Decreased expression of the NLRP6 inflammasome is associated with increased intestinal permeability and inflammation in obesity with type 2 diabetes.

BACKGROUND: Obesity-associated dysfunctional intestinal permeability contributes to systemic chronic inflammation leading to the development of metabolic diseases. The inflammasomes constitute essential components in the regulation of intestinal homeostasis. We aimed to determine the impact of the inflammasomes in the regulation of gut barrier dysfunction and metabolic inflammation in the context of obesity and type 2 diabetes (T2D). METHODS: Blood samples obtained from 80 volunteers (n = 20 normal weight, n = 21 OB without T2D, n = 39 OB with T2D) and a subgroup of jejunum samples were used in a case-control study. Circulating levels of intestinal damage markers and expression levels of inflammasomes as well as their main effectors (IL-1ß and IL-18) and key inflammation-related genes were analyzed. The impact of inflammation-related factors, different metabolites and Akkermansia muciniphila in the regulation of inflammasomes and intestinal integrity genes was evaluated. The effect of blocking NLRP6 by using siRNA in inflammation was also studied. RESULTS: Increased circulating levels (P < 0.01) of the intestinal damage markers endotoxin, LBP, and zonulin in patients with obesity decreased (P < 0.05) after weight loss. Patients with obesity and T2D exhibited decreased (P < 0.05) jejunum gene expression levels of NLRP6 and its main effector IL18 together with increased (P < 0.05) mRNA levels of inflammatory markers. We further showed that while NLRP6 was primarily localized in goblet cells, NLRP3 was localized in the intestinal epithelial cells. Additionally, decreased (P < 0.05) mRNA levels of Nlrp1, Nlrp3 and Nlrp6 in the small intestinal tract obtained from rats with diet-induced obesity were found. NLRP6 expression was regulated by taurine, parthenolide and A. muciniphila in the human enterocyte cell line CCL-241. Finally, a significant decrease (P < 0.01) in the expression and release of MUC2 after the knockdown of NLRP6 was observed. CONCLUSIONS: The increased levels of intestinal damage markers together with the downregulation of NLRP6 and IL18 in the jejunum in obesity-associated T2D suggest a defective inflammasome sensing, driving to an impaired epithelial intestinal barrier that may regulate the progression of multiple obesity-associated comorbidities.

High pre-Delta and early-Omicron SARS-CoV-2 seroprevalence detected in dried blood samples from Kinshasa (D.R. Congo).

Studies on the impact of the COVID-19 pandemic in sub-Saharan Africa have yielded varying results, although authors universally agree the real burden surpasses reported cases. The primary objective of this study was to determine SARS-CoV-2 seroprevalence among patients attending Monkole Hospital in Kinshasa (D.R. Congo). The secondary objective was to evaluate the analytic performance of two chemiluminescence platforms: Elecsys® (Roche) and VirClia® (Vircell) on dried blood spot samples (DBS). The study population (N = 373) was recruited in two stages: a mid-2021 blood donor cohort (15.5% women) and a mid-2022 women cohort. Crude global seroprevalence was 61% (53.9%-67.8%) pre-Delta in 2021 and 90.2% (84.7%-94.2%) post-Omicron in 2022. Anti-spike (S) antibody levels significantly increased from 53.1 (31.8-131.3) U/mL in 2021 to 436.5 (219.3-950.5) U/mL in 2022 and were significantly higher above 45 years old in the 2022 population. Both platforms showed good analytic performance on DBS samples: sensitivity was 96.8% for IgG (antiN/S) (93.9%-98.5%) and 96.0% (93.0%-98.0%) for anti-S quantification. These results provide additional support for the notion that exposure to SARS-CoV-2 is more widespread than indicated by case-based surveillance and will be able to guide the pandemic response and strategy moving forward. Likewise, this study contributes evidence to the reliability of DBS as a tool for serological testing and diagnosis in resource-limited settings.

The slowdown of new infections by human retroviruses has reached a plateau in Spain.

The 2022 annual meeting of the HTLV & HIV-2 Spanish Network was held in Madrid on December 14. We summarize here the main information presented and discussed at the workshop and review time trends for human retroviral infections in Spain. As transmissible agents, infections by human retroviruses are of obligatory declaration. Until the end of 2022, the Spanish national registry had recorded 451 cases of HTLV-1, 821 of HTLV-2, and 416 of HIV-2. For HIV-1, estimates are of 150 000 people currently living with HIV-1 and 60 000 cumulative deaths due to AIDS. During year 2022, new diagnoses in Spain were of 22 for HTLV-1, 6 for HTLV-2, and 7 for HIV-2. The last updated figures for HIV-1 are from 2021 and counted 2786 new diagnoses. The slowdown in yearly infections for HIV-1 in Spain points out that new strategies are needed to achieve the United Nations 95-95-95 targets by 2025. For the remaining neglected human retroviral infections, their control might be pushed throughout four interventions: (1) expanding testing; (2) improving education and interventions aimed to reduce risk behaviors; (3) facilitating access to antiretrovirals as treatment and prevention, including further development of long-acting formulations; and (4) increasing vaccine research efforts. Spain is a 47 million population country in South Europe with strong migration flows from HTLV-1 endemic regions in Latin America and Sub-Saharan Africa. At this time universal HTLV screening has been implemented only in the transplantation setting, following the report of 5 cases of HTLV-associated myelopathy shortly after transplantation of organs from HTLV-1 positive donors. There are four target populations for expanding testing and unveiling asymptomatic carriers responsible for silent HTLV-1 transmissions: (1) migrants; (2) individuals with sexually transmitted infections; (3) pregnant women; and (4) blood donors.

SARS-CoV-2 susceptibility and COVID-19 illness course and outcome in people with pre-existing neurodegenerative disorders: systematic review with frequentist and Bayesian meta-analyses.

BACKGROUND: People with neurodegenerative disease and mild cognitive impairment (MCI) may have an elevated risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may be disproportionally affected by coronavirus disease 2019 (COVID-19) once infected. AIMS: To review all eligible studies and quantify the strength of associations between various pre-existing neurodegenerative disorders and both SARS-CoV-2 susceptibility and COVID-19 illness course and outcome. METHOD: Pre-registered systematic review with frequentist and Bayesian meta-analyses. Systematic searches were executed in PubMed, Web of Science and preprint servers. The final search date was 9 January 2023. Odds ratios (ORs) were used as measures of effect. RESULTS: In total, 136 primary studies (total sample size n = 97 643 494), reporting on 268 effect-size estimates, met the inclusion criteria. The odds for a positive SARS-CoV-2 test result were increased for people with pre-existing dementia (OR = 1.83, 95% CI 1.16-2.87), Alzheimer's disease (OR = 2.86, 95% CI 1.44-5.66) and Parkinson's disease (OR = 1.65, 95% CI 1.34-2.04). People with pre-existing dementia were more likely to experience a relatively severe COVID-19 course, once infected (OR = 1.43, 95% CI 1.00-2.03). People with pre-existing dementia or Alzheimer's disease were at increased risk for COVID-19-related hospital admission (pooled OR range: 1.60-3.72). Intensive care unit admission rates were relatively low for people with dementia (OR = 0.54, 95% CI 0.40-0.74). All neurodegenerative disorders, including MCI, were at higher risk for COVID-19-related mortality (pooled OR range: 1.56-2.27). CONCLUSIONS: Our findings confirm that, in general, people with neurodegenerative disease and MCI are at a disproportionally high risk of contracting COVID-19 and have a poor outcome once infected.

Prediction of effective humoral response to SARS-CoV-2 vaccines in healthy subjects by cortical thickness of post-vaccination reactive lymphadenopathy.

PURPOSE: To study the association between ultrasound cortical thickness in reactive post-vaccination lymph nodes and the elicited humoral response and to evaluate the performance of cortical thickness as a predictor of vaccine effectiveness in patients with and without a previous history of COVID-19 infection. METHODS: A total of 156 healthy volunteers were recruited and followed prospectively after receiving two COVID-19 vaccination doses using different protocols. Within a week after receiving the second dose, an axillary ultrasound of the ipsilateral vaccinated arm was performed, and serial post-vaccination serologic tests (PVST) were collected. Maximum cortical thickness was chosen as a nodal feature to analyze association with humoral immunity. Total antibodies quantified during consecutive PVST in previously-infected patients and in coronavirus-naïve volunteers were compared (Mann-Whitney U test). The association between hyperplastic-reactive lymph nodes and effective humoral response was studied (odds ratio). The performance of cortical thickness in detecting vaccination effectiveness was evaluated (area under the ROC curve). RESULTS: Significantly higher values for total antibodies were observed in volunteers with a previous history of COVID-19 infection (p < 0.001). The odds ratio associating immunized coronavirus-naïve volunteers after 90 and 180 days of the second dose with a cortical thickness ≥ 3 mm was statistically significant (95% CI 1.52-6.97 and 95% CI 1.47-7.29, respectively). The best AUC result was obtained comparing antibody secretion of coronavirus-naïve volunteers at 180 days (0.738). CONCLUSIONS: Ultrasound cortical thickness of reactive lymph nodes in coronavirus-naïve patients may reflect antibody production and a long-term effective humoral response elicited by vaccination. CLINICAL RELEVANCE STATEMENT: In coronavirus-naïve patients, ultrasound cortical thickness of post-vaccination reactive lymphadenopathy shows a positive association with protective antibody titers against SARS-CoV-2, especially in the long term, providing new insights into previous publications. KEY POINTS: • Hyperplastic lymphadenopathy was frequently observed after COVID-19 vaccination. • Ultrasound cortical thickness of reactive post-vaccine lymph nodes may reflect a long-term effective humoral response in coronavirus-naïve patients.

Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: First report in Europe.

BACKGROUND & AIM: Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global. METHODS: Orthohepevirus C RNA was retrospectively evaluated in 2 cohorts of patients in Spain. The first cohort included patients with acute hepatitis without etiological diagnosis after screening for hepatotropic virus infection. The second cohort included patients diagnosed with acute HEV infection, defined as positivity for anti-HEV-IgM antibodies and/or detectable HEV RNA in serum. RESULTS: Cohort 1 comprised 169 patients (64.4% male, median age 43 years) and cohort 2 comprised 98 individuals (68.3% male, median age 45 years). Of the individuals included in Cohort 1, two (1.18%; 95% CI 0.2-3.8) had detectable Orthohepevirus C RNA in serum. In Cohort 2, of the 98 included patients, 58 showed detectable HEV RNA, while 40 only showed positivity for IgM antibodies. Among those bearing only IgM antibodies, Orthohepevirus C RNA was detected in 1 (2.5%; 95% CI 0.06-13.1) individual. All strains were consistent with genotype C1. The infection resulted in mild self-limiting acute hepatitis in 2 patients. Infection caused severe acute hepatitis in the remaining patient who died as a result of liver and renal failure. CONCLUSIONS: We described 3 cases of Orthohepevirus C in patients with acute hepatitis, resulting in the first description of this infection in Europe. The prevalence obtained in our study suggests that Orthohepevirus C could be an emerging disease in Europe. LAY SUMMARY: We describe the first cases of acute hepatitis related to rat hepatitis E virus in Europe. The prevalence found in our study suggest that rat hepatitis E virus could be considered an emerging disease in Europe.

Validation of a sustainable internationally monitored cervical cancer screening system using a visual smartphone inspection in Kinshasa, Democratic Republic of Congo.

OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of a cervical cancer screening program based on visual inspection with acetic acid and Lugol's iodine using a smartphone in a sub-urban area of very low resources in Kinshasa (Democratic Republic of Congo). METHODS: This cross-sectional validation study was conducted at Monkole Hospital and it included women between the ages of 25-70 years after announcing a free cervical cancer screening campaign through posters placed in the region of our hospital. Questionnaires collected sociodemographic and behavioral patients characteristics. In the first consultation, we gathered liquid-based cytology samples from every woman. At that time, local health providers performed two combined visual inspection techniques (5% acetic acid and Lugol's iodine) while a photograph was taken with a smartphone. Two international specialists evaluated the results of the smartphone cervicography. When a visual inspection was considered suspicious, patients were offered immediate cryotherapy. Cytological samples were sent to the Pathology Department of the University of Navarra for cytological assessment and human papillomavirus (HPV) DNA genotyping. RESULTS: A total of 480 women participated in the study. The mean age was 44.6 years (range 25-65). Of all the patients, only 18.7% were infected with HPV (75% had high-risk genotypes). The most frequent high-risk genotype found was 16 (12.2%). The majority (88%) of women had normal cytology. After comparing combined visual inspection results with cytology, we found a sensitivity of 66.0%, a specificity of 87.8%, a positive predictive value of 40.7%, and a negative predictive value of 95.3% for any cytological lesion. The negative predictive value for high-grade lesions was 99.7%. CONCLUSIONS: Cervical cancer screening through combined visual inspection, conducted by non-specialized personnel and monitored by experts through smartphones, shows encouraging results, ruling out high-grade cytological lesions in most cases. This combined visual inspection test is a valid and affordable method for screening programs in low-income areas.

Highly Sensitive and Specific Multiplex Antibody Assays To Quantify Immunoglobulins M, A, and G against SARS-CoV-2 Antigens.

Reliable serological tests are required to determine the prevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to characterize immunity to the disease in order to address key knowledge gaps in the coronavirus disease 2019 (COVID-19) pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and enzyme-linked immunosorbent assays (ELISAs) with their higher precision, dynamic range, throughput, miniaturization, cost-efficiency, and multiplexing capacity. We developed three qSAT assays for IgM, IgA, and IgG against a panel of eight SARS-CoV-2 antigens, including spike protein (S), nucleocapsid protein (N), and membrane protein (M) constructs. The assays were optimized to minimize the processing time and maximize the signal-to-noise ratio. We evaluated their performances using 128 prepandemic plasma samples (negative controls) and 104 plasma samples from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 5 were asymptomatic, 51 had mild symptoms, and 48 were hospitalized. Preexisting IgG antibodies recognizing N, M, and S proteins were detected in negative controls, which is suggestive of cross-reactivity to common-cold coronaviruses. The best-performing antibody/antigen signatures had specificities of 100% and sensitivities of 95.78% at ≥14 days and 95.65% at ≥21 days since the onset of symptoms, with areas under the curve (AUCs) of 0.977 and 0.999, respectively. Combining multiple markers as assessed by qSAT assays has the highest efficiency, breadth, and versatility to accurately detect low-level antibody responses for obtaining reliable data on the prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity and their kinetics, required for vaccine development to combat the COVID-19 pandemic.

HTLV-1 infection in solid organ transplant donors and recipients in Spain.

BACKGROUND: HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. METHODS: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. RESULTS: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. CONCLUSION: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.

Increasing importance of European lineages in seeding the hepatitis C virus subtype 1a epidemic in Spain.

BackgroundReducing the burden of the hepatitis C virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the dynamic pattern of HCV spread. In Spain, ongoing transmission of HCV is mostly fuelled by people who inject drugs (PWID) infected with subtype 1a (HCV1a).AimOur aim was to map how infections spread within and between populations, which could help formulate more effective intervention programmes to halt the HCV1a epidemic in Spain.MethodsEpidemiological links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected between 2014 and 2016, and 1,317, 1,291 and 1,009 samples collected abroad between 1989 and 2016 were reconstructed using sequences covering the NS3, NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to a flexible Bayesian discrete phylogeographic inference method.ResultsThe transmission network structure of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively from North America and European countries. The latter became increasingly relevant and have dominated in recent times. Export from Spain to other countries in Europe was also strongly supported, although Spain was a net sink for European HCV1a lineages. Spatial reconstructions showed that the epidemic in Spain is diffuse, without large, dominant within-country networks.ConclusionTo boost the effectiveness of local intervention efforts, concerted supra-national strategies to control HCV1a transmission are needed, with a strong focus on the most important drivers of ongoing transmission, i.e. PWID and other high-risk populations.

Factors that lead to changes in sexual behaviours after a negative HIV test: protocol for a prospective cohort study in Kinshasa.

BACKGROUND: Considering the high percentage of couples in which one or both members are HIV negative, the frequency of transmission among non-regular partners and the probabilities of non-disclosure, attention should be paid to people getting a negative HIV test at the Voluntary Counseling and Testing (VCT). Research has shown that a negative HIV test may be followed by a change in sexual behaviours. In Sub-Saharan Africa, where most HIV infections occur, there are few studies that have analysed the factors associated with changes in sexual risk behaviours after a negative HIV test at the VCT clinic. The aim of this project is to evaluate the specific factors associated with changes in sexual behaviours, three months after a negative result in an HIV test, and to analyse the effect of counseling and testing on HIV-related knowledge of participants in an outpatient centre of Kinshasa (Democratic Republic of Congo). METHODS AND DESIGN: Prospective cohort study from December 2014 until March 2016. People 15-60 year old that received VCT at Monkole Hospital (Kinshasa) were followed three months after they got a negative HIV test. In a face-to-face interview, participants replied to a baseline and a follow-up research questionnaire on HIV-related knowledge, attitudes and behaviours. At follow-up respondents were also offered a new HIV test and additional HIV counseling. Four hundred and fifteen participants completed the baseline questionnaire and 363 (87 %) came back for their 3-month follow up. DISCUSSION: This is the first longitudinal study in the DRC that evaluates the factors associated with changes in sexual behaviours after a negative HIV test at the VCT. Participants attending the VCT services within a clinical setting are a good study population as they can be good transmitters of preventive information for other people with no access to health facilities.

Effects of previous episodes of influenza and vaccination in preventing laboratory-confirmed influenza in Navarre, Spain, 2013/14 season.

We estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in Navarre, Spain, in season 2013/14. Patients with medically-attended influenza-like illness (MA-ILI) in hospitals (n = 645) and primary healthcare (n = 525) were included. We compared 589 influenza cases and 581 negative controls. MA-ILI related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the same virus subtype or MA-ILI during weeks when more than 25% of swabs were positive for this subtype. Persons with previous MA-ILI had 30% (95% confidence interval (CI): -7 to 54) lower risk of MA-ILI, and those with previous MA-ILI related to A(H1N1)pdm09 or A(H3N2) virus, had a, respectively, 63% (95% CI: 16-84) and 65% (95% CI: 13-86) lower risk of new laboratory-confirmed influenza by the same subtype. Overall adjusted vaccine effectiveness in preventing laboratory-confirmed influenza was 31% (95% CI: 5-50): 45% (95% CI: 12-65) for A(H1N1)pdm09 and 20% (95% CI: -16 to 44) for A(H3N2). While a previous influenza episode induced high protection only against the same virus subtype, influenza vaccination provided low to moderate protection against all circulating subtypes. Influenza vaccine remains the main preventive option for high-risk populations.

Nipah Virus: A Multidimensional Update.

Nipah virus (NiV) is an emerging zoonotic paramyxovirus to which is attributed numerous high mortality outbreaks in South and South-East Asia; Bangladesh's Nipah belt accounts for the vast majority of human outbreaks, reporting regular viral emergency events. The natural reservoir of NiV is the Pteropus bat species, which covers a wide geographical distribution extending over Asia, Oceania, and Africa. Occasionally, human outbreaks have required the presence of an intermediate amplification mammal host between bat and humans. However, in Bangladesh, the viral transmission occurs directly from bat to human mainly by ingestion of contaminated fresh date palm sap. Human infection manifests as a rapidly progressive encephalitis accounting for extremely high mortality rates. Despite that, no therapeutic agents or vaccines have been approved for human use. An updated review of the main NiV infection determinants and current potential therapeutic and preventive strategies is exposed.

Human T-lymphotropic virus-1 infection among Latin American pregnant women living in Spain.

Objectives: Human T-lymphotropic virus (HTLV) antenatal screening is not mandatory in Spain. Surveys conducted decades ago reported HTLV-1 seroprevalence rates of 0.2% among foreign pregnant women in Spain. The migrant flow to Spain from HTLV-1 endemic regions in Latin America and sub-Saharan Africa has increased during the last decade. Currently, 25% of pregnant women in Spain are foreigners. Methods: From January 2021 to October 2023 a cross-sectional study was carried out in all consecutive pregnant women attended at eleven Spanish clinics. A commercial enzyme immunoassay (EIA) was used for screening of serum HTLV-1/2 antibodies. Reactive samples were confirmed by immunoblot. Results: A total of 9813 pregnant women with a median age of 34 years-old were examined. Native Spaniards were 6977 (76.5%). Of 2147 foreigners (23.5%), 903566 (9.9%) were Latin Americans, 416 (4.5%) North Africans, 293 (3.2%) from Romania, and 196 (2.1%) from sub-Saharan Africa. A total of 47 samples were EIA reactive but only five were confirmed as HTLV-1 positive using immunoblot. Infected women came from Paraguay, Colombia, the Dominican Republic, Venezuela and Peru. All but one were primigravida, with ages ranging from 20 to 33 years-old. One was HIV-1 positive, and another was infected with Chlamydia trachomatis. Conclusion: The overall seroprevalence for HTLV-1 among pregnant women in Spain is 0.05% but rises ten-fold (0.55%) among Latin Americans. This rate is higher than in surveys conducted decades ago. Our results support that anti-HTLV testing should be part of antenatal screening in Spain in pregnant women coming from Latin America, as it is already done with Chagas disease.

Effectiveness of the trivalent influenza vaccine in Navarre, Spain, 2010-2011: a population-based test-negative case-control study.

BACKGROUND: Some studies have evaluated vaccine effectiveness in preventing outpatient influenza while others have analysed its effectiveness in preventing hospitalizations. This study evaluates the effectiveness of the trivalent influenza vaccine in preventing outpatient illness and hospitalizations from laboratory-confirmed influenza in the 2010-2011 season. METHODS: We conducted a nested case-control study in the population covered by the general practitioner sentinel network for influenza surveillance in Navarre, Spain. Patients with influenza-like illness in hospitals and primary health care were swabbed for influenza testing. Influenza vaccination status and other covariates were obtained from health care databases. Using logistic regression, the vaccination status of laboratory-confirmed influenza cases was compared with that of test-negative controls, adjusting for age, sex, comorbidity, outpatient visits in the previous 12 months, health care setting, time between symptom onset and swabbing, period and A(H1N1)pdm09 vaccination. Effectiveness was calculated as (1-odds ratio)x100. RESULTS: The 303 confirmed influenza cases (88% for A(H1N1)pdm09 influenza) were compared with the 286 influenza test-negative controls. The percentage of persons vaccinated against influenza was 4.3% and 15.7%, respectively (p<0.001). The adjusted estimate of effectiveness was 67% (95% CI: 24%, 86%) for all patients and 64% (95% CI: 8%, 86%) in those with an indication for vaccination (persons age 60 or older or with major chronic conditions). Having received both the 2010-2011 seasonal influenza vaccine and the 2009-2010 pandemic influenza vaccine provided 87% protection (95% CI: 30%, 98%) as compared to those not vaccinated. CONCLUSION: The 2010-2011 seasonal influenza vaccine had a moderate protective effect in preventing laboratory-confirmed influenza.

Rocahepevirus ratti as an Emerging Cause of Acute Hepatitis Worldwide.

The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised individuals. In addition to the common strains of hepatitis E virus (HEV-A), known as Paslahepevirus balayani, pathogenic to humans, a genetically highly divergent rat origin hepevirus (RHEV) can cause hepatitis possessing a potential risk of cross-species infection and zoonotic transmission. Rocahepevirus ratti, formerly known as Orthohepevirus C, is a single-stranded RNA virus, recently reassigned to Rocahepevirus genus in the Hepeviridae family, including genotypes C1 and C2. RHEV primarily infects rats but has been identified as a rodent zoonotic virus capable of infecting humans through the consumption of contaminated food or water, causing both acute and chronic hepatitis cases in both animals and humans. This review compiles data concluding that 60% (295/489) of RHEV infections are found in Asia, being the continent with the highest zoonotic and transmission potential. Asia not only has the most animal cases but also 16 out of 21 human infections worldwide. Europe follows with 26% (128/489) of RHEV infections in animals, resulting in four human cases out of twenty-one globally. Phylogenetic analysis and genomic sequencing will be employed to gather global data, determine epidemiology, and assess geographical distribution. This information will enhance diagnostic accuracy, pathogenesis understanding, and help prevent cross-species transmission, particularly to humans.

Corrigendum: Increased levels of interleukin-36 in obesity and type 2 diabetes fuels adipose tissue inflammation by inducing its own expression and release by adipocytes and macrophages.

[This corrects the article DOI: 10.3389/fimmu.2022.832185.].

Effect of the Hematocrit and Storage Temperature of Dried Blood Samples in the Serological Study of Mumps, Measles and Rubella.

Dried blood spots (DBSs) are an economical and convenient alternative to serum/plasma, which allow for the serological and molecular study of different pathogens. Sixty-four blood samples were collected by venipuncture and spotted onto Whatman™ 903 cards to evaluate the utility of DBSs and the effect of the storage temperature for 120 days after sample collection to carry out serological diagnosis. Mumps, measles and rubella IgG were investigated from DBSs and plasma using an automated chemiluminescent immunoassay. Using a calculated optimal cut-off value, the serological evaluation of mumps, measles and rubella using DBSs achieved high sensitivity (100%, 100% and 82.5%, respectively) and specificity (100%, 87.5% and 100%, respectively). The correlation observed between the plasma and the DBSs processed after sample collection was high (0.914-0.953) for all antibodies studied, both considering hematocrit before sample elution or not. For the different storage conditions, the correlation with plasma was high at 4 °C (0.889-0.925) and at -20 °C (0.878-0.951) but lower at room temperature (0.762-0.872). Measles IgG results were more affected than other markers when DBSs were stored at any temperature for 120 days. To summarize, hematocrit does not affect the processing of DBSs in the study of serological markers of mumps, measles and rubella. DBS stability for serological diagnosis of mumps and rubella is adequate when samples are stored at -20 °C or 4 °C, but not at room temperature, for a period of 4 months.

Impact of storage time in dried blood samples (DBS) and dried plasma samples (DPS) for point-of-care hepatitis C virus (HCV) RNA quantification and HCV core antigen detection.

The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log10 IU/mL (DBS) and 0.3 log10 IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values. IMPORTANCE Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.