Inge Panum Jensen

Few microorganisms associated with bacterial vaginosis may constitute the pathologic core: a population-based microbiologic study among 3596 pregnant women

OBJECTIVE To evaluate the association between various microorganisms isolated from the genital tract in pregnant women with bacterial vaginosis. STUDY DESIGN A cross-sectional population-based study among pregnant women addressed at their first antenatal visit before 24 full gestational weeks from the referring area of the Department of Obstetrics and Gynecology at Odense University Hospital, Denmark, from November 1992 to February 1994. The main outcome measures were prevalence of various microorganisms and statistical estimates of interactions (crude, adjusted, and relative odds ratios) between the microorganisms isolated from the lower genital tract in pregnant women with and without clinical diagnosis of bacterial vaginosis. RESULTS Three thousand five hundred ninety-six (3596) pregnant women were asked to participate. Of the 3596 pregnant women 3174 (88.4%) agreed to participate before 24 full gestational weeks. After controlling for the presence of other microorganisms, strong associations between Gardnerella vaginalis, anaerobic bacteria, Mycoplasma hominis, and present bacterial vaginosis were found. Similarly Lactobacillus spp. were found to be associated with the absence of bacterial vaginosis. The combination of G. vaginalis and anaerobic bacteria and/or M. hominis was found in 59.6% of the cases with bacterial vaginosis and in 3.9% of the cases without bacterial vaginosis (odds ratio 36.4, 95% confidence interval 27.8 to 47.8). The crude odds ratio was found to be as high as 74.8 (95% confidence interval 32.3 to 174.1) when the combination of G. vaginalis, M. hominis, anaerobic bacteria, and no Lactobacillus spp. was associated with bacterial vaginosis. CONCLUSION There is a microbial foundation for bacterial vaginosis, and it is possibly due to an intermicrobial interaction in which the microorganisms G. vaginalis, anaerobic bacteria, and M. hominis are dominating, indicating that these constitute the pathologic core of bacterial vaginosis.

An epidemic of parvovirus B19 in a population of 3596 pregnant women: a study of sociodemographic and medical risk factors

Objectives To estimate the incidence of human parvovirus B19 among pregnant women before and during an epidemic, to elucidate possible sociodemographic and medical risk factors during pregnancy and to estimate the association between parvovirus B19 infection and negative pregnancy outcome.

Maturation of rubella IgG avidity over time after acute rubella infection

BACKGROUND As the incidence of rubella has diminished, the proportion of unspecific rubella IgM reactivity among all samples with rubella IgM reactivity has increased. It is important to distinguish IgM reactivity caused by primary infection from that caused by reinfection or persistence, especially in pregnant women, as termination of pregnancy should be considered when primary rubella is diagnosed during the first trimester. OBJECTIVES To elucidate the changes over time of the avidity of rubella IgG antibodies after acute rubella infection. STUDY DESIGN Serial samples, 84, were collected from 15 patients up to 4-5 months after acute rubella infection. Rubella specific IgG avidity was tested by the eluting principle adding 35 mM diethylamine to the washing buffer of a commercially available rubella IgG ELISA. As controls, 137 samples from women with remote rubella and 94 samples from patients with a rubelliform rash, were tested. RESULTS The avidity index increased steadily in all patients during the observation time. A low avidity index (< 40%) was seen up to 6 weeks after onset of rash. A high avidity index (> 60%) was not observed until 13 weeks after infection and only in four of the 15 patients during the observation time. CONCLUSIONS An increase of rubella IgG antibody avidity was seen during the whole observation time but was most pronounced during the first 3 months after onset of rash. Measurement of rubella IgG avidity is a good supplemental test for cases with rubella IgM reactivity to confirm or exclude a recent rubella infection.

Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country

OBJECTIVE To compare detection of respiratory syncytial virus (RSV) for diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in different clinical settings in a community study in Guinea‐Bissau.

Assessment of the specificity of a commercial human parvovirus B19 IgM assay

BACKGROUND It is important to investigate a possible cross-reaction of anti-rubella IgM in the IDEIA Parvovirus B19 IgM test because many B19 infections are either asymptomatic or have clinical symptoms similar to those of rubella virus infections. Epstein-Barr virus (EBV) IgM, cytomegalovirus (CMV) IgM, measles IgM and rheumatoid factor (RF) IgM cross-reactions were also studied. OBJECTIVES In the period from February to September 1994 (including a parvovirus B19 epidemic) more than 10,000 serum samples were examined for parvovirus B19 IgM in Denmark. This gave an opportunity to evaluate the commercial IDEIA Parvovirus B19 ELISA kit (DAKO A/S, Glostrup, Denmark), which was used routinely at Statens Serum Institut from the beginning of 1994 and onwards. STUDY DESIGN A total of 123 parvovirus B19 IgM positive sera were tested for reactivity in rubella IgM EIA. A total of 78 rubella IgM positive sera, 60 EBV VCA-IgM positive sera, 30 CMV IgM positive sera and 24 measles virus IgM positive sera were tested for reaction in IDEIA Parvovirus B19 IgM test. Finally, 25 parvovirus IgM positive sera were tested for specific IgM against measles virus, EBV (VCA), CMV and for RF. RESULTS One anti-B19 IgM positive serum sample reacted positively in the rubella IgM test. Of rubella IgM positive serum samples 4% cross-reacted in IDEIA Parvovirus B19 IgM test, as did 17 and 20% of EBV VCA-IgM and CMV IgM positive serum samples respectively. None of measles virus IgM positive serum samples cross-reacted in the IDEIA Parvovirus B19 IgM test. Of 25 initially parvovirus B19 IgM positive sera 20% cross-reacted in EBV VCA IgM test and 8% in the CMV IgM test. None reacted positively in measles virus IgM test; 28% showed weak reactivity in RF IgM test. CONCLUSIONS Precautions must be taken when results of IgM assays are interpreted. Epidemiological and clinical observations must be considered.

Routine diagnosis of herpes simplex virus (HSV) encephalitis by an internal DNA controlled HSV PCR and an IgG-capture assay for intrathecal synthesis of HSV antibodies

BACKGROUND The development of antiviral therapy increases the need for rapid, sensitive and reliable methods or combination of methods for diagnosis and monitoring herpes simplex encephalitis, HSE. OBJECTIVES Evaluation of diagnostic performance of three successively developed HSV PCR assays when combined with a new capture ELISA for HSV intrathecal antibody production (ITT). STUDY DESIGN During a 3.6 year period a total of 4.206 CSF and serum samples from about 4.140 hospitalized patients with a tentative diagnosis of HSE were analyzed by a new ELISA for ITT. 1.962 CSF samples were examined also by PCR. Clinical signs and symptoms and additional tests were obtained on all ITT and/or PCR positive patients. In 1993 the PCR was a double PCR. In 1994 the PCR was a single PCR with internal inhibition control. Positive samples were confirmed by a different confirmative PCR to increase the specificity. From 1995 the PCR was as in 1994 but samples were no longer divided in the serology routine laboratory. RESULTS A total of 33 HSE cases was found (incidence 1.8 HSE per million people). All patients were treated with aciclovir. Three patients died, 9 patients had primary infection, 2 patients had HSE previously, and 2 patients relapsed. Only 11 patients recovered satisfactory. Of all 37 positive ITT 7 were unlikely positive. False positive PCR was seen in 1993 and 1994, due to sample-to-sample contamination during division of samples, but was not seen since 1995 when this procedure was changed. The test results depended on the state of the disease. Thus, the sensitivity, specificity, PPV and NPV for ITT were highest when performed more than 1 week after debut of symptoms whereas these values were highest using PCR within the first week. CONCLUSION Routine PCR diagnosis of HSE type 1 and 2 is a highly sensitive and specific method that should be performed together with serological ITT to cover the whole time span from debut of symptoms to several weeks after hospitalization.

Diagnosing Bacteremia at a Danish Hospital Using One Early Large Blood Volume for Culture

The objective of the study was to evaluate the yield of a blood culture based on inoculating 40 ml of blood drawn from 1 venipuncture. During a 3-year period (1990-1992) 1351 (19.3%) of 6994 blood culture sets were positive. The increased yield of true bacteremic events using 40 ml instead of 30 ml of blood per blood culture was estimated to be 4.2%. Contaminants were isolated in 5% of the blood culture sets, with coagulase negative staphylococci being the most frequently isolated contaminants (3.2%, 1.3% of the culture bottles). In most of cases, contaminants were only isolated in 1 or 2 of the 4 bottles of the set. Furthermore, a positive correlation was observed between the number of positive culture bottles and the recovery of a clinically-significant microorganism. Neither the frequency nor the interpretations of positive blood culture events with microorganisms of questionable significance were major obstacles. In conclusion, the spectrum and yield of microorganisms drawing 40 ml of blood from one venipuncture into 4 culture bottles was satisfactory. The method bears obvious advantages from a clinical point of view, since usually only 1 venipuncture is needed before institution of antibiotic treatment.

Duration of secretory IgM and IgA antibodies to respiratory syncytial virus in a community study in Guinea-Bissau.

Respiratory syncytial virus (RSV) is probably the single major cause of lower respiratory infection (LRI) among infants worldwide. Its relative importance may be underestimated, as the diagnosis is based on antigen detection and antigen may only be detectable in the early phase of infection. We have therefore assessed the duration of secretory IgM and IgA antibody responses and whether assays for these antibodies can be used to improve the diagnosing of RSV-associated infections. During two RSV epidemics in Guinea-Bissau, 32 RSV antigen-positive children with LRI were followed with sequential nasopharyngeal suction on days 7, 14, 30, 60 and 120 in the first epidemic and every fortnight for 6 mo after the second epidemic to measure the duration of secretory IgM and IgA responses. Nearly all of the children had an IgM response during the first month after infection. The response ratio was highest on days 7 and 14, being 84% and 71%, respectively. After 30 d the IgM response decreased rapidly. Among 27 age- and sex-matched controls, only 1 child was positive for IgM. During the second epidemic, when the children were followed more intensively, half of the children were IgM-positive after the acute phase of infection. A secondary response may be more likely in children with low IgM responses in the acute phase (RR = 2.08 (95% confidence interval (CI) 0.92-4.70)). The IgA response was highest on days 28 and 42 after antigen detection, 72% having a detectable IgA response within the first 1.5 mo. Among 27 controls, only 2 were IgA-positive (7%). In the second epidemic with more intensive follow-up, 62% (8/13) of the IgA-positive children had a response that lasted 10 wk. Of the children with no persistent IgA response, half (5/10) had a subsequent IgA-positive response after the first 42 d. All of these children had a simultaneous IgM-positive response. When 29 of the children were tested after an epidemic when they were 1-3-y-old, >80% again had high IgM (24/29, 82%) and IgA (28/29, 94%) levels. Among samples collected over a 1-y period from infants with LRI in a community morbidity surveillance conducted at the local health centre and via paediatric outpatient consultation, 17% (110/659) were antigen-positive, 26% (171/659) IgM-positive and 38% (248/659) either antigen- or IgM-positive. IgM responses are short-lived among infants and may therefore be used as an indication of recent RSV infection among children with LRI. Using both antigen and IgM detection may significantly improve our detection of RSV infections.

Secretory IgM and IgA antibodies to respiratory syncytial virus in nasopharyngeal aspirates: a diagnostic supplement to antigen detection

BACKGROUND RSV-shedding during an RSV-infection declines dramatically after the first week of infection. It could be of interest to be able to diagnose RSV-infection for a longer period of time by detection of specific RSV-IgM and RSV-IgA in nasopharyngeal aspirates (NPA) in order to minimize unnecessary antibiotics. OBJECTIVES To evaluate an ELISA to detect specific RSV-IgM and RSV-IgA in NPA as a supplement to RSV-antigen detection. STUDY DESIGN A total of 104 NPA from 101 children (median age 9 months) with acute respiratory disease (group 1) admitted to hospital and consecutive NPA (collected on day 0, 7, 14, 30 and 60) from 11 children (median age 3 months) with a proven RSV infection (group 2) were collected. All NPA from group 1 were analysed for RSV-antigen, RSV-IgM and RSV-IgA. NPA from group 2 were analysed for RSV-IgM and RSV-IgA. RESULTS Thirty-five NPA in group 1 were positive for RSV-antigen and 64 were positive for RSV-antigen test alone found 44% and the RSV-IgM test alone found 80%. In group 2 8/11 (73%) has an excellent RSV-IgM response day 7, the rest responded later. Only 5/11 (46%) had a less pronounced RSV-IgA response on day 7, three cases responded later and three did not respond at all. RSV-IgM disappeared in 8/11 (73%) and RSV-IgA in 7/8 (88%) between day 30-60. CONCLUSIONS Specific RSV-IgM is a valuable supplement to RSV-antigen detection for the diagnosis of acute and recent RSV infection.

Mothers may transmit RSV infection more easily or severely to sons than daughters: community study from Guinea-Bissau.

Opposite gender transmission may increase the severity of certain infections. If infections transmitted from mother to son were more severe than from mother to daughter this might explain severe diseases among boys, particularly in small families with few individuals contributing to transmission. Among children from Guinea-Bissau, we tested whether mothers with recent respiratory syncytial virus exposure (positive IgM and IgA antibody responses) were more likely to have male than female children with respiratory syncytial virus antigen positive acute lower respiratory tract infection. Children with acute lower respiratory tract infection were identified at a paediatric clinic (n=348), a health centre (n=270), and in a community morbidity survey (n=525), 14.2% (162/1143) having respiratory syncytial virus antigen. An equal number of boys and girls had acute lower respiratory tract infection, but boys were more likely to have respiratory syncytial virus detected (prevalence ratio=1.36 (1.01–1.81)), this difference being particularly marked in the rainy season. With recent respiratory syncytial virus exposure of mother, boys were twice as likely to have respiratory syncytial virus detected (prevalence ratio=2.04 (1.18–3.53)), the difference being marked in the rainy season. There was no gender difference in respiratory syncytial virus infection among children of RSV negative mothers. We conclude that mothers may transmit respiratory syncytial virus more easily or severely to sons.