Correlation between polymerase chain reaction and cervical cytology for detection of human papillomavirus infection in women with and without dysplasia.

The aim of this study was to compare the ability of two methods, the polymerase chain reaction (PCR) and cervical cytology, to detect HPV infection. The study population included 222 randomly selected women without dysplasia (controls) and 91 women with histologically confirmed dysplasia (CIN II-III) (cases). In women without dysplasia, 8.6% had cytological signs of HPV infection, whereas 15.3% were HPV DNA positive by PCR. In women with dysplasia, 72.5% had cytological signs of HPV infection, whereas 90.1% were HPV PCR positive. The statistical agreement between the two diagnostic methods was low (controls: kappa = 0.26, cases: kappa = -0.03). In total, PCR failed to detect 17 of 85 women with cytological signs of HPV infection, whereas cervical cytology failed to detect 48 of 116 HPV PCR-positive women. In women with dysplasia, but not in women without dysplasia, the oncogenic HPV types were associated with cytological signs of HPV infection.

Prevalence of human papillomavirus in cervical scrapes, as analyzed by PCR, in a population-based sample of women with and without cervical dysplasia.

HPV is suspected of being a major cause of cancer of the uterine cervix. To understand the risk of disease in the general population of women, it is important to estimate the prevalence of HPV infection in a random population-based sample of women without disease. In this study, a total of 231 randomly selected women without dysplasia (controls) were examined, and compared with 103 women with histologically confirmed CIN II-III (patients). The prevalence of HPV DNA in cervical scrapes was determined by general nested PCR, which was expected to detect any relevant HPV type commonly found in cervical samples. The nested positive samples were typed with type-specific PCR. In the general nested PCR, 15% of the controls were positive, compared to 91% of the patients. In the population-based sample, 2.2% had HPV types 6 and 11 and 10% had types 16, 18, 31, and 33. In both groups, HPV DNA was observed less frequently in women above than below the age of 30. The results are among the few population-based figures on the prevalence of HPV in women, and provide a baseline for understanding the risk of developing cancer of the uterine cervix, and determining the proportion of women to be included in intervention studies.

Restriction endonuclease analysis of adenovirus type 3 isolated in Norway from 1970 to 1991.

Forty-three strains of adenovirus type 3 isolated from patients in Norway between 1970 and 1991 were analyzed with four restriction endonucleases. Bg1 II was the most discriminative enzyme. Five genotypes were identified and one of these has not been described before (Ad3a12). During both the epidemics in this period, new genotypes were introduced into the population. The same genotypes were identified in Norway as have previously been found in the northern parts of Europe, America and the Soviet Union.

Herpes simplex virus and human papillomavirus in a population-based case-control study of cervical intraepithelial neoplasia grade II-III.

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.

Susceptibility of continuous lines of monkey kidney cells to influenza and parainfluenza viruses in the presence of trypsin.

LLC-MK2, GMK AH-1, BSC-1, and Vero cells were compared in titrations of recent isolates and laboratory strains of influenza A and B and parainfluenza types 1, 2, and 3 viruses. About the same titres, as determined by haemadsorption in cell cultures, were obtained in LLC-MK2, GMK AH-1, and BSC-1 cells when trypsin had been added to the medium, whereas the Vero cells were less sensitive to the influenza virus strains tested. Virus titres were usually low in the absence of trypsin. A laboratory strain of parainfluenza 2 virus reached about the same titres in medium without as in medium with trypsin, possibly owing to prior adaptation by passages in Vero cells. Comparative titrations of influenza A, and parainfluenza 1 and 3 viruses suggested the same susceptibility of LLC-MK2 cells with trypsin as of primary monkey kidney cells. Re-isolation experiments from 38 clinical specimens showed LLC-MK2 cells to be as efficient as primary monkey kidney cells for isolation of influenza and parainfluenza viruses, whereas the susceptibility of the other cell lines to clinical material has not yet been tested on a larger scale. It is concluded that a continuous line of monkey kidney cell culture may be acceptable as an alternative to primary monkey kidney cells for the isolation of influenza and parainfluenza viruses from patients.

An epidemic of rotavirus-associated gastroenteritis in a nursing home for the elderly.

92 cases of acute gastroenteritis were registered among 256 individuals during an outbreak in a nursing home for the elderly, the majority of patients being between 70 and 90 years of age. Most cases appeared in 4 of the 8 wards; 66% of the inmates of these wards became ill. Characteristic symptoms were initial nausea and vomiting followed by diarrhoea and low fever. A number of patients were severely ill. One patient died. Rotavirus infection was diagnosed by virus detection and/or antibody titre rise during the acute phase of the illness in 13 of 16 patients examined. At the end of the outbreak, high titres of complement-fixing antibodies against rotavirus (greater than or equal to 64) were detected in serum from 21/22 patients convalescing from the disease, as compared to only 5/45 individuals with no signs of disease. It is tentatively suggested that the outbreak became extensive and rather severe because of lowered immunity against rotavirus infection among the elderly.

Antibodies to cytomegalovirus-induced pre-early nuclear antigen in the anticomplement-immunofluorescent test in comparison to IgG and IgM antibodies in the indirect and direct enzyme-linked immunosorbent assay in diagnosing cytomegalovirus infections.

Development of antibody to pre-early nuclear antigen (anti-PENA) in persons with primary cytomegalovirus (CMV) infection was tested in serial serum specimens of four renal transplant patients and four patients undergoing open heart surgery using the anticomplement-immunofluorescent test (ACIF). In patients undergoing open heart surgery seroconversion of anti-PENA was mostly concomitant with the rise of IgG or IgM antibodies determined in the indirect or direct enzyme-linked immunosorbent assay (ELISA) whereas in all renal transplant patients developing anti-PENA a delayed rise of this antibody compared to IgG and IgM antibodies was observed. Significant rise of anti-PENA accompanied by an increase of IgG and IgM antibodies in indirect and direct ELISA was also found in three patients undergoing open heart surgery with recurrent CMV-infection. Anti-PENA was shown to persist longer than IgM antibody. Moreover, anti-PENA was present in the serum of nearly two-thirds of 30 persons with IgG antibody but without IgM antibody. It is concluded that antibody determination to PENA can serve as an additional means of diagnosing primary and recurrent CMV infections. Because of its long persistence only seroconversion or significant rise of this antibody may be considered evidence of infection. In some patients a delayed development of anti-PENA must be taken into consideration.

[Amantadine and rimantadine against influenza A]. / Amantadin og rimantadin mot influensa A.

Amantadine and the analogue rimantadine have an antiviral effect on influenza A virus and are approximately 60% effective in preventing illness. The drugs are administered orally, and peak plasma concentration is achieved at two hours after a single dose. Side effects occur in 5-20% of the cases, but generally mild and transient and seen mainly with doses of more than 200 mg a day. This paper describes the mechanism of action and the pharmacokinetics of the drugs, and refers to some important clinical trials. Amantadine has been used in Norway to treat Parkinson's disease since 1972. The licensing of the amantadine and rimantadine for use against influenza A in this country is also discussed.

Respiratory syncytial virus infections in Oslo 1972--1978. II. Clinical and laboratory studies.

Patient records from 422 children admitted to hospital during 6 winter outbreaks of RSV infection were examined retrospectively. Bronchiolitis (255 patients) and pneumonia (98 patients) were the most common diagnoses. Otitis media (76 patients) occurred as a complication to these conditions. Children at risk for contracting severe illness caused by RSV were infants below the age of one year, more often boys than girls. Of the children older than two years, 32% had already been diagnosed as asthmatics. Children with otitis media had more often positive bacteriological findings from nasopharyngeal swabs than children with bronchiolitis only. No such significant difference was found between patients with bronchiolitis and pneumonia. Rapid virus diagnosis by immunofluorescence led to a decreasing utilisation of antibiotics in patients with bronchiolitis and to a shorter stay in hospital. The value of antibiotics in these infections is discussed.

Effect of fractions of Ethiopian And Norwegian colostrum on rotavirus and Escherichia coli heat-labile enterotoxin.

Samples of colostrum from both Ethiopian and Norwegian women contained antirotavirus activities of immunoglobulin and non-immunoglobulin nature. No significant differences in rotavirus immunoglobulin A or in rotavirus-inhibiting activity were found between samples from the two countries. The non-immunoglobulin inhibitory activity was trypsin sensitive and heat stable (100 degrees C for 10 min). Escherichia coli heat-labile enterotoxin antibodies were measured in the colostrum samples by enzyme-linked immunosorbent assay. No E. coli enterotoxin-specific immunoglobulin A was detected, possibly due to the high background caused by the nonspecific adsorption of immunoglobulin A to the enzyme-linked immunosorbent assay plates in the absence of toxin. A total of 5 of 15 Ethiopian colostrum samples and 0 of 11 Norwegian colostrum samples neutralized the effect of E. coli heat-labile enterotoxin on YI adrenal cells. Both the Ethiopian and the Norwegian colostrum samples contained a non-immunoglobulin enterotoxin-inhibitory activity when the toxin was measured by enzyme-linked immunosorbent assay. This inhibitory activity was not trypsin sensitive, and extraction by chloroform-methanol indicated that the inhibitor was of a lipid nature.

Bronchopulmonary obstruction in children with respiratory virus infections.

Among 873 children hospitalized with confirmed respiratory viral infections, 492 suffered from bronchopulmonary obstruction. Respiratory syncytial virus infections were dominant among the patients with bronchopulmonary obstruction (80%). The majority of patients with rhinovirus infections suffered from bronchopulmonary obstruction (57%). Two main groups of children at risk from developing bronchopulmonary obstruction during respiratory virus infections were found: 1) infants, suffering from bronchiolitis, mainly due to respiratory syncytial virus, and 2) children of all ages with bronchial asthma, among whom acute attacks were precipitated by virus infections, mainly rhinovirus and respiratory syncytial virus infections. The pathogenesis of bronchopulmonary obstruction during respiratory virus infections is discussed.

The effect of human milk fractions on rotavirus in relation to the secretory IgA content.

Human milk from healthy Norwegian women was fractionated by ammonium sulphate precipitation and gel filtration. The protein content, lactoferrin and secretory IgA were measured. Specific antirotavirus IgA, detected by indirect immunofluorescence was found in one out of five milk samples before fractionation, while a more concentrated immunoglobulin fraction from the other four milk samples contained such IgA. Before fractionation, 3 of 5 milk samples neutralized human rota-virus infection of LLC-MK2 cells, whereas concentrated, IgA-rich fractions of all 5 milk samples neutralized human rotavirus. Some fractions without detectable IgA also neutralized human rotavirus. This suggests that human milk contains rotavirus specific IgA as well as rotavirus neutralizing activity of non-immunoglobulin nature.

Virus-specific IgM antibodies in acute gastroenteritis due to a reovirus-like agent (rotavirus).

62 serum samples from 24 patients with rotavirus gastroenteritis were tested for IgM antibodies against a bovine rotavirus by an indirect fluorescent antibody technique. IgM antibodies were detected in one or more of the serum samples from all but one of the patients. IgM antibodies were not detected in samples obtained from 11 of the patients after the 5th week of illness. Absorption of sera for IgG with Staphylococcus aureus increased the sensitivity of the IgM antibody test. It is concluded that the presence of IgM antibodies against bovine rotavirus in a patient's serum, as measured by the present technique, does suggest a recent rotavirus infection. On the other hand, the lack of IgM antibodies in the serum of a child with acute gastroenteritis between the second and the 5th week of illness tends to exclude rotavirus as a cause of the disease.

Nebulised beclomethasone dipropionate in recurrent obstructive episodes after acute bronchiolitis.

Forty four children with recurrent obstructive episodes after acute bronchiolitis in infancy were treated with nebulised beclomethasone dipropionate or placebo for eight weeks in a randomised double-blind study. They were seen monthly for a year afterwards, and also if they had acute respiratory illnesses with or without bronchopulmonary obstruction. The two treatment groups were well matched. The children receiving active treatment had significantly fewer symptomatic respiratory illnesses and fewer episodes of bronchopulmonary obstruction during the follow up period. The children given placebo had significantly higher obstructive scores during the study period, and they were treated with inhaled beta 2 agonists and theophylline for longer periods of time during the follow up period. The results suggest that nebulised beclomethasone dipropionate may have prolonged effects on subsequent asthmatic symptoms after termination of treatment in children with recurrent obstructive episodes after acute bronchiolitis.

Respiratory syncytial virus infections in Oslo 1972--1978. I. Virological and epidemiological studies.

Respiratory syncytial virus (RSV) infection was diagnosed in 464 children admitted to hospital with acute respiratory disease from autumn 1972 to spring 1978. The virological surveillance was approximately 70%. As a rule, RSV infections occurred in distinct outbreaks in late autumn and winter together with a marked increase in the number of children admitted to hospital with acute lower respiratory tract disease. The incidence in children less than 1 year of age was about 10/1000 children/year. Spread of the infection from one end of the city to the other was discernible in 2 outbreaks. More children than expected with siblings were admitted to hospital because of RSV infection, but no correlation could be observed with some other socioeconomic factors. A negative correlation was observed between RSV disease and mean air temperature and hours of sunshine per month. Rapid immunofluorescence diagnosis of RSV on cells from nasopharyngeal secretions was adopted and became comparable to cell culture technique. The rapid method has become an important adjunct to the clinical management of these patients and the method will form the basis for further epidemiological studies.

Acute bronchiolitis in infancy. The relationship to later recurrent obstructive airways disease.

Fifty-one infants admitted to hospital because of acute bronchiolitis were followed until 2 years of age. Sixty per cent had three or more attacks of bronchopulmonary obstruction, and the remainder two or less attacks. The children with three or more attacks also had more respiratory infections. They had younger parents and their close relatives more often had respiratory atopic illness. The children with three or more attacks wheezed for a longer time after the bronchiolitis. No difference was found for breast-feeding, neonatal respiratory complications, crowded homes, parental smoking and other social factors. To detect children at risk of recurrent obstructive airways disease after bronchiolitis, a discriminant analysis was performed. The discriminant function classified 28 of the 31 children with recurrent obstructive episodes as belonging to the risk group, and 18 of the 20 children with two or less episodes to the non-risk group.

Intratypic genome variability of echovirus type 30 in part of the VP4/VP2 coding region.

The genetic relationship of 33 echovirus type 30 (E30) isolates associated with three different outbreaks of meningitis in Norway and one outbreak in USA was assessed using direct sequencing of amplicons derived from a region covering part of the capsid proteins VP4 and VP2. The E30 sequences were compared to each other, and to other enteroviruses. Less sequence variation was observed between the isolates from a single outbreak (2-3%) than between groups of isolates from different outbreaks (4-9%). All observed nucleotide substitutions were amino acid silent. Homology between enteroviruses obtained from GenEMBL and the nucleotide consensus sequence generated from the E30 isolates varied between 44.8% (coxsackievirus A24) and 72.6% (coxsackievirus A9). Comparing the E30 sequences in this part of the genome with other enteroviruses, E30 clearly belongs to the coxsackie B-like virus group.

Rotavirus infections in families. A clinical and virological study.

Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection.