peptide or recombinant protein, which corresponded to different B19 epitopes, as coating antigens. RESULTS: B19 IgM and IgG were seen in 10 out of 20 (50%) Italian and in 20 out of 51 (39.2%) Rumanian children with AIDS, in contrast to none out of 17 Italian and one out of 22 Rumanian controls (P less than 0.001). In addition, two Italian controls (11.8%), two Rumanian children with AIDS (3.9%), and two Rumanian controls (9.1%) had B19 IgM alone. Specific IgG alone was detected in eight (40%) Italian and 14 (27.5%) Rumanian children with AIDS, and in seven (41.2%) Italian and four (10.2%) Rumanian controls. CONCLUSIONS: While it is possible to attribute some B19 infections in Rumanian children to blood transfusion, the source was unknown for Italian children. However, in three of the Italian children who had B19 IgM and IgG persistently for 15-22 months, and in a 2-month-old Italian infant with B19 IgM and IgG, HIV might have activated a congenital or perinatally-acquired B19 infection.

A cyclized peptide for studies of human parvovirus B19 infection.

Synthetic peptides corresponding to human parvovirus B19 sequences were evaluated for immunoreactivity with the sera of infected persons. A cyclized peptide deduced from the N terminus of viral protein VP2 and containing the amino acids 284-307 showed a high reactivity with IgM class antibodies when comparing seropositive and seronegative sera.

Thyroid hormone activates transcription from the promoter regions of some human nuclear-encoded genes of the oxidative phosphorylation system.

Thyroid hormone (T3) modulates the mRNA levels for cytochrome c and the adenine nucleotide translocator-2 (ANT2) in adult rat liver. Here we show that T3 activates expression of a reporter gene driven from the human cytochrome c1 and ANT2 promoters transfected into human choriocarcinoma JEG3 cells. By contrast, the human F1-ATPase beta-subunit promoter responded marginally, thus providing a pattern of differential expression similar to that earlier observed in rats in vivo. T3-activation is dependent on co-expression of the thyroid hormone receptor (TR alpha1). Co-expression of both the TR and RXR receptors had no additional effect. Transient transfection of deletion constructs showed that T3 activation is retained by the proximal regions of the cytochrome c1 and ANT2 promoters, and, in the case of cytochrome c1, is lost upon removal of a fragment containing the transcription initiator ((nucleotides) (nt) + 1 to + 100). The promoter regions supporting T3-activation of the reporter genes appear to lack strong DNA binding sites for TR and retinoid X receptor (RXR).

Immunity to and immunization against measles, rubella and mumps in patients after autologous bone marrow transplantation.

Humoral immunity to measles, rubella and mumps was studied in 63, 36 and 16 patients 1, 2 and 3 years, respectively after autologous bone marrow transplantation (ABMT). Serologic examination was performed using antibody-ELISA. One year after ABMT, 7/57 patients (12%) who were seropositive to measles before ABMT, became seronegative, 8/44 (18%) to rubella and 3/51 (6%) to mumps. Among patients who were retested at 2 and 3 years, three more patients became seronegative to measles, one to rubella, and three to mumps. Nine of 12 children who had previously been immunized against measles were seropositive before ABMT, 3/7 to rubella and 5/7 to mumps, respectively. After ABMT, 5/9 became seronegative to measles, none to rubella and 2/5 to mumps. Six seronegative children were immunized with a live trivalent attenuated measles, mumps, and rubella vaccine 1 to 2 years after ABMT. Two children seroconverted to measles, six to rubella, and four to mumps. No side effects were observed. Most adult patients who have had the diseases of measles, rubella, or mumps naturally remain seropositive, while children who have been immunized commonly lose their immunity after ABMT.

Multiple viral infections in HIV-infected children with chronically-evolving hepatitis.

Hepatic involvement was investigated in 31 children with perinatal HIV-1 infection, who were followed for 2-82 months (mean 30.5). Liver disease, as revealed by increased aminotransferase levels, liver biopsy or necroscopy, was diagnosed in 18 children (58%), of which 7 (22.5%) had acute hepatitis and 11 (35.5%) showed chronic liver disease. Overall, 40 persistently active or recurrent viral infections, as demonstrated by positive culture and/or detection of serum DNA, specific IgM, IgA and high levels of IgG, were revealed in the children with liver disease, while 12 similar infections were detected in 13 children without liver disease (p < 0.001). In particular, the children with liver disease showed a significantly (p < 0.002) higher incidence of cytomegalovirus (CMV) infections than children without liver disease (13 versus 3). Moreover, hepatitis C and B virus infections were revealed only in children with liver disease (5 and 1 patients, respectively). Clinical outcome showed a significantly (p < 0.001) higher mean survival in the children without liver disease than those with liver disease (47.5 versus 18.2 months). In fact, nine of the children with liver disease (50%) died, as opposed to only one of the children without liver disease (7.7%; p = 0.01). Based on these findings, liver disease is indicative of a poor prognosis in children with HIV infection, being related to the presence of multiple active viral infections.

Combination ELISAs for antiviral antibodies in CSF and serum in patients with neurological symptoms and in healthy controls.

A combination enzyme-linked immunosorbent assay (ELISA) was designed to improve the estimation of serum: cerebrospinal fluid (CSF) antiviral IgG ratios. Microplate wells were coated with five different virus antigens. Serum and CSF from 66 patients referred for CSF serology and from 21 healthy controls were studied. In a comparison with serum: CSF IgG titre ratios, absorbance ratios were found to be suitable for the evaluation of intrathecal antiviral IgG synthesis. A slight blood-brain barrier (BBB) disturbance affected only the passage of albumin over the BBB, whereas a more pronounced BBB defect resulted in increased IgG levels in the CSF. Intrathecal antiviral IgG synthesis was demonstrated in 15 patients with viral CNS infections or inflammatory diseases. Very high serum: CSF antiviral IgG titre ratios and absorbance ratios, found in six patients, were interpreted as signs of diminished IgG passage over the BBB due to impaired CSF circulation.

IgG antibodies to human herpesvirus-6 in children and adults and in primary Epstein-Barr virus infections and cytomegalovirus infections [corrected].

Antibody titers against human herpesvirus-6 (HHV-6) were determined in 80 healthy adults and 100 children and teenagers from Sweden to gain information on the role of the virus and its epidemiology. Based on a positive immunofluorescence titer of 1:10 and above, about 85% of the adults and children were seropositive with 60% seropositivity of children below age one year. Titers were generally higher in patients with simultaneous EBV or CMV infection, yet crossreactivity appeared essentially no problem. HHV-6 thus is ubiquitous like other herpesviruses. Primary infection seems to occur early in life, and reactivation or delayed primary infection may be associated with a variety of disorders.

Studies on alkaline phosphatase isoenzymes. Relation to gamma-glutamyltransferase and lactate dehydrogenase isoenzymes.

Gamma-Glutamyltransferase (GT) and isoenzymes of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been studied in 282 cases with increased S-ALP and in 18 chronic alcoholics with normal routine liver tests. There was a high degree of correlation between S-GT and the bile (alpha 1) and liver (alpha 2) fractions of S-ALP. Fractionation of alkaline phosphatases sometimes yielded clinical information, which could not be obtained by determinations of S-ALP and S-GT only. The presence of alpha 1-ALP and increased S-GT appeared to be more sensitive indicators of ethanol-induced liver involvement than other liver tests, including LDH-5/LDH-4 ratios.

Serology of respiratory viruses in relation to asthma and bronchial hyperresponsiveness.

Do individuals with serological evidence of infections with respiratory viruses have an increased prevalence of asthma or bronchial hyperresponsiveness (BHR)? Antibodies to four common respiratory viruses were measured in the sera of 81 subjects without a history of a recent respiratory infection. The subjects underwent an interview, spirometry, a methacholine provocation test and skin prick tests. In sera where virus antibodies were found, IgG titer values of > or = 1:40 were regarded as evidence of a recent infection. A significant relationship was found between serological markers of a recent respiratory syncytial (RS) virus infection and physician diagnosed asthma (odds ratios (OR) 14.5, 95% confidence intervals (CI) 1.4-151) or BHR (OR 12.7, 95% CI 1.2-132)(p < 0.05). Furthermore, the total blood eosinophil count was significantly higher in subjects with serological signs of a current or recent RS virus infection than in those without such signs (364 +/- 198 x 10(6)/L and 175 +/- 118 x 10(6)/L respectively, p < 0.05). In conclusion, a recent RS viral infection may be an important factor in the induction of symptoms and signs suggestive of asthma.

[BK and JC viruses--2 polyomaviruses causing disease in immunosuppressed patients]. / BK- och JC-virus--två polyomavirus som orsakar sjukdom hos immunsupprimerade.

BK and JC viruses are two polyoma viruses designated by the initials of the patients from whom they were first isolated. After the primary infection, usually occurring in childhood or early school age, the viruses become latent. Reactivation occurs during immunosuppression, and the BK virus has been shown to be the main cause of viral hemorrhagic cystitis in bone marrow transplanted patients, while the JC virus has been found to cause progressive multifocal leukoencephalopathy, PML. The paper consists in a report of results obtained with an established method for the amplification of BK and JC virus DNA. Of 20 urine specimens from patients with hemorrhagic cystitis, 13 were found to be BK virus-positive. Post-transplantation follow-up shows that the virus continues to remain detectable for long periods. JC virus positivity was found in central nervous system material (a cerebrospinal spinal fluid specimen in one case) from two PML patients.

A new peptide for human parvovirus B19 antibody detection.

A serological assay for human parvovirus B19 was developed. Linear overlapping synthetic peptides were synthesised according to parts of open reading frames 1 and 2. A region at the N-terminus of viral protein VP2 detected serological reactivity in indirect enzyme-linked immunosorbent assays for IgG and IgM with known seropositive human sera. A cyclized peptide taken from this region, amino acids 284-307, gave the best selective reactivity with seropositive and seronegative sera. The peptide assay appears suitable for further studies of B19 infections and their complications.

Intradermal immunization with reduced doses of human diploid cell strain rabies vaccine: evaluation of antibody response by ELISA and mixed hemadsorption test.

The antibody response to the rabies human diploid cell strain vaccine was compared after pre-exposure immunization with 0.1 ml intradermal (i.d.) and 1.0 ml subcutaneous (s.c.) vaccination. After primary immunization, 2 doses of vaccine 1 month apart, all vaccinees in the two groups had antibody titers detectable by ELISA. However, the mean antibody titer after the 0.1 ml i.d. doses (5.9 EU/ml) was half of what was obtained after the 1.0 ml s.c. doses (12.2 EU/ml). Likewise, though all vaccinees responded on the 1-year booster dose the mean antibody level after i.d. vaccination (8 EU/ml) was 2.5 times lower than after 1.0 ml s.c. dose (21.5 EU/ml). At 1 year 70% of the vaccinees had detectable antibody levels irrespective of vaccination route. A few individuals responded to one of their i.d. doses with only minor titer rises which is supposed to be due to inadvertent s.c. injection of the i.d. dose.

Evaluation of a synthetic-peptide enzyme-linked immunosorbent assay for immunoglobulin M to human parvovirus B19.

A synthetic peptide corresponding to a part of the virus protein 1-virus protein 2 overlapping region of human parvovirus B19 was used in an indirect enzyme-linked immunosorbent assay. Antibodies of the immunoglobulin (Ig) M class were measured in serum samples from patients with erythema infectiosum and controls. In comparison with an IgM assay using native B19 viral antigen, the peptide antigen assay was 92% sensitive and 87% specific. B19 IgM reactivities were seen in a limited number of children with other viral diseases. Specific IgM reactivities to short synthetic viral peptides have previously been reported only with Epstein-Barr virus. Since other sources of viral antigen are limited, the peptide antigen assay may be a useful alternative for the diagnosis of B19-associated disease in human beings.

A 5-year follow-up study of suicide attempts.

Seventy-five patients were admitted to the ward of the Lund Suicide Research Center following a suicide attempt. After 5 years, the patients were followed up by a personal semistructured interview covering sociodemographic, psychosocial and psychiatric areas. Ten patients (13%) had committed suicide during the follow-up period, the majority within 2 years. They tended to be older at the index attempt admission, and most of them had a mood disorder in comparison with the others. Two patients had died from somatic diseases. Forty-two patients were interviewed, of whom 17 (40%) had reattempted during the follow-up period, most of them within 3 years. Predictors for reattempt were young age, personality disorder, parents having received treatment for psychiatric disorder, and a poor social network. At the index attempt, none of the reattempters had diagnoses of adjustment disorders or anxiety disorders. At follow-up, reattempters had more psychiatric symptoms (SCL-90), and their overall functioning (GAF) was poor compared to those who did not reattempt. All of the reattempters had long-lasting treatment ( > 3 years) as compared to 56% of the others. It is of great clinical importance to focus on treatment strategies for the vulnerable subgroup of self-destructive reattempters.

A prospective study of antibodies against parvovirus B19 in pregnancy.

BACKGROUND: Parvovirus infection during pregnancy has been reported to be associated with spontaneous abortion and fetal loss. OBJECTIVE: To show the incidence of antibodies against Parvovirus B19 early in pregnancy and sero-reactivities during and after pregnancy. STUDY DESIGN: In a prospective study during a non-epidemic period, 457 women admitted to an antenatal care center were included. Serum samples were collected at 7-13, 21, and 33 weeks of gestation, and 7-9 weeks after delivery. METHOD: Samples were evaluated for parvovirus specific IgG and IgM against two different parvovirus antigens. RESULTS AND CONCLUSION: Parvovirus specific antibodies were present in 81% of the women in the first sample. Six women (six of 88 susceptible, 6.8%) seroconverted and 28 women (28/369, 7.6%) boosted their antibody response during or after pregnancy. All gave birth to healthy infants. One woman free of symptoms experienced an intrauterine fetal death at 37 weeks of gestation. She had no rise in B19 antibodies during pregnancy, but parvovirus DNA was found in maternal serum samples and in the placenta.

Effect of primary Epstein-Barr virus infection on human herpesvirus 6, cytomegalovirus, and measles virus immunoglobulin G titers.

Immunoglobulin G antibody titers to human herpesvirus 6 (HHV-6), measles virus, and cytomegalovirus (CMV) were examined in serum samples from 31 patients with Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). Sera were drawn sequentially from the same patients less than or equal to 7 days until 3 years after onset of IM. In seropositive patients, there was a significant decrease with time after IM of the immunoglobulin G titers to the three viruses in the majority of patients; HHV-6 IgG titers decreased in 80%, measles virus IgG titers decreased in 75%, and CMV IgG titers decreased in 67%. Four patients contracted CMV infection during the observation period after IM. In these, HHV-6 IgG titers increased, while EBV and measles virus IgG titers remained essentially stationary. Polyclonal B-cell stimulation during IM is suggested to augment antiviral titers in general, but the increases of HHV-6 IgG titers during EBV and CMV infections may also be due to selective stimulation of memory B cells by related antigens or to reactivation of HHV-6 during infection with these herpesviruses.

Polymerase chain reaction with double primer pairs for detection of human parvovirus B19 induced aplastic crises in family outbreaks.

Parvovirus B19 DNA can be detected by polymerase chain reaction with double primer pairs (nested PCR). Recent infection was documented by a retrospective serological study using Parvoscan-B19 enzyme linked immunosorbent assay (EIA) for detection of B19 human parvovirus IgM and IgG antibodies in serum or plasma specimens. In 3 families B19 outbreaks caused aplastic crises necessitating blood transfusion in 5 children and 1 adult with hereditary sphaerocytosis. Four members from 2 of the families had clinically overt haemolytic anaemia prior to the event. Two members in another family presented with an aplastic crisis disclosing the underlying chronic haemolytic disease. All 7 patients were identified as PCR positive in serum samples taken 3-14 days after the onset of symptoms. Comparison with dot blot hybridization revealed detectable DNA in only 2/3 PCR positive patients. Thus, nested PCR is more sensitive than the dot blot hybridization method and is therefore a suitable complement to the antibody assay for identifying recent B19 infection.

Serology of chlamydia in relation to asthma and bronchial hyperresponsiveness.

Antibodies to the 3 strains of chlamydia were measured in the sera of 197 subjects; 122 with asthma-related symptoms and 75 from the general population. The subjects underwent a structured interview, spirometry, a methacholine provocation test and skin-prick tests. For chlamydia antibodies, IgG titer values of > or = 1:512 and/or IgM > or = 1:16 were regarded as evidence of a current or recent infection while IgG levels < 1:512 and > 1:32 were regarded as indicative of a previous infection. For Chlamydia pneumoniae, a relationship was found between current or recent infection and wheezing (odds ratio (OR) 6.0, confidence intervals (CI) 1.3-28) and also between IgA antibodies and bronchial hyperresponsiveness (BHR) (OR 3.3, CI 1.3-8.3). For Chlamydia trachomatis, serological signs of a previous infection were found significantly more often in subjects who reported having had asthma at some time: (OR 3.2, CI 1.4-7.1), asthma during the last year (OR 3.2, CI 1.4-7.1), wheezing during the last year (OR 4.2, CI 1.6-6.6) and in those who had BHR (OR 2.7, CI 1.2-6.1). We conclude that a relationship may exist between Chlamydia pneumoniae and Chlamydia trachomatis infections and asthma-related symptoms and BHR.