Evaluation of treatment with two weeks of doxycycline on macrolide-resistant strains of Mycoplasma genitalium: a retrospective observational study.

BACKGROUND: Increasing macrolide resistance makes treatment of Mycoplasma genitalium infections challenging. The second-line treatment is moxifloxacin, an antibiotic drug best avoided due to the potential of severe side effects and interactions. This study evaluates the effects of treatment with doxycycline 100 mg twice daily for 2 weeks as an alternative to moxifloxacin. METHODS: This retrospective observational study examined the medical records of patients testing positive for macrolide resistant Mycoplasma genitalium from January 1st, 2016 to September 1st, 2019 in Trondheim, Norway. Information regarding symptoms as well as clinical and microbiological cure was collected. RESULTS: 263 infections from 259 patients (161 females/98 males) were examined. 155 (58.9%) had a negative test of cure following treatment. 34.7% of symptomatic patients not achieving microbiological cure experienced symptom relief or clearance. There was no statistical difference between bacterial loads in symptomatic versus asymptomatic patients. The mean difference was 1.6 × 105 copies/ml (95% CI - 1.4 × 105-4.8 × 105, p = 0.30) for women and 1.4 × 106 copies/ml (95% CI -4.0 × 105-3.2 × 106, p = 0.12) for men. CONCLUSIONS: The cure rate of doxycycline in this study is higher than previously reported. This adds support to doxycycline's role in treatment before initiating treatment with less favorable drugs such as moxifloxacin.

Transmission of infection from non-isolated patients with COVID-19 to healthcare workers.

Insufficiently protected healthcare workers (HCWs), defined as high-risk contacts of patients with coronavirus disease 2019 (COVID-19), are routinely quarantined. This study evaluated the transmission of infection from a symptomatic patient with COVID-19 to 60 HCWs exposed at ≤2 m for ≥15 min or during aerosol-generating procedures. Following ≥106 unique high-risk contacts, none of the HCWs tested positive for severe acute respiratory syndrome coronavirus-2 RNA or developed antibodies. The HCWs reported adherence to basic infection control procedures. These results are in accordance with other reports, and should reassure HCWs and further stimulate broader evaluation of the foundation for the current practice of home quarantining non-symptomatic HCWs.

A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts.

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10-5 ). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.

Bacterial Load in Daily Urine Samples of Patients Infected with Mycoplasma genitalium, Mutation Analysis, and Response to Treatment.

Objective. Increasing macrolide resistant strains of Mycoplasma genitalium is a challenge, and to differentiate between treatment failure and reinfection a timely test of cure (TOC) is warranted. The aim of this study was to evaluate the best time for TOC after five days' treatment of Mycoplasma genitalium infection with azithromycin. Methods. Nineteen patients with positive PCR for Mycoplasma genitalium in urine provided urine samples daily for 2 weeks and on days 21, 28, and 35. Samples were tested by a commercial qPCR and by sequencing of the 23S rRNA gene. Results. Eight patients with a wild type of Mycoplasma genitalium responded successfully within four days after treatment initiation. Eleven patients had a mutation in the 23S rRNA gene. These samples exhibited high variations in bacterial load, and some patients tested negative at several time points during the observation period. Conclusions. Day-to-day fluctuations in the mutation samples allow for false negative TOC during the first 5 weeks after start of treatment. Due to increasing macrolide resistance of Mycoplasma genitalium, pretreatment mutation analysis is recommended. When a wild type is verified, TOC performed one week after initiation of treatment is suggested.

Cytomegalovirus antibody status at 17-18 weeks of gestation and pre-eclampsia: a case-control study of pregnant women in Norway.

OBJECTIVE: To assess the association between maternal cytomegalovirus (CMV) antibodies in mid-pregnancy and pre-eclampsia. DESIGN: Nested case-control study. SETTING: Pregnancies registered in the Norwegian Mother and Child Cohort Study (MoBa): a large population-based pregnancy cohort (1999-2006). SAMPLE: A cohort of 1500 women with pre-eclampsia and 1000 healthy pregnant women. METHODS: Plasma samples and pregnancy-related information were provided by the MoBa. Antibody status (CMV IgG and CMV IgM) and levels (CMV IgG) at 17-18 weeks of gestation were determined by enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOME MEASURE: A diagnosis of pre-eclampsia, as defined in the Medical Birth Registry of Norway. RESULTS: There was no evidence of an effect of CMV IgG seropositivity on the likelihood of developing pre-eclampsia, and CMV IgG antibody levels among women who were seropositive did not differ between groups. Adjusted for maternal age, parity and smoking, the odds ratio for pre-eclampsia in women seropositive for CMV IgG was 0.89 (95% CI 0.74-1.05; P = 0.17). The proportions of women who were seropositive for IgM did not differ between women with pre-eclampsia and women who were healthy (P = 0.98). Among nulliparous women, the proportion of women who were seropositive for CMV IgG was slightly lower among women with pre-eclampsia (53.5%) than among healthy women (59.8%) (P = 0.03). Subgroup analyses were performed for women with early or late onset pre-eclampsia, with preterm delivery and/or with neonates that were small for gestational age, but antibody status did not differ between pre-eclampsia subtypes and controls. CONCLUSIONS: The presence of maternal antibodies to CMV was not associated with pre-eclampsia in our study. The results suggest that CMV infection is unlikely to be a major cause of pre-eclampsia.

Prevalence of GB virus C (also called hepatitis G virus) markers in Norwegian blood donors.

GB virus C (GBV-C), also called hepatitis G virus (HGV), occurs worldwide, but the clinical significance of this virus is still unclear. Plasma samples from 1,001 blood donors were tested by reverse transcription PCR using primers from the NS5 region and by a commercial enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G antibodies against the putative envelope of HGV (anti-HGV E2). GBV-C/HGV RNA was present in the plasma from 2.5% of the blood donors, and anti-HGV E2 antibodies could be detected in 10.5% of the samples. Only one of the blood donors with viremia had elevated levels of alanine aminotransferase. Among ELISA-positive donors, there was a significantly higher percentage (16.5%) of individuals who had been treated by acupuncture than individuals who had not been given this treatment (9.4%). No other variables showed significant differences. Screening of medical records from 401 recipients of blood from PCR-positive donors revealed no association with liver disease. Four of 12 partners (33%) were HGV RNA positive, and sequence analyses of the strains showed that four of the couples probably were infected with the same strains, while strains from different couples were not identical. Anti-HGV E2 antibodies were detected in serum samples from four other partners. The prevalence of GBV-C/HGV among blood donors in our region is dramatically higher than the prevalence of hepatitis C virus (0.03%).

[Hepatitis C virus infection among pregnant women and their children in Norway]. / Hepatitt C-virusinfeksjon hos gravide og barn i Norge.

Estimates indicate the births of 6 to 78 children vertically infected with hepatitis C virus infection each year in Norway. There is insufficient knowledge of the magnitude of this health problem and the National Institute of Public Health commissioned the authors to approach issues relating to vertical transmission of hepatitis C virus (HCV) infection in Norway. The risk of vertical transmission of HCV appears to be associated with the titre of the maternal viral load. Vertical transmission from nonviraemic mothers has not been demonstrated. No postexposure prophylaxis exists. There is a lack of association between vertical HCV transmission and delivery mode and no association with breast feeding. Universal screening for HCV infection among pregnant women is not recommended. Children born to women known to be HCV-positive should be followed up with antibody and polymerase chain reaction investigations in order to clarify their HCV status. More studies of HCV infection among pregnant women and their children in Norway are needed.

Chlamydia pneumoniae not detected in temporal artery biopsies from patients with temporal arteritis.

In a recent report Chlamydia pneumoniae (C. pneumoniae), examined with both immunohistochemistry and polymerase chain reaction (PCR), was detected in positive temporal artery biopsies from patients with temporal arteritis (TA). Our aim was to examine whether C. pneumoniae could be detected in patients with TA recruited from a high endemic area of TA in southern Norway. Twenty paraffin-embedded temporal artery biopsies showing convincing inflammation in the vessel wall with lymphocytic infiltration (giant cells in 12 biopsies) from 20 patients with TA were examined for the presence of C. pneumoniae using an established PCR technique. All examined TA patients (mean age 74.4 (SD 7.5) years, 75% females) fulfilled the ACR-1990 criteria. C. pneumoniae was not detected in any of the biopsies. In conclusion, our results indicate that C. pneumoniae, at least in the population of southern Norway, does not have any pathogenetic role in TA.

Retesting and follow-up of first-catch urines from men yield variable results with three Chlamydia trachomatis nucleic acid amplification tests.

First-catch urines from 276 asymptomatic male military recruits were screened by polymerase chain reaction for the detection of Chlamydia trachomatis. Eight initially positive specimens were retested by polymerase chain reaction, ligase chain reaction and transcription-mediated amplification. Urine specimens from six (2.2%) subjects were considered to contain C. trachomatis. However, retesting of serially collected urines from five of these six subjects using different nucleic acid amplification methods showed some discrepancy. This may have a major impact on the efficacy of screening programs for C. trachomatis in low prevalence populations.

Sentinel surveillance of Chlamydia trachomatis infection in women terminating pregnancy.

AIMS: To evaluate demographic characteristics of women terminating their pregnancy for sentinel surveillance of Chlamydia trachomatis infection and to report changing prevalences of C trachomatis over time within this study population. DESIGN: Screening for C trachomatis in women seeking induced abortion was introduced in 1984 at the Department of Gynecology, Regional Hospital, Trondheim, Norway. Over the study years our department has used a precoded medical record covering sociodemographic, medically relevant data, also recording outcome of the C trachomatis test. Throughout the study the Department of Microbiology applied cell culture, enzyme immunoassay, and, during the most recent years a nucleic acid test to identify C trachomatis. STATISTICAL METHODS: Chi square test for linear trend and unconditional logistic regression. RESULTS: Over the study period, women having induced abortion were characterised by being most often single and more often at younger age. The overall age-adjusted prevalence of C trachomatis declined from 9.2% in 1985 to 3.6% in 1995, the major decline occurring from 1987 to 1991, and affected all age-groups simultaneously. There was a 60% decrease in odds ratio of having a C trachomatis infection from 1985 to 1991, and the crude and the adjusted odds ratios did not differ for any year examined. CONCLUSION: Women deciding on pregnancy termination have demographic characteristics that identify high-risk groups for C trachomatis infection. Despite these characteristics, which were relatively constant over the study period, the study population changed from being a high- to a low-prevalence population of C trachomatis.

PIP: Given the finding of a significant association between postabortion endometritis/salpingitis and the occurrence of Chlamydia trachomatis at the time of induced abortion, the Regional Hospital of Trondheim, Norway, initiated C trachomatis screening in all abortion patients in 1984. Screening is also performed at antenatal, family planning, and general practitioner visits. This study tracked the prevalence of C trachomatis from 1985 to 1995 as well as changes in the demographic characteristics of abortion patients. During the study period, the number of induced abortions varied from 872 in 1985 to 905 in 1989 and 756 in 1995. Most notable was an increase in the proportion of unmarried cohabitating women undergoing abortion and a 40% decrease in married abortion patients. The overall age-adjusted prevalence of C trachomatis declined from 9.2% in 1985 to 3.6% in 1995. The adjusted odds ratio of chlamydia infection decreased by more than 60% from 1985-91, followed by only minor changes. Age and marital status were the only demographic factors significantly predictive of chlamydia infection. The prevalence of C trachomatis was highest among teenagers and decreased significantly with increasing age. Single and cohabitating women were at greater risk of infection than married women. The number of chlamydia screenings performed each year increased from 2200 in 1985 to over 30,000 (almost 50% of sexually active women 15-44 years of age) in 1989. This high screening level, and subsequent treatment of infection, appears to have turned induced abortion patients from a high- to a low-prevalence population.

IUD users in Norway are at low risk for genital C. trachomatis infection.

From May 1993 to April 1995, 30 general practitioners located at 13 general practice settings in the city of Trondheim, central Norway, recruited 957 eligible participants in a prospective use-effectiveness study on performance of two copper IUDs. In this report we focus on screening for C. trachomatis at insertion and its possible effect on cause-related terminations during the first 90 days after insertion. All women were screened at IUD insertion for C. trachomatis. All specimens were analyzed applying a nucleic acid test (rRNA, GenProbe). Five out of 957 women (0.5%) were positive for C. trachomatis. All were treated within two weeks of diagnosis. No cases of pelvic inflammatory disease were diagnosed during the first three months of the study. Screening of C. trachomatis at IUD insertion is not recommended in Norwegian women because of the extremely low prevalence of C. trachomatis in those who choose IUD as their primary contraceptive method. Recommendations for universally screening women for sexually transmitted diseases at IUD insertion should be based upon review of local/national prevalence data.

PIP: During May 1993 to April 1995, in Norway, 30 general practitioners at 13 different centers in Trondheim recruited 957 parous women, 18-45 years old, in a prospective use-effectiveness study of 2 copper releasing IUDs. They screened for Chlamydia trachomatis infection at insertion. Researchers aimed to examine the effect of C. trachomatis infection on cause-related terminations during the first 3 months of use. Five (0.5%) women tested positive for C. trachomatis infection. All 5 women received antibiotic treatment within 9-15 days after IUD insertion. One woman with chlamydia infection experienced partial IUD expulsion at 9 days. The remaining women continued IUD use without complications. 57 (6/100 women-months) women requested removal of the IUD during the first 90 days of use. No woman requested removal for pelvic inflammatory disease or bleeding and pain. Based on these findings, the authors do not recommend screening for C. trachomatis at IUD insertion in Norwegian women because the prevalence of chlamydia infection was very low in IUD users. They suggest that any recommendations for universal screening of new IUD users for sexually transmitted diseases (STDs) be based upon a review of local/national STD prevalence data.

Detection of cytomegalovirus using 'boosted' nested PCR.

As a part of a study of an outbreak of CMV infections in a neonatal care intensive care unit, a modified nested PCR was developed for detection of CMV DNA in clinical specimens. Standard nested PCR involves a critical step; passage of PCR products from the first reaction round to the second round. We have adapted a 'boosted' nested PCR which implies amplification in one single step, thus reducing the contamination problems. Nasopharyngeal aspirates and urine samples from patients with perinatal CMV infections, breast milk from some of their mothers, amniotic fluids, urine samples and lymphocytes from seropositive healthy adults were examined by PCR and culture. In the total of 614 of clinical specimens, the PCR test yielded positive results in 51 samples from 14 patients, whereas CMV was isolated in 25 samples from 11 cases only. All samples from healthy individuals were negative. CMV DNA was detected in all culture-positive samples, but all samples from healthy adults were negative. 29/68 culture negative specimens were positive by PCR. No cross-reactivity to other herpes viruses or to human DNA was observed. Our findings show a high sensitivity and a high specificity of the 'boosted' nested PCR. We conclude that the described PCR method can be used for the rapid detection of CMV in clinical specimens with a greatly reduced risk of contamination, and it has proved to be a very useful tool in diagnostic work.

Evaluation of five commercial tests for detection of immunoglobulin M antibodies to human parvovirus B19.

The following commercial tests for detection of immunoglobulin M antibodies to human parvovirus B19 were evaluated: Ideia Parvovirus B19-IgM, MRL Diagnostics Human Parvovirus B19 IgM ELISA, Parvoscan-B19, and Biotrin Parvo B19 IgM EIA and IF. A total of 203 serum specimens from patients who probably have current B19 infections or have other viral infections and sera with rheumatoid factor were investigated. Between 75 and 79 of 102 serum samples from patients thought to have current B19 infections yielded positive results with the different tests. Ideia had the highest specificity (94.8%), while Parvoscan showed a specificity of only 70.1%. Our evaluation results show that Ideia, MRL, and Biotrin EIA and IF can be recommended for diagnostic purposes.

The variable clinical picture of arthritis induced by human parvovirus B19. Report of seven adult cases and review of the literature.

Seven patients with arthritis due to infection with human parvovirus B19 are reported, and the literature association reviewed. B19 virus arthritis most frequently affects young to middle aged women and occurs predominantly during the first six months of the year. The majority of cases have oligoarthritis or polyarthritis, and the joints most often involved are the proximal interphalangeal joints and knees. Of the seven patients reported, one case developed systemic lupus erythematosus, one case evolved into erosive, seropositive rheumatoid arthritis while one case was subsequently diagnosed as undifferentiated connective tissue disease.