Comprehensive Disease Control Research Articles

Elimination of Decapod iridovirus 1 (DIV1) infection at high water temperature: a new environmental control strategy

AbstractDecapod iridovirus 1 (DIV1) poses a major challenge to sustainable shrimp farming and poses a serious hazard to aquaculture industry. This study investigated the complex interaction between DIV1 infection and water temperature, focusing on the effect of high temperature on DIV1 infection due to Penaeus monodon. Using models of latent and acute infection, the study revealed the response of P. monodon to DIV1 under different conditions. In the experimental set-up, the effect of high water temperature (34 ± 1 °C) compared with room temperature (26 ± 1 °C) was investigated. DIV1 replication was significantly inhibited in the high-temperature group (H), resulting in complete viral elimination within 15 days. DIV1 did not resurface even after return to room temperature (26 ± 1 °C), indicating sustained antiviral effects. Compared with the room temperature (26 ± 1 °C) group (N), the H group showed a 100% reduction in the incidence of latent and acute infection. Exposure to high water temperature directly impaired the viability of DIV1, enhancing the immune system of P. monodon, and expediting metabolic processes for efficient DIV1 clearance. The study highlights the significant inhibitory effects of high water temperature (34 ± 1 °C) on DIV1 infection in P. monodon, resulting in viral eradication. This discovery offers a potential strategy for mitigating DIV1 infections in shrimp aquaculture, prompting further investigation into underlying mechanisms. Optimising parameters and protocols for high-temperature treatment is crucial for viral control. Exploring the broader implications of the findings on other viral infections in crustacean aquaculture could provide valuable insights for comprehensive disease prevention and control.

P678 Long-term efficacy, safety and health-related quality of life in patients who achieved comprehensive disease control with filgotinib in SELECTION: analysis of ~3 years in SELECTIONLTE

Abstract Background Filgotinib (FIL), an oral, once-daily, Janus kinase 1 inhibitor, was approved for Ulcerative Colitis (UC) treatment after the phase 2b/3 SELECTION trial (NCT02914522). In SELECTION, a greater proportion of FIL200 mg (FIL200)-treated than placebo-treated patients achieved comprehensive disease control (CDC), a stringent multi-component endpoint. We examined the long-term outcomes of achieving CDC in patients continuing on FIL200 in the ongoing long-term extension (LTE) study SELECTIONLTE (NCT02914535). Methods This interim analysis included adult patients with UC who completed SELECTION and received ≤144 weeks of FIL200 in the LTE (up to data cut-off 24/02/22). CDC (biomarker remission, endoscopic improvement, IBDQ remission and partial Mayo Clinic Score [pMCS] remission achieved concurrently) was assessed at SELECTION week 58 (LTE baseline [BL]). Mean pMCS and IBDQ score, use of corticosteroids (CS) and incidence of TEAEs and serious TEAEs in the LTE were compared between SELECTION CDC achievers and non-achievers. A mixed model for repeated measures was fitted on pMCS and IBDQ score, with CDC achiever status, study visit and the interaction between CDC achiever status and study visit as fixed effects; p values were nominal. Results We analysed 148 patients (CDC achievers, n=41; CDC non-achievers, n=107). Mean pMCS was stable in CDC achievers (0.44, LTE BL; 0.50, LTE week 144) and decreased in CDC non-achievers (1.49, LTE BL; 0.77, LTE week 144; Figure). Mean IBDQ score was stable in CDC achievers (204.05, LTE BL; 197.21, LTE week 144) and increased in CDC non-achievers (181.55, LTE BL; 196.37, LTE week 144; Figure). There was a significant beneficial effect of achieving CDC on pMCS and IBDQ score overall (pMCS: fixed effect estimate: −0.5542, p=0.0025; IBDQ score: fixed effect estimate: 13.1585, p=0.0042). There was a significant interaction between achieving CDC and study visit for IBDQ score (p=0.0183), with the benefit of achieving CDC lessening by week 144. Generally, a lower proportion of CDC achievers used CS than non-achievers; 2.4–7.3% of CDC achievers used CS vs 1.9–15.9% of CDC non-achievers. Incidence of TEAEs and serious TEAEs were stable over time and similar between CDC achievers and non-achievers. Conclusion Follow-up for ~3 years showed high levels of long-term benefit with continued FIL200 treatment. Achieving comprehensive disease control at the end of the randomized trial with FIL200 was associated with long-term efficacy, improved HRQoL and low overall use of CS. This may demonstrate the value of filgotinib-induced achievement of CDC in UC disease course. The safety profile of FIL200 was consistent between CDC achievers and non-achievers, suggesting an acceptable long-term benefit–risk profile.

P772 Comprehensive disease control in patients with Ulcerative Colitis: refinement of a multi-component endpoint using data from the filgotinib SELECTION trial

Abstract Background Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement. We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). Methods CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was visualized in UpSet plots. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components). Results At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve pMCS remission compared with 5.0%, 10.1% and 6.0% who did not achieve IBDQ remission, biomarker remission and endoscopic improvement, respectively (Figure). Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions. Conclusion CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

P734 Super-responders in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab maintenance therapy: A post hoc analysis of the LIBERTY-CD study

Abstract Background The LIBERTY-CD study demonstrated a broad level of benefit for subcutaneous (SC) infliximab (IFX) maintenance therapy compared with placebo in patients (pts) with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous IFX induction. Characterising subgroups of pts with different levels of response could help to better position SC IFX therapy. Methods This was a post hoc analysis of 231 pts from the CT-P13 SC arm of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019). Unsupervised group-based trajectory modelling (GBTM) was conducted to deconvolute cohort-level data into response trajectories. Longitudinal patient reported outcomes (PRO-2: abdominal pain and stool frequency) were used to investigate whether pts who received SC IFX maintenance therapy cluster into response trajectories. Efficacy endpoints (clinical remission, endoscopic response and remission, corticosteroid-free remission and comprehensive disease control [CDC] rate) were analysed and compared between different trajectories. Trough levels of IFX (TLI) were evaluated by trajectory throughout the treatment period. Baseline characteristics were analysed in a descriptive manner to explore predictors for super-response. Results Four distinct trajectories were clearly separated and stabilised around Week (W) 10–14 (Figure): rapid and sustained improvement (super-responders, n=61), rapid, but slightly less drastic than super-responders, then sustained improvement (fast responders, n=56), gradual then sustained improvement (slow responders, n=63) and partial improvement during the maintenance phase (limited responders, n=51). Super-responders had the highest rates of W54 clinical remission (73.8%; p=0.002), endoscopic response (63.9%; p=0.009), corticosteroid-free remission (63.6%; p=0.007), endoscopic remission (42.6%; p=0.094) and CDC (37.7%; p=0.013) among trajectories (Table). Super-responders also maintained the highest TLI from W10 throughout the maintenance period. Super-responders showed a trend towards lower baseline body weight, body mass index and oral corticosteroid use, but higher Crohn’s Disease Activity Index score and prior biologic/Janus kinase inhibitor use compared to other trajectories. Conclusion Distinct subpopulations with different levels of responses were detected by GBTM using data from a large group of pts with moderate-to-severe active CD who were treated with SC IFX for 1 year. Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response.

Stereotactic Radiosurgery of Multiple Brain Metastases: A Review of Treatment Techniques.

The advancement of systemic targeted treatments has led to improvements in the management of metastatic disease, particularly in terms of survival outcomes. However, brain metastases remain less responsive to systemic therapies, underscoring the significance of local interventions for comprehensive disease control. Over the past years, the threshold for treating brain metastases through stereotactic radiosurgery has risen. Yet, as the number of treated metastases increases, treatment complexity and duration also escalate. This trend has made multi-isocenter radiosurgery treatments, such as those with the Gamma Knife, challenging to plan and lengthy for patients. In contrast, single-isocenter approaches employing linear accelerators offer an efficient and expeditious treatment option. This review delves into the literature, comparing different linear-accelerator-based techniques with each other and in relation to dedicated systems, focusing on dosimetric considerations and feasibility.

S917 Mirikizumab Achieved Comprehensive Disease Control in Patients With Ulcerative Colitis From Phase 3 LUCENT-1 and LUCENT-2 Trials

S917 Mirikizumab Achieved Comprehensive Disease Control in Patients With Ulcerative Colitis From Phase 3 LUCENT-1 and LUCENT-2 Trials

Global, regional, and country-level cost of leptospirosis due to loss of productivity in humans.

Leptospirosis, a prevalent zoonotic disease with One Health priority and a disease of poverty, lacks global economic burden estimates. This study aims to determine the global, regional, and country-level cost of leptospirosis due to loss of productivity. The cost of leptospirosis due to loss of productivity (referred to as productivity cost hereafter) was estimated by converting the disability-adjusted life years (DALYs) lost due to leptospirosis to a monetary value using the per capita gross domestic product (GDP). The country-specific DALYs lost were obtained from the global burden of leptospirosis study published previously. Non-health GDP per capita (GDP- per capita health expenditure) was used for the cost conversion of DALYs. Country-specific GDP and health expenditure data were obtained from the World Bank data repositories. Estimates were done using both nominal and international dollars. The estimated global productivity cost of leptospirosis in 2019 was Int$ 29.3 billion, with low and high estimates ranging from Int$ 11.6 billion to 52.3 billion. China (Int$ 4.8 billion), India (Int$ 4.6 billion), Indonesia (Int$ 2.8 billion), Sri Lanka (Int$ 2.1 billion), and the United States (Int$ 1.3 billion) had the highest productivity cost due to leptospirosis. Eight out of 10 countries with the highest burden were in the Asia-Pacific region. In addition, lower-middle-income countries had an annual productivity cost of Int$ 13.8 billion, indicating that the disease is poverty-related. Although significant, the cost estimate due to loss of productivity is merely a fraction of the overall economic burden of this disease, which also includes other direct, indirect, and intangible costs. The existing partial estimates of the different components of economic cost suggest a profound economic burden that demands the inclusion of leptospirosis in the global health agenda for comprehensive disease control and prevention efforts, including vaccine development.

Pathogenicity, Mycotoxin Production, and Control of Potato Dry Rot Caused by Fusarium spp.: A Review.

Fusarium dry rot is one of the major potato diseases during storage after harvest, which not only results in quality degradation but also causes great economic losses. The disease can be elicited by some species of Fusarium, and the pathogenic fungi of Fusarium causing potato dry rot are considerably diverse in various countries and regions. The disease caused by Fusarium spp. is associated with mycotoxins accumulation, which has phytotoxic and mycotoxic effects on humans and animals. Chemical synthetic fungicide is considered the main control measure for the Fusarium dry rot of potato; nevertheless, it is unfortunate that persistent application inevitably results in the emergency of a resistant strain and environmental contamination. A comprehensive disease control strategy includes potato cultivar selection, appropriate cultural practices (crop rotation, cultivate pattern, fertilization, and irrigation), harvesting processes and postharvest treatments (harvesting, classification, packaging, wound healing), and storage conditions (environmental disinfection, temperature, humidity and gas composition) along with the application of fungicide pre-harvest or post-harvest. Recently, emerging studies have indicated that eco-friendly strategies include physical control, chemical methods (such as the application of generally-recognised-as-safe (GRAS) compounds or chemical (elicitors) and biological control have been introduced to combat the Fusarium dry rot of potato.

Long-term sentinel surveillance of enteroviruses in Gwangju, South Korea, 2011–2020

Human enteroviruses (EVs) are associated with a broad spectrum of diseases. To understand EV epidemiology, we present longitudinal data reflecting changing EV prevalence patterns in South Korea. We collected 7160 specimens from patients with suspected EV infections in ten hospitals in Gwangju, Korea during 2011–2020. RNA extraction and real-time reverse transcription polymerase chain reaction using EV-specific probes and primers were performed. EV genotyping and phylogenetic analysis were performed; EVs were detected in 3076 samples (43.0%), and the annual EV detection rate varied. EV infection rates did not differ with sex, and children aged ≤ 4 years were the most prone to EV infection; this trend did not change over time. Overall, 35 different EV types belonging to four distinctive species and rhinoviruses were identified. Although serotype distribution changed annually, the most frequently observed EVs were EV-A71 (13.1% of the cases), CVA6 (8.3%), CVB5 (7.6%), CVA16 (7.6%), CVA10 (7.5%), E18 (7.5%), E30 (7.0%), and E11 (5.0%) during 2011–2020. The predominant EV genotypes by clinical manifestation were CVB5 for aseptic meningitis; EV-A71 for hand, foot, and mouth disease cases; and CVA10 for herpangina. These results will aid the development of vaccines against EV infection and allow comprehensive disease control.

P624 Investigating the symptom burden among European patients with moderate-to-severe Crohn’s disease using a real-world survey

Abstract Background Despite treatment, patients with Crohn’s disease (CD) experience symptoms that affect their health-related quality of life (HRQoL). Understanding how CD affects HRQoL reveals valuable insight into disease impact. We aimed to examine the disease burden in patients with moderate-to-severe CD in remission vs not in remission using real-world, gastroenterologist (GE)- and patient-reported data. Methods Data were drawn from the Adelphi Inflammatory Bowel Disease (IBD) Disease Specific Programme,1 a point-in-time survey conducted in France, Germany, Italy and Spain from October 2020 to March 2021. GEs collected data from the next 5–8 consecutive patients (≥18 years old, not involved in clinical trials) with a CD diagnosis who they saw in clinical practice. GEs reported patient demographics, clinical characteristics (including remission status) and treatment history. Patients completed questionnaires on their treatment satisfaction, symptoms and HRQoL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] and EQ-5D scores). Scores were compared among patients in remission vs not in remission using propensity score matching (PSM). Results Overall, 133 GEs reported on 538 patients with CD (Table 1). Overall, 66.0% of patients were employed, and of those not working, 24.3% were not working due to CD. Most patients (70.9%) had received ≥2 lines of treatment and 43.3% of patients were receiving a tumour necrosis factor (TNF) inhibitor. Of 427 patients from whom complete data were available and were therefore included in PSM analyses, 70.0% (n=299) were in remission. Although patients in remission were generally less likely than those not in remission to experience CD symptoms, they were still moderately likely to experience symptoms such as fatigue/tiredness and abdominal pain (Figure 1). Similarly, whilst patients in remission had better mean SIBDQ and EQ-5D scores than those not in remission, their scores still indicated diminished HRQoL (Figure 2). Of patients for whom symptom data were provided, 39.2% were either not satisfied with their current treatment or believed that better disease control could be achieved. A higher proportion of patients who were dissatisfied with their treatment reported residual symptoms than those who were satisfied, especially abdominal pain, non-bloody diarrhoea and fatigue/tiredness (Figure 3). Characteristics of patients in remission with mucosal healing were similar regardless of whether remission was confirmed by endoscopy. Conclusion A substantial proportion of patients with CD, even those in remission, experience high symptom burden and diminished HRQoL despite treatment. There is a need for therapies that provide more comprehensive disease control. 1. Anderson P et al. Curr Med Res Opin 2008:24;3063–72.

Construction of IPA decision model for diabetes prevention and control based on economy and importance

Objective: To determine the priority of diabetes prevention and control measures in the perspective of the economy and importance, and provide theoretical support for guiding relevant departments to implement measures based on actual economic level. Methods: An online survey was conducted on the importance, feasibility and implementation of major chronic disease prevention and control measures in 488 national demonstration areas for comprehensive chronic disease prevention and control. The content of the survey was divided into individual and group levels, with 10 dimensions and 44 measures, to obtain the scores of the economy and importance. IPA model was used to divide the dimension index of diabetes prevention and control into quadrants. The standardized factor load coefficient of the second-order confirmatory factor analysis was used to determine the priority of dimension index in the same quadrant. The priority of prevention and control measures in each dimension was determined by the discriminant parameter of project response theory. Results: The mean scores of economy and importance were 66.50 and 89.94, respectively, and the matrix was divided into four quadrants. The first quadrant was the "highest priority" with high importance and economy, including medical insurance and family doctors, health education, high-risk detection and intervention, patient management and community action. The second quadrant was characterized as high importance but low economy, which was the priority for improvement, including only one dimension of complication screening. The third quadrant was the lowest priority due to low importance and economy, including personal health service evaluation and follow-up, environmental support, diabetes co-infection prevention and glycemic policy. The last quadrant had low importance but high economy, which was the second improvement level. The priority measures in different quadrants were: (1) the highest priority: blood lipid control, occupational site, prevention and control work plan, blood glucose testing, family doctor contract service; (2) the priority improvement: annual neuropathy screening; (3)the lowest priority: universal access to risk scoring, healthy eating, healthy dining innovations and tuberculosis screening. Conclusion: IPA model can be used to construct a decision-making model for diabetes prevention and control and determine the priority of corresponding measures.

Grapevine viruses in Mexico: studies and reports

Objective: To contribute to the knowledge of the diversity of viruses and the viral diseases reported in grapevines in Mexico, in order to benefit producers and develop comprehensive viral disease control strategies. Design/methodology/approach: The literature search was conducted in databases such as Scopus, Google Scholar, and EBSCO host, using the following keywords alone or in combination: "virus", "plant", "grapevine", and "Mexico". In addition, the INIFAP database was consulted, alongside undergraduate and postgraduate dissertation theses. Results: Only one academic file was found published in an indexed international journal, using the publication finder software; the report corresponds to a grapevine virus present in Mexico. However, based on all the consulted sources, several viral diseases associated with nine grapevine viruses have been reported in Mexico. These species have been grouped into seven genera and six families. The reports come from Aguascalientes (56%) and Baja California (44%). Three registered viral species are associated with the leafroll complex, three with rugose wood, one with fleck, one with infectious degeneration, and one with red blotch disease. Findings/conclusions: Several grapevine viruses associated with major diseases have been reported in Mexico. Unfortunately, most of the reports lack detail and follow-up, and they are not readily available for international researchers; therefore, the lack of knowledge about this subject in Mexico is significant. Monitoring the epidemiology of viral diseases in the grapevine —a national and international relevant crop— is necessary.

Analysis of Healthy Housing and TB Prevalence in Yogyakarta City

Environmental health is one of the determinants factors toward the public health status. Transmission of tuberculosis (TB) is influenced by environmental factors. Based on previous TB data in local study, it shows that urban areas (urban) have a high case rate. Therefore, this study aims to reveal the disparity of urban TB sufferers, especially in the city of Yogyakarta based on indicators of the physical environment of the house from the coverage of healthy households. The method of study used is quantitative descriptive analysis of secondary data. The data used were the physical environment of the house which is obtained from healthy housing data and TB prevalence data in Yogyakarta City. The secondary data spread over 18 Public Health Centers in Yogyakarta City. The data collected include healthy housing data and BTA (+) cases data in the study scope using total sampling technique. Based on the trend analysis, it was found that there was a significant trend in data. The higher percentage of non-healthy housing coverage wasassociated in line with the higher the TB prevalence rate. It can be concluded that the physical environment factor of the house as an indicator of a healthy housing is closely related to the incidence of TB in Yogyakarta City. Environmental quality studies need to be carried out for comprehensive TB disease control towards elimination (End TB 2030) which is in line with national programs and SDGs goals.

Reduction of Chronic Wasting Disease Prion Seeding Activity following Digestion by Mountain Lions.

ABSTRACTChronic wasting disease (CWD) is a transmissible prion disease first observed in the 1960s in North America. This invariably fatal disease affects multiple cervid species in the wild and in captivity. In addition to the several known transmission pathways involving cervid host species, prions have been detected in the feces of crows and coyotes after consumption of experimentally spiked tissues. This raises questions about the role of cervid consumers in the perpetuation of CWD. Mountain lions have been shown to preferentially select CWD-infected prey and are also apparently resistant to infection. In this study, two captive mountain lions were fed ground mule deer muscle tissue spiked with brain-derived CWD prions, and lion feces were collected for 1 week afterward. The input brain and resulting fecal materials were analyzed using the highly sensitive real-time quaking-induced conversion (RT-QuIC) assay to quantify prion seeding activity. We recovered only 2.8 to 3.9% of input CWD prions after passage through the mountain lions’ gastrointestinal tracts. Interestingly, CWD prions were shed only in the first defecation following consumption. Our data support the possibility that mountain lions feeding upon infected carcasses could excrete CWD prions in their feces over a short period of time but also suggest that most of the ingested prions are eliminated or sequestered by this large predator.IMPORTANCE CWD prions appear to spread naturally among susceptible cervid species in captivity and in the wild. A better understanding of all the ways these prions move, persist, and subsequently infect target species through the environment is critical to developing comprehensive disease control strategies. In our study, we show limited, transient pass-through of CWD prions in an apex predator, the mountain lion, using the highly sensitive RT-QuIC assay on feces collected after lions were fed prion-spiked muscle tissue. Prions were detected in feces only in the first defecation after exposure. Moreover, the amount of CWD prions recovered in feces was reduced by >96% after passing through the lion digestive system. This indicates that mountain lions may have some potential to distribute CWD prions within their home ranges but that they also effectively eliminate most of the CWD prions they consume.

The importance of vaccine stockpiling to respond to epidemics and remediate global supply shortages affecting immunization: strategic challenges and risks identified by manufacturers

While stockpiling vaccines adds another layer of complexity to vaccine manufacturing, it constitutes a crucial component of comprehensive disease preparedness and control strategies in public health management. Stockpiling provides the ability to immediately respond to epidemics, disease outbreaks, vaccine shortages or stock-outs at local, regional or global levels. Some stockpiles are static, not shipped until an emergency occurs; other stockpiles are rotating with vaccines used in on-going routine immunization programmes. Programmatic use indicates which vaccines to stockpile, the nature of the stockpile and the amount of vaccine to be held at any time. For immediate shipment, fully released product must be stockpiled with the challenge of monitoring remaining shelf-life requirements and the potential risk of expiry. Existing stockpiles are managed and financed globally under the purview of international organizations in the global immunization community, except for buffer stocks held by manufacturers for short periods. The added challenges to manufacturers of stockpiling vaccines, including storage, human resources and other related costs including vaccine destruction when no longer useable, needs to be recognized. This is all the more so with the likelihood of vaccine stockpiling becoming more prominent with changing disease patterns due to climate change and population movements, as well as the significant investment in the research and development of new epidemic prevention vaccines. While vaccine stockpiles managed and financed globally provide rapid response to country requests, more attention is needed in the future to ways that vaccine stockpiling can be brought under the direct purview of individual countries or regional groupings.

Extra-Articular Manifestations and Comorbidities in Psoriatic Disease: A Journey Into the Immunologic Crosstalk.

Psoriatic arthritis (PsA) is a chronic inflammatory disease primarily affecting peripheral and axial joints, with the possible presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease. Recently, the concept of psoriatic disease (PsD) has been proposed to define a systemic condition encompassing, in addition to joints and EAMs, some comorbidities (e.g., metabolic syndrome, type II diabetes, hypertension) that can affect the disease outcome and the achievement of remission. EAMs and comorbidities in PsA share common immunopathogenic pathways linked to the systemic inflammation of this disease; these involve a broad variety of immune cells and cytokines. Currently, various therapeutics are available targeting different cytokines and molecules implicated in the inflammatory response of this condition; however, despite an improvement in the management of PsA, comprehensive disease control is often not achievable. There is, therefore, a big gap to fill especially in terms of comorbidities and EAMs management. In this review, we summarize the clinical aspects of the main comorbidities and EAMs in PsA, and we focus on the immunopathologic features they share with the articular manifestations. Moreover, we discuss the effect of a diverse immunomodulation and the current unmet needs in PsD.

Analysis of comprehensive surveillance results of respiratory tract infectious diseases in Taizhou, 2012-2019

Objective To understand the epidemiological characteristics of influenza-like illness (ILI) cases and severe acute respiratory infection (SARI) cases in Taizhou, so as to provide a basis for scientific prevention and control strategies. Methods The basic information of ILI and SARI cases and throat swab specimens were collected from the sentinel hospital and 13 respiratory pathogens were detected by RT-PCR method.χ2 test was used as statistical analysis method. Results From April 2012 to December 2019, with epidemic peaks in autumn and winter, the percentages of ILI visits (ILI%) and SARI visits (SARI%) were 7.27% and 2.44%, respectively. Finally, 956 ILI case specimens and 557 SARI case specimens were detected. The positive detection rates of the two types of cases were 50.84% (486/956) and 39.14% (218/557), separately. Streptococcus pneumoniae (SP), influenza virus (Flu), Haemophilus influenzae (HI) and Human rhinovirus (HRV) were the dominant pathogens in Taizhou city from April 2012 to December 2019, and their detection rates were 14.81%, 9.25%, 9.39% and 7.73%, respectively. The total mixed infection rate was 30.11% (212/704), which was mainly caused by SP complicated with other pathogenic infections. The positive rate of pathogen detection in the low-age group was higher than that in the high-age group, and the detection rate of children under 5 years old was 34.83% (χ2=54.47, P Conclusions The incidence of comprehensive respiratory tract surveillance in sentinel hospitals in Taizhou City showed that the peak of the epidemic was in autumn and winter, and SP, Flu, HI, and HRV were main pathogens in this area. In the age group under 15 years old, the detection rate was higher. Comprehensive respiratory disease prevention and control measures should be taken for key populations.

Frailty as a novel predictor of achieving comprehensive disease control (CDC) in rheumatoid arthritis

BackgroundFrailty is a construct recently introduced in the context of inflammatory joint diseases. To date, it is not clear if frailty can act as a negative factor in the achievement of comprehensive disease control (CDC) in patients suffering from rheumatoid arthritis (RA).AimTo verify whether frailty is a factor hindering the achievement of CDC in patients with RA starting a biologic drug.MethodsRA patients requiring a treatment with a biologic drug were included. Patients were classified as achieving or not achieving CDC after 12 months of treatment. Patients were classified as non-frail, mildly frail, moderately frail and severely frail according to the Comprehensive Rheumatologic Assessment of Frailty (CRAF). Frailty was tested using the Mann–Whitney or Kruskal-Wallis test for continuous variables and chi-square test or Fisher’s exact test for comparison with categorical variables. A multivariable logistic regression was performed to identify factors associated with prediction of CDC achievers.ResultsA total of 214 RA patients were followed for 12 months, 14.5% achieved CDC. Eighty-four (39.3%) patients were non-frail, 57 (26.6%) were mildly frail, 14 (6.5%) were moderately frail and 59 (27.6%) were severely frail. The multivariable logistic regression analysis identified the CRAF score at baseline as an independent variable for CDC achievement at 12 months (p = 0.0040).DiscussionFrailty is a frequent condition in RA patients and reduces the chances of achieving CDC.ConclusionsFrailty, measured by CRAF, reduced the likelihood of CDC achievement in RA patients treated with a biologic agent.Key Points• Frailty is an under-researched condition in rheumatoid arthritis affecting more than 60% of patients.• Frailty is a condition that hinders the achievement of comprehensive disease control after 1 year of treatment with biological drugs in patients with rheumatoid arthritis.

Jujube witches' broom phytoplasma effectors SJP1 and SJP2 induce lateral bud outgrowth by repressing the ZjBRC1-controlled auxin efflux channel.

Comprehensively controlling phytoplasma-associated jujube witches' broom (JWB) disease is extremely challenging for the jujube industry. Although the pathogenesis of phytoplasma disease has been highlighted in many plant species, the release of lateral buds from dormancy under JWB phytoplasma infection has not been characterized in woody perennial jujube. Here, two 16SrV-B group phytoplasma effectors, SJP1 and SJP2, were experimentally determined to induce witches' broom with increased lateral branches. In vivo interaction and subcellular localization analyses showed that both SJP1 and SJP2 were translocated from the cytoplasm to the nucleus to target the CYC/TB1-TCP transcription factor ZjBRC1. The N- and C-terminal coiled-coil domains of SJP1 and SJP2 were required for the TCP-binding ability. ZjBRC1 bound directly to the auxin efflux carrier ZjPIN1c/3 promoters and down-regulated their expression to promote the accumulation of endogenous auxin indole-3-acetic acid in jujube calli. Furthermore, JWB phytoplasma infection suppressed ZjBRC1 accumulation and induced ZjPIN1c/3 expression to stimulate lateral bud outgrowth. Therefore, SJP1 and SJP2 stimulate lateral bud outgrowth, at least partly, by repressing the ZjBRC1-controlled auxin efflux channel in jujube, representing a potential strategy for comprehensive phytoplasma-associated disease control and a resource for gene editing breeding to create new cultivars with varying degrees of shoot branching.

Violence and abuse experiences and associated risk factors during the COVID-19 outbreak in a population-based sample of Norwegian adolescents

BackgroundThe lockdowns occurring across society because of the COVID-19 pandemic have had far-reaching consequences for children and adolescents. One immediate concern was what the impact of the comprehensive disease control measures on rates of violence and abuse against children and adolescents would be. ObjectiveWe aimed to establish rates of child abuse and degree of family conflict during the first COVID-19 lockdown spring 2020. Additionally, we aimed to investigate associations between preexisting and concurrent risk factors and abuse during these unique times. Participants and settingA total of 3545 Norwegian 13- to 16-year-olds participated in this study. A total of 1944 of these had provided data 1 year before the lockdown. MethodsWe used a web survey format to assess abuse exposure and associated risk factors. The survey was administered in schools during school hours in June 2020, shortly after the reopening of schools after the first lockdown. ResultsIn this sample 8.2% reported psychological abuse during lockdown, 2.4% had experienced physical abuse and 1.4% sexual abuse. For online sexual abuse, the rate was 5.6% during this time period. Adolescents did not report an increase in family conflict. Concurrently perceived family affluence and family risk factors were most strongly associated with physical abuse during lockdown (OR = 11.01(95% CI 5.32–22.84); OR = 5.36 (95% CI 2.69–10.67)), but also other types of child maltreatment. Analyses across assessment points suggested that prior victimization was the most accurate predictor of abuse experiences during lockdown (OR = 3.84 (95% CI 2.85–5.20)). ConclusionsThe negative consequences of the COVID-19 preventative measures struck the adolescent population unevenly. The findings underscore the need for targeted measures to mitigate the negative outcomes of health-related crises for adolescents in risk groups such as those with low family affluence and prior abuse experiences.