Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria ...is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-
IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.
Abstract
Reports suggest an increased risk of tuberculosis (TB) in people with chronic airway diseases (CADs) such as chronic obstructive pulmonary disease (COPD), but evidence has not been ...systematically reviewed. We performed a systematic review by searching MEDLINE and Embase for studies published from 1 January 1993 to 15 January 2021 reporting the association between the incident risk of TB in people with CADs (asthma, COPD and bronchiectasis). Two reviewers independently assessed the quality of individual studies. We included nine studies, with two from low-income high TB burden countries. Three cohort studies reported a statistically significant independent association between COPD and the risk of TB in high-income countries (n=711 389). Hazard ratios for incident TB ranged from 1.44 to 3.14 adjusted for multiple confounders including age, sex and comorbidity. There was large between-study heterogeneity (I2=97.0%) across studies. The direction of effect on the TB risk from asthma was inconsistent. Chronic bronchitis or bronchiectasis studies were limited. The small number of available studies demonstrated an increased risk of TB in people with COPD; however, the magnitude of the increase varies by setting and population. Data in high TB burden countries and for other CADs are limited.
BACKGROUNDAn estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is ...one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key elements of tuberculosis prevention.OBJECTIVESThis review provides a comprehensive summary of recent evidence and state-of-the-art updates on advancements to prevent tuberculosis in various settings and high-risk populations.SOURCESWe identified relevant studies in the literature and synthesized the findings to provide an overview of the current state of tuberculosis prevention strategies and latest research developments.CONTENTWe present the current knowledge and recommendations regarding tuberculosis prevention, with a focus on M. bovis Bacille-Calmette-Guérin vaccination and novel vaccine candidates, tests for latent infection with M. tuberculosis, regimens available for tuberculosis preventive treatment and recommendations in low- and high-burden settings.IMPLICATIONSEffective tuberculosis prevention worldwide requires a multipronged approach that addresses social determinants, and improves access to tuberculosis detection and to new short tuberculosis preventive treatment regimens. Robust collaboration and innovative research are needed to reduce the global burden of tuberculosis and develop new detection tools, vaccines, and preventive treatments that serve all populations and ages.
The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of ...effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. We also briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system patient, and operational characteristics.
To develop and test a simple system for recording and reporting the diagnosis and treatment of latent tuberculosis infection and to compare the effects of passive and active tracing of child contacts ...on indicators of such infection.
We revised Burkina Faso's latent tuberculosis infection register and quarterly tuberculosis reporting form. Subsequently, coverage of the routine screening of contacts, who were younger than five years, for active tuberculosis and the corresponding percentages of such contacts who, if eligible, initiated preventive therapy were measured, nationwide, between 1 April 2016 and 31 March 2017. In 2016, we evaluated indicators of latent tuberculosis infection in the Hauts-Bassins region before and after community health workers had begun the active tracing of contacts who were younger than five years.
In Burkina Faso, during our study period, 3717 cases of pulmonary tuberculosis and 1166 corresponding contacts who were younger than five years were reported as the result of routine screening and passive contact tracing. The overall contact:index ratio was 0.31 and corresponding screening coverage was 82.0% (956/1166) and proportion of children starting on preventive treatment was 90.5% (852/941). Active tracing in Hauts-Bassins led to a substantially higher contact/index ratio (1.83) and screening coverage (99.3%; 145/146).
The newly established recording and reporting system proved feasible and user-friendly and allowed measurement of global indicators of latent tuberculosis infection. Compared with active tracing, passive tracing led to much lower estimates of the numbers of child contacts.
•WHO screening criteria and alternative screening tools to guide AlereLAM and FujiLAM testing have suboptimal diagnostic accuracy in HIV-positive medical inpatients.•Thus, AlereLAM testing should be ...implemented in all HIV-positive medical inpatients alongside routine molecular diagnostic testing.•If commercially available, FujiLAM could substantially improve detection of tuberculosis.
WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria followed by AlereLAM if screen positive) with AlereLAM and FujiLAM (a novel LF-LAM test) testing in all HIV-positive inpatients.
We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were (1) AlereLAM or FujiLAM for screening tests/strategies and (2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM testing in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively.
We obtained data from all 5 identified studies (n = 3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/μL) had high sensitivities but low specificities; cough (≥2 weeks), hemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 88% and 96%, respectively. In 2 studies that collected sputum and non-sputum samples for Xpert and/or culture, diagnostic yield of sputum Xpert was 40–41%, AlereLAM was 39–76%, and urine Xpert was 35–62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 61%, 81%, and 92% of all cases, respectively.
WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis.
None.
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 and treating with antibiotics to prevent progression to tuberculosis disease, known as tuberculosis preventive treatment (TPT). Novel tuberculosis vaccines are in development and phase 3 efficacy trials are imminent. The development of effective, shorter, and safer TPT regimens has broadened the groups eligible for TPT beyond people with HIV and child contacts of people with tuberculosis; future vaccine trials will be undertaken in an era of increased TPT access. Changes in the prevention standard will have implications for tuberculosis vaccine trials of disease prevention, for which safety and sufficient accrual of cases are crucial. In this paper, we examine the urgent need for trials that allow the evaluation of new vaccines and fulfil the ethical duty of researchers to provide TPT. We observe how HIV vaccine trials have incorporated preventive treatment in the form of pre-exposure prophylaxis, propose trial designs that integrate TPT, and summarise considerations for each design in terms of trial validity, efficiency, participant safety, and ethics.
BackgroundTuberculosis infection (TBI) testing and treatment are fundamental to achieve TB elimination ambitions. Among household contacts (HHCs) of TB patients, the uptake of TBI testing is limited, ...in part due to a lack of gold standard test and challenges associated with implementation, which vary by available tests. Our study evaluated the prevalence of TBI among HHCs and determined concordance of QuantiFERON-TB-Gold-Plus (QFT-Plus) to QIAreach QuantiFERON-TB (QIAreach), a new field-friendly lateral-flow-nanoparticle-fluorescence assay.MethodsIn a cross-sectional study in Lesotho, South Africa and Tanzania, blood samples were collected from HHCs at an initial household visit using a single lithium heparin tube for paired QFT-Plus and QIAreach processing, testing and interpretation following manufacturer’s guidelines. TBI prevalence was determined using QFT-Plus result. We assessed percentage agreement between QFT-Plus and QIAreach using Cohen’s Kappa.ResultsWe enrolled 964 HHCs 321 in Lesotho, 300 in South Africa, and 343 in Tanzania. Of this, 465 HHCs had paired results, of whom 65% (302/465) were females with a median age of 27 years (interquartile range: 13, 45). TBI prevalence was 51% (236/465). Among HHCs with paired results, 42% (197/465) were positive and 34% (156/465) negative on both assays, while 24% (112/465) had discordant results. Total agreement was 78% 353/451, 95% Confidence Interval (CI): 74 – 82, kappa = 0.5627, p<0.001 with a positive agreement of 77% (197/255, 95% CI: 71 – 82) and a negative agreement of 80% (157/195, 95% CI: 74 – 85).ConclusionAmong HHCs in three high-burden countries, we identified a high TBI prevalence. QIAreach demonstrated a moderate concordance against QFT-Plus. However, in the absence of a gold standard test, it is difficult to interpret the implication of this finding. Further research is needed to understand its usability in this population, specifically if it addresses field implementation challenges associated with similar TBI tests.
Metodos Se reviso el registro de infeccion tuberculosa latente de Burkina Faso y el formulario trimestral de informacion sobre la tuberculosis. Posteriormente, se midio la cobertura de los examenes ...de deteccion rutinarios a los contactos, menores de cinco anos, para la tuberculosis activa y los porcentajes correspondientes de contactos que, de ser aptos, iniciaron la terapia preventiva a nivel nacional, entre el 1 de abril de 2016 y el 31 de marzo de 2017. En 2016, se evaluaron los indicadores de infeccion tuberculosa latente en la region de Hauts-Bassins antes y despues de que los trabajadores comunitarios de la salud empezaran el seguimiento activo de los contactos menores de cinco anos.
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