Richard Anthony

Richard Anthony
National Institute for Public Health and the Environment (RIVM) | RIVM · Centre for Infectious Disease Control (CIb)

PhD

About

139
Publications
11,825
Reads
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2,247
Citations
Additional affiliations
August 2016 - present
National Institute for Public Health and the Environment (RIVM)
Position
  • Senior Researcher
June 2011 - May 2016
Royal Tropical Institute
Position
  • Project Manager
May 1996 - May 2001
The Kings College
Position
  • Researcher

Publications

Publications (139)
Article
In the Netherlands, local laboratories are involved in the primary diagnosis of tuberculosis. Positive Mycobacterium tuberculosis complex cultures are sent to the National Institute for Public Health and the Environment (RIVM) for species identification, epidemiological typing, and screening for resistance by Whole Genome Sequencing (WGS). Occasion...
Article
Moxifloxacin is an attractive drug for the treatment of isoniazid-resistant rifampicin-susceptible tuberculosis (TB) or drug-susceptible TB complicated by isoniazid intolerance. However, co-administration with rifampicin decreases moxifloxacin exposure. It remains unclear whether this drug-drug interaction has clinical implications. This retrospect...
Article
Full-text available
Whole genome sequencing (WGS) can be used for molecular typing and characterisation of Mycobacterium tuberculosis complex (MTBC) strains. We evaluated the systematic use of a WGS-based approach for MTBC surveillance involving all European Union/European Economic Area (EU/EEA) countries and highlight the challenges and lessons learned to be consider...
Article
Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence and drug susceptibility testing (DST)...
Article
Full-text available
The global control of Tuberculosis remains elusive, and Bacillus Calmette-Guérin (BCG) -the most widely used vaccine in history—has proven insufficient for reversing this epidemic. Several authors have suggested that the mass presence of vaccinated hosts might have affected the Mycobacterium tuberculosis (MTB) population structure, and this could i...
Article
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Beijing strains of Mycobacterium tuberculosis (lineage 2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian Pacific coast have exhibited a multidrug resistant (MDR) phenotype. We sought to evaluate the clonality and sublineage of Beijing strains circulating...
Article
Objectives: For the past decade, the epidemic of multidrug resistance tuberculosis (MDR-TB) stays high in China. We investigated the possible driving forces behind the epidemics from phylogenetic and historical perspectives. Methods: 420 representative strains were selected from the first national drug resistance survey based on their genotypes,...
Article
Full-text available
Background Whole 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...
Preprint
Full-text available
Beijing strains of Mycobacterium tuberculosis (lineage2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian pacific coast exhibited a multidrug resistant (MDR) phenotype, in contrast with the phenotype observed in Beijing isolates from other South-American co...
Article
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Background: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community ben...
Article
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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 reliabili...
Article
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Background: Tuberculosis (TB) remains a serious public health threat worldwide. Theoretically ultimate resolution of whole genome sequencing (WGS) for Mycobacterium tuberculosis complex (MTBC) strain classification makes this technology very attractive for epidemiological investigations. Objectives: To summarize the evidence available in peer-re...
Article
Full-text available
Pyrazinamide (PZA) is unique in that it is a component of the first line therapy for drug sensitive tuberculosis and in most current and experimental treatments also for multi drug resistant tuberculosis. Furthermore, PZA has been shown to help to ensure lasting cure and prevent relapse in shorter multi drug regimens. PZA is a prodrug. Mycobacteria...
Article
M/XDR-TB has become an increasing threat in high burden countries but also in affluent regions due to increased international travel and globalization. Carbapenems are earmarked as potentially active drugs for the treatment of M. tuberculosis . To better understand the potential of carbapenems for the treatment of M/XDR-TB, the aim of this review w...
Article
Full-text available
Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2–3 months will cure...
Article
Full-text available
Bedaquiline, a new antituberculosis drug, has already been used in >50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This article aims to review currently identified mechanisms of resistance and the emergence of bedaquiline resistance, and discuss strategies to delay the resista...
Article
Bedaquiline, a new antituberculosis drug, has already been used in >50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This article aims to review currently identified mechanisms of resistance and the emergence of bedaquiline resistance, and discuss strategies to delay the resista...
Article
Full-text available
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 (...
Data
Characteristics of the 93 non-epidemiologically linked patients, presented per VNTR cluster. (DOCX)
Data
Characteristics of the 41 epidemiologically linked patients presented per VNTR cluster. (DOCX)
Article
A low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However,...
Article
Full-text available
Real time PCR has become a dominant method for the highly sensitive detection of pathogens in clinical material. Real time PCR can generate a fluorescence signal by using fluorescence labelled probes, allowing us to detect and semi quantify the amount of amplified DNA. Here we test the variability of the detection system and cost implications of th...
Data
S1 Dataset-data statistical analyses Figure 1 and Table 4. (XLSX)
Data
S2 Dataset-figure 2 probe titratie LC comparison. (XLSX)
Data
S3 Dataset- data not shown line 243 signal to noise test. (XLS)
Data
S4 Dataset-data not shown line 248 all data maintenance. (XLSX)
Article
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DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved...
Article
We are far away from the days when tuberculosis (TB) accounted for 1 in 4 deaths during the 19th century. However, Mycobacterium tuberculosis complex (MTBC) strains are still the leading cause of morbidity and mortality by a single infectious disease, with 9.6 million cases and 1.5 million deaths reported. One-third of the world's population is est...
Article
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Background: In many countries, Mycobacterium tuberculosis (Mtb) isolates are routinely subjected to VNTR typing to investigate Mtb transmission. Unexpectedly, cross border clusters have been identified among African refugees in the Netherlands and Denmark, although transmission in these countries was unlikely. Whole genome sequencing (WGS) was appl...
Article
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Background: Since 2004, variable number of tandem repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates has been applied on a structural basis in The Netherlands to study the epidemiology of tuberculosis (TB). Although this technique is faster and technically less demanding than the previously used restriction fragment length polymorp...
Article
Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the re...
Article
Full-text available
Simple effective tools to monitor the long treatment of tuberculosis (TB) are lacking. Easily measured host derived biomarkers have been identified but need to be validated in larger studies and different population groups. Here we investigate the early response in IP-10 levels (between day 0 and day 7 of TB therapy) to identify bacteriological sta...
Article
Full-text available
Background The ongoing epidemic of multidrug-resistant tuberculosis (MDR-TB) in Georgia highlights the need for more effective control strategies. A new regimen to treat MDR-TB that includes pyrazinamide (PZA) is currently being evaluated and PZA resistance status will largely influence the success of current and future treatment strategies. PZA su...
Article
Full-text available
BACKGROUND To cope with the emergence of multidrug-resistant tuberculosis (MDR-TB), new molecular methods that can routinely be used to screen for a wide range of drug resistance related genetic markers in the Mycobacterium tuberculosis genome are urgently needed. OBJECTIVE To evaluate the performance of multiplex ligaton-dependent probe amplifica...
Article
Full-text available
We describe the population structure of a representative collection of 3,133 Mycobacterium tuberculosis isolates, collected within the framework of a national resistance survey from 2007 in China. Genotyping data indicate that the epidemic strains in China can be divided into seven major complexes, of which 92% belonged to the East Asian (mainly Be...
Article
Full-text available
Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2–3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme con...
Article
Introduction: Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecu...
Article
Full-text available
Pyrazinamide (PZA) is included in the 2016 World Health Organization multidrug-resistant tuberculosis treatment guidelines and is a key component of most ongoing clinical trials investigating novel antibiotic combinations. PZA resistance is associated with worse tuberculosis treatment outcomes. Unfortunately, for such an important drug, phenotypic...
Article
For the past decades, an acidic pH has been used to render Mycobacterium tuberculosis susceptible to pyrazinamide for in vitro testing. Here, we show that at the standard breakpoint concentration and reduced culture temperatures, pyrazinamide (PZA) is active against tuberculosis (TB) at neutral pH. This finding should help unravel the mechanism of...
Preprint
Full-text available
Mycobacterium tuberculosis ( Mtb ) lineage identification and typing of clinical isolates in general is performed only retrospectively. The results are rarely linked to drug susceptibility testing (DST) or patient data. Consequently, the association between Mtb lineage, (multi)drug resistance and treatment history is not fully explored at the local...
Article
Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in...
Article
Full-text available
Background: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate...
Article
Mycobacterium tuberculosis genotype distribution is different between West and Central Indonesia, but there are no data on the most Eastern part, Papua. We aimed to identify the predominant genotypes of Mycobacterium tuberculosis responsible for tuberculosis in coastal Papua, their transmission, and the association with patient characteristics. A t...
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Background: Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance. Methods: In a decision-analytical model we simulated a cohort of patients diagnosed wit...
Article
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Background: Many patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal...
Article
Full-text available
In contrast to most other anti-mycobacterial drugs where - particularly in multidrug resistant (MDR) strains - a limited number of resistance mutations dominate, pyrazinamide (PZA) resistance associated mutations remain highly diverse with limited clustering. This apparent lack of evolutionary selection for successful PZA resistance mechanisms dese...
Article
Full-text available
Little is known about drug-resistant tuberculosis (TB) and its transmission in Papua, which has one of the highest rates of TB in Indonesia. We examined genotypic drug resistance patterns using multiplex ligation-dependent probe amplification and the degree of molecular clustering using 24-locus mycobacterial interspersed repetitive units-variable...
Article
Full-text available
We studied genomic variation in a previously selected collection of isogenic Mycobacterium tuberculosis laboratory strains subjected to one or two rounds of antibiotic selection. Whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, one intergenic), in addition to drug resistance-conferrin...
Article
Full-text available
To assess the spread of the Mycobacterium tuberculosis Beijing genotype among patients with multidrug-resistant and extensively resistant tuberculosis in Bulgaria, we genotyped 188 (72%) of 261 microbiologically confirmed resistant isolates obtained during 2007-2011. The estimated prevalence of the Beijing genotype among these patients was 3.2%.
Data
Full-text available
Additional methods used and genotyping characteristics found for the identified Mycobacterium tuberculosis Beijing strains isolated in Bulgaria during 2007–2011.