A retrospective cohort study of Epstein-Barr virus infection status and systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) and the Epstein-Barr virus (EBV) are very closely related. This study estimated the impact of EBV infection status on clinical manifestations and disease remission in patients with SLE. METHOD: A retrospective study was performed using electronic health records of patients with SLE. The SLE disease activity index (SLEDAI-2 K) was used to assess disease activity. VCAIgM or EAIgM positive or EBVDNA copies ≥ 50 IU/mL were defined as lytic infection group, EBNA-IgG or VCAIgG-positive and who were negative for both VCAIgM and EAIgM with EBVDNA copies < 50 IU/mL were defined as the latent infection group. The endpoint (disease remission) was defined as a decrease in SLEDAI-2 K score of ≥ 1 grade or ≥ 4 points from baseline. The association between EBV infection status and disease remission was assessed using propensity score weighting and multivariable Cox regression models. RESULTS: There were 75 patients with SLE in the EBV lytic infection group and 142 patients in the latent infection group. The SLEDAI-2 K score was higher in the lytic infection group (10.00 (6.25, 16.00) vs. 8.00 (5.00, 10.00), Z = 3.96, P < 0.001). There was a significant difference in the effect of EBV lytic infection on disease remission compared to latent infection (HR 0.30, 95% CI 0.19-0.49, P < 0.001). CONCLUSIONS: Patients with SLE with lytic EBV infection have higher disease activity and take longer to achieve remission. Our study furthers our understanding of the relationship between SLE and EBV infection and may inform better treatment practices in the future.

Analysis of spatial-temporal distribution characteristics and natural infection status of SFTS cases in Hefei from 2015 to 2021.

BACKGROUND: To analyze the prevalence and spatial-temporal characteristics of severe fever with thrombocytopenia syndrome (SFTS), clustering mode of transmission, and the serological dynamic detection results in multiple areas in Hefei from 2015 to 2021, and to provide the basis for SFTS prevention and control. METHOD: Case data were obtained from the Chinese Disease Control and Prevention Information System. Information on the clustering outbreak was obtained from the outbreak investigation and disposal report. Population latent infection rate information was obtained from field sampling in multiple-incidence counties in 2016 and 2021 by multi-stage random sampling. Epi data3.2 and SPSS 16.0 softwares were used to perform a statistical analysis of the data on SFTS cases, and QGIS 3.26 software was used to draw the incidence map with township (street) as unit. RESULTS: The an average annual reported incidence rate of SFTS in Hefei from 2015 to 2021 was 0.65/100,000, and the case fatality rate was 9.73%. The overall prevalence of SFTS epidemics in Hefei City showed a fluctuating upward trend from 2015 to 2021 (χ2trends = 103.353, P < 0.001). Chaohu City, Feixi County, Feidong County and Lujiang County ranked the top 4 in the city in terms of average annual incidence rate. The number of epidemic-involved towns (streets) kept increasing ((χ2trend = 47.640, P = 0.000)). Co-exposure to ticks accounted for the majority of clustered outbreaks and also human-to-human outbreaks. Population-based latent infection rate surveys were conducted in four SFTS multi-incidence counties, with 385 people surveyed in 2016 and 403 people surveyed in 2021, increasing the population-based latent infection rate from 6.75% to 10.91%, just as the incidence rate increased. CONCLUSIONS: The incidence rate of SFTS in Hefei is obviously regional, with an expanding trend in the extent of the epidemic involved. Co-exposure to ticks accounted for the majority of clustered outbreaks and the latent infection rate cannot be ignored.

Screening for Latent Infections Among Users of High-Risk Immunosuppressants: A Cross-Sectional Analysis From the Veterans Health Administration Healthcare System.

OBJECTIVES: Guidelines recommend screening for latent hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) before initiating biologics or targeted synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) to avoid reactivation of life-threatening infections. The extent to which such screening occurs in the national Veterans Health Administration (VA) healthcare system is unknown. METHODS: Using data from the Veterans Affairs' (VA) Corporate Data Warehouse, we performed a cross-sectional analysis of veterans receiving b/ts DMARDs between October 1, 2017, and September 30, 2019. We calculated the proportion of patients with screening completed for latent HBV, HCV, and TB between October 1, 1999 and September 30, 2019. Patient characteristics associated with complete screening were evaluated using mixed-effects multivariate logistic regression models. We also examined facility-level factors associated with high versus lower performance. RESULTS: A total of 51,764 unique patients from 129 VA facilities received b/ts DMARDs from 2017 to 2019. Of these, 63% had complete screening. Among the 11,006 patients identified as new users, 64% had complete screening. Higher screening rates were observed among Hispanic/Latinx and Black/African American patients, users of B-cell therapies, and patients who had seen oncology subspecialists. Substantial variation was observed across facilities, with complete screening ranging from 13% to 98% of patients. Higher screening rates were associated with highly complex, urban, and higher-volume facilities. CONCLUSIONS: Approximately two-thirds of veterans taking b/ts DMARDs have received guideline-recommended screening for HBV, HCV, and TB, but substantial facility variation was observed. Performance measures, robust multidisciplinary workflows, and electronic health record-based tools to feed information back to providers may improve screening rates for low-performing facilities.

HIV and Chagas Disease: An Evaluation of the Use of Real-Time Quantitative Polymerase Chain Reaction to Measure Levels of Trypanosoma cruzi Parasitemia in HIV Patients in Cochabamba, Bolivia.

This cross-sectional study evaluated epidemiologic characteristics of persons living with HIV (PWH) coinfected with Trypanosoma cruzi in Cochabamba, Bolivia, and estimated T. cruzi parasitemia by real-time quantitative polymerase chain reaction (qPCR) in patients with and without evidence of reactivation by direct microscopy. Thirty-two of the 116 HIV patients evaluated had positive serology for T. cruzi indicative of chronic Chagas disease (27.6%). Sixteen of the 32 (50%) patients with positive serology were positive by quantitative polymerase chain reaction (qPCR), and four of the 32 (12.5%) were positive by direct microscopy. The median parasite load by qPCR in those with CD4+ < 200 was 168 parasites/mL (73-9951) compared with 28.5 parasites/mL (15-1,528) in those with CD4+ ≥ 200 (P = 0.89). There was a significant inverse relationship between the degree of parasitemia estimated by qPCR from blood clot and CD4+ count on the logarithmic scale (rsBC= -0.70, P = 0.007). The correlation between T. cruzi estimated by qPCR+ blood clot and HIV viral load was statistically significant with rsBC = 0.61, P = 0.047. Given the significant mortality of PWH and Chagas reactivation and that 57% of our patients with CD4+ counts < 200 cells/mm3 showed evidence of reactivation, we propose that screening for chronic Chagas disease be considered in PWH in regions endemic for Chagas disease and in the immigrant populations in nonendemic regions. Additionally, our study showed that PWH with advancing immunosuppression have higher levels of estimated parasitemia measured by qPCR and suggests a role for active surveillance for Chagas reactivation with consideration of treatment with antitrypanosomal therapy until immune reconstitution can be achieved.

Risk of hepatitis B virus reactivation following ruxolitinib treatment in patients with myeloproliferative neoplasms.

Objectives The aim of this retrospective analysis was to assess the incidence of hepatitis B virus (HBV) reactivation among patients with myeloproliferative neoplasms (MPN) during and after ruxolitinib treatment. Methods Between February 2013 and February 2020, 224 patients with MPN were treated using ruxolitinib at Peking Union Medical College Hospital. Of these, 6 had chronic, and 56 had resolved HBV infection, including 43 patients who received combination treatment with thalidomide, prednisone, and stanozolol (TSP) during ruxolitinib treatment. Results Two patients with chronic HBV infection who did not take any antiviral prophylaxis developed HBV reactivation and hepatitis flare. The other four patients with chronic HBV infection, who took antiviral prophylaxis before ruxolitinib treatment, did not develop HBV reactivation. Also, no patients with resolved HBV infection received antiviral prophylaxis and developed HBV reactivation. Conclusion This study demonstrated that HBV reactivation and hepatitis flare might commonly occur a few months after initiating ruxolitinib treatment in patients with chronic HBV infection who did not take antiviral prophylaxis, especially in combination with TSP. Still, it was extremely rare in patients with resolved HBV infection.

Latent toxoplasmosis and vitamin D concentration in humans: three observational studies.

Numerous recent studies show that vitamin D deficiency potentiates various chronic physical and psychiatric disorders and diseases. It has been shown that a similar range of disorders is also associated with latent infection with Toxoplasma gondii (Nicolle et Manceaux, 1908). For instance, among cancer, diabetes and schizophrenia patients, we find a higher prevalence of both toxoplasmosis and vitamin D deficiency. Theoretically, therefore, vitamin D deficiency could be the missing link between toxoplasmosis and these disorders. We tested this hypothesis by searching for decreased vitamin D levels in the serum of subjects infected with T. gondii (furthermore called Toxoplasma-infected subjects) in two cross-sectional and one case-control study. Results of the first cross-sectional study (N = 72) suggest that Toxoplasma-infected neurasthenic patients have non-significantly lower levels of calcidiol than Toxoplasma-free patients (study A: P = 0.26 in women, P = 0.68 in men). However, two other studies (study B: N = 400; study C: N = 191) showed a non-significantly higher concentration of vitamin D in Toxoplasma-infected subjects than in Toxoplasma-free subjects both in men (study B: P = 0.70, study C: P = 0.55) and in women (study B: P = 0.64, study C: P = 0.12). Taken together, our preliminary results thus do not support the hypothesis that toxoplasmosis could be associated with vitamin D decrease.

High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19.

BACKGROUND: Systemic reactivation of herpesviruses may occur in intensive care unit (ICU) patients and is associated with morbidity and mortality. Data on severe Coronavirus disease-19 (COVID-19) and concomitant reactivation of herpesviruses are lacking. METHODS: We selected patients admitted to ICU for confirmed COVID-19 who underwent systematic testing for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human-herpes virus-6 (HHV-6) DNAemia while in the ICU. We retrospectively analysed frequency, timing, duration and co-occurrence of viral DNAemia. RESULTS: Thirty-four patients were included. Viremia with EBV, CMV, and HHV-6 was detected in 28 (82%), 5 (15%), and 7 (22%) patients, respectively. EBV reactivation occurred early after ICU admission and was associated with longer ICU length-of-stay. CONCLUSIONS: While in the ICU, critically ill patients with COVID-19 are prone to develop reactivations due to various types of herpesviruses.

Aggravation of symptom severity in adult attention-deficit/hyperactivity disorder by latent Toxoplasma gondii infection: a case-control study.

Toxoplasma gondii (T. gondii) has a high worldwide prevalence and an underestimated impact on neuropsychiatric disorders. Previous studies related T. gondii to disorders associated with the dysfunctional dopaminergic system. However, an association between T. gondii infection and adult attention-deficit/hyperactivity disorder (ADHD) has not yet been studied. In a sex- and age-matched case-control study, we investigated the seropositivity, serointensity, and avidity of latent T. gondii infection in adult ADHD patients and examined the influence of those variables on the symptomatology of ADHD. Of 140 participants, 20.0% were seropositive for anti-T. gondii IgG and 0% for anti-T. gondii IgM. T. gondii seropositivity was associated with 2.8-fold increase in the odds of ADHD in a confounder-adjusted multivariable analysis. Age and consumption of raw/undercooked meat were confirmed as significant predictors of T. gondii seropositivity. Multiple linear regression analysis of self-rated ADHD-related symptom severity in all participants revealed a significant association with T. gondii seropositivity, elevated IgG titers (serointensity), and stronger anti-T. gondii IgG avidity. Overall symptom severity was increased in seropositive ADHD patients compared to seronegative subjects with ADHD. In particular, hyperactivity was significantly associated with serointensity. We conclude that there is a high rate of T. gondii seropositivity in adults with ADHD. Additionally, our results suggest a clinical impact of latent T. gondii infection on ADHD-related symptoms in a serointensity- and avidity-dependent manner.

CEACAM3 decreases asthma exacerbations and modulates respiratory syncytial virus latent infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with childhood asthma. Nevertheless, not all children exposed to RSV develop asthma symptoms, possibly because genes modulate the effects of RSV on asthma exacerbations. OBJECTIVE: The purpose of this study was to identify genes that modulate the effect of RSV latent infection on asthma exacerbations. METHODS: We performed a meta-analysis to investigate differentially expressed genes (DEGs) of RSV infection from Gene Expression Omnibus datasets. Expression quantitative trait loci (eQTL) methods were applied to select single nucleotide polymorphisms (SNPs) that were associated with DEGs. Gene-based analysis was used to identify SNPs that were significantly associated with asthma exacerbations in the Taiwanese Consortium of Childhood Asthma Study (TCCAS), and validation was attempted in an independent cohort, the Childhood Asthma Management Program (CAMP). Gene-RSV interaction analyses were performed to investigate the association between the interaction of SNPs and RSV latent infection on asthma exacerbations. RESULTS: A total of 352 significant DEGs were found by meta-analysis of RSV-related genes. We used 38 123 SNPs related to DEGs to investigate the genetic main effects on asthma exacerbations. We found that eight RSV-related genes (GADD45A, GYPB, MS4A3, NFE2, RNASE3, EPB41L3, CEACAM6 and CEACAM3) were significantly associated with asthma exacerbations in TCCAS and also validated in CAMP. In TCCAS, rs7251960 (CEACAM3) significantly modulated the effect of RSV latent infection on asthma exacerbations (false-discovery rate <0.05). The rs7251960 variant was associated with CEACAM3 mRNA expression in lung tissue (p for trend=1.2×10-7). CEACAM3 mRNA was reduced in nasal mucosa from subjects with asthma exacerbations in two independent datasets. CONCLUSIONS: rs7251960 is an eQTL for CEACAM3, and CEACAM3 mRNA expression is reduced in subjects experiencing asthma exacerbations. CEACAM3 may be a modulator of RSV latent infection on asthma exacerbations.

Epstein-Barr virus infection in patients with chronic gastritis without Helicobacter pylori infection.

BACKGROUND/AIMS: The association of Epstein-Barr virus (EBV) with gastric malignancies has been proven by many studies in the literature. However, information about EBV-associated inflammation/gastritis remains limited. The aim of this study is to establish the prevalence of latent EBV infection in patients with chronic gastritis without H. pylori infection. MATERIALS AND METHODS: In this study, 119 patients with gastritis without H. pylori infection were included. Furthermore, 28 patients with H. pylori gastritis were included in the study as a control group. Chromogenic in situ hybridization (EBV-encoded RNA) and immunohistochemistry (LMP-1 antibody) were performed in all 147 cases. The prevalence of EBV and its relationship with age, sex, the affected part of the stomach, the density of inflammation, inflammatory activity, intestinal metaplasia, and atrophy were analyzed. RESULTS: In this study, 14 cases showed positive immunostaining for EBV. EBV positivity was seen mostly in the lymphoid tissue (13 cases), but it was also detected at the gastric epithelium (7 cases). The mean age of the patients was 44 years, which was slightly younger than that of the EBV-negative cases (48 years). The inflammation density was higher in EBV-positive cases than the EBV-negative gastritis cases (p=0.002). Intestinal metaplasia was detected in 7% of the cases. EBV-positive cases had a higher incidence of atrophy without intestinal metaplasia (21% vs 3.8% without EBV). CONCLUSION: EBV was detected in 12% of the cases with gastritis without H. pylori infection. Endoscopic follow-up may be appropriate for patients with gastritis, who have atrophy without intestinal metaplasia and are H. pylori negative but EBV positive.