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.

Prevalence of Paid Sex and Associated Factors Among Women and Men Attending HIV Voluntary Counseling and Testing in Kinshasa, Democratic Republic of the Congo: A Prospective Cohort.

Paid sex is associated with HIV and other sexually transmitted infections, which are highly prevalent in Sub-Saharan Africa (SSA). However, few data exist on this sexual practice among the general population in SSA, including the Democratic Republic of the Congo, where data on paid sex mainly comes from sex workers. In the DRC, most HIV Voluntary Counseling and Testing (VCT) centers do not discuss paid sex as a risk factor. Thus, we aimed to analyze the prevalence of paid sex, its associated factors and association with HIV among women and men attending HIV VCT at a reference hospital in Kinshasa. From 2016 to 2018, the Observational Kinshasa AIDS Initiative cohort analyzed the impact of HIV VCT on changes in HIV knowledge, attitudes, and sexual behaviors at follow-up. Participants aged 15-69 years were HIV tested and interviewed at baseline and at 6- and 12-month follow-ups. At baseline, participants were asked about their history of "ever" having had exchanged sex for money. At both follow-ups, the frequency of this practice was referred to as "the previous 6 months." Descriptive, bivariate, and multivariate logistic regression analyses were carried out to evaluate the prevalence of paid sex, its associated factors, and the association between paid sex and HIV. Statistical analyses were performed with Stata 15.1. Among 797 participants at baseline, 10% of those sexually experienced reported having ever had paid sex (18% men and 4% women, p < 0.001). At 6 and 12-month follow-ups, 5% and 2%, respectively. Paid sex was significantly and independently associated with being male (aOR = 2.7; 95% CI = 1.4-5.2), working or studying (aOR = 2.8; 95% CI = 1.5-5.0), daily newspaper reading (aOR = 4.4; 95% CI = 1.7-11.2); daily/weekly alcohol consumption (aOR = 3.3; 95% CI = 1.8-6.1), first sexual intercourse before age 15 years (aOR = 2.3; 95% CI = 1.1-5.0), multiple sexual partners (aOR = 4.1; 95% CI = 2.2-7.7), and extragenital sexual practices (aOR = 2.4; 95% CI = 1.3-4.4). A high religiosity (daily/weekly church attendance and praying) was inversely associated with paid sex (aOR = 0.1; 95% CI = 0.0-0.4). The high prevalence of paid sex among people attending HIV VCT in Kinshasa, associated with other sexual and consumption risk behaviors, highlights the need to include paid sex among the risk factors mentioned in HIV prevention counseling.

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.

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.

Primoinfección por parvovirus B19: análisis de 46 pacientes / Acute parvovirus B19 infection: analysis of 46 patients

INTRODUCCIÓN: La infección por parvovirus B19 (PVB19) tiene una incidencia elevada y distribución mundial. Su espectro clínico es amplio, destacando las manifestaciones cutáneas, articulares y hematológicas. El objetivo del presente estudio fue estudiar epidemiología y manifestaciones clínico-analíticas de la primoinfección por PVB19. Pacientes y método: Estudio retrospectivo (10 años) de pacientes con serología IgM positiva para PVB19. Se incluyeron 46 pacientes y se estudiaron sus características demográficas, clínicas y analíticas. RESULTADOS: La primoinfección fue más prevalente en mujeres (ratio 2,2:1), y en edad media de 41años. La afectación articular fue la más frecuente (65%). En más de la mitad de los pacientes (24 casos) se observaron alteraciones cutáneas: exantema (28%), megaloeritema (9%), afectación «en guantes y calcetines» (6,5%), afectación periflexural (4%) y edema (4%). De entre las alteraciones hematológicas destacó la anemia (35%). El cuadro clínico se autolimitó en 1-2 semanas en la mayoría de los pacientes. CONCLUSIONES: A pesar de que existe un espectro clínico variable, las poliartralgias y el exantema maculopapular generalizado junto con fiebre y anemia son las manifestaciones típicas y más frecuentes de la primoinfección por PVB19 y suelen autolimitarse

INTRODUCTION: Parvovirus B19 (PVB19) infection has a high incidence and worldwide distribution. It has a broad clinical spectrum, with skin, joint and haematological manifestations being the most common. The objective of this study was to determine the epidemiology and clinical-analytical manifestations of acute PVB19 infection. PATIENTS AND METHODS: A retrospective study of patients with a positive IgM serology for PVB19 (10 years). Forty-six patients were included and their demographic, clinical and analytical characteristics were analyzed. RESULTS: Primary infection was most prevalent in women (ratio 2.2:1) aged 41 (mean age). Joint involvement was the most common manifestation (65%). Skin abnormalities were observed in more than half of patients (24 cases): rash (28%), megalerythema (9%), "gloves and socks" involvement (6.5%), periflexural rash (4%) and oedema (4%). Anaemia was the main haematological alteration (35%). The symptoms were self-limiting and resolved in 1-2 weeks in most patients. CONCLUSIONS: Although there is a variable clinical spectrum, polyarthralgias and generalized maculopapular rash with fever and anaemia are the typical and most frequent manifestations of primary infection by PVB19 and are usually self-limiting

Diferencias entre las ondas gripales de verano y de otoño durande la pandemia de gripe (H1N1) 2009 en Navarra / Differences between summer and fall waves of influenza in the pandemic (H1N1) 2009 in Navarre, Spain

Fundamento: La gripe (H1N1) 2009 produjo en Navarra una onda en verano y otra en otoño de 2009. El objetivo de este trabajo es comparar las características de ambas ondas epidémicas. Métodos: Analizamos la notificación individualizada de gripe, las confirmaciones virológicas en la red centinela de atención primaria, y los casos hospitalizados con confirmación de gripe en Navarra y comparamos los periodos de verano (semanas 21 a 39 de 2009) y otoño-invierno (semanas 40 de 2009 a 20 de 2010). Resultados: Durante 2009 hubo dos ondas de gripe A(H1N1)2009, con picos en julio y noviembre. En verano (semana 21 a 39) se notificaron 4.389 casos de síndrome gripal, siendo los más afectados los adultos jóvenes (58% entre 15 y 44 años). La mayor incidencia se registró tras las fiestas de San Fermín (92 casos por 100.000 en la semana 29) con retorno inmediato a niveles basales. En otoño se produjo una segunda onda que alcanzó tasas 7 veces mayores (667 casos por 100.000 en la semana 45) y se mantuvieron 9 semanas por encima del umbral epidémico, siendo el grupo de edad más afectado el de niños de 5 a 14 años (111 por 1000). En el pico de las dos ondas el porcentaje de frotis confirmados para gripe superó el 60%. Durante el verano se produjeron 66 ingresos con confirmación de gripe (H1N1)2009, y en otoño 158. La proporción de casos que requirieron ingresos en hospital fue mayor en verano (1,5%) que en otoño (0,8%; p<0,0001). Conclusión: La circulación de la gripe fue mucho menor en verano. La aparición de casos graves se produjo tanto en momentos con alta como con baja incidencia de síndromes gripales(AU)

Background: Two waves of influenza (H1N1)2009 were produced in Navarre in 2009, one in the summer and the other in the fall. We aim to compare the characteristics of the two epidemic waves. Methods: We analysed individual influenza reports, virological confirmations in the primary care sentinel network, and hospitalised cases with confirmed influenza in Navarre. We compared the summer period (week 21 to 39 in 2009) with the fall-winter period (week 40 in 2009 to 20 in 2010). Results: Two waves of influenza A(H1N1)2009 occurred during 2009, with peaks in July and November. In the summer (week 21 to 39) 4389 cases of influenza syndrome were reported, with young adults the most affected group (58% aged 15-44 years). The highest incidence was registered after the San Fermin fiesta (92 cases per 100,000 population in week 29), with immediate return to baseline levels. A second wave occurred in the fall, with rates up to 7 times higher (667 cases per 100,000 in week 45); they remained above the epidemic threshold for 9 weeks, with children aged 5-14 years (111 per 1000) the most affected group. In the peak of both waves the percentage of smears confirmed for influenza reached 60%. During the summer there were 66 admissions with confirmed influenza (H1N1)2009, and 158 than in the fall. The proportion of cases requiring admission to hospital was higher in the summer (1.5%) than in fall (0.8%: p<0,0001). Conclusion: Influenza circulation was much lower in the summer. Serious cases occurred in periods of both high and low incidence of influenza syndromes(AU)

Influencia de los tiempos entre el inicio de síntomas, la toma de frotis nasofaríngeo y su procesamiento en laboratorio en la detección de gripe / Effect of the time between symptom onset, swabbing and testing on the detection of influenza virus

Introducción La vigilancia epidemiológica de la gripe requiere la recogida de frotis nasofaríngeos en atención primaria para su análisis en laboratorios de referencia. Evaluamos la influencia en el resultado de laboratorio, de los tiempos transcurridos desde el inicio de síntomas hasta la recogida del frotis (TSF) y desde entonces hasta su procesamiento en laboratorio (TFL).Métodos Analizamos las muestras recogidas en la red centinela de gripe de Navarra en la temporada 2009-2010. Los hisopados se conservaron refrigerados hasta su estudio mediante RT-PCR y cultivo viral. Se analizó el porcentaje de positividad a gripe en función del TSF y del TFL mediante regresión logística. Resultados Se analizaron 937 frotis y 373 (40%) fueron positivos para gripe mediante RT-PCR. El TSF osciló entre 0-15 días. En el análisis ajustado por periodo, laboratorio y edad, la detección del virus de la gripe descendió a menos de la mitad en el cultivo cuando el TSF era de 4-5 días (OR = 0,47; IC 95% 0,24-0,94), y en la RT-PCR, cuando el TSF era mayor de 5 días (OR = 0,24; IC 95% 0,09-0,65). El TFL no afectó de forma significativa al resultado de muestras procesadas por RT-PCR (OR por día transcurrido = 0,96; IC 95% 0,88-1,04), ni por cultivo viral (OR por día transcurrido = 0,97; IC 95% 0,89-1,06).Conclusiones Un TSF superior a 3 días redujo la probabilidad de confirmación de gripe, afectando más al cultivo que a la PCR. El TFL dentro de un rango de dos semanas no afectó de forma relevante al resultado de la RT-PCR ni del cultivo (AU)

Background Influenza surveillance requires the collection of nasopharyngeal swabs in Primary Care for testing in reference laboratories. We evaluated the influence on the laboratory results of the time since the onset of symptoms to swabbing (TSS) and from then until laboratory processing (TSL).Methods We analysed swabs collected in the Sentinel Network of Navarra during the 2009-2010 influenza season. The samples were kept refrigerated until analysed by RT-PCR and viral culture. We analysed the percentage of positive swabs to influenza virus in accordance with the TSS and TSL by logistic regression. Results From a total of 937 swabs, 373 (40%) were positive for influenza by RT-PCR. The TSS ranged from 0-15 days. In the adjusted analysis by period, laboratory and age, having a positive influenza culture decreased to less than half when the TSS was 4-5 days (OR=0.47; 95% CI, 0.24-0.94), and having a positive RT-PCR decreased when the TSS was 5 days or more (OR=0.24, 95% CI, 0.09-0.65). TSL does not significantly affect the result of the RT-PCR (OR by each day=0.96; 95% CI, 0.88-1.04), or the result of the viral culture (OR by each day=0.97, 95% CI, 0.89-1.06).Conclusions A TSS over 3 days reduced the likelihood of confirmation of influenza, affecting the viral culture more than the RT-PCR. A TSL within a range of two weeks had no significant effect on the results of the RT-PCR or the viral culture (AU)