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Publications (419)
Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines coul...
Recent studies using sensitive aerosol sampling and detection methodologies, have enumerated aerosolized Mycobacterium tuberculosis (Mtb) across a spectrum of tuberculosis states in a high-burdened setting. To estimate the Mtb exposure rate we used a Bayesian inference approach to fit a reversible catalytic model to age-specific, respiratory bioaer...
Introduction
Efforts to improve medication access in low-and middle-income countries, particularly in Sub-Saharan Africa, have made progress, especially in the fight against infectious diseases such as tuberculosis. However, challenges exist in establishing effective pharmacovigilance systems. The PhArmacoVIgilance Africa (PAVIA) project was commit...
Background
Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobact...
Potential Mycobacterium tuberculosis ( Mtb ) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb from TB clinic attendees following diagnosis and through six months’ follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and c...
The current active/latent paradigm of tuberculosis (TB) largely neglects the documented spectrum of disease. Lack of consistency on definitions, terminology and diagnostic criteria for different TB states constrains progress in research and product development required to achieve TB elimination.
We reached consensus on a set of conceptual states, r...
Background
Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis ( Mtb ) transmission is unknown, especially compared to individuals who report symptoms at the time of diagno...
The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of...
Objective
To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation.
Design
Multicenter, retrospective cohort study.
Methods
We utilized the data from st...
A new tuberculosis (TB) vaccine is a high priority. However, the classical development pathway is a major deterrent. Most TB cases arise within two years after M. tuberculosis exposure, suggesting a three-year trial period should be possible if sample size is large to maximise the number of early exposures. Increased sample size could be facilitate...
Background
An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National Pharmacovigilance System. Consequently, the crucial function of monitoring and ensuring the availability of safe medicines in these settings cannot be guaranteed considering the...
Digital transformation in health care has a lot of opportunities to improve access and quality of care. However, in reality not all individuals and communities are benefiting equally from these innovations. People in vulnerable conditions, already in need of more care and support, are often not participating in digital health programs. Fortunately,...
Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials. Conventional phase 3 trials provide information on the...
Introduction
The WHO End-TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach.
Methods
We pooled individual TB screening epi...
To assess sex disparities in tuberculosis in Vietnam, we conducted a nested, case-control study based on a 2017 tuberculosis prevalence survey. We defined the case group as all survey participants with laboratory-confirmed tuberculosis and the control group as a randomly selected group of participants with no tuberculosis. We used structural equati...
Background:
We conducted a retrospective population-based study to describe longitudinal patterns of prevalence, incidence, discontinuation, resumption, and durability of substantial HIV risk behaviors (SHR) for PrEP eligibility.
Methods:
The study was conducted among HIV-negative study participants aged 15-49 years that participated in survey r...
Stages of tuberculosis disease can be delineated by radiology, microbiology, and symptoms, but transitions between these stages remain unclear. In a systematic review and meta-analysis of studies of individuals with untreated tuberculosis who underwent follow-up (34 cohorts from 24 studies, with a combined sample of 139 063), we aimed to quantify p...
Background:
Prevalence surveys show a substantial burden of subclinical (asymptomatic but infectious) tuberculosis, from which individuals can progress, regress, or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of tuberculosis disease.
Methods:
We created a deterministic framework of untreated t...
Approximately 10·6 million people worldwide develop tuberculosis each year, representing a failure in epidemic control that is accentuated by the absence of effective vaccines to prevent infection or disease in adolescents and adults. Without effective vaccines, tuberculosis prevention has relied on testing for Mycobacterium tuberculosis infection...
Background:
Subclinical tuberculosis has been increasingly recognized as a separate state in the spectrum of the disease. However, evidence on the transmissibility of subclinical tuberculosis is still inconclusive.
Methods:
We reanalysed the data from the 2007 combined tuberculosis prevalence and tuberculin surveys in Vietnam. Poisson regression...
Rationale: Knowledge of the potential for aerosol release of Mycobacterium tuberculosis (Mtb) during disease, treatment, recovery, and asymptomatic carriage is fundamental to understanding tuberculosis (TB) transmission.
Objectives: To quantify viable aerosolized Mtb from TB clinic attendees.
Methods: 102 presumptive TB patients from two informal s...
New tuberculosis vaccine candidates that are in the development pipeline need to be studied in people with HIV, who are at high risk of acquiring Mycobacterium tuberculosis infection and tuberculosis disease and tend to develop less robust vaccine-induced immune responses. To address the gaps in developing tuberculosis vaccines for people with HIV,...
Introduction
The WHO End-TB Strategy emphasises early diagnosis and screening of tuberculosis (TB) in high-risk groups, including migrants. We analysed TB yield data from four large migrant TB screening programmes to inform TB policy.
Methods
We pooled routinely collected individual TB screening episode data from Italy, the Netherlands, Sweden, an...
BACKGROUND
Key stages in TB disease can be delineated by radiology, microbiology and symptoms, but transition between relevant stages remains unclear. We sought to quantify progression and regression across the spectrum of TB disease by systematically reviewing studies of individuals with untreated TB undergoing follow up.
METHODS
We searched PubM...
Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgentl...
Background
Individuals with bacteriologically confirmed pulmonary tuberculosis disease (TB) that do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis ( Mtb ) transmission is unknown, especially compared to individuals who report symptoms at time of diagnosis...
BACKGROUND
Protection against infection by the bacille Calmette-Guérin vaccine against Mycobacterium tuberculosis remains a subject of controversy. We investigated the association between BCG vaccination at birth and infection by M. tuberculosis.
MATERIAL AND METHODS
This was a secondary analysis of data from tuberculin skin test (TST) surveys in...
Background
Xpert MTB/Rif, a molecular test to detect tuberculosis (TB), has been proven to have high sensitivity and specificity when compared with liquid culture in clinical settings. However, little is known about its performance in community TB screening.
Methods
In Vietnam, a national TB prevalence survey was conducted in 2017. Survey particip...
Many new TB vaccine candidates in the development pipeline need to be studied in people with HIV. People with HIV are at high risk of developing Mycobacterium tuberculosis (Mtb) infection and TB disease and tend to develop less robust vaccine induced immune responses. Many questions remain unanswered regarding priority vaccine indications, clinical...
Background:
Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Tha...
Background
An ecological relationship between economic development and reduction in tuberculosis prevalence has been observed. Between 2007 and 2017, Việt Nam experienced rapid economic development with equitable distribution of resources and a 37% reduction in tuberculosis prevalence. Analysing consecutive prevalence surveys, we examined how the r...
Rapid, accurate, sputum-free tests for tuberculosis (TB) triage and confirmation are urgently needed to close the widening diagnostic gap. We summarise key technologies and review programmatic, systems, and resource issues that could affect the impact of diagnostics. Mid-to-early-stage technologies like artificial intelligence-based automated digit...
Background:
The utility of using PrEP eligibility assessments to identify eligibility in general populations has not been well studied in sub-Saharan Africa. We used the Rakai Community Cohort Study to conduct a cross-sectional analysis to estimate PrEP eligibility and a cohort analysis to estimate HIV incidence associated with PrEP eligibility....
Objective
Incipient Tuberculosis (ITB) refers to Mycobacterium tuberculosis infection that is likely to progress to active disease in the absence of treatment, but without clinical signs, symptoms, radiographic or microbiological evidence of disease. Biomarker‐based tests to diagnose incipient TB hold promise for better prediction and, through TB p...
To eliminate tuberculosis globally, a new, effective, and affordable vaccine is urgently needed, particularly for use in adults and adolescents in low-income and middle-income countries. We have created a roadmap that lists the actions needed to accelerate tuberculosis vaccine research and development using a participatory process. The vaccine pipe...
Background
Chest X-ray (CXR) screening is a useful diagnostic tool to test individuals at high risk of tuberculosis (TB), yet image interpretation requires trained human readers who are in short supply in many high TB burden countries. Therefore, CXR interpretation by computer-aided detection software (CAD) may overcome some of these challenges, bu...
Background
Pulmonary tuberculosis (TB) infection can manifest in different states including sub-clinical tuberculosis (scTB) that is commonly defined as confirmed TB without having the classical symptoms (commonly persistent cough for ≥2 weeks). This narrow definition likely poses limitations for surveillance and control measures. The aims of the c...
China is one of the high-burden countries for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Moxifloxacin is one of the critical antituberculosis drugs for MDR/RR-TB treatment.
Objective
South Africa’s infant Bacille Calmette Guerin (BCG) vaccine policy changed from percutaneous (PC) BCG Japan to intradermal (ID) BCG Denmark in 2000. This study investigated whether this change in infant BCG vaccination had any durable impact on TB incidence rates (IR) into adolescence.
Methods
The Cape Town electronic TB register provide...
BACKGROUND: Diagnostic tools to identify incipient or subclinical TB stages will be helpful for preventive intervention. A simple biomarker to predict TB may be the monocytes to lymphocytes ratio (ML ratio) in peripheral blood.METHODS: We assessed the relationship between multiple time-updated ML ratio measurements and incidence of TB in people liv...
Background
New medicines have become available for the treatment of drug-resistant tuberculosis (DR-TB) and are introduced in sub-Saharan Africa (SSA) by the national TB programs (NTPs) through special access schemes. Pharmacovigilance is typically the task of national medicines regulatory agencies (NMRAs), but the active drug safety monitoring and...
Background: Prevalence surveys have found a substantial burden of subclinical (asymptomatic but infectious) TB, from which individuals can progress, regress or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of TB disease.
Methods: We created deterministic framework of TB disease with progression and...
Background:
Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain.
Objective:
To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2...
Background: New medicines have become available for the treatment of drug-resistant tuberculosis (DR-TB) and are introduced in sub-Saharan Africa (SSA) by the national TB programs (NTPs) through special access schemes. Pharmacovigilance is typically the task of national medicines regulatory agencies (NMRAs), but the active drug safety monitoring an...
Objectives
To examine changes in the screening, diagnosis, treatment and management of drug-resistant tuberculosis (DRTB) patients, and investigate the impacts of DRTB-related policies on patients of different demographic and socioeconomic characteristics.
Design
A retrospective cohort study using registry data, plus a survey on DRTB-related polic...
Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-po...
Background
A decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improveme...
Background:
Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Despite being central to ongoing TB transmission, no routine diagnostic assay exists to measure Mtb in bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples have been limited to individuals with sputum-positive pulmonary TB....
An amendment to this paper has been published and can be accessed via the original article.
Background: Most studies evaluating the effect of Xpert MTB/RIF testing for tuberculosis (TB) concluded that it did not reduce overall mortality compared to usual care. We conducted a systematic review to assess whether key study design and execution features contributed to earlier identification of patients with TB and decreased pre-treatment loss...
[This corrects the article DOI: 10.1371/journal.pone.0232142.].
BACKGROUND: Tuberculosis incidence varies seasonally in many settings. However, the role of seasonal variation in reactivation vs. transmission is unclear. METHODS: We reviewed data on TB notifications in Cape Town, South Africa, from 1903 to 2017 (exclusive of 1995–2002, which were unavailable). Data from 2003 onward were stratified by HIV status,...
Background:
Retreatment tuberculosis (TB) disease is common in high-prevalence settings. The risk of repeated episodes of recurrent TB is unknown. We calculated the rate of recurrent TB per subsequent episode by matching individual treatment episodes over a period of 13 years.
Methods:
All recorded TB episodes in Cape Town between 2003-2016 were...
Introduction
Tuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second national TB prevalence survey was conducted in 2017–2018 to assess the current burden of TB disease in the country.
Method
Eighty-two clus...
Background
Mass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.
Methods
Between May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected...
Following publication of the original article [1], it was brought to the authors' attention that one of the names in the author list had been provided with the incorrect spelling.
Achieving the ambitious targets for global tuberculosis (TB) control, will require an increased emphasis on preventing development of active disease in those with latent TB infection (LTBI) by preventative treatment or vaccination [1]. New shortened regimens of 1–3 months duration potentially allow much wider and more effective use of preventive th...
Abstract Background Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, w...