Timothy Rodwell

Timothy Rodwell
University of California, San Diego | UCSD · Department of Medicine

MD, PhD, MPH

About

184
Publications
30,927
Reads
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4,133
Citations
Citations since 2016
85 Research Items
3052 Citations
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Introduction
Tim Rodwell is a Professor and physician in the Department of Medicine at UCSD, and a senior scientific advisor at FIND, Geneva Switzerland. He is trained in Medicine, infectious disease ecology, epidemiology and molecular epidemiology. Since 1995, his research has been primarily focused on development and evaluation of molecular diagnostics for infectious diseases with an emphasis on tuberculosis (TB)
Additional affiliations
June 2008 - present
University of California, San Diego
Position
  • Professor (Associate)

Publications

Publications (184)
Article
Background: Previous retrospective and in vitro studies suggest that use of later generation fluoroquinolones may reduce mortality risk and improve treatment outcomes for drug-resistant tuberculosis patients, including individuals resistant to a fluoroquinolone. Meta-analysis results are mixed and few studies have examined this relationship prospe...
Article
Full-text available
Rapid molecular diagnostics have great potential to limit the spread of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis (Mtb) genome that confer phenotypic drug resistance. However, there is little data published regarding the relationships between the detected Mtb...
Article
Full-text available
Increasingly complex drug-resistant tuberculosis (DR-TB) is a major global health concern and one of primary reasons why TB is now the leading infectious cause of death worldwide. Rapid characterization of a DR-TB patient's complete drug resistance profile would facilitate individualized treatment in place of empiric treatment, improve treatment ou...
Article
Full-text available
Molecular diagnostic methods based on the detection of mutations conferring drug resistance are promising technologies for rapidly detecting multidrug-/extensively drug-resistant tuberculosis (M/XDR TB), but large studies of mutations as markers of resistance are rare. The Global Consortium for Drug-Resistant TB Diagnostics analyzed 417 Mycobacteri...
Article
Full-text available
Objectives Human mitochondrial cell-free DNA (Mt-cfDNA) may serve as a useful biomarker for infectious processes. We investigated Mt-cfDNA dynamics in patients with pulmonary mycobacterial infections to determine if this novel biomarker could be used to differentiate disease states and severity. Methods Patients with pulmonary tuberculosis (PTB),...
Article
Full-text available
BACKGROUND: Xpert® MTB/RIF, a rapid, molecular TB diagnostic assay, can detect Mycobacterium tuberculosis and rifampin resistance directly from clinical sputum samples in <2 h with high sensitivity and specificity. The added diagnostic value of Xpert over smear microscopy at a national level in Myanmar has not been previously reported.METHODS: We e...
Article
Full-text available
Background: The Latinx population in the United States has experienced high rates of infection, hospitalization, and death since the beginning of the COVID-19 pandemic. There is little data on the knowledge, attitude, and practices (KAP) specifically in Latinx communities in the United States. Objective: We aimed to assess COVID-19 KAP and vacci...
Article
Full-text available
Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estim...
Article
Full-text available
Background Whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex has become an important tool in diagnosis and management of drug-resistant tuberculosis. However, data correlating resistance genotype with quantitative phenotypic antimicrobial susceptibility testing (AST) are scarce. Methods In a prospective multicentre observational...
Article
Studies have shown that variants in bedaquiline-resistance genes can occur in isolates from bedaquiline-naive patients. We assessed the prevalence of variants in all bedaquiline-candidate-resistance genes in bedaquiline-naive patients, investigated the association between these variants and lineage, and the effect on phenotype. We used whole-genome...
Article
Shoulder height, hind foot length, and photogrammetric craniofacial measurements were collected from male African elephants (Loxodonta africana) in Etosha National Park, Namibia across a multi-year period in order to estimate ages within this population. Consistent with other populations, we found strong linear relationships between measurements of...
Article
Background: Molecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for Mycobacterium tuberculosiscomplex (MTBC). We aimed to generate a WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: A c...
Preprint
BACKGROUND Background: The Latinx population in the United States have experienced high rates of infection, hospitalization, and death since the beginning of the COVID-19 pandemic. There is little data on the knowledge, attitude, and practices in specifically Latinx communities in the United States. OBJECTIVE We conducted a study to assess COVID-1...
Article
Full-text available
Background Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Method...
Article
Full-text available
While there has been progress in detection of drug resistant tuberculosis globally, WHO estimates only about half of the patients with bacteriologically confirmed tuberculosis were tested for rifampicin resistance over the past two years. To close this drug resistance diagnostic gap, an expansion of testing for rifampicin and isoniazid resistance i...
Article
Full-text available
Outside of the ongoing COVID-19 pandemic, tuberculosis is the leading cause of infectious disease mortality globally. Currently, there is no commercially available point-of-care diagnostic that is rapid, inexpensive, and highly sensitive for the diagnosis of active tuberculosis disease. Here we describe the development and optimization of a novel,...
Article
Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and t...
Article
Full-text available
Background Detection of tuberculosis disease (TB) and timely identification of Mycobacterium tuberculosis (Mtb) strains that are resistant to treatment are key to halting tuberculosis transmission, improving treatment outcomes, and reducing mortality. Methods We used 332,657 Xpert MTB/RIF assay results, captured as part of the Myanmar Data Utiliza...
Article
Full-text available
Background Tuberculosis (TB) is the most common co-infection among people living with HIV, but HIV positivity is associated with a lower Mycobacterium tuberculosis (MTB) bacillary load in sputum, making TB often difficult to diagnose with current diagnostic solutions. GeneXpert MTB/RIF (Cepheid, USA), a rapid, molecular diagnostic assay, has transf...
Preprint
BACKGROUND Extensively drug-resistant tuberculosis (XDR-TB) continues to be a serious threat to global public health, due in part to the lack of accurate and efficient diagnostic devices for XDR-TB. A prospective clinical study in an intended-use cohort was designed to evaluate the Akonni Biosystems XDR-TB TruArray® and Lateral Flow Cell (XDR-LFC),...
Article
Background The lack of accurate and efficient diagnostic devices for extensively drug-resistant tuberculosis (XDR-TB) makes it a severe threat to global public health. A prospective clinical study in an intended-use cohort was designed to evaluate the Akonni Biosystems XDR-TB TruArray and lateral flow cell (XDR-LFC) to address this gap in tuberculo...
Preprint
BACKGROUND Recent epidemiological data indicates that minority groups, especially Hispanic communities, experience a higher rate of infection, hospitalization, and death due to COVID-19. It is important to understand the nature of this health disparity and what socioeconomic or behavioral factors are putting Hispanic communities and other minority...
Article
Background: Recent epidemiological data indicates that minority groups, especially Hispanic communities, experience a higher rate of infection, hospitalization, and death due to Coronavirus Disease of 2019 (COVID-19). It is important to understand the nature of this health disparity and what socioeconomic or behavioral factors are putting Hispanic...
Article
Despite the WHO's call for universal drug susceptibility testing for all patients being evaluated for tuberculosis (TB), a lack of rapid diagnostic tests which can fully describe TB resistant patterns is a major challenge in ensuring that all persons diagnosed with drug-resistant TB are started on an appropriate treatment regime. We evaluated the a...
Article
Full-text available
Targeted Next Generation Sequencing (tNGS) has emerged as a comprehensive alternative to existing methods for drug susceptibility testing (DST) of Mycobacterium tuberculosis from patient sputum samples for clinical diagnosis of drug resistant TB (DR-TB). However, the complexity of sequencing platforms has limited their uptake in low-resource settin...
Article
Full-text available
Robust clinical specimen nucleic acid extraction instrumentation and methods are critical to the performance of downstream molecular diagnostics for the diagnosis of drug resistant tuberculosis (DR TB). Currently there is a high level of interest in sequencing-based solutions for rapid and comprehensive DR TB testing from primary specimens (i.e. sp...
Article
Full-text available
Background: Mobile health (mHealth) interventions have the potential to improve health through patient education and provider engagement while increasing efficiency and lowering costs. This raises the question of whether disparities in access to mobile technology could accentuate disparities in mHealth mediated care. This study addresses whether p...
Article
The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform...
Article
Whole genome sequencing (WGS) of Mycobacterium tuberculosis has rapidly progressed from a research tool to a clinical application for the diagnosis and management of tuberculosis and in public health surveillance. This development has been facilitated by drastic drops in cost, advances in technology and concerted efforts to translate sequencing dat...
Article
Background: Clinical phenotypic fluoroquinolone susceptibility testing of Mycobacterium tuberculosis (Mtb ) is currently based on Mtb growth at a single critical concentration, which provides limited information for a nuanced clinical response. We propose using specific resistance-conferring Mtb mutations in gyrA together with population pharmacoki...
Article
Full-text available
Background Accurate, comprehensive, and timely detection of drug-resistant tuberculosis (TB) is essential to inform patient treatment and enable public health surveillance. This is crucial for effective control of TB globally. Whole-genome sequencing (WGS) and targeted next-generation sequencing (NGS) approaches have potential as rapid in vitro dia...
Data
Prospective analysis plan. (DOCX)
Data
Clarification of Illumina’s role and contribution to project. (PDF)
Data
WGS variant call percent agreement. WGS, whole-genome sequencing. (DOCX)
Article
Full-text available
Tuberculosis is the primary infectious disease killer worldwide, with a growing threat from multidrug- resistant cases. Unfortunately, classic growth-based phenotypic drug susceptibility testing (DST) remains difficult, costly and time-consuming, while current rapid molecular testing options are limited by the diversity of antimicrobial resistant g...
Article
Full-text available
A personalized approach based on a patient's or pathogen’s unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to findable, accessible, interoperable, and reusable (FAIR) guiding principles. Moreover, effective precision medicine requires stan...
Article
Full-text available
BACKGROUND The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHO...
Technical Report
Full-text available
Next-generation sequencing (NGS) has great potential as a method for rapidly diagnosing drugresistant tuberculosis (DR-TB) in diverse clinical reference laboratory settings worldwide. The NGS approach overcomes many of the significant challenges associated with conventional phenotypic testing as well as the limitations of other less comprehensive m...
Article
Directly observed therapy (DOT) is a cornerstone of tuberculosis (TB) control. DOT has been criticised as paternalistic, but it has also been argued that the interaction with healthcare workers (HWs) can be a source of support for patients. We explored the experience of patients in antituberculosis treatment, with the aim of understanding the balan...
Article
Full-text available
There are many resources available to mycobacterial researchers, including culture collections around the world that distribute biomaterials to the general scientific community, genomic and clinical databases, and powerful bioinformatics tools. However, many of these resources may be unknown to the research community. This review article aims to su...
Article
Full-text available
Background Growth-based drug susceptibility testing (DST) is the reference standard for diagnosing drug-resistant tuberculosis (TB), but standard time to result (TTR) is typically ≥ 3 weeks. Rapid tests can reduce that TTR to days or hours, but accuracy may be lowered.In addition to the TTR and test accuracy, the cost of a diagnostic test may affec...
Article
Full-text available
A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence. Raw genotype–phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical a...
Article
Full-text available
Performance of the Xpert MTB/RIF assay, designed to simultaneously detect Mycobacterium tuberculosis complex (MTBC) and rifampin (RIF) resistance, has been well documented in low-resource settings with high TB-incidence. However, few studies have assessed its accuracy in low TB incidence settings. We evaluated the performance of Xpert MTB/RIF using...
Article
Full-text available
Pyrazinamide (PZA) is an important first-line drug in all existing and new tuberculosis (TB) treatment regimens. PZA-resistance in M. tuberculosis is increasing, especially among M/XDR cases. Noted issues with PZA Drug Susceptibility Testing (DST) have driven the search for alternative tests. This study provides a comprehensive assessment of PZA mo...
Article
Non published Abstract Objective: To assess the performance of the microscopic observation drug susceptibility (MODS) assay for the detection of M/XDR-TB in high-burden, resource-limited settings in a multinational prospective clinical study. Setting: Samples from 1,128 M/XDR-TB suspects were collected between April 2012 and June 2013 in India, Mo...
Article
Setting: Tuberculosis (TB) hospital in Mumbai, India. Objective: To describe the mobility patterns of persons with suspected drug-resistant tuberculosis (DR-TB) and to assess whether there were significant differences in demographic or risk characteristics based on mobility. Design: Observational cohort study of TB clinic patients at risk for...
Article
Directly observed therapy (DOT) is a cornerstone of tuberculosis (TB) control. DOT has been criticised as paternalistic, but it has also been argued that the interaction with healthcare workers (HWs) can be a source of support for patients. We explored the experience of patients in antituberculosis treatment, with the aim of understanding the balan...
Article
Full-text available
Since 2002, there has been a gradual worldwide 1.3% annual decrease in the incidence of tuberculosis (TB). This is an encouraging statistic; however, it will not achieve the World Health Organization’s goal of eliminating TB by 2050, and it is being compounded by the persistent global incidence of drug-resistant tuberculosis (DR-TB) acquired by tra...