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Background Obesity has been shown to increase the risk of severe outcomes and death for influenza virus infections. However, we do not understand the influence of obesity on susceptibility to infection or on nonsevere influenza outcomes. Methods We performed a case-ascertained, community-based study of influenza transmission within households in Nicaragua. To investigate whether obesity increases the likelihood of influenza infection and symptomatic infection we used logistic regression models. Results Between 2015 and 2018, a total of 335 index cases with influenza A and 1506 of their household contacts were enrolled. Obesity was associated with increased susceptibility to symptomatic H1N1pdm infection among adults (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.08–4.06) but not children, and this association increased with age. Among adults with H1N1pdm infection, obesity was associated with increased likelihood of symptoms (OR, 3.91; 95% CI, 1.55–9.87). For middle-aged and older adults with obesity there was also a slight increase in susceptibility to any H1N1pdm infection (OR, 1.20; 95% CI, .62–2.34). Body mass index (BMI) was also linearly associated with increased susceptibility to symptomatic H1N1pdm infection, primarily among middle-aged and older women (5-unit BMI increase OR, 1.40; 95% CI, 1.00–1.97). Obesity was not associated with increased H3N2 susceptibility or associated symptoms. Conclusions We found that, among adults, obesity is associated with susceptibility to H1N1pdm infection and with symptoms associated with H1N1pdm infection, but not with susceptibility to H3N2 infection or associated symptoms. These findings will help target prevention efforts and therapeutics to this high-risk population.

BackgroundAn immune correlate of protection from SARS-CoV-2 infection is urgently needed.MethodsWe used an ongoing household cohort with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity. Sequencing was performed to determine circulating strains of SARS-CoV-2. We investigated the protection associated with seropositivity resulting from prior infection, the anti-spike antibody titers needed for protection, and we compared the severity of first and second infections.ResultsIn March 2021, 62.3% of the cohort was seropositive. After March 2021, gamma and delta variants predominated. Seropositivity was associated with 69.2% protection from any infection (95% CI: 60.7%-75.9%), with higher protection against moderate or severe infection (79.4%, 95% CI: 64.9%-87.9%). Anti-spike titers of 327 and 2,551 were associated with 50% and 80% protection from any infection; titers of 284 and 656 were sufficient for protection against moderate or severe disease. Second infections were less severe than first infections (Relative Risk (RR) of moderated or severe disease: 0.6, 95% CI: 0.38-0.98; RR of subclinical disease:1.9, 95% CI: 1.33-2.73).ConclusionsPrior infection-induced immunity is protective against infection when predominantly gamma and delta SARS-CoV-2 circulated. The protective antibody titers presented may be useful for vaccine policy and control measures. While second infections were somewhat less severe, they were not as mild as ideal. A strategy involving vaccination will be needed to ease the burden of the SARS-CoV-2 pandemic.

Dengue virus serotypes 1-4 (DENV1-4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly-reactive antibodies. A first DENV infection is thought to induce antibodies that wane over two years to titers that can subsequently enhance severe dengue disease, causing large dengue epidemics. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies. Low dengue disease incidence following the recent Zika pandemic led to the hypothesis that ZIKV infection is also transiently cross-protective. We investigated antibody kinetics in 4189 children up to 11 years after one and multiple DENV and ZIKV infections in longitudinal cohorts in Nicaragua. We used a DENV inhibition enzyme linked immunosorbent assay (iELISA), which measures antibodies associated with protection against dengue and Zika disease and with enhancement of dengue disease severity. Surprisingly, we found that overall DENV iELISA titers stabilized by 8 months post-primary DENV infection to a half-life longer than a human life and waned, although gradually, after secondary DENV infection. Similarly, DENV iELISA titers were stable or rose after primary ZIKV infection but declined in individuals with histories of DENV and ZIKV infection. In contrast, kinetics of anti-ZIKV antibodies post-ZIKV infection were similar regardless of prior DENV immunity. We observed heterogeneity in DENV iELISA titer, suggesting that individual antibody titer setpoint, rather than waning, is important for future dengue disease risk. Together, these findings change our understanding of anti-flavivirus antibody kinetics and have implications for measuring vaccine efficacy and for predicting future dengue and Zika outbreaks.

Background There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings. Methods We followed 2338 people in Managua, Nicaragua, aged, A community-based cohort in Managua, Nicaragua, had very high severe acute respiratory syndrome coronavirus 2 seropositivity but lower-than-expected severity. Overall, 69% of infections were asymptomatic or subclinical and 1.1% of infections were severe. Seropositivity was associated with 93.6% protection from symptomatic reinfection through March 2021.

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate., Author summary Zika virus (ZIKV) gained global attention during an explosive outbreak in the Americas in 2015–16 when it was causally associated with the constellation of birth defects now termed congenital Zika syndrome (CZS). However, a substantial proportion of gestational ZIKV infections result in babies without apparent birth defects. Could there be other factors that influence ZIKV pathogenicity? For example, it is well-established that pre-existing immunity to one dengue virus (DENV) serotype can enhance the severity of a secondary DENV infection. ZIKV is antigenically closely related to DENV, but whether DENV-specific antibodies enhance the severity of ZIKV infection is unclear. To answer this question, we used our non-human primate model of ZIKV to assess the impact of pre-existing immunity to DENV on ZIKV pathogenesis during pregnancy. We did not observe any difference in ZIKV replication in plasma between macaques that were immune to DENV and those that were not. However, there was more ZIKV vRNA detected in the placenta of macaques immune to DENV, suggesting DENV immunity could enhance ZIKV infection of the placenta. As vaccines to both DENV and ZIKV are developed, it remains critical to understand the risks of DENV immunity for pregnant women exposed to ZIKV.

Introduction: Elevated plasma α-klotho (αKl) protects against several ageing phenotypes and has been proposed as a biomarker of a good prognosis for different diseases. The beneficial health effects of elevated plasma levels of soluble αKl (SαKl) have been likened to the positive effects of exercise on ageing and chronic disease progression. It has also been established that molecular responses and adaptations differ according to exercise dose. The aim of this study is to compare the acute SαKl response to different exercise interventions, cardiorespiratory, and strength exercise in healthy, physically active men and to examine the behavior of SαKl 72h after acute strength exercise.Methods: In this quasi-experimental study, plasma SαKl was measured before and after a cardiorespiratory exercise session (CR) in 43 men, and strength exercise session (ST) in 39 men. The behavior of SαKl was also examined 24, 48, and 72h after ST.Results: Significant differences (time×group) were detected in SαKl levels (p=0.001; d=0.86) between CR and ST. After the ST intervention, SαKl behavior varied significantly (p=0.009; d=0.663) in that levels dropped between pre- and post-exercises (p=0.025; d=0.756) and were also significantly higher compared to pre ST values at 24h (p=0.033; d=0.717) and at 48h (p=0.015; d=0.827).Conclusions: SαKl levels increased in response to a single bout of cardiorespiratory exercise; while they decreased immediately after strength exercise, levels were elevated after 24h indicating different klotho protein responses to different forms of exercise.

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

Background: In recent years, tropical countries have faced consecutive explosive epidemics of chikungunya, Zika, and now COVID-19, each of which have featured large proportions of subclinical infections. Spatial studies of epidemics typically use case-only datasets to estimate incidence rates (cases/total population), often misinterpreting them as infection risks (infections/total population) or disease risks (cases/infected population). Methods: We examined these three measures in a pediatric cohort (N≈3,000) over two chikungunya epidemics and one Zika epidemic and in a household cohort (N=1,793) over one COVID-19 epidemic in Nicaragua. We used generalized additive models, the intra-cluster correlation coefficient, cluster detection analyses, geostatistical models, and spatiotemporal models to characterize the spatial epidemiology of each epidemic and examine the limitations of the case-only incidence rate. Results: Across analyses and all epidemics, case-based incidence rates considerably underestimated both infection and disease risks, resulting in a high and spatially non-uniform degree of bias. The spatial infection risk differed from the spatial disease risk, showing that areas with many infections did not necessarily have many cases. Typical case-only approaches precluded a full understanding of the spatial contours of immunity. Standard incidence cluster analyses unpredictably resembled either clusters of infection or disease risk across all epidemics. Spatiotemporal modeling of disease incidence revealed less pronounced dynamics than spatiotemporal modeling of infection risk. Interpretation: During epidemics of pathogens that cause large numbers of subclinical infections, misinterpreting incidence rates, as is common, results in substantial bias, a general finding applicable to many pathogens of high human concern. Funding Information: This study was supported by grants R01 AI099631 (AB), P01 AI106695 (EH), R01 AI120997 (AG), and U19 AI118610 (EH) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Institutes of Health Centers of Excellence for Influenza Research and Surveillance [contract: HHS 272201400006C (AG)]; and the Open Philanthropy Project Fund for the production of recombinant SARS-CoV-2 spike protein, its receptor binding domain, and antibodies at the University of Michigan Center for Structural Biology. FBC was partially supported by a supplement to grant P01 AI106695. Declaration of Interests: Authors declare that they have no competing interests. Ethics Approval Statement: The Pediatric Dengue Cohort Study (PDCS) was approved by Institutional Review Boards of the University of California, Berkeley, the University of Michigan, Ann Arbor, and the Nicaraguan Ministry of Health. The Household Influenza Cohort Study (HICS) was approved by the University of Michigan, Ann Arbor and the Nicaraguan Ministry of Health. Participants’ parents or legal guardians provided written informed consent. Subjects six years and older provided verbal assent.

Influenza is associated with primary viral and secondary bacterial pneumonias; however, the dynamics of this relationship in populations with varied levels of pneumococcal vaccination remain unclear. We conducted nested matched case-control studies in 2 prospective cohorts of Nicaraguan children aged 2–14 years: 1 before pneumococcal conjugate vaccine introduction (2008–2010) and 1 following introduction and near universal adoption (2011–2018). The association between influenza and pneumonia was similar in both cohorts. Participants with influenza (across types/subtypes) had higher odds of developing pneumonia in the month following influenza infection. These findings underscore the importance of considering influenza in interventions to reduce global pneumonia burden.

Dengue virus (DENV) and Zika virus (ZIKV) belong to the flavivirus genus and are antigenically closely related. They also share the same mosquito vector and can cause similar symptoms upon infection. However, DENV and ZIKV infections lead to different clinical sequelae and treatments, therefore, clinicians need rapid and accurate diagnostics capable of distinguishing between the two diseases. Methods: We employed the immuno-magnetic assay technology on a microfluidic cartridge (ViroTrack Sero Zika IgG/IgM) for diagnosis of ZIKV infection based on the aggregation of magnetic nanoparticles. We carried out three serological studies including samples from the Dominican Republic, USA, and Nicaragua, aimed at detecting ZIKV-specific IgG and IgM using the ViroTrack Sero Zika IgG/IgM test. Results: The seroconversion results were comparable with ZIKV IgG and IgM reactivity measured by the commercial ZIKV ELISA kit. The sensitivity and specificity for both ZIKV IgG and IgM tested by the ViroTrack Sero Zika IgG/IgM was approximately 98% and 93%, respectively. Conclusion: Serological detection of ZIKV infection by the new ViroTrack Sero Zika IgG/IgM test shows promising performance and limited cross-reactivity with DENV.

Background Many influenza studies assume that symptomatic and asymptomatic cases have equivalent antibody responses. Methods This study examines the relationship between influenza symptoms and serological response. Influenza-positive index cases and household members in Managua, Nicaragua, during 2012–2017 were categorized by symptom status. Results Antibody response was assessed using hemagglutination inhibition assays (HAI). Among 510 cases, 74.5% had ≥4-fold increase in HAI antibodies, and 75.3% had febrile illness. In a logistic regression model, febrile cases had 2.17 times higher odds of a ≥4-fold titer rise compared to asymptomatic cases (95% confidence interval, 1.02–4.64). Conclusions Studies relying on serological assays may not generalize to asymptomatic infections.

Background Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined. Methods We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0–14 years from 2011 through 2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian nonlinear survival model to estimate pneumonia hazard following influenza. Results Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR], 2.7 [95% confidence interval {CI}, 1.9–3.9]). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR, 3.7 [95% CI, 2.0–6.9]), followed by influenza B and A(H3N2). Participants’ odds of pneumonia following influenza were not constant, showing distinct peaks 0–6 days (mOR, 8.3 [95% CI, 4.8–14.5] days) and 14–20 (mOR, 2.5 [95% CI, 1.1–5.5] days) after influenza infection. Conclusions Influenza is a significant driver of both primary and secondary pneumonia among children. The presence of distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.

We investigated humoral immune response to influenza A(H1N1)pdm infection and found 32 (22%) of the infected individuals identified by PCR failed to produce a ≥ 4-fold hemagglutinin inhibition assay (HAI) response; a subset of 18 (56%) produced an alternate antibody response (against full-length HA, HA stalk, or neuraminidase). These individuals had lower pre-existing HAI antibody titers and showed a pattern of milder illness. An additional subset of 14 (44%) did not produce an alternate antibody response, had higher pre-existing antibody titers against full-length & stalk HA, and were less sick. These findings demonstrate that some individuals mount an alternate antibody response to influenza infection. In order to design more broadly protective influenza vaccines it may be useful to target these alternate sites. These findings support that there are influenza cases currently being missed by solely implementing HAI assays, resulting in an underestimation of the global burden of influenza infection.

Background: Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations. Methods: We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls. Findings: The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other. Interpretation: There is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries. Keywords: Dengue, Genetics, Risk, GWAS, Ancestry

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn&acute, s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014&ndash, 2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 &plusmn, 2.5 years. The median EEN duration was 8 weeks (IQR 6.6&ndash, 8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn&rsquo, s Disease activity index [wPCDAI] &lt, 12.5). Faecal calprotectin (FC) levels (&mu, g/g) decreased significantly after EEN (830 [IQR 500&ndash, 1800] to 256 [IQR 120&ndash, 585] p &lt, 0.0001). Patients with wPCDAI &le, 57.5, FC &lt, 500 &mu, g/g, CRP &gt, 15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6&ndash, 8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn&rsquo, s disease regardless of the location of disease and disease activity.

In 2015, a Zika epidemic in Brazil began spreading throughout the Americas. Zika virus (ZIKV) entered Managua, Nicaragua, in January 2016 and caused an epidemic that peaked in July–September 2016. ZIKV seropositivity was estimated among participants of pediatric (n = 3,740) and household (n = 2,147) cohort studies, including an adult-only subset from the household cohort (n = 1,074), in Managua. Seropositivity was based on a highly sensitive and specific assay, the Zika NS1 blockade-of-binding ELISA, which can be used in dengue-endemic populations. Overall seropositivity for the pediatric (ages 2–14), household (ages 2–80), and adult (ages 15–80) cohorts was 36, 46, and 56%, respectively. Trend, risk factor, and contour mapping analyses demonstrated that ZIKV seroprevalence increased nonlinearly with age and that body surface area was statistically associated with increasing seroprevalence in children. ZIKV seropositivity was higher in females than in males across almost all ages, with adjusted prevalence ratios in children and adults of 1.11 (95% CI: 1.02–1.21) and 1.14 (95% CI: 1.01–1.28), respectively. No household-level risk factors were statistically significant in multivariate analyses. A spatial analysis revealed a 10–15% difference in the risk of ZIKV infections across our 3-km-wide study site, suggesting that ZIKV infection risk varies at small spatial scales. To our knowledge, this is the largest ZIKV seroprevalence study reported in the Americas, and the only one in Central America and in children to date. It reveals a high level of immunity against ZIKV in Managua as a result of the 2016 epidemic, making a second large Zika epidemic unlikely in the near future.

Epidemiologic studies indicate that obesity increases the risk of severe complications and death from influenza virus infections, especially in elderly individuals. This work investigates the effect of obesity on the duration of viral shedding within household transmission studies in Managua, Nicaragua, over 3 seasons (2015-2017). Symptomatic obese adults were shown to shed influenza A virus 42% longer than nonobese adults (adjusted event time ratio [ETR], 1.42; 95% confidence interval [CI], 1.06-1.89); no association was observed with influenza B virus shedding duration. Even among paucisymptomatic and asymptomatic adults, obesity increased the influenza A shedding duration by 104% (adjusted ETR, 2.04; 95% CI, 1.35-3.09). These findings suggest that obesity may play an important role in influenza transmission.

This report outlines the structure of and summarizes the recommendations made at the 5th International Conference on Reanalysis (ICR5), attended by 259 participants from 37 countries, in Rome (Italy), on 13-17 November 2017. It first summarizes the conference structure. Then, the key recommendations of ICR5 are given for the five main conference topics: production; observations (data rescue and preparation); data assimilation methods; quality assurance of reanalysis; and applications in science, services, and policymaking. Lastly, five high-level recommendations are proposed to managing agencies on how best to advance the field of reanalyses, which serves tens of thousands of users, via enhanced research, development, and operations.

Serologic testing remains crucial for Zika virus diagnosis. We found that urea wash in a Zika virus nonstructural protein 1 IgG ELISA distinguishes secondary dengue virus infection from Zika virus infection with previous dengue (sensitivity 87.5%, specificity 93.8%). This test will aid serodiagnosis, serosurveillance, and monitoring of Zika complications in dengue-endemic regions.

The database of the Global Influenza B Study was created by collecting surveillance datasets from each of the participating countries. These national datasets are owned by the participating countries, and thus cannot be shared publicly. Researchers interested in obtaining the country-specific datasets may contact the individuals listed below for further details regarding data access.Argentina (Santa Fe Province): Gabriela Kusznierz (labconi@yahoo.com.ar)Australia: Kate Pennington (kate.pennington@health.gov.au)Bhutan: Sonam Wangchuk (swangchuk@health.gov.bt)Brazil: Cláudio Maierovitch Pessanha Henriques (claudio.henriques@saude.gov.br)Cameroon: Guy Vernet (vernet@pasteur-yaounde.org)Chile: Rodrigo Fasce (rfasce@ispch.cl)China: Feng Luzhao (fenglz@chinacdc.cn)Costa Rica: Alexey W. Clara (wclara@cdc.gov)Ecuador: Alfredo Bruno (alfredobruno@yahoo.es)El Salvador: Alexey W. Clara (wclara@cdc.gov)England: Maria Zambon (maria.zambon@phe.gov.uk)Guatemala: Alexey W. Clara (wclara@cdc.gov)Honduras: Alexey W. Clara (wclara@cdc.gov)Indonesia: Herman Kosasih (hermaninarespond@gmail.com)Italy: Caterina Rizzo (caterina.rizzo@iss.it)Ivory Coast: Herve A. Kadjo (hervekadjo@pasteur.ci)Kazakhstan: Gulzhan Muratbayeva (hnv2@cdc.gov)Kenya: Joshua Mott (zud9@cdc.gov)Madagascar: Jean-Michel Heraud (jmheraud@pasteur.mg)Morocco: Amal Barakat (amal.barakat@yahoo.fr)New Zealand: Sue Huang (sue.huang@esr.cri.nz)Nicaragua: Alexey W. Clara (wclara@cdc.gov)Panama: Alexey W. Clara (wclara@cdc.gov)Portugal: Ana Paula Rodrigues (ana.rodrigues@insa.min-saude.pt)Singapore: Vernon Lee (vernonljm@hotmail.com)South Africa: Cheryl Cohen (cherylc@nicd.ac.za)Turkey: Meral Akcay Ciblak (ciblakm@yahoo.com)Ukraine: Alla Mironenko (miralla@ukr.net)Viet Nam: Le Thi Quinh Mai (lom9@hotmail.com); International audience; BACKGROUND:Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases).METHODS:For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity.RESULTS:The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play.CONCLUSIONS:These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

In this low-income country setting, ≈16% of household contacts acquired infections from index patients, despite high oseltamivir use., During August 2012–November 2014, we conducted a case ascertainment study to investigate household transmission of influenza virus in Managua, Nicaragua. We collected up to 5 respiratory swab samples from each of 536 household contacts of 133 influenza virus–infected persons and assessed for evidence of influenza virus transmission. The overall risk for influenza virus infection of household contacts was 15.7% (95% CI 12.7%–19.0%). Oseltamivir treatment of index patients did not appear to reduce household transmission. The mean serial interval for within-household transmission was 3.1 (95% CI 1.6–8.4) days. We found the transmissibility of influenza B virus to be higher than that of influenza A virus among children. Compared with households with 4 household contacts appeared to have a reduced risk for infection. Further research is needed to model household influenza virus transmission and design interventions for these settings.

More information about influenza in low- and middle-income countries could guide the establishment of pediatric influenza vaccine programs. This study (1) characterizes the burden of influenza in infants, and (2) compares signs and symptoms by prior influenza vaccination or influenza illness. Newborns from Managua, Nicaragua, were followed for two years. Data came from primary medical appointments, PCR testing, and parents’ daily symptom diaries. Logistic regression models estimated associations between preceding vaccination or illness and influenza incidence. Linear models compared duration of illness by prior vaccination or influenza illness. Among 833 infants, 31% had PCR-positive influenza, and 28% were vaccinated against influenza. Four (&lt, 0.5%) were fully vaccinated. Overall, influenza incidence was 21.0 (95% confidence interval (CI): 18.8, 23.2) per 100 person-years. Incidence was lower among those with prior influenza compared with those without preceding illness or vaccination (OR: 0.64, 95% CI: 0.44, 0.94). Partially vaccinated children had 1 day less fever than those without prior illness or vaccination (p = 0.049). A large proportion of children &lt, 2 years in Nicaragua contract influenza. Illness was attenuated for those partially vaccinated. Since few children were fully vaccinated, future studies will need to consider the effectiveness of a two-dose vaccination schedule.

Resumen Introduccion Las manifestaciones neurologicas son frecuentes en los pacientes afectos de enfermedad inflamatoria intestinal, y en muchas ocasiones, son infradiagnosticadas. Pueden preceder a la aparicion de la clinica intestinal. Algunas de ellas pueden ser irreversibles y potencialmente mortales. La afectacion tromboembolica es una complicacion rara, mas frecuente en pacientes afectos de colitis ulcerosa, y favorecida por un estado de hipercoagulabilidad multifactorial. Pacientes y metodologia Aportamos el caso de un paciente pediatrico con enfermedad de Crohn refractaria a tratamiento, quien 3 anos despues del inicio de la enfermedad presenta una trombosis venosa cerebral. Revisamos todos los casos pediatricos descritos en la literatura y realizamos un estudio comparativo con nuestro caso. Resultados Se describen 18 pacientes en edad pediatrica que presentan trombosis de senos venosos cerebrales como manifestacion extradigestiva de su enfermedad intestinal, siendo esta complicacion mas frecuente en la colitis ulcerosa (61,1%). La trombocitosis y la anemia ferropenica son los factores de riesgo mas comunmente encontrados, junto con algunas alteraciones geneticas de la coagulacion. El tratamiento realizado en la mayoria de los pacientes se basa en heparina y anticoagulacion oral, presentando una evolucion favorable de la clinica neurologica mas del 75% de ellos. Conclusion La afectacion vascular cerebral es una complicacion rara en este tipo de pacientes, pero un diagnostico y tratamiento precoces son imprescindibles para una buena evolucion.

Background The explosive spread of Zika virus (ZIKV) and associated microcephaly present an urgent need for sensitive and specific serodiagnostic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent reports of enhanced ZIKV replication by dengue-immune sera have raised concerns about the role of previous DENV infection on the risk and severity of microcephaly and other ZIKV complications. Methods Enzyme-linked immunosorbent assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were established to test acute, convalescent phase, and post-convalescent phase serum/plasma samples from reverse-transcription polymerase chain reaction-confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58 secondary DENV, and 16 primary DENV1 infections. Results ZIKV-NS1 immunoglobulin M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within 1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV infections with a sensitivity of 87.5% and specificity of 81.3%. These findings were supported by analysis of sequential samples. Conclusions An algorithm for ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV infection during pregnancy to understand the epidemiology, pathogenesis, and complications of ZIKV in dengue-endemic regions.

Background We sought to characterize dengue virus (DENV) infections among febrile children enrolled in a pediatric cohort study who were clinically diagnosed with a non-dengue illness ("C cases"). Methods DENV infections were detected and viral load quantitated by real-time reverse transcription-polymerase chain reaction in C cases presenting between January 2007 and January 2013. Results One hundred forty-one of 2892 C cases (4.88%) tested positive for DENV. Of all febrile cases in the study, DENV-positive C cases accounted for an estimated 52.0% of patients with DENV viremia at presentation. Compared with previously detected, symptomatic dengue cases, DENV-positive C cases were significantly less likely to develop long-lasting humoral immune responses to DENV, as measured in healthy annual serum samples (79.7% vs 47.8%; P < .001). Humoral immunity was associated with viral load at presentation: 40 of 43 patients (93.0%) with a viral load ≥7.0 log10 copies/mL serum developed the expected rise in anti-DENV antibodies in annual samples versus 13 of 68 (19.1%) patients with a viral load below this level (P < .001). Conclusions Antibody responses to DENV-positive C cases differ from responses to classic symptomatic dengue. These findings have important implications for DENV transmission modeling, immunology, and epidemiologic surveillance.

This study measures the extent to which the gender perspective is taken into account in Occupational Health & Safety (OHS) management and proposes an innovative approach for managing it. This work is an exploratory study of the relations between women’s OHS and Corporate Social Responsibility (CSR) through the examination of the main management practices that literature supports in a survey conducted at 117 companies in Spain with different levels of commitment to gender equality. Overall, the practices in question are found to be deployed to a moderate extent and their impact is limited. The most relevant initiatives are those related to the prevention, punishment and eradication of sexual harassment in the workplace and violence against women. Our findings indicate that compliance with the law and the importance of external recognition in CSR are main drivers in promoting the gender perspective in OHS. A coherent framework is suggested for addressing women’s OHS management based on a voluntary, preventive, systematic approach that goes beyond sexual and reproductive issues, namely the CSR.

Latest estimates suggest 390 million infections of dengue occur each year, of which 100 million results in symptomatic disease. The new clinical classification proposed by WHO-TRD 2009 simplifies dengue fever (DF) into dengue (D) and severe dengue (SD) w...

Advanced metastatic melanoma, one of the most aggressive skin malignancies, is currently without reliable therapy. The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone which exerts many pharmacological activities against cancer-inflammation. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we demonstrate that mangiferin interferes with inflammation, lipid and calcium signaling which selectively inhibits multiple NFkB target genes including interleukin-6, tumor necrosis factor, interferon gamma, vascular endothelial growth factor receptor 2, plasminogen activator urokinase, matrix metalloprotease 19, C-C Motif Chemokine Ligand 2 and placental growth factor. This abrogates angiogenic and invasive processes and capillary tube formation of metastatic melanoma cells as well as human placental blood vessel explants in-vitro and blocks angiogenesis characteristic of the chicken egg chorioallantoic membrane assay and in melanoma syngeneic studies in vivo. The results obtained in this research illustrate promising anti-angiogenic effects of the natural glucosylxanthone mangiferin for further (pre)clinical studies in melanoma cancer patients.

Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations. Fil: Todd, Robert E.. Woods Hole Oceanographic Institution; Estados Unidos Fil: Chavez, Francisco. Monterey Bay Aquarium Research Institute; Estados Unidos Fil: Clayton, Sophie. Old Dominion University; Estados Unidos Fil: Cravatte, Sophie E.. Centre National de la Recherche Scientifique. Institut de Recherche pour le Développement; Francia. Universite de Toulouse; Francia Fil: Goes, Marlos P.. University of Miami; Estados Unidos Fil: Graco, Michelle I.. Instituto del Mar del Peru; Perú Fil: Lin, Xiaopei. Ocean University of China; China Fil: Sprintall, Janet. University of California; Estados Unidos Fil: Zilberman, Nathalie V.. University of California; Estados Unidos Fil: Archer, Matthew. California Institute of Technology; Estados Unidos Fil: Arístegui, Javier. Universidad de Las Palmas de Gran Canaria; España Fil: Balmaseda, Magdalena A.. European Centre for Medium-Range Weather Forecasts; Reino Unido Fil: Bane, John M.. University of North Carolina; Estados Unidos Fil: Baringer, Molly O.. Atlantic Oceanographic and Meteorological Laboratory ; Estados Unidos Fil: Barth, John A.. State University of Oregon; Estados Unidos Fil: Beal, Lisa M.. University of Miami; Estados Unidos Fil: Brandt, Peter. Geomar-Helmholtz Centre for Ocean Research Kiel; Alemania Fil: Calil, Paulo H.. Universidade Federal do Rio Grande; Brasil Fil: Campos, Edmo. Universidade de Sao Paulo; Brasil Fil: Centurioni, Luca R.. University of California; Estados Unidos Fil: Chidichimo, María Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; Argentina Fil: Cirano, Mauro. Universidade Federal do Rio de Janeiro; Brasil Fil: Cronin, Meghan F.. National Oceanic and Atmospheric Administration. Pacific Marine Environmental Laboratory; Estados Unidos Fil: Curchitser, Enrique N.. Rutgers University; Estados Unidos Fil: Davis, Russ E.. University of California; Estados Unidos Fil: Dengler, Marcus. Geomar-Helmholtz Centre for Ocean Research Kiel; Alemania Fil: DeYoung, Brad. Memorial University of Newfoundland; Canadá Fil: Dong, Shenfu. University of Miami; Estados Unidos Fil: Escribano, Ruben. Universidad de Concepción; Chile Fil: Fassbender, Andrea J.. Monterey Bay Aquarium Research Institute; Estados Unidos

Background Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes. Methods At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained. Discussion With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure. Trial registration NCT02856984. Registered August 5, 2016. Retrospectively registered.

Summary Background Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants. Methods The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015–16 and 2016–17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period (2015–16) in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses. Findings Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenza-positive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2·6 (95% CI 2·0–3·6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis. Interpretation If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes. Funding US Centers for Disease Control and Prevention.

Background Respiratory syncytial virus (RSV) causes substantial morbidity and mortality among children worldwide, commonly through acute lower respiratory tract infections (ALRI). To assess the incidence rate of symptomatic RSV illness among young children, we conducted a prospective birth cohort study following children from 0–2 years of age in Managua, Nicaragua. Methods Children meeting the testing criteria (fever, history of fever, or severe respiratory symptoms [apnea, stridor, nasal flaring, wheezing, chest indrawing, and/or central cyanosis]) were tested for RSV infections using real-time reverse transcriptase-polymerase chain reaction. An acute lower respiratory infection was defined as a diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity. The incidence rate was calculated, and 95% confidence intervals were estimated using a Poisson distribution. Results A total of 833 children participated in the cohort: 289 (34.7%) had at least 1 episode of laboratory-confirmed RSV, and 156 (18.7%) of had an episode of RSV-associated ALRI (RSV-ALRI). The incidence rate of symptomatic RSV was 248.1 cases per 1000 person-years (95% confidence interval [CI] 223.2–275.7). While infants aged 6–11 months had the highest incidence of symptomatic RSV (361.3/1000 person-years, 95% CI 304.4–428.8), infants, Around one-third of medical deaths among Nicaraguan children under 2 years were respiratory syncytial virus–associated, suggesting it’s an important driver of infant mortality in highly vaccinated populations with little human immunodeficiency virus or malaria.

Summary Background Paedeatric Zika remains an understudied topic. WHO and the Pan American Health Organization (PAHO) Zika case definitions have not been assessed in children. We aimed to characterise clinical profiles and evaluate the diagnostic performance of the WHO and PAHO case definitions in a large cohort of paediatric Zika cases. Methods From January, 2016 to February, 2017, encompassing the major 2016 Zika epidemic, participants in the Pediatric Dengue Cohort Study (PDCS) in Managua, Nicaragua, were encouraged to visit the study health centre at first indication of any illness. PDCS participants were aged 2–14 years, healthy at enrolment, and recruited before the initiation of the present study. Molecular and serological assays were used to test participants exhibiting any of four broad clinical profiles suspected of resulting from a symptomatic Zika virus infection. These clinical profiles were: fever and at least two of headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, and leukopenia; fever and at least two of nausea or vomiting, rash, aches and pains, positive tourniquet test, leukopenia, and any dengue warning sign; undifferentiated fever without evident cause, with or without any other clinical finding; and afebrile rash with or without any other clinical finding. We characterised acute clinical findings (signs, symptoms, and complete blood counts) in both Zika cases and non-Zika cases. Findings We prospectively followed a cohort of about 3700 children, of which 1110 were deemed eligible for inclusion. Four participants with laboratory-confirmed Zika (three co-infections with dengue virus, one missing complete blood count data) and two participants who were non-Zika cases (missing complete blood count data) were excluded from analysis. We analysed 556 laboratory-confirmed Zika and 548 non-Zika cases. The WHO case definition captured 176 confirmed Zika cases, and the PAHO definition 109 confirmed Zika cases, who presented with the most clinical findings and a dengue-like clinical profile. The remaining two thirds of Zika cases, principally characterised by undifferentiated fever or afebrile rash, were missed. Among Zika cases, rash (n=440)—particularly generalised erythematous rash (n=334)—fever (n=333), leukopenia (n=217), and headache (n=203) were most common and peaked within 3 days of illness onset. The most common Zika presentation over the first week of illness was rash only (n=80). The sensitivity of Zika case definitions increased across paediatric age (from 11·3% to 56·1% for the WHO case definition and from 6·0% to 36·6% for the PAHO case definition), as the prevalence of most clinical findings (particularly arthralgia) increased with age, irrespective of previous dengue virus infection. Consequently, Zika manifested differently across paediatric age; older Zika cases presented with a dengue-like clinical profile while younger Zika cases presented with undifferentiated fever or afebrile rash. Interpretation We provide the most thorough description of paediatric Zika to date. Most paediatric Zika cases go undetected under the WHO and PAHO case definitions, suggesting that current standards for Zika case ascertainment require revision. Zika manifests with mild but differing clinical profiles across paediatric age, presenting major challenges to diagnosis, surveillance, and efforts to control future Zika epidemics. Funding US National Institutes of Health.

Background Influenza causes a substantial burden worldwide, and current seasonal influenza vaccine has suboptimal effectiveness. To develop better, more broadly protective vaccines, a more thorough understanding is needed of how antibodies that target the influenza virus surface antigens, hemagglutinin (HA) (including head and stalk regions) and neuraminidase (NA), impact influenza illness and virus transmission. Methods We used a case-ascertained, community-based study of household influenza virus transmission set in Managua, Nicaragua. Using data from 170 reverse transcriptase–polymerase chain reaction (RT-PCR)–confirmed influenza virus A(H1N1)pdm infections and 45 household members with serologically confirmed infection, we examined the association of pre-existing NA, hemagglutination inhibiting, and HA stalk antibody levels and influenza viral shedding and disease duration using accelerated failure time models. Results Among RT-PCR–confirmed infections in adults, pre-existing anti-NA antibody levels ≥40 were associated with a 69% (95% confidence interval [CI], 34–85%) shortened shedding duration (mean, 1.0 vs 3.2 days). Neuraminidase antibody levels ≥80 were associated with further shortened shedding and significantly shortened symptom duration (influenza-like illness, 82%; 95% CI, 39–95%). Among RT-PCR–confirmed infections in children, hemagglutination inhibition titers ≥1:20 were associated with a 32% (95% CI, 13–47%) shortened shedding duration (mean, 3.9 vs 6.0 days). Conclusions Our results suggest that anti-NA antibodies play a large role in reducing influenza illness duration in adults and may impact transmission, most clearly among adults. Neuraminidase should be considered as an additional target in next-generation influenza virus vaccine development. We found that antibodies against neuraminidase were associated with significantly shortened viral shedding, and among adults they were also associated with shortened symptom duration. These results support neuraminidase as a potential target of next-generation influenza virus vaccines.

The understanding of immunological interactions among the four dengue virus (DENV) serotypes and their epidemiological implications is often hampered by the lack of individual-level infection history. Using a statistical framework that infers full infection history, we analyze a prospective pediatric cohort in Nicaragua to characterize how infection history modulates the risks of DENV infection and subsequent clinical disease. After controlling for age, one prior infection is associated with 54% lower, while two or more are associated with 91% higher, risk of a new infection, compared to DENV-naive children. Children >8 years old have 55% and 120% higher risks of infection and subsequent disease, respectively, than their younger peers. Among children with ≥1 prior infection, intermediate antibody titers increase, whereas high titers lower, the risk of subsequent infection, compared with undetectable titers. Such complex dependency needs to be considered in the design of dengue vaccines and vaccination strategies., Lack of knowledge of individual infection history hinders understanding of immunological interactions among DENV serotypes. Here, the authors introduce a framework to infer the relationship between unobserved infection history and subsequent infection and disease risk, and find complex dependencies.

Little is known about enduring memory B cell (MBC) responses to Zika virus (ZIKV) and their relationship with circulating antibodies. Here we comprehensively assess MBC frequency and specificity alongside serum binding and neutralizing antibody responses to ZIKV ~2 weeks and ~8 months postinfection in 31 pediatric subjects with 0, 1 or >1 prior infections with the related dengue virus (DENV). ZIKV infection elicits a robust type-specific MBC response, and the majority of late convalescent anti-ZIKV serum neutralizing activity is attributable to ZIKV-specific antibodies. The number of prior DENV infections does not influence type-specific or cross-reactive MBC responses, although ZIKV has the highest cross-reactivity with DENV3. DENV cross-reactive MBCs expanded by ZIKV infection decline in number and proportion by late convalescence. Finally, ZIKV induces greater cross-reactivity in the MBC pool than in serum antibodies. Our data suggest immunity to DENV only modestly shapes breadth and magnitude of enduring ZIKV antibody responses., Here, Andrade et al. assess the memory B cell (MBC) and antibody response to Zika virus (ZIKV) in individuals with and without prior dengue virus (DENV) infection and find that ZIKV infection elicits a robust and specific MBC response that is only modestly affected by the number of prior DENV infections.

Leishmaniasis is defined as a set of diseases of very varied clinical presentation produced by obligate intracellular parasites belonging to the genus Leishmania. They have been classified by the World Health Organization in category I of infectious diseases and are part of neglected tropical pathologies. Leishmania infantum mainly affects children under five years of age and has been associated with an increase in the appearance of cutaneous and visceral leishmaniasis. The search for new therapeutic alternatives remains a challenge and in silico studies are alternative tools to solve this problem. With the main objective of identify potentially effective compounds against Leishmania infantum through in silico studies, artificial Intelligence techniques implemented in the WEKA program and molecular descriptors 0D-2D of DRAGON software are used in this research. A new database was created and the clusters analysis (AC) k-means was used to design the training and prediction series. Four models were obtained with the following techniques: IBk, J48, MLP and SMO that reached percentages of classification higher than 80% for training and prediction series, whose predictive power was confirmed through external and internal validation procedures. The use of the models obtained in the virtual screening of the international database DrugBank and synthesis compounds allowed the optimal identification of 120 new potentially active compounds against Leishmania infantum amastigote form.

Purpose Manifestations of infection and the degree of influenza virus vary. We hypothesized that the nose/throat microbiota modifies the duration of influenza symptoms and viral shedding. Exploring these relationships may help identify additional methods for reducing influenza severity and transmission. Methods Using a household transmission study in Nicaragua, we identified secondary cases of influenza virus infection, defined as contacts with detectable virus or a greater than 4-fold change in hemagglutinin inhibition antibody titer. We characterized the nose/throat microbiota of secondary cases before infection and explored whether the duration of symptoms and shedding differed by bacterial community characteristics. Results Among 124 secondary cases of influenza, higher bacterial community diversity before infection was associated with longer shedding duration (Shannon acceleration factor [AF]: 1.61, 95% confidence interval [CI]: 1.24, 2.10) and earlier time to infection (Shannon AF: 0.72, 95% CI: 0.53, 0.97; Chao1 AF: 0.992, 95% CI: 0.986, 0.998). Neisseria and multiple other oligotypes were significantly associated with symptom and shedding durations and time to infection. Conclusions The nose/throat microbiota before influenza virus infection was associated with influenza symptoms and shedding durations. Further studies are needed to determine if the nose/throat microbiota is a viable target for reducing influenza symptoms and transmission.

La esclerosis múltiple compromete la capacidad motora y cognitiva de los afectados, implicando afectación psicológica en diversas áreas de su vida. En este trabajo pretendemos evaluar la depresión, la ansiedad y la inadaptación de pacientes con esclerosis múltiple, así! como analizar las posibles diferencias en función de distintas variables sociodemográficas. La muestra está formada por 60 enfermos (38,33 % hombres y 61,67 % mujeres) con una edad media de 44,38 años (DT = 9,5). Todos ellos han cumplimentado la escala de inadaptación (Echeburúa, Corral y Fernández Montalvo 2000) y la escala de ansiedad y depresión hospitalaria (HADS; Zigmond y Snaith 1983). Los resultados muestran una media en ansiedad de 7,48 (DT = 3,62) y en depresión de 6,98 (DT = 4,34). En cuanto a la escala de inadaptación, los pacientes presentan una interferencia global de 2,87 (DT = 1,33) en un rango de 0-5, siendo el ámbito más afectado el de «Trabajo y/o estudios» (media = 3,08; DT!= 1,61) y el menos afectado el de «Vida familiar» (media = 1,72; DT = 1,38). Los análisis muestran diferencias significativas en función del género en ansiedad (t = 2,61; p-valor = 0,013), depresión (t = 2,75; p-valor = 0,008) e interferencia global (t = 1,93; p-valor = 0,059). Las diferencias en función del género también son significativas en «Relación de pareja» (t = 2,26; pvalor = 0,029). Respecto a la situación laboral, se han obtenido diferencias en todas las áreas de interferencia, así como en la inadaptación global (pvalor = 0,002). Estos datos evidencian afectación emocional en los pacientes, en línea con estudios anteriores, observándose diferencias en función de distintas variables, información valiosa para iniciar programas de prevención/intervención que mejoren el afrontamiento de la enfermedad. Multiple Sclerosis alters motor and cognitive capacity, implying psychological affectation in diverse areas of their lives. The aim of this paper is to evaluate depression, anxiety and adjustment in patients who suffer from Multiple Sclerosis, and to analyze differences depending on several socio-demographic variables. The sample includes 60 patients (38.33 % men and 61.67 % women), whose average age is 44,38 (SD = 9,5). They have all completed the Unadaptability Scale (Echeburúa, Corral & Fernández Montalvo 2000) and Hospital Anxiety and Depression Scale (HADS; Zigmond and Snaith 1983). The results show a mean score of 7.48 (SD = 3.62) in anxiety, and 6.98 (SD = 4.34) in depression. Regarding Unadaptability Scale, the global score is of 2.87 (SD = 1.33) in a 0-5 rank. The most affected area is “Work and/or studies” (Mean = 3.08; SD = 1.61) and the least affected “Family life” (Mean = 1.72; SD = 1.38). Analysis show significant differences according to the gender in anxiety (t = 2.61; p-value = 0.013), depression (t = 2.75; p-value = 0.008) and global unadaptability (t = 1.93; p-value = 0.059). Differences according to the gender are also significant in “Couple’s relationship” (t = 2.26; p-value = 0.029). Regarding employment status, differences in all unadaptability areas and in global unadaptability have been found (p-value = 0.02). These data evidence emotional disturbances in patients, in line with prior research, showing differences according to several variables. This represents valuable information to initiate prevention/intervention programmes to improve disease’s coping.

Fuzzy Cognitive Maps (FCM) are dedicated to modeling complex dynamic systems and has been widely studied. One of those studies probed that Computing with Words (CWW) is very effective to improve the interpretability and transparency of FCM. Learning methods to calculate the weight matrix in a map are the target of hundreds of studies in various parts of the world. These methods allow the map to learn or evolve towards a better state, but always taking into account that the output must be evaluated and compared using a real scenario. Reinforcement Learning has, within its performance, one of the possible answers to this problem, aimed at improving the classification capacity of the map and thus improving the learning of its weights. This paper presents a new learning method for Fuzzy Cognitive Maps. The proposal was evaluated using international databases and the experimental results show a satisfactory performance.