An increase in sudden unexpected cardiac deaths among young Swedish orienteers during 1979-1992

BACKGROUND: Sixteen cases of sudden unexpected cardiac death, 15 males andone female, are known to have occurred among young Swedish orienteersfrom 1979 to 1992, of which seven cases occurred between 1989and 1992. This is considered to be indicative of an increaseddeath rate. RESULTS: Histopathological evaluation showed myocarditis in a higherthan expected proportion of cases. In one such case, which westudied before the sudden unexpected death occurred, the victimhad suffered a Chlamydia pneumoniae infection verified by serology,and a nucleotide sequence was found in the heart and lung bymeans of the polymerase chain reaction (PCR) that hybndizedwith a probe specific for that organism. Male Swedish orienteersdo not, however, seem to have an increased rate of exposureto this agent. No further sudden unexpected deaths among youngorienteers have occurred over the past 3·5 years. Atthe beginning of that period, attempts were made to modify traininghabits and attitudes.     

Quantitative PCR-enhanced immunoassay for measurement of enteroviral immunoglobulin M antibody and diagnosis of aseptic meningitis

A PCR-enhanced immunoassay (PIA) to detect enterovirus (EV) immunoglobulin M (IgM) for diagnosis of recent EV infection was recently developed. This test was compared with another EV IgM capture technique, the solid-phase reverse immunosorbent test (SPRIST). Fourteen of 43 serum samples from aseptic meningitis patients were positive by PIA, whereas 10 were positive by SPRIST. One of 39 control serum samples was weakly positive by PIA. A single-serum-dilution real-time PCR-based PIA for EV IgM (quantitative PIA [QPIA]) was also developed and evaluated against PIA, SPRIST, an EV IgM radioimmunoassay (RIA), and clinical data. A mixture of 12 EVs was used as the antigen. Results from investigating four groups of serum samples were as follows. (i) The nine PIA-positive serum samples in group 1 were all positive by QPIA. (ii) Group 2 consisted of 59 serum samples from aseptic meningitis patients. Nineteen of 30 serum samples (63%) taken at hospital admission were positive by QPIA. Of these, 17 were positive in EV PCR. (iii) None of the 30 control serum samples in group 3 were positive by QPIA. (iv) For the 24 serum samples in group 4, of which 11 were positive and 13 were negative by RIA, the QPIA results were completely concordant. The sensitivity and specificity of QPIA for diagnosis of EV infection were 70 and 80%, respectively. QPIA provides a rational strategy for the detection of EV IgM, allows the use of viral antigens with minimal purification, and needs no virus-specific reagents apart from those in the PCR. QPIA is a generally applicable method for the detection of viral IgM in IgM capture assays.     

Immune response to a single peptide containing an immunodominant region of hepatitis C virus core protein: the isotypes and the recognition site.

We have used one single peptide covering the 17 N-terminal amino acids of the hepatitis C virus (HCV) core protein (c) to analyse the human immune response against B-cell epitope(s) within this region. The sequence MSTNPKPQRKTKRNTNR was obtained from two sequenced HCV genomes, and the peptide was synthesized by a newly developed method. The peptide was assayed with 144 human sera which had all been assayed for antibodies to HCV (anti-HCV) using commercial assays. Forty-nine sera were found to be positive for anti-HCV using these assays; 40 of these were found to be positive with our anti-HCV IgG peptide assay. The class (IgM, IgG) and subclass (IgA1, IgG1-4) specific reactions were determined using the polyclonal and monoclonal anti-HCV peptide enzyme immunoassays. Isotypes of mainly IgG1 and IgG3, but also IgG4, IgM and IgG2, gave specific reactions with this region. Using omission peptide analogues of the region 1-18, the sequence RKTKRNTN within residues 9-16 was common to 34 out of 37 sera of which the IgG antibody binding site could be mapped. It is unusual for a single peptide assay to have such high sensitivity since B cell epitopes within a protein are often discontinuous. It seems that at least 80% of HCV infected individuals develop antibodies of various isotypes to the antigenic site RKTKRNTN, located in the N-terminal portion of the HCV core. Thus, the immune response to this peptide should be further investigated with regard to the reactive Ig isotypes developing during HCV infection.     

Early diagnosis of enteroviral meningitis by detection of specific IgM antibodies with a solid-phase reverse immunosorbent test (SPRIST) and mu-capture EIA.

A solid-phase reverse immunosorbent test (SPRIST) and a mu-capture enzyme immunosorbent assay (EIA) for detection of enterovirus-specific IgM antibodies were evaluated for enterovirus diagnosis of aseptic meningitis in 160 consecutive patients from whom enterovirus (11 different serotypes) were isolated in 64. In patients with an enterovirus isolate and/or four-fold titre rise in the complement fixation test (CFT) for enterovirus, specific enterovirus IgM antibodies were detected on the day of admission to hospital in 48% by SPRIST and in 50% by EIA and 4-6 days after onset of symptoms in 71% by SPRIST and 79% by EIA. A significant increase in titre was observed between serum sampled on the day of admission and 2 days later in 38% by SPRIST and in 41% by EIA. These results indicate that the IgM antibody response appears early in the course of aseptic meningitis. Since both SPRIST and EIA provide rapid results the tests may be of differential diagnostic value and the IgM antibody kinetics may be utilized for diagnosis during the acute phase of aseptic meningitis. With optimized serum sampling the positive outcome was 76% in SPRIST and 82% in EIA among patients with positive virus isolation and/or CFT for enterovirus. In 67 patients virus isolation and CFT for enterovirus yielded negative results as well as all non-enteroviral diagnostic tests. Thirty-eight of these patients were positive by SPRIST and/or EIA and in half of these 38 a significant titre rise and/or fall in SPRIST and/or EIA was recorded. The majority of these IgM-positive patients became ill in the late summer or autumn, i.e., the "enterovirus season."(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiology of hepatitis B in Somalia: inference from a cross-sectional survey of serological markers

Hepatitis B markers were determined by radioimmunoassay in 383 adults from different areas of Somalia and in 135 pregnant females and 428 children from Mogadishu. The highest incidence of HBsAg among adults was among nomadic males (20/85; 23%). The frequencies were lower in males from the agricultural and coastal area, i.e. 16/93 (17%) and 14/98 (14%) respectively. The lowest frequency of HBsAg was among women from the coastal area (6/72; 8%). Among the pregnant women 14 were positive for HBsAg, none of whom had HBeAg. Low levels of positivity for HBsAg were found both among children under 4 years and among those between 4 and 13 years of age - 3/94 (3%) and 5/128 (4%) respectively. In the age group 15-19 years, 50% showed seroconversion from HBeAg to anti-HBe. 7 out of 41 HBsAg carriers of ages over 20 had HBeAg. Early seroconversion from HBeAg to anti-HBe and a low level of HBsAg positivity in children indicate that vertical transmission is not important in Somalia. The low frequency of HBsAg in Mogadishu children may have one of the following explanations: (i) the infection occurs during adolescence, (ii) Mogadishu is a low-prevalence area and the examined adults were not born in Mogadishu, or (iii) a change in hepatitis B epidemiology has taken place in the area during the last 2 decades and the relatively higher prevalence of HBsAg in adults might reflect higher rates of infection in their childhood.     

Minor role of hepatitis B virus in the causation of chronic liver disease in Somalia indicated by a case-control study.

Chronic liver disease (CLD) is frequent in Somalia. In a case-control study, 116 in-patients with CLD were compared with the same number of age and sex matched controls. Demographic variables, use of drugs, symptoms and signs, serological markers for hepatitis B virus (HBV) and serum alpha-foetoprotein (AFP) were assessed. Hepatitis B surface antigen (HBsAg) was found in 44 cases of which 17 had antibodies to hepatitis D virus (anti-HD) and 7 had hepatitis B e antigen (HBeAg). Twenty-three controls were HBsAg-positive, of whom 3 had anti-HD and one HBeAg. Increased relative risks (95% confidence intervals in parentheses) were 2.5 (1.3-4.5) for HBsAg, 6.5 (1.7-21.5) for anti-HD, and 7.4 (0.9-66.5) for HBeAg. Despite the association between the presence of HBV markers and CLD, 62% of the cases had no markers indicating current HBV infection. This was reflected in the low risk attributable to chronic HBV infection (22.6%), which was lower than that in patients with CLD in other African populations with a high HBsAg carrier rate. The prevalence of HBV markers did not differ between cases with AFP greater than 100 ng/ml and those with AFP less than 100 ng/ml. The former were characterized by male predominance, shorter duration of symptoms, and larger mean liver size, indicative of malignancy. The mean age of HBsAg-positive cases with AFP greater than 100 ng/ml was significantly lower (by 7.7 years) than that of HBsAg-negative cases with AFP greater than 100 ng/ml. Among the CLD patients with AFP less than 100 ng/ml, 48 were HBsAg-negative. These cases differed significantly from the other 68 cases in that more were females (35% against 16%), more originated from an agricultural area (56% against 30%), and more were regular consumers of drugs (48% against 28%). In conclusion, factors as yet undefined play a considerable role in the causation of CLD in Somalia. The possibility of determining the role of hepatitis C virus (HCV) awaits the development of more specific assays for anti-HCV antibodies.     

A longterm follow-up study of children born to women with contagious diseases at delivery

Data are presented from a long-term follow-up study of 308 live born children to women admitted post partum to the Department of Infectious Diseases (DID), Danderyd Hospital, Sweden, during a 10-year period (1975-1984) for avoiding nosocomial transmission of infections in the obstetrical wards. The rate of stillbirths (1/309 deliveries) was not higher than reported for all births in Stockholm. 20% of the live born children were transferred within 24 h after birth to the pediatric department for observation, but half of them could return to their mothers at the DID within 6 days (generally 3 days). Four newborns were treated at an intensive care unit. Only 3 fatalities occurred, all of them among newborns to mothers with an overt infection at delivery. The fatality rate (1.8%) was significantly higher among the newborns of these mothers than normally (0.3%) noted among all children born in Stockholm county during the period studied. Two of the 3 newborns, who all died within 3 days of life, had a low birth weight (600 and 1,000 g). The total number of newborns with low birth weights (less than 2,500 g) was, however, not higher in the above-mentioned group of newborns than for all children born in Stockholm county 1980. None of the 3 fatalities was caused by infection transmitted from the mother. No further deaths occurred. Infections in pregnancy at term, at birth or post partum were transmitted from the women to 41 (13%) of their newborns.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reactivity of sera from patients with liver disease with glutaraldehyde-treated erythrocytes: role for false positive results in hemagglutination tests

The use of glutaraldehyde as a coupling reagent in the passive hemagglutination test (HA) has gained wide application, especially for the coating of red blood cells (RBC) with glutaraldehyde-polymerized human serum albumin (pHSA), for studies of the albumin receptor on hepatitis B surface antigen (HBsAg) or for the detection of anti-albumin antibodies (AAA). Here we report a previously unrecognized reactivity with glutaraldehyde-treated RBC mainly with sera from patients with liver disease. The highest incidences of this reaction were found in patients with acute viral hepatitis A and B, namely 44 of 50 (88%) and 31 of 50 (62%) respectively. In 234 HBsAg carriers the frequency was low (3%). This reactivity was also observed in 19 of 50 sera from patients with chronic liver disease documented by biopsy, but not in sera from 68 healthy subjects. By immunofluorescence on glutaraldehyde-treated RBC it was shown that the corresponding antibodies belonged mainly to the IgM class. In all HBsAg-negative patients studied the HA titer against glutaraldehyde-treated RBC was in agreement with the titer against RBC coated with pHSA or pBSA (polymerized bovine serum albumin). Absorption with pHSA abolished the reaction with glutaraldehyde-treated RBC in 7 of 8 sera, suggesting a common reactivity between glutaraldehyde-polymerized HSA and glutaraldehyde-treated RBC. Apart from the possible clinical importance of these antibodies, their existence is a possible source of false positive results when glutaraldehyde is used as a coupling reagent for immunological assays, in particular with sera from patients with liver diseases.     

Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study

Determination of anti-hepatitis E virus (anti-HEV) antibodies is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Serum samples from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection, were analyzed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E, respectively. The range of sensitivity for anti-HEV detection was broad (42% to 96%); this was reflected in the detection limit, which varied up to 19-fold for IgM and 17-fold for IgG between assays. HEV RNA was analyzed in all patients and in those blood donors reactive for anti-HEV in any assay, and it was found in 26 individuals. Among all of the assays, both anti-HEV IgG and IgM were detected in 10 of those individuals. Twelve had only IgG and, in 7 of those 12, IgG was only detected with the two most sensitive assays. Three of the HEV-RNA-positive samples were negative for anti-HEV IgM and IgG in all assays. With the two most sensitive assays, anti-HEV IgG was identified in 16% of the blood donor samples and in 66% of patients with suspected HEV infection. Because several HEV-RNA-positive samples had only anti-HEV IgG without anti-HEV IgM or lacked anti-HEV antibodies, analysis for HEV RNA may be warranted as a complement in the laboratory diagnosis of ongoing HEV infection.