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Introduction: Menstrual disorders are commonly reported after COVID-19 vaccination and heavy menstrual bleeding was added to the product information of the COVID-19 vaccines of Moderna and Pfizer. The aim of this review, using a systematic search, is to provide an overview of available literature on the risk of menstrual disorders after COVID-19 vaccination. Methods: The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. A PubMed search was performed on 15 August 2023, including solely quantitative studies in English and Dutch. Results: A total of 61 studies were included, of which 40 were cross-sectional studies, 18 cohort studies, and three self-controlled case series. Outcomes included a wide variety of menstrual disorders, including changes in cycle length (n = 54), changes in the amount of bleeding (n = 44), changes in menses length (n = 30), changes in the experience of (pre)menstrual pain (n = 21), and breakthrough bleeding (n = 18). All included studies found a higher percentage of at least one menstrual disorder in the first cycle after different types of COVID-19 vaccination and after different doses. Discussion: In conclusion, evidence suggests that COVID-19 vaccines may cause menstrual changes in women of reproductive age. However, there is a need for more longitudinal studies because of important limitations in the study designs of many of the included studies. Although menstrual changes are short-lived and predominantly mild, it is important for women and healthcare professionals to be informed about these potential adverse reactions and to assess these events in clinical trials on vaccines. [ABSTRACT FROM AUTHOR]

Introduction:Menstrual disorders are commonly reported after COVID-19 vaccination and heavy menstrual bleeding was added to the product information of the COVID-19 vaccines of Moderna and Pfizer. The aim of this review, using a systematic search, is to provide an overview of available literature on the risk of menstrual disorders after COVID-19 vaccination. Methods: The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. A PubMed search was performed on 15 August 2023, including solely quantitative studies in English and Dutch. Results: A total of 61 studies were included, of which 40 were cross-sectional studies, 18 cohort studies, and three self-controlled case series. Outcomes included a wide variety of menstrual disorders, including changes in cycle length (n = 54), changes in the amount of bleeding (n = 44), changes in menses length (n = 30), changes in the experience of (pre)menstrual pain (n = 21), and breakthrough bleeding (n = 18). All included studies found a higher percentage of at least one menstrual disorder in the first cycle after different types of COVID-19 vaccination and after different doses. Discussion: In conclusion, evidence suggests that COVID-19 vaccines may cause menstrual changes in women of reproductive age. However, there is a need for more longitudinal studies because of important limitations in the study designs of many of the included studies. Although menstrual changes are short-lived and predominantly mild, it is important for women and healthcare professionals to be informed about these potential adverse reactions and to assess these events in clinical trials on vaccines. [ABSTRACT FROM AUTHOR]

Background: Growing international migration has increased the complexity of tuberculosis transmission patterns. Italy's decision to close its borders in 2018 made of Spain the new European porte entrée for migration from the Horn of Africa (HA). In one of the first rescues of migrants from this region at the end of 2018, tuberculosis was diagnosed in eight subjects, mainly unaccompanied minors.Methods: Mycobacterium tuberculosis isolates from these recently arrived migrants were analysed by Mycobacterial Interspersed Repetitive-Unit/Variable-Number of Tandem Repeat (MIRU-VNTR) and subsequent whole genome sequencing (WGS) analysis. Data were compared with those from collections from other European countries receiving migrants from the HA and a strain-specific PCR was applied for a fast searching of common strains. Infections in a cellular model were performed to assess strain virulence.Results: MIRU-VNTR analysis allowed identifying an epidemiological cluster involving three of the eight cases from Somalia (0 single-nucleotide polymorphisms between isolates, HA cluster). Following detailed interviews revealed that two of these cases had shared the same migratory route in most of the trip and had spent a long time at a detention camp in Libya. To confirm potential en route transmission for the three cases, we searched the same strain in collections from other European countries receiving migrants from the HA. MIRU-VNTR, WGS and a strain-specific PCR for the HA strain were applied. The same strain was identified in 12 cases from Eritrea diagnosed soon after their arrival in 2018 to the Netherlands, Belgium and Italy. Intracellular replication rate of the strain did not reveal abnormal virulence.Conclusions: Our study suggests a potential en route transmission of a pan-susceptible strain, which caused at least 15 tuberculosis cases in Somalian and Eritrean migrants diagnosed in four different European countries. [ABSTRACT FROM AUTHOR]

Background: Drug-susceptibility testing (DST) of Mycobacterium tuberculosis complex (MTBC) isolates by the Mycobacteria Growth Indicator Tube (MGIT) approach is the most widely applied reference standard. However, the use of WGS is increasing in many developed countries to detect resistance and predict susceptibility. We investigated the reliability of WGS in predicting drug susceptibility, and analysed the discrepancies between WGS and MGIT against the first-line drugs rifampicin, isoniazid, ethambutol and pyrazinamide.Methods: DST by MGIT and WGS was performed on MTBC isolates received in 2016/2017. Nine genes and/or their promotor regions were investigated for resistance-associated mutations: rpoB, katG, fabG1, ahpC, inhA, embA, embB, pncA and rpsA. Isolates that were discrepant in their MGIT/WGS results and a control group with concordant results were retested in the MGIT, at the critical concentration and a lower concentration, and incubated for up to 45 days after the control tube became positive in the MGIT.Results: In total, 1136 isolates were included, of which 1121 were routine MTBC isolates from the Netherlands. The negative predictive value of WGS was ≥99.3% for all four first-line antibiotics. The majority of discrepancies for isoniazid and ethambutol were explained by growth at the lower concentrations, and for rifampicin by prolonged incubation in the MGIT, both indicating low-level resistance.Conclusions: Applying WGS in a country like the Netherlands, with a low TB incidence and low prevalence of resistance, can reduce the need for phenotypic DST for ∼90% of isolates and accurately detect mutations associated with low-level resistance, often missed in conventional DST. [ABSTRACT FROM AUTHOR]

The clinical phenotype of zoonotic tuberculosis and its contribution to the global burden of disease are poorly understood and probably underestimated. This shortcoming is partly because of the inability of currently available laboratory and in silico tools to accurately identify all subspecies of the Mycobacterium tuberculosis complex (MTBC). We present SNPs to Identify TB (SNP-IT), a single-nucleotide polymorphism-based tool to identify all members of MTBC, including animal clades. By applying SNP-IT to a collection of clinical genomes from a UK reference laboratory, we detected an unexpectedly high number of M. orygis isolates. M. orygis is seen at a similar rate to M. bovis, yet M. orygis cases have not been previously described in the United Kingdom. From an international perspective, it is possible that M. orygis is an underestimated zoonosis. Accurate identification will enable study of the clinical phenotype, host range, and transmission mechanisms of all subspecies of MTBC in greater detail. [ABSTRACT FROM AUTHOR]

Background: Patients with Mycobacterium tuberculosis isolates sharing identical DNA fingerprint patterns can be epidemiologically linked. However, municipal health services in the Netherlands are able to confirm an epidemiological link in only around 23% of the patients with isolates clustered by the conventional variable number of tandem repeat (VNTR) genotyping. This research aims to investigate whether whole genome sequencing (WGS) is a more reliable predictor of epidemiological links between tuberculosis patients than VNTR genotyping. Methods: VNTR genotyping and WGS were performed in parallel on all Mycobacterium tuberculosis complex isolates received at the Netherlands National Institute for Public Health and the Environment in 2016. Isolates were clustered by VNTR when they shared identical 24-loci VNTR patterns; isolates were assigned to a WGS cluster when the pair-wise genetic distance was ≤ 12 single nucleotide polymorphisms (SNPs). Cluster investigation was performed by municipal health services on all isolates clustered by VNTR in 2016. The proportion of epidemiological links identified among patients clustered by either method was calculated. Results: In total, 535 isolates were genotyped, of which 25% (134/535) were clustered by VNTR and 14% (76/535) by WGS; the concordance between both typing methods was 86%. The proportion of epidemiological links among WGS clustered cases (57%) was twice as common than among VNTR clustered cases (31%). Conclusion: When WGS was applied, the number of clustered isolates was halved, while all epidemiologically linked cases remained clustered. WGS is therefore a more reliable tool to predict epidemiological links between tuberculosis cases than VNTR genotyping and will allow more efficient transmission tracing, as epidemiological investigations based on false clustering can be avoided. [ABSTRACT FROM AUTHOR]

Background: From 2007 to 2010, (the southern part of) the Netherlands experienced a large Q fever epidemic, with more than 4,000 reported symptomatic cases. Approximately 1 – 5% of the acute Q fever patients develop chronic Q fever. A high IgG antibody titre against phase I of Coxiella burnetii during follow-up is considered a marker of chronic Q fever. However, there is uncertainty about the significance and cause of persistence of high IgG phase I antibody titres in patients that do not have any additional manifestations of chronic Q fever. We studied whether continued or repeated exposure to the source of infection could explain elevated IgG phase I antibody levels. Methods: A case–control study was performed to analyze predictors for possible chronic Q fever. Possible chronic Q fever cases (n = 53) are patients with phase I IgG antibody titre ≥1:1,024 at any point in the 9 – 18 months after acute Q fever diagnosis, with a negative PCR test result for C. burnetii DNA and without other disease manifestations. Controls (n = 110) are acute Q fever patients that did not develop chronic Q fever, and who consistently had phase I IgG antibody titre <1:1,024 during the 9 – 18 months follow-up. Binary logistic regression was performed to analyze the effect of living close to an infected farm on the high antibody titres. A longitudinal analysis described the serological profiles of cases and controls. Results: Proximity to infected farms and contact with animal placental material were not associated with an increased risk for possible chronic Q fever. Possible chronic Q fever patients have high IgG phase II as well as IgG phase I antibody titres, even after 48 months of follow-up. Conclusion: We were unable to explain the cause of persistent high IgG phase I titres among possible chronic Q fever patients by being continuously exposed to the source of infection. [ABSTRACT FROM AUTHOR]

Aims: During the COVID‐19 vaccination campaigns, the number of reports of menstrual abnormalities increased rapidly. Here, we describe the nature and potential risk factors associated with menstrual abnormalities based on spontaneously reporting data as well as data from a prospective cohort event monitoring (CEM) study as these are poorly studied. Methods: Reports of menstrual abnormalities received by the Netherlands Pharmacovigilance Centre Lareb in the spontaneous reporting system between February 2021 and April 2022 were summarized. In addition, logistic regression analysis was performed on the reported menstrual abnormalities in the CEM study to assess the association between person characteristics, prior SARS‐CoV‐2 infection and use of hormonal contraceptives and the occurrence of menstrual abnormalities after vaccination. Results: We analysed over 24 000 spontaneous reports of menstrual abnormalities and over 500 episodes (among 16 929 included women) of menstrual abnormalities in the CEM study. The CEM study showed an incidence of 41.4 per 1000 women aged ≤54 years. Amenorrhoea/oligomenorrhoea and heavy menstrual bleeding collectively accounted for about half of all abnormalities reported. Significant associations were observed for the age group 25–34 years (odds ratio 2.18; 95% confidence interval 1.45–3.41) and the Pfizer vaccine (odds ratio 3.04; 95% confidence interval 2.36–3.93). No association was observed for body mass index and presence of most comorbidities assessed. Conclusion: The cohort study showed a high incidence of menstrual disorders among women aged ≤54 years, and this observation was supported by the analysis of spontaneous reports. This suggests that a relation between COVID‐19 vaccination and menstrual abnormalities is plausible and should be further investigated. [ABSTRACT FROM AUTHOR]