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Impact of evidence-based programmatic adaptations in addressing the persistence and recrudescence of trachoma in Kajiado County, Kenya.
Get PDFBACKGROUND: Confirmatory trachoma-plus surveys conducted in 2021 revealed persistent and recrudescent trachoma transmission in Kajiado West, South and Central subcounties. These findings prompted targeted investigations and programmatic adaptations to improve intervention effectiveness.
METHODS: Mass drug administration (MDA) coverage improvements were validated through Coverage Evaluation Surveys (CESs). Impact was monitored via prevalence surveys from 2021 to 2024, which included ocular swabs and dried blood spots (DBS) from children. Ocular swabs were tested for Chlamydia trachomatis (Ct) using GeneXpert IV PCR, while DBS were analysed for anti-Pgp3 antibodies using a multiplex bead assay.
RESULTS: CESs showed significant increases in MDA coverage: Kajiado West (56.9% to 88.2%), South (81.2% to 95.3%) and Central (69.3% to 95.3%). Trachomatous inflammation-follicular prevalence declined in all subcounties-Kajiado West (13.8% to 6.6%), South (8.1% to 5.2%), Central (18.0% to 8.0%)-and Ct infection rates dropped below 1%. Seroconversion rate trends varied, with increases in West and Central and a decrease in South.
CONCLUSIONS: The programmatic adaptations were effective in achieving high treatment coverage and in reducing active trachoma and infection, with varying trends in transmission dynamics. This resulted in major progress towards elimination of trachoma and areas with residual infection requiring closer monitoring to sustain progress
The impact of primary care networks on emergency hospitalisations in the English NHS: An interrupted time series analysis.
Get PDFRecent years have seen an emergence of collaborative primary care models in the English National Health Service and other international health systems. Primary Care Networks (PCNs) were introduced in England in July 2019, marking the first time collaboration between general practices was incentivised through a nationwide policy. While participation was not mandatory, nearly all general practices joined a PCN, largely due to strong financial incentives. Our study aim was to estimate the impact of PCNs on emergency hospitalisations using an interrupted time series design. Quarterly data between October 2016 and March 2023 from the North West London Whole Systems Integrated Care dataset was used to construct two primary outcomes: all-cause and ambulatory care sensitive conditions (ACSC) emergency hospitalisations, as well as Accident and Emergency attendances, considered as a secondary outcome. Furthermore, we analysed whether the impact of PCNs varied based on practice characteristics. A reduction in all-cause and ACSC hospitalisations was observed following the PCNs' introduction, until the start of the COVID-19 pandemic. The analysis also revealed a smaller reduction in ACSC hospitalisations among practices with more deprived patient populations and larger populations of patients with long-term conditions. While PCNs' implementation appears to have led to a reduction in emergency hospitalisations in North West London, this effect was only observed in the very short term as it stopped with the COVID-19 pandemic. Future studies should examine the effect across England and evaluate their continued impact
COVID-19 diagnosis within five days of symptoms onset among healthcare workers in Malawi; Non-randomized control trial of self-testing using Ag-RDTs.
Get PDFEfficient and sustainable models of Corona Virus Disease of 2019 (COVID‑19) screening among healthcare workers (HCWs) such as self-testing are essential for averting transmission within and outside health care facilities. We compared the number of confirmed early COVID‑19 positive diagnoses (defined as COVID‑19 cases diagnosed within five days of symptoms onset) among HCW in self-testing arm using Antigen Rapid Diagnostic Test kits (Ag-RDT) and standard of care arm (SOC) who were offered COVID‑19 testing if they presented at the clinic with any COVID‑19 symptoms. Twelve primary healthcare facilities in Blantyre, Malawi, were purposively allocated (1:1) aiming for geographical and size balance in a 2-arm non-randomised cluster trial (ISRCTN: 17596113), available from https://doi.org/10.1186/ISRCTN17596113. Arm-1 was SOC and Arm-2 was COVID 19 self-testing (C19ST). HCWs in the C19ST arm had twice-weekly COVID‑19 Ag-RDT self-testing. The primary outcome compared by arm the harmonic mean number of early COVID‑19 positive diagnoses among HCWs. Analysis was by intention-to-treat using cluster-level summaries and t-test, with adjustment for imbalance. Participation was 99.8% among eligible HCWs across all facilities (1081/1083). Of the 1081 participating, 612 (56.6%) and 469 (43.4%) were in SOC and C19ST arm, respectively. Mean age was 35.5y (sd: 9.3); 183/612 (29.9%) in SOC were male, compared to 166/469 (35.3%) in C19ST; overall prior vaccination was 80.0% with no difference between SOC, (81.5%) and C19ST (78.0%). Follow-up at exit (12 weeks) was high (SOC: [94%]; C19ST: [87.6%]) and a harmonic mean of 1 and 4 HCWs had early COVID‑19 diagnosis in SOC and C19ST arms, respectively. COVID‑19 self-testing using Ag-RDTs provided a safe, quick, and reliable model for identifying early-onset symptomatic and asymptomatic COVID‑19 positive HCW. Self-testing was feasible to integrate for routine screening among HCW potentially reducing disruption to health services. This model has potential for wide scale up programmatically especially in resource-constrained settings
Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis.
Get PDFTick-borne encephalitis (TBE) is a viral infection of the central nervous system, caused by the tick-borne encephalitis virus (TBEV) presenting clinically as meningitis, meningoencephalitis, and meningoencephalomyelitis. To investigate genetic susceptibility to TBE, and its severe forms, we conducted a genome-wide association study in the European population comprising 1,600 TBE cases and 9,699 controls. We identified several suggestive (p < 1 × 10-5) intronic and exonic variants in ABCG1, the only gene significantly associated with TBE susceptibility. These variants were shown to influence ABCG1 expression in peripheral blood, a finding corroborated by RNA expression analysis. In vitro inhibition or silencing of ABCG1 significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of ABCG1 in TBEV biology. Additionally, we detected a genome-wide significant variant within TEX41, located downstream of ZEB1, associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity
A Mycobacterium tuberculosis Mbox controls a conserved, small upstream ORF via a translational expression platform and Rho-dependent termination of transcription.
No full textMagnesium is vital for bacterial survival, and its homeostasis is tightly regulated. Intracellular pathogens like Mycobacterium tuberculosis (Mtb) often face host-mediated magnesium limitation, which can be counteracted by upregulating the expression of Mg2+ transporters. This upregulation may be via Mg2+-sensing regulatory RNA such as the Bacillus subtilis ykoK Mbox riboswitch, which acts as a transcriptional "OFF-switch" under high Mg2+ conditions. Mtb encodes two Mbox elements with strong similarity to the ykoK Mbox. In the current study, we characterize the Mbox encoded upstream of the Mtb pe20 operon, which is required for growth in low Mg2+/low pH. We show that this switch operates via a translational expression platform and Rho-dependent transcription termination, which is the first such case reported for an Mbox. Moreover, we show that the switch directly controls a small ORF encoded upstream of pe20 We have annotated this highly conserved uORF rv1805A, but its role remains unclear. Interestingly, a homologous gene exists outside the Mbox-regulated context, suggesting functional importance beyond magnesium stress. Overall, this study uncovers a dual mechanism of riboswitch-regulation in Mtb, combining translational control with Rho-mediated transcription termination. These findings expand our understanding of RNA-based gene regulation in mycobacteria, with implications for pathogenesis and stress adaptation
Performance of the Self-Controlled Case Series With Active Comparators for Drug Safety Signal Detection Using Merative MarketScan Research Databases.
Get PDFBACKGROUND: Despite testing of epidemiological methods in US Claims databases for signal detection, such data sources have not become a routine capability. The Self Controlled Case Series (SCCS) is one of the most promising methods for drug safety signal detection using Real World Data, and incorporating active comparators could potentially improve its performance by addressing confounding by indication. OBJECTIVES: This study aims to evaluate the performance of the SCCS with and without active comparators for signal detection using US Merative MarketScan Commercial Claims and Medicare databases. METHODS: We applied the SCCS to macrolide and fluoroquinolone antibiotics, using amoxicillin and cefalexin as active comparators. In total, 7 drugs and 30 outcomes from all organ classes were selected. We developed a reference set of 104 positive controls and 58 negative controls, using a taxonomy framework to ensure the selected drug outcome pairs are theoretically well suited to the SCCS design. A two-year observation period with a 30-day risk window after each dispensing was used. Diagnostic performance was measured using sensitivity and specificity with respect to the product labels. RESULTS: The SCCS without active comparators achieved sensitivities of 0.73 and 0.72 and specificities of 0.68 and 0.62 in commercial and Medicare claims, respectively, for pairs with sufficient power. Active comparators increased specificity up to 0.84 and 0.86, respectively, in Commercial Claims and Medicare but decreased sensitivity to 0.45 and 0.36. CONCLUSIONS: MarketScan databases are potentially suitable for drug safety signal detection due to their large size and information contained. Using a carefully designed reference set of drug-outcome pairs well suited to the study design, the SCCS, while imperfect, performed comparably to optimal settings identified in previously published studies. Active comparators did not enhance overall performance but showed improved specificity by better controlling confounding by indication at the cost of reduced sensitivity
A Cross-Sectional Survey Exploring the Willingness of Hong Kong People to Use Teleconsultation in Primary Care During the COVID-19 Pandemic.
Get PDFObjectives: To investigate the willingness of the general Hong Kong population to use teleconsultation in primary care and the factors affecting their decisions and to ascertain the medical problems for which people will consider using teleconsultation in primary care. The study was a cross-sectional territory-wide random population survey on adults recruited through a computer-assisted telephone interview system. Outcome Measures: Outcomes were the proportion of the general Hong Kong population indicating their willingness to use teleconsultation in primary care; the drivers and barriers affecting their willingness; and the medical problems in primary care for which people would consider using teleconsultation. Results: After applying population weighting, 51.6% of the study respondents were found to be willing to use teleconsultation in primary care. The main drivers were possessing the perception that teleconsultation would serve the majority of their health problems (odds ratio [OR] = 3.693, p < 0.001), provision of government subsidy (OR = 3.567, p < 0.001), and ownership of a computer/tablet (OR = 2.116, p < 0.001). A major barrier for people's reluctance to use teleconsultation in primary care was having an education level of primary or below (OR = 0.388, p = 0.002). The majority of people had reasonable expectations on which medical conditions teleconsultation could be helpful but misunderstandings did exist. Conclusion: Our survey estimated that more than half of the general Hong Kong population was willing to use teleconsultation in primary care. Health care service providers and the government should address the drivers and barriers and clarify any misconceptions if teleconsultation is to be further developed in the Hong Kong primary care system
Accelerating access to diagnostic tools: perspectives from the joint international tropical medicine meeting 2023.
Get PDFAge at infection as a key predictor of cyst burden in pigs experimentally infected with Taenia solium.
Get PDFBACKGROUND: Taenia solium cysticercosis is a zoonotic parasitic disease with significant public health implications, particularly in endemic regions of low- and middle-income countries. In pigs, cyst burden varies widely, with most harboring fewer than 10 cysts and only a small fraction carrying high cyst loads. Age has been identified as a key factor influencing infection susceptibility. However, inconsistencies in previous studies have hindered clear characterization of infection patterns and immunity. In this study, we conducted controlled experiments involving the infection of pigs with T. solium eggs to evaluate the relationship between pig age and susceptibility to infection. METHODS: A total of 52 pigs from northern Peru, aged 4 to 22 weeks, were experimentally infected with T. solium eggs to examine age-related differences in cyst burden. Pigs were housed individually under controlled conditions and fed commercial pig diets. Infections were administered using an esophageal catheter, delivering 20,000 T. solium eggs in gelatin capsules. Six age groups were studied using a standardized egg pool to ensure consistency across infection rounds. After 10 weeks, necropsies were performed to count cysts in all muscles, the brain, and other organs. Weekly serological tests monitored seroconversion. Statistical models were used to analyze cyst counts and assess the effects of age and other predictors. RESULTS: The number of live, degenerated, and total cysts was overdispersed, making a negative binomial model the most suitable choice to represent the data and their dependence on age at infection. Younger pigs showed low median live cyst count, similar to older pigs, while median cyst burden increased in pigs infected at intermediate ages, around natural weaning age. The negative binomial regression showed that age and a covariate inversely related to age at infection were significantly associated with cyst count at necropsy. Other covariates such as egg pool viability and sex did not significantly affect model performance. Serological tests confirmed seroconversion in all pigs. CONCLUSIONS: Our results show that younger pigs display partial protection against the development of cysticerci compared to those infected at the natural weaning age (around 9 to 12 weeks of age). Additionally, infection susceptibility then decreases with age in a way that is consistent with previous literature
Two Decades Later: Long-Term Multisystem Sequelae and Subclinical Organ Dysfunction in Sudan Ebola Virus (SUDV) Survivors of the 2000 Outbreak.
Get PDFBackground: Despite repeated re-emergence of Sudan ebolavirus (SUDV), its long-term human toll remains under-characterised. We assessed multisystem clinical, biochemical, and psychosocial outcomes ~25 years after the 2000 Gulu outbreak. Methods: We conducted a cross-sectional evaluation of 45 survivors of laboratory-confirmed SUDV and 30 age- and gender-matched community controls from the same region. Symptoms were assessed as current at the study visit using a structured checklist; for each symptom present, we recorded severity and duration from onset to the visit date. Standardised clinical examinations, haematological and biochemical assessments, anxiety and depression screening, and structured interviews on social support and stigma were performed. Group comparisons were assessed with Wilcoxon rank-sum and χ2/Fisher's exact tests; correlations were assessed with Spearman's ρ. Findings: Core physiological indices (vital signs, BMI, blood pressure, and body temperature) and mental health were comparable between survivors and controls. Nevertheless, survivors reported ongoing symptoms, including joint pain and visual impairment each in 36% (16/45), fatigue in 18% (8/45), and neurological symptoms in 13% (6/45). Subclinical laboratory deviations centred on hepatic and platelet biology: elevated total bilirubin occurred in 14% of survivors versus 6.7% of controls; thrombocytopenia or platelet morphological abnormalities in 12% versus 3.3%; haemoglobin abnormalities in 6% versus 0%. Among survivors, albumin and mean platelet volume declined with age (both p ≤ 0.03). Psychological morbidity was low (normal anxiety 82% (37/45; and normal depression 80% (36/45). Yet a social paradox emerged, despite universal post-outbreak support, 98% (44/45) described enduring stigma. To minimise differential recall bias, symptom inventories were not collected from controls; consequently, between-group comparisons for symptom prevalence were not performed, and symptom inferences are restricted to survivors and framed descriptively. Interpretation: A quarter-century after infection, SUDV survivors show preserved systemic physiology but carry chronic musculoskeletal, sensory, and neurological sequelae, alongside a discrete subclinical profile implicating hepatic function and platelet biology. Psychological resilience coexists with near-universal, persistent stigma, indicating that material support did not achieve full psychosocial reintegration. Given the lack of virological and deep immune profiling, proposed pathogenetic mechanisms, such as antigen persistence or immune-mediated injury, remain speculative and hypotheses-generating only. These findings argue for survivor-centred long-term care, embedded with epidemic preparedness frameworks that integrate musculoskeletal rehabilitation, ophthalmic and neurological services with comprehensive mental health care, and sustained anti-stigma community engagement. This dissociation, including short-lived support alongside enduring stigma, indicates that humanitarian relief alone does not secure durable psychosocial reintegration and should be complemented by long-horizon, survivor-centred services and community engagement. Funding: This study was supported by the Coalition for Epidemic Preparedness Innovations (CEPI) under the Universal Protocol for Standardising Assays and Advancing Vaccine Immunogenicity Assessments for Emerging and Re-emerging Viral Threats, implemented through the Uganda Virus Research Institute (UVRI) as part of CEPI's Centralised Laboratory Network (CLN)