69832 research outputs found
Sort by
Reported Tuberculosis Symptoms: An Inadequate Classifier of Disease State.
No full textAround half of people identified with tuberculosis (TB) during prevalence surveys do not report symptoms, prompting increased interest in the public health implications of asymptomatic TB (aTB), as distinct from symptomatic TB (sTB). A recent World Health Organization report proposes investigating the optimal treatment for aTB, stratifying notification data by symptom status, and publishing incidence estimates based on sTB. We have concerns that the proposed use of aTB/sTB case definitions for surveillance, burden estimation, and clinical management is not supported by evidence. Although TB symptoms are linked to disease severity, we show that self-reported symptoms are an inadequate classifier of disease state, heavily influenced by context and substantial interviewer variability, and TB symptoms may frequently have alternative causes. We advocate for the adoption of more robust measures of severity, better reflecting underlying pathophysiology. Research on the TB disease spectrum should prioritize more objective severity metrics, alongside or instead of symptom-based classification
Gut Prevotella stercorea associates with protection against infection in rural African children.
Get PDFUnderstanding how the gut microbiome confers immune protection in early life remains a fundamental challenge, particularly in high-infection-burden, underrepresented populations. Here, we analyse longitudinal stool microbiome and illness data from 633 Gambian children aged 7-37 months enroled in a randomised, double-blind iron supplementation trial (NCT02941081). The primary endpoint was correction of iron deficiency anaemia, and the secondary endpoint was diarrhoea incidence and other adverse events; IHAT was non-inferior to ferrous sulphate for iron correction and showed fewer moderate-to-severe diarrhoea episodes. Using 16S rRNA sequencing at three timepoints (Days 1, 15, and 85), we find that children who remained infection-free harboured a consistently higher relative abundance of Prevotella stercorea, a keystone taxon of non-industrialised gut ecologies. In contrast, Escherichia coli and other opportunistic pathogens were enriched in children who developed infections. These taxonomic signatures were temporally stable and embedded within distinct, co-occurring microbial networks. Strikingly, higher P. stercorea abundance was inversely associated with both infection frequency and duration, with the greatest differences observed in children aged 1-2 years, potentially explaining their increased infectious risk. Our findings reveal a Prevotella-dominated enterotype associated with reduced infection risk, with implications for vaccine responsiveness, child survival, and microbiota-targeted interventions in global child health
Long short-term memory-based deep learning model for the discovery of antimicrobial peptides targeting Mycobacterium tuberculosis.
Get PDFMOTIVATION: Tuberculosis, caused by Mycobacterium tuberculosis, remains a global health challenge driven by rising antibiotic resistance. Antimicrobial peptides offer a promising alternative due to membrane-disruptive activity and low resistance potential, yet the scarcity of TB-specific AMP data constrains targeted development. We present a reproducible deep learning protocol that integrates long short-term memory networks with transfer learning to classify and generate TB-active peptides.
RESULTS: Classifiers were pretrained on a large corpus of general AMPs and fine-tuned on curated TB-specific sequences using frozen encoder and full backpropagation strategies. We benchmarked four model variants [unidirectional and bidirectional long short-term memories (LSTMs), with and without attention] on a held-out TB test set; the unidirectional LSTM with a frozen encoder achieved the best performance (accuracy 90%, AUC 0.97). In parallel, LSTM-based generative models were trained to produce de novo TB-active peptides. A generator trained exclusively on TB data produced 94 of 100 peptides predicted as antimicrobial by AMP Scanner, outperforming transfer learning-based generators. Generated peptides were evaluated for antimicrobial activity, toxicity, structure, and AMP-like physicochemical traits, and four candidates shared ≥84% identity with known TB-AMPs.
AVAILABILITY AND IMPLEMENTATION: The complete model and data can be found at: https://github.com/linfeng-wang/TB-AMP-design
Lifetime exposure to modifiable risks and later‐life cognition impairment: the British 1946 birth study
Get PDFAbstract
Background
Using an age‐homogenous population‐based sample studied since birth with prospective ‐data collected across the life course, we examined the cumulative and individual relationships between modifiable risks and later‐life cognitive impairment. We examine the role of childhood cognition and socioeconomic position (SEP) in these relationships.
Method
Lifetime exposure to fourteen modifiable dementia risks from the 2024 Lancet commission were derived in the 1946 British Birth Cohort (Table 1) (
n
= 1239, 52% female). Exposures (yes/no) were categorised into three epochs: early‐ [≤36yrs], mid‐ [43‐53yrs], and later‐adulthood [60‐69yrs]); categorised into (0) never exposed, (1) exposed once, (2) exposed ≥2; and summed (max=28). 25% of individuals had cognitive impairment based on a validated threshold (≤88/100) on the Addenbrooke's Cognitive Examination (ACE‐III) administered at 69yrs. Logistic regression models were used to assess relationships between cognitive impairment and exposures.
Result
Participants on average were exposed to 6 (43%) exposures (range:0‐12) (Figure 1). Greater risk exposure (either exposure across another life course period, or to an additional exposure) was associated with cognitive impairment at 69yrs (OR=1.13 [95% CI:1.08‐1.19],
p
<0.01) (Figure 2). This relationship was attenuated by 50% with adjustment for sex, childhood cognition and SEP, but remained robust (OR=1.07 [95 CI: 1.02‐1.14],
p
<0.01).
In individual models, low education, hypertension, long‐term smoking, physical inactivity, long‐term depression and visual impairment were associated with cognitive impairment; alcohol use was linked to a
decreased
risk of cognitive impairment (Figure 3a). However, in mutual adjustment models including childhood cognition and SEP, the only exposures that remained robust were low education and physical inactivity, alongside childhood cognition and SEP (Figure 3b).
Conclusion
While several exposures were associated with cognitive impairment at 69yrs, mostly in a dose‐response manner, the only robust independent relationships were for education and physical inactivity. Baseline cognitive function and social class are also important prediction exposures for later‐life cognitive impairment. These findings emphasise the importance of promoting education, physical activity and improving earlier life socioeconomic status in dementia prevention strategies and demonstrate the potential of longitudinal cohort studies for exploring viable modifiable risks
Investigating the effects of brain and cardiovascular health on white matter microstructural properties: a comparison of stable and converting normal appearing white matter
Get PDFAbstract
Background
Diffusion weighted imaging (DWI) measures white matter (WM) microstructure (WMMS), with changes in various DWI metrics seen in Alzheimer's disease (AD) progression
1
. Using data from Insight46
3–5
, a British population‐based birth cohort, we previously found poorer WMMS in normal appearing WM (NAWM) age 70 had sex‐dependent associations with higher midlife blood pressure and cardiovascular risk, as well as concurrent WM hyperintensity volume (WMHV) and β‐Amyloid (Aβ) burden
2
. Here we explore whether these findings reflect poorer WMMS in areas of NAWM that remained normal appearing ∼2.5 years later, or in areas that later became WMH.
Method
Using data from
N
= 302 Insight46 participants who were scanned for a second time ∼2.5 years later, we used linear regression to re‐examine the previously identified significant relationships with NAWM integrity
2
, as well as sex interactions in men and women that remained robust in the smaller follow‐up sample, separately in “stable” (remained NAWM) and “converting” (converted to WMH) regions (Figure 1). WMMS metrics were fractional anisotropy (FA), mean diffusivity (MD) and neurite density index (NDI)
2
. Analyses were adjusted for sex and age as well as total intracranial volume (TIV) for models with WMHV and Aβ.
Result
Summary statistics are shown in Table 1. The associations shown in the total NAWM
2
persisted in stable regions (Figure 2). Stronger associations were observed in the converting NAWM, particularly with WMHV at age 70. There was also a significant association between BP at age 53 and FA and MD in males in the converting NAWM, which was only observed in women in the whole region
2
. The effect of Aβ on MD in men was robust in both regions.
Conclusion
Previously demonstrated associations with poorer WMMS (age, midlife cardiovascular risk factors, WMHV and Aβ)
2
were not driven solely by NAWM on the verge of becoming WMH. However, stronger effects observed in converting NAWM suggest higher midlife BP, poorer WMMS and WMH development are part of a continuous, related process, particularly in men. The similar effect of Aβ burden in men in the stable and unstable NAWM suggests the effects of Aβ on WMMI are not driven by tissue later converting to WMH
Comparing the test performance of dried-blood-spot and plasma HIV recent infection testing samples in a nationally scaled sex worker programme in Zimbabwe.
Get PDFRecency testing can provide strategic insights as to whether a person newly diagnosed with HIV recently acquired their infection or not. To understand potential biases associated with HIV recency testing, we explored the extent sample type influences whether a person is assigned as being recent. Implementing a laboratory-based Recent Infection Testing Algorithm (RITA) across the Centre for Sexual Health and HIV/AIDS Research (CeSHHAR) key populations programme in Zimbabwe between October 2021 and January 2023, we compared plasma-based and dried-bloodspot (DBS) HIV recency samples. Over the study period, 24,976 individual female sex workers HIV tested, of whom 9.5% (2,363/24,979) newly tested HIV positive. Of these 2,363 women, 55.5% (1311/2,363) were offered and gave consent for a sample to be taken for DBS recency and viral load testing, among whom 11.7% (153/1,311) were classified as having a recent infection. A subset of 464 women were offered and consented to paired sample collection, among whom 10.1% (47) and 12.3% (57) of plasma and DBS samples, respectively, were classified as recent. Overall, categorical determination was good, with 97% of results concordant. Of 58 women with paired sample collection who had a test result classified as recent, 46 (79.3%) were concordant recent on both DBS and plasma, with 12 (20.7%) being discordant. Of these 12 women's samples, 11 were deemed long-standing by the plasma assay but recent by the paired DBS, and one deemed long-standing by DBS but recent by the paired plasma sample. On average, plasma samples had a higher normalised optical density than DBS samples (mean difference of 0.53). Depending on use-case and setting, there are trade-offs when considering DBS or plasma-based samples between test performance and ease of implementation. Our data can help inform statistical adjustments to harmonise cut-offs on DBS and plasma assays, thereby improving the use and interpretation of recency assays in population-level HIV surveillance activities
Acceptability of Digital Adherence Technologies to support people with drug-susceptible TB in South Africa.
Get PDFBACKGROUND: Tuberculosis (TB) remains a challenge in South Africa, with an estimated 280,000 new cases reported in 2022. Digital Adherence Technologies (DATs) may be important tools to improve adherence to TB treatment. However, there is limited knowledge about facilitators and barriers to implementing these technologies in South Africa. METHODS: This qualitative study was embedded within the Adherence Support Coalition to End TB cluster-randomised trial which implemented the two technologies: a smart pillbox and/or a cell phone-based strategy similar to 99DOTS (labels), plus differentiated care, to support people with drug-sensitive TB (PWTB). In-depth interviews were conducted with purposively sampled participants comprising PWTB, Healthcare Workers (HCWs) and stakeholders. Inductive thematic analysis was used for data analysis, while the Unified Theory of Acceptance and Use of Technology (UTAUT) framework served as the overarching framework to synthesize and summarise the findings. FINDINGS: Sixty-eight interviews were conducted: 35 with PWTB and 33 with HCWs and stakeholders. Facilitating factors for the pillbox were alarm reminder, storage, ease of use, not requiring a phone, social support, and portability. Barriers to the pillbox were that some found the box unportable and others experienced box malfunctioning. Facilitating factors for the labels were ease of use among the young, daily confirmation messages, social support, privacy, and portability. Barriers to implementing these DATs were older age, illiteracy, forgetting to send the SMS, lacking understanding, no cell phone access, power cuts, and unresolvable technical glitches. While differentiated care improved the client-provider relationship, some PWTB felt home visits were stigmatising. HCWs and stakeholders expressed willingness to scale up DATs because they improved their working conditions, and it was advantageous for the PWTB. CONCLUSIONS: Smart pillbox and labels had features which favoured their acceptability and there were also DAT specific barriers. DATs may improve person-centredness in TB care. Future guidelines should consider acceptability, differing situations, and allowing flexibility to possibly increase uptake and utilisation of DATs
The climate and health nexus in Europe and central Asia: a technical brief
Get PDFThis document summarizes the key evidence of the multiple links between climate change and health in Europe and central Asia.
It was produced to provide background information on the current knowledge about climate-related health effects for the Pan-European Commission on Climate and Health (PECCH) – an independent advisory group convened by the WHO Regional Office for Europe to raise the political profile, awareness and support for stronger action to address the health impacts of climate change
Clinical Stage of Retinoblastoma Based on Presenting Signs of 4578 Patients from 121 Countries.
Get PDFPURPOSE: To investigate the associations between presenting signs and clinical stage of retinoblastoma at diagnosis in a global sample of patients with retinoblastoma.
DESIGN: Cross-sectional analysis.
PARTICIPANTS: Treatment-naïve children who were diagnosed with retinoblastoma at 1 of 259 retinoblastoma referral centers across 121 countries during 2017 and 2019.
METHODS: Presenting characteristics of patients who were diagnosed with retinoblastoma incidentally in 2017 and 2019 from 2 cross-sectional studies were analyzed. We examined the associations between presenting clinical sign (leukocoria, strabismus, orbital mass, orbital cellulitis, red eye, iris color change, and hyphema) and presenting stage of retinoblastoma.
MAIN OUTCOME MEASURES: Main outcome measures included frequency of clinical and pathologic stage per the American Joint Committee on Cancer Staging Manual, Eighth Edition; extraocular stage per the International Retinoblastoma Staging System (IRSS); and intraocular classification at presentation.
RESULTS: A total of 4578 patients with retinoblastoma were included, 54.4% of whom were male, with a median age at presentation of 23.1 months. Patients with orbital mass and orbital cellulitis presented at later stages compared with those with leukocoria and strabismus. All signs, except for orbital mass, were seen more commonly in patients with curable disease (IRSS stages 0, I, and II): strabismus, 94.8%; leukocoria, 90.1%; iris changes, 89.7%; hyphema, 84.2%; red eye, 82.1%; orbital cellulitis, 66.7%; and orbital mass, 33.7%. Leukocoria was the most common presenting sign regardless of national income level, and the second most common sign was strabismus in high-income countries and orbital mass in low-income countries.
CONCLUSIONS: Any child with unexplained orbital cellulitis, persistent red eye, unexplained hyphema, orbital mass, or other changes in the iris or anterior chamber of the eye should undergo a dilated fundus examination to rule out retinoblastoma. Some patients with these signs can present with early stage and curable disease.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article
Trachoma prevalence surveys in 15 indigenous and non-indigenous evaluation units in Brazil, 2018-2023.
Get PDFBACKGROUND: To provide the groundwork for a future declaration of elimination of trachoma as a public health problem in Brazil, we conducted house-to-house surveys following WHO methodological guidance.
METHODS: An observational cross-sectional study was conducted in 10 non-indigenous and five indigenous evaluation units (EUs) from 2018 to 2023; data on six EUs are reported here for the first time. Two-stage cluster sampling was used: 30 clusters per EU, and 30 households per cluster. We estimated the prevalence of trachomatous inflammation-follicular (TF) in 1-9-y-olds and trachomatous trichiasis (TT) unknown to the health system in those aged ≥15 y. Data on sanitary conditions were collected in household interviews.
RESULTS: In all EUs, TF prevalence was below the elimination threshold (5%). TT prevalence was lower than the 0.2% threshold in 14 EUs. In 'Noroeste Cearense' mesoregion, TT prevalence was 0.22% (95% CI 0.06 to 0.44%), but statistical analysis showed a 58% likelihood of TT elimination in this EU. In three indigenous EUs, >10% of households had no sanitary facilities and high percentages of open defecation.
CONCLUSIONS: It is highly likely that trachoma has been eliminated as a public health problem in all the EUs surveyed. The findings on sanitary conditions mandate public policies to overcome socioenvironmental inequalities