Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

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 diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

Risk of long COVID main symptoms after SARS-CoV-2 infection: a systematic review and meta-analysis.

This review aimed to summarise the relative risk (RR) of the main symptoms of long COVID in people infected with SARS-CoV-2 compared to uninfected controls, as well as the difference in health-related quality of life (HRQoL) after infection. MEDLINE, EMBASE, PubMed, NLM-LitCovid, WHO-COVID-19, arXiv and Europe-PMC were searched up to 23rd March 2022. Studies reporting risk (four or more weeks after infection) of fatigue, shortness of breath, and cognitive dysfunction, as well as comparative HRQoL outcomes, were included. Pairwise random-effects meta-analyses were performed to pool risks of individual symptoms. Thirty-three studies were identified; twenty studies reporting symptom risks were included in the meta-analyses. Overall, infection with SARS-CoV-2 carried significantly higher risk of fatigue (RR 1.72, 95% confidence intervals [CIs] 1.41, 2.10), shortness of breath (RR 2.60, 95% CIs 1.96, 3.44), memory difficulties (RR 2.53, 95% CIs 1.30, 4.93), and concentration difficulties (RR 2.14, 95% CIs 1.25, 3.67). Quality of life findings were varied and comparisons between studies were challenging due to different HRQoL instruments used and study heterogeneity, although studies indicated that severe hospitalised COVID is associated with a significantly poorer HRQoL after infection. These risks are likely to constantly change as vaccines, reinfections, and new variants alter global immunity.

Asymptomatic but infectious - The silent driver of pathogen transmission. A pragmatic review.

Throughout 2020, COVID-19 interventions prioritised symptomatic individuals despite growing evidence of pre-symptomatic and asymptomatic transmission. From the pandemic we have learned that global health is slow to quantify asymptomatic disease transmission and slow to implement relevant interventions. While asymptomatic infectious periods exist for nearly all pathogens, it is frequently ignored during case finding, and there are limited research efforts to understand its potential to drive small scale outbreaks, epidemics and pandemics. We conducted a pragmatic review on 15 key pathogens including SARS-CoV-2 and Ebola to demonstrate substantial variation in terminology around asymptomatic infectious individuals, and varying proportions of asymptomatic amongst prevalent infectious cases (0-99 %) and their contribution to transmission (0-96 %). While no pattern was discernible by pathogen type (virus, bacteria, parasite) or mode of transmission (direct, indirect or mixed), there are multiple lessons to learn from previous and current control programmes. As found during the COVID-19 pandemic, overlooking asymptomatic infectious individuals can impede disease control. Improving our understanding of how asymptomatic individuals can drive epidemics can strengthen our efforts to control current pathogens, and improve our preparedness for when the next new pathogen emerges..

Durability of Vaccine-Induced and Natural Immunity Against COVID-19: A Narrative Review.

Vaccines developed against SARS-CoV-2 have proven to be highly effective in preventing symptomatic infection. Similarly, prior infection with SARS-CoV-2 has been shown to provide substantial protection against reinfection. However, it has become apparent that the protection provided to an individual after either vaccination or infection wanes over time. Waning protection is driven by both waning immunity over time since vaccination or initial infection, and the evolution of new variants of SARS-CoV-2. Both antibody and T/B-cells levels have been investigated as potential correlates of protection post-vaccination or post-infection. The activity of antibodies and T/B-cells provide some potential insight into the underlying causes of waning protection. This review seeks to summarise what is currently known about the waning of protection provided by both vaccination and/or prior infection, as well as the current information on the respective antibody and T/B-cell responses.

Impact of COVID-19 Disruptions on Global BCG Coverage and Paediatric TB Mortality: A Modelling Study.

The impact of COVID-19 disruptions on global Bacillus Calmette-Guérin (BCG) coverage and paediatric tuberculosis (TB) mortality is still unknown. To fill this evidence-gap and guide mitigation measures, we estimated the impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality. First, we used data from multiple sources to estimate COVID-19-disrupted BCG vaccination coverage. Second, using a static mathematical model, we estimated the number of additional paediatric TB deaths in the first 15 years of life due to delayed/missed vaccinations in 14 scenarios-varying in duration of disruption, and magnitude and timing of catch-up. We estimated a 25% reduction in global BCG coverage within the disruption period. The best-case scenario (3-month disruption, 100% catch-up within 3 months) resulted in an additional 886 (0.5%) paediatric TB deaths, and the worst-case scenario (6-month disruption with no catch-up) resulted in an additional 33,074 (17%) deaths. The magnitude of catch-up was found to be the most influential variable in minimising excess paediatric TB mortality. Our results show that ensuring catch-up vaccination of missed children is a critical priority, and delivery of BCG alongside other routine vaccines may be a feasible way to achieve catch-up. Urgent action is required to support countries with recovering vaccination coverages to minimise paediatric deaths.

The growth and strategic functioning of One Health networks: a systematic analysis.

BACKGROUND: The recent increase in attention to linkages between human health, animal health, and the state of the environment has resulted in the rapid growth of networks that facilitate collaboration between these sectors. This study ascertained whether duplication of efforts is occurring across networks, which stakeholders are being engaged, and how frequently monitoring and evaluation of investments is being reported. METHODS: This study is a systematic analysis of One Health networks (OHNs) in Africa, Asia, and Europe. We defined an OHN as an engagement between two or more discrete organisations with at least two of the following sectors represented: animal health, human health, and the environment or ecosystem. Between June 5 and Sept 29, 2017, we systematically searched for OHNs in PubMed, Google, Google Scholar, and relevant conference websites. No language restrictions were applied, but we were only able to translate from English and French. Data about OHNs, including their year of initiation, sectors of engagement, regions of operation, activities conducted, and stakeholders involved, were extracted with a standardised template and analysed descriptively. FINDINGS: After screening 2430 search results, we identified and analysed 100 unique OHNs, of which 86 were formed after 2005. 32 OHNs covered only human and animal health, without engaging with the role of the environment on health. 78 OHNs involved academic bodies and 78 involved government bodies, with for-profit organisations involved in only 23 and community groups involved in only ten. There were few collaborations exclusively between networks in the developing world (four OHNs) and only 15 OHNs reported monitoring and evaluation information. The majority of OHNs worked on supporting communication, collaboration, information sharing, and capacity building. INTERPRETATION: Amid concerns about there being insufficient strategic direction and coordination in the growth of OHNs, our study provides empirical evidence about limitations in stakeholder representation, apparently absent or ambiguous monitoring and evaluation structures, and potential areas of duplication. The collective strategic functioning of OHNs might be improved by more transparent reporting of goals and outcomes of OHN activities, as well as more collaborations led by networks within the developing world and increased attention to environmental health. FUNDING: None.

The parturient in the interventional radiology suite: New frontier in obstetric anaesthesia.

The anaesthesiologist's presence during interventional radiology (IR) is increasing due to increasingly ill patients and intricate procedures. The management of a parturient in IR suite is complex in terms of logistics of an unfamiliar procedure in an unfamiliar area. The literature available is largely written by radiologists with little attention paid to anaesthetic details and considerations. In the Indian scenario, in the absence of hybrid operating rooms (ORs), logistics involve transport of a parturient back and forth between the IR suite and the OR. As members of a multidisciplinary team, anaesthesiologists should utilise their expertise in fluid management, transfusion therapy and critical care to prevent and treat catastrophic events that may accompany severe peri-partum bleeding. Ensuring familiarity with the variety of IR procedures and the peri-procedure requirements can help the anaesthesiologist provide optimum care in the IR suite.

Crystal structure of {2,2'-[ethyl-enebis(nitrilo-methanylyl-idene)]diphenolato-κ(4) O,N,N',O'}oxidovanadium(IV) methanol monosolvate.

Two independent mol-ecules of the title solvated complex, [V(C16H14N2O2)O]·CH3OH, also known as [N,N'-bis-(salicyl-idene)ethyl-enedi-amine]-oxidovanadium(IV) or vanadyl salen, crystallize in the asymmetric unit. Each disordered methanol solvent mol-ecule [occupancy ratios 0.678 (4):0.322 (4) and 0.750 (5):0.250 (5)] is linked to a [N,N'-bis-(salicyl-idene)ethyl-enedi-amine]-oxidovanadium(IV) mol-ecule by an O-H⋯O hydrogen bond and to others by C-H⋯O hydrogen bonds. The resulting extended structure consists of a bilayer of mol-ecules parallel to the ab plane. Despite the fact that solvates are common in complexes derived from substituted analogues of the N,N'-bis-(salicyl-idene)ethyl-enedi-amine ligand, the title solvate is the first one of [N,N'-bis-(salicyl-idene)ethyl-enedi-amine]-oxidovanadium(IV) to be structurally characterized. The two vanadyl species have very similar inter-nal geometries, which are best characterized as distorted square-based pyramidal with the vanadium atom displaced from the N2O2 basal plane by 0.5966 (9) Šin the direction of the doubly-bonded oxide ligand.