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Article ; Online: SARS-CoV-2 transmitters have more than three times higher viral loads than non-transmitters - Practical use of viral load for disease control.

Jajou, R / Mutsaers-van Oudheusden, Ajg / Verweij, J J / Rietveld, A / Murk, J L

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

2022 Volume 150-151, Page(s) 105131

Abstract: Background: Quantitative results of SARS-CoV-2 testing reported as viral load copies/mL can provide valuable information, but are rarely used in practice. We analyze whether viral load in the upper respiratory tract is correlated with transmission and ... ...

Abstract	Background: Quantitative results of SARS-CoV-2 testing reported as viral load copies/mL can provide valuable information, but are rarely used in practice. We analyze whether viral load in the upper respiratory tract is correlated with transmission and disease course and how this information can be used in practice. Study design: Municipal Health Service (MHS) and clinical patients ≥18 years tested positive for SARS-CoV-2 with RT-PCR between June 1 and September 25, 2020 were included. Transmission was defined as an index having at least one contact tested positive. Test delay was defined as the time between symptom onset and SARS-CoV-2 testing. Results: 683 patients were included (656 MHS and 27 clinical patients). The viral load was considerably lower among clinical patients compared to MHS patients: median log Conclusion: Indexes that transmitted SARS-CoV-2 had more than three times higher viral loads than non-transmitters. Viral load information can be useful during source and contact tracing to prioritize indexes with highest risk of transmission, taking into account the test delay.
MeSH term(s)	COVID-19 ; COVID-19 Testing ; Humans ; SARS-CoV-2 ; Serologic Tests ; Viral Load
Language	English
Publishing date	2022-03-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1446080-4
ISSN	1873-5967 ; 1386-6532
ISSN (online)	1873-5967
ISSN	1386-6532
DOI	10.1016/j.jcv.2022.105131
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Zs.A 3790: Show issues

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Article ; Online: Menstrual abnormalities after COVID-19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient-reported data.

Duijster, Janneke W / Schoep, Mark E / Nieboer, Theodoor E / Jajou, Rana / Kant, Agnes / van Hunsel, Florence

British journal of clinical pharmacology

2023 Volume 89, Issue 10, Page(s) 3126–3138

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Female ; Humans ; Cohort Studies ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Netherlands/epidemiology ; Patient Reported Outcome Measures ; Prospective Studies ; Vaccination/adverse effects ; Menstruation Disturbances/etiology ; Adult ; Middle Aged
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-06-25
Publishing country	England
Document type	Journal Article
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15799
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Zs.A 1118: Show issues

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Article ; Online: Whole genome sequencing as the ultimate tool to diagnose tuberculosis.

van Soolingen, Dick / Jajou, Rana / Mulder, Arnout / de Neeling, Han

International journal of mycobacteriology

2016 Volume 5 Suppl 1, Page(s) S60–S61

Abstract: In the past two decades, DNA techniques have been increasingly used in the laboratory diagnosis of tuberculosis (TB). The (sub) species of the Mycobacterium tuberculosis complex are usually identified using reverse line blot techniques. The resistance is ...

Abstract	In the past two decades, DNA techniques have been increasingly used in the laboratory diagnosis of tuberculosis (TB). The (sub) species of the Mycobacterium tuberculosis complex are usually identified using reverse line blot techniques. The resistance is predicted by the detection of mutations in genes associated with resistance. Nevertheless, all cases are still subjected to cumbersome phenotypic resistance testing. The production of a strain-characteristic DNA fingerprint, to investigate the epidemiology of TB, is done by the 24-locus variable number tandem repeat (VNTR) typing. However, most of the molecular techniques in the diagnosis of TB can eventually be replaced by whole genome sequencing (WGS). Many international TB reference laboratories are currently working on the introduction of WGS; however, standardization in the international context is lacking. The European Centre for Infectious Disease Prevention and Control in Stockholm, Sweden organizes a yearly round of quality control on VNTR typing and in 2015 for the first time also WGS. In this first proficiency study, only three out of eight international TB laboratories produced WGS results in line with those of the reference laboratory. The whole process of DNA isolation, purification, quantification, sequencing, and analysis/interpretation of data is still under development. In this presentation, many aspects will be covered that influence the quality and interpretation of WGS results. The turn-around-time, analysis, and utility of WGS will be discussed. Moreover, the experiences in the use of WGS in the molecular epidemiology of TB in The Netherlands are detailed. It can be concluded that many difficulties still have to be conquered. The state of the art is that bacteria still have to be cultured to have sufficient quality and quantity of DNA for succesful WGS. The quality of sequencing has improved significantly over the past 7years, and the detection of mutations has, therefore, become more reliable. The resistance mutations detected in WGS are in line with the ones visualized in reverse line blot techniques. The turnover in the genome of M. tuberculosis is very low, ∼0.3-0.5 mutations per genome per year. However, there is a wide variation in the occurrence of mutations per strain and genotype. Still, the resolution of WGS in epidemiological typing is higher than that in VNTR typing; previously suggested epidemiological links by VNTR typing are sometimes refuted on the basis of WGS. Although WGS offers the highest resolution in typing, in a country like The Netherlands, there are many strains with a limited genetic distance up to 100 mutations, without an apparent epidemiological link between the respective cases. These lookalikes are presumably even more prevalent in settings where predominant genotypes of M. tuberculosis are circulating. In summary, WGS seems to yield a more reliable prediction of resistance by the (lack of) detection of mutations in all 25 genes ever associated with resistance. This may within a short while prevent the need for many phenotypic resistance tests. Although more robust algorithms need to be developed, the recognition of the (sub) species in the M. tuberculosis complex seems possible. The first detailed studies on the population structure of M. tuberculosis strains in The Netherlands provide more resolution in typing but also an interesting observation that a part of the strains are genetically so conserved that they are separated by less than 100 mutations. This demands a more extended and accurate validation and understanding of the utility of WGS in the epidemiology of TB.
Language	English
Publishing date	2016-12
Publishing country	Netherlands
Document type	Journal Article
ISSN	2212-554X
ISSN (online)	2212-554X
DOI	10.1016/j.ijmyco.2016.10.036
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Article ; Online: Towards standardisation: comparison of five whole genome sequencing (WGS) analysis pipelines for detection of epidemiologically linked tuberculosis cases.

Jajou, Rana / Kohl, Thomas A / Walker, Timothy / Norman, Anders / Cirillo, Daniela Maria / Tagliani, Elisa / Niemann, Stefan / de Neeling, Albert / Lillebaek, Troels / Anthony, Richard M / van Soolingen, Dick

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin

2020 Volume 24, Issue 50

Abstract: BackgroundWhole genome sequencing (WGS) is a reliable tool for studying tuberculosis (TB) transmission. WGS data are usually processed by custom-built analysis pipelines with little standardisation between them.AimTo compare the impact of variability of ... ...

Abstract	BackgroundWhole genome sequencing (WGS) is a reliable tool for studying tuberculosis (TB) transmission. WGS data are usually processed by custom-built analysis pipelines with little standardisation between them.AimTo compare the impact of variability of several WGS analysis pipelines used internationally to detect epidemiologically linked TB cases.MethodsFrom the Netherlands, 535
MeSH term(s)	Disease Transmission, Infectious ; Epidemiological Monitoring ; Humans ; Minisatellite Repeats ; Molecular Epidemiology/methods ; Multilocus Sequence Typing/methods ; Mycobacterium tuberculosis/classification ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/isolation & purification ; Netherlands ; Polymorphism, Single Nucleotide ; Tandem Repeat Sequences ; Tuberculosis/diagnosis ; Tuberculosis/epidemiology ; Tuberculosis/transmission ; Whole Genome Sequencing/methods
Language	English
Publishing date	2020-01-13
Publishing country	Sweden
Document type	Comparative Study ; Journal Article
ZDB-ID	1338803-4
ISSN	1560-7917 ; 1025-496X
ISSN (online)	1560-7917
ISSN	1025-496X
DOI	10.2807/1560-7917.ES.2019.24.50.1900130
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Zs.A 5066: Show issues

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Article ; Online: WGS more accurately predicts susceptibility of Mycobacterium tuberculosis to first-line drugs than phenotypic testing.

Jajou, Rana / van der Laan, Tridia / de Zwaan, Rina / Kamst, Miranda / Mulder, Arnout / de Neeling, Albert / Anthony, Richard / van Soolingen, Dick

The Journal of antimicrobial chemotherapy

2019 Volume 74, Issue 9, Page(s) 2605–2616

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Antitubercular Agents/pharmacology ; Genotype ; Humans ; Incidence ; Microbial Sensitivity Tests ; Mutation ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Netherlands/epidemiology ; Reproducibility of Results ; Tuberculosis/epidemiology ; Tuberculosis/microbiology ; Whole Genome Sequencing
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2019-05-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkz215
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 124: Show issues

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Article ; Online: Integrative transnational analysis to dissect tuberculosis transmission events along the migratory route from Africa to Europe.

Journal of travel medicine

2021 Volume 28, Issue 4

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Africa ; Cluster Analysis ; Europe ; Genotype ; Humans ; Mycobacterium tuberculosis/genetics ; Tuberculosis/epidemiology
Language	English
Publishing date	2021-04-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1212504-0
ISSN	1708-8305 ; 1195-1982
ISSN (online)	1708-8305
ISSN	1195-1982
DOI	10.1093/jtm/taab054
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Zs.A 4120: Show issues

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Article ; Online: Correction: Epidemiological links between tuberculosis cases identified twice as efficiently by whole genome sequencing than conventional molecular typing: A population-based study.

Jajou, Rana / de Neeling, Albert / van Hunen, Rianne / de Vries, Gerard / Schimmel, Henrieke / Mulder, Arnout / Anthony, Richard / van der Hoek, Wim / van Soolingen, Dick

PloS one

2018 Volume 13, Issue 5, Page(s) e0197556

Abstract: This corrects the article DOI: 10.1371/journal.pone.0195413.]. ...

Abstract	[This corrects the article DOI: 10.1371/journal.pone.0195413.].
Language	English
Publishing date	2018-05-14
Publishing country	United States
Document type	Journal Article ; Published Erratum
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0197556
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Article ; Online: Occurrence and Nature of Double Alleles in Variable-Number Tandem-Repeat Patterns of More than 8,000 Mycobacterium tuberculosis Complex Isolates in The Netherlands.

Jajou, Rana / Kamst, Miranda / van Hunen, Rianne / de Zwaan, Carolina Catherina / Mulder, Arnout / Supply, Philip / Anthony, Richard / van der Hoek, Wim / van Soolingen, Dick

Journal of clinical microbiology

2018 Volume 56, Issue 2

Abstract: Since 2004, variable-number tandem-repeat (VNTR) typing ... ...

Abstract	Since 2004, variable-number tandem-repeat (VNTR) typing of
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Child ; Child, Preschool ; DNA, Bacterial/genetics ; Female ; Genetic Drift ; Genetic Loci ; Genome, Bacterial/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Minisatellite Repeats/genetics ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/isolation & purification ; Netherlands/epidemiology ; Polymorphism, Single Nucleotide ; Prevalence ; Risk Factors ; Sequence Analysis, DNA ; Tuberculosis/epidemiology ; Tuberculosis/microbiology ; Young Adult
Chemical Substances	DNA, Bacterial
Language	English
Publishing date	2018-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.00761-17
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Zs.A 1188: Show issues

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Article ; Online: A Predominant Variable-Number Tandem-Repeat Cluster of Mycobacterium tuberculosis Isolates among Asylum Seekers in the Netherlands and Denmark, Deciphered by Whole-Genome Sequencing.

Jajou, Rana / de Neeling, Albert / Rasmussen, Erik Michael / Norman, Anders / Mulder, Arnout / van Hunen, Rianne / de Vries, Gerard / Haddad, Walid / Anthony, Richard / Lillebaek, Troels / van der Hoek, Wim / van Soolingen, Dick

Journal of clinical microbiology

2018 Volume 56, Issue 2

Abstract: In many countries, ...

Abstract	In many countries,
MeSH term(s)	Adolescent ; Adult ; Africa ; Aged ; Child ; Cluster Analysis ; DNA, Bacterial/genetics ; Denmark ; Female ; Genome, Bacterial/genetics ; Genotype ; Humans ; Male ; Middle Aged ; Minisatellite Repeats/genetics ; Mycobacterium tuberculosis/classification ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/isolation & purification ; Netherlands ; Polymorphism, Single Nucleotide ; Refugees ; Tuberculosis/microbiology ; Young Adult
Chemical Substances	DNA, Bacterial
Language	English
Publishing date	2018-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.01100-17
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Article ; Online: Epidemiological links between tuberculosis cases identified twice as efficiently by whole genome sequencing than conventional molecular typing: A population-based study.

Jajou, Rana / de Neeling, Albert / van Hunen, Rianne / de Vries, Gerard / Schimmel, Henrieke / Mulder, Arnout / Anthony, Richard / van der Hoek, Wim / van Soolingen, Dick

PloS one

2018 Volume 13, Issue 4, Page(s) e0195413

Abstract: 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% ...

Abstract	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.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Minisatellite Repeats ; Molecular Typing ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/isolation & purification ; Netherlands/epidemiology ; Polymorphism, Single Nucleotide ; Prospective Studies ; Registries ; Tuberculosis/diagnosis ; Tuberculosis/epidemiology ; Whole Genome Sequencing ; Young Adult
Language	English
Publishing date	2018-04-04
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0195413
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