Previous research has demonstrated that various properties of infectious diseases can be inferred from online search behaviour. In this work we use time series of online search query frequencies to ...gain insights about the prevalence of COVID-19 in multiple countries. We first develop unsupervised modelling techniques based on associated symptom categories identified by the United Kingdom's National Health Service and Public Health England. We then attempt to minimise an expected bias in these signals caused by public interest-as opposed to infections-using the proportion of news media coverage devoted to COVID-19 as a proxy indicator. Our analysis indicates that models based on online searches precede the reported confirmed cases and deaths by 16.7 (10.2-23.2) and 22.1 (17.4-26.9) days, respectively. We also investigate transfer learning techniques for mapping supervised models from countries where the spread of the disease has progressed extensively to countries that are in earlier phases of their respective epidemic curves. Furthermore, we compare time series of online search activity against confirmed COVID-19 cases or deaths jointly across multiple countries, uncovering interesting querying patterns, including the finding that rarer symptoms are better predictors than common ones. Finally, we show that web searches improve the short-term forecasting accuracy of autoregressive models for COVID-19 deaths. Our work provides evidence that online search data can be used to develop complementary public health surveillance methods to help inform the COVID-19 response in conjunction with more established approaches.
To estimate of the number of children younger than 5 years who were household contacts of people with tuberculosis and were eligible for tuberculosis preventive treatment in 2017.
To estimate the ...number of eligible children, we obtained national values for the number of notified cases of bacteriologically confirmed pulmonary tuberculosis in 2017, the proportion of the population younger than 5 years in 2017 and average household size from published sources. We obtained global values for the number of active tuberculosis cases per household with an index case and for the prevalence of latent tuberculosis infection among children younger than 5 years who were household contacts of a tuberculosis case through systematic reviews, meta-analysis and Poisson regression models.
The estimated number of children younger than 5 years eligible for tuberculosis preventive treatment in 2017 globally was 1.27 million (95% uncertainty interval, UI: 1.24-1.31), which corresponded to an estimated global coverage of preventive treatment in children of 23% at best. By country, the estimated number ranged from less than one in the Bahamas, Iceland, Luxembourg and Malta to 350 000 (95% UI: 320 000-380 000) in India. Regionally, the highest estimates were for the World Health Organization (WHO) South-East Asia Region (510 000; 95% UI: 450 000-580 000) and the WHO African Region (470 000; 95% UI: 440 000-490 000).
Tuberculosis preventive treatment in children was underutilized globally in 2017. Treatment should be scaled up to help eliminate the pool of tuberculosis infection and achieve the End TB Strategy targets.
One-third to one-quarter of the world's population is estimated to have latent tuberculosis infection (LTBI) 1. These infected persons are at risk for developing active disease with a lifetime risk ...of reactivation estimated to be 5–10% 2. Prevention of reactivation of LTBI in population groups with higher risk of progression to active disease than the general population, is critical to end the global TB epidemic 3.
There is a need for reliable serological assays to determine accurate estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence. Most single target antigen assays have ...shown some limitations in Africa. To assess the performance of a multi-antigen assay, we evaluated a commercially available SARS-CoV-2 Multi-Antigen IgG assay for human coronavirus disease 2019 (COVID-19) in Nigeria.
Validation of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was carried out using well-characterized SARS-CoV-2 reverse transcription polymerase chain reactive positive (97) and pre-COVID-19 pandemic (86) plasma panels. Cross-reactivity was assessed using pre-COVID-19 pandemic plasma specimens (213) from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS).
The overall sensitivity of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was 75.3% 95% CI: 65.8%- 82.8% and specificity was 99.0% 95% CI: 96.8%- 99.7%. The sensitivity estimate increased to 83.3% 95% CI: 70.4%- 91.3% for specimens >14 days post-confirmation of diagnosis. However, using the NAIIS pre-pandemic specimens, the false positivity rate was 1.4% (3/213).
Our results showed overall lower sensitivity and a comparable specificity with the manufacturer's validation. There appears to be less cross-reactivity with NAIIS pre-pandemic COVID-19 specimens using the xMAP SARS-CoV-2 Multi-Antigen IgG assay. In-country SARS-CoV-2 serology assay validation can help guide the best choice of assays in Africa.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Advances in discovery and validation of diagnostic, prognostic and treatment-monitoring transcriptomic signatures of tuberculosis (TB) disease could accelerate the goal to end TB. We conducted a ...review to evaluate whether mRNA transcriptomics technologies are sufficiently mature to develop accurate next-generation TB diagnostic tests. Early studies tended to be limited in sample size, diversity of population groups, sample collection and processing methods, while recent prospective studies have addressed these limitations. Some of the existing signatures could be used for triage; however, high cost and complexity could limit their use. For a confirmatory test, setting an optimal cut-off to maintain specificity across populations and settings is a challenge. mRNA signatures have shown the potential to quantitatively monitor response to treatment. No prognostic signatures can accurately predict progression to active TB over 2 years while short term prediction is possible. The management strategy should be defined for individuals with positive prognostic tests.
Development of this manuscript was supported by funding received from the Stop TB Partnership and USAID for the New Diagnostics Working Group. The funders had no role in paper design, article selection and review, interpretation, or writing of the paper.
The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 ...mg·L
cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs).
Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal-external cross-validation to evaluate performance.
We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg·L
cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg·L
cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively.
CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L
cut-off or in a CPM depends on available resources.
IntroductionThe successful scale-up of a latent tuberculosis (TB) infection testing and treatment programme is essential to achieve TB elimination. However, poor adherence compromises its therapeutic ...effectiveness. Novel rifapentine-based regimens and treatment support based on behavioural science theory may improve treatment adherence and completion.Methods and analysisA pragmatic multicentre, open-label, randomised controlled trial assessing the effect of novel short-course rifapentine-based regimens for TB prevention and additional theory-based treatment support on treatment adherence against standard-of-care. Participants aged between 16 and 65 who are eligible to start TB preventive therapy will be recruited in England. 920 participants will be randomised to one of six arms with allocation ratio of 5:5:6:6:6:6: daily isoniazid +rifampicin for 3 months (3HR), routine treatment support (control); 3HR, additional treatment support; weekly isoniazid +rifapentine for 3 months (3HP), routine treatment support; weekly 3HP, additional treatment support ; daily isoniazid +rifapentine for 1 month (1HP), routine treatment support; daily 1HP, additional treatment support. Additional treatment support comprises reminders using an electronic pillbox, a short animation, and leaflets based on the perceptions and practicalities approach. The primary outcome is adequate treatment adherence, defined as taking ≥90% of allocated doses within the pre-specified treatment period, measured by electronic pillboxes. Secondary outcomes include safety and TB incidence within 12 months. We will conduct process evaluation of the trial interventions and assess intervention acceptability and fidelity and mechanisms for effect and estimate the cost-effectiveness of novel regimens. The protocol was developed with patient and public involvement, which will continue throughout the trial.Ethics and disseminationEthics approval has been obtained from The National Health Service Health Research Authority (20/LO/1097). All participants will be required to provide written informed consent. We will share the results in peer-reviewed journals.Trial registration numberEudraCT 2020-004444-29.
Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the ...performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein NCP immunoglobulin G IgG, Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58 days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations.
COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and ...its treatment.
Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach.
Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics.
COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19.
NIHR RID-TB Program (RP-PG-0217-20009).
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