scholarly journals Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia

2021 ◽  
Author(s):  
Kelvin Mokaya Abuga ◽  
John Muthii Muriuki ◽  
Sophie M Uyoga ◽  
Kennedy Mwai ◽  
Johnstone Makale ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Bacterial Growth ◽  
Iron Status ◽  
Plasmodium Falciparum Malaria ◽  
Hospitalized Children ◽  
Soluble Transferrin Receptor ◽  
Community Based ◽  
Increased Risk ◽  
Life Threatening ◽  
The Relationship

Background: Severe malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth, within the Salmonella-containing vacuole. Methods: We first investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged ≤5 years between August 1998 and October 2019 (n=75,015). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malaria anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA alone (n=33); (3) NTS alone (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. Results: In hospitalized children SMA, but not other malaria phenotypes, was associated with an increased risk of NTS (adjusted OR 2.88 [95% CI 1.97, 4.23]; P<0.0001). Risk of NTS increased by 30% with each 1g/dl decrease in hemoglobin concentrations. In hospitalized children median hepcidin levels were lower in the SMA+NTS (9.3 ng/mL [interquartile range 4.7, 49.8]) and SMA (31.1 ng/mL [5.5, 61.2]) groups, compared to levels in those with CM (90.7 ng/mL [38.7, 176.1]) or NTS (105.8 ng/mL [17.3, 233.3]), despite similar ferritin and CRP levels. Soluble transferrin receptor levels were lower in the CM group compared to the other hospitalized groups. Conclusion: SMA was associated with increased risk of NTS and with reduced hepcidin levels. We hypothesized that reduced hepcidin might allow increased movement of iron into the Salmonella-containing vacuole favoring bacterial growth.

scholarly journals Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia

Haematologica ◽  
2021 ◽  
Author(s):  
Kelvin M. Abuga ◽  
John Muthii Muriuki ◽  
Sophie M. Uyoga ◽  
Kennedy Mwai ◽  
Johnstone Makale ◽  
...  
Keyword(s):  
Bacterial Growth ◽  
Iron Status ◽  
Plasmodium Falciparum Malaria ◽  
Asymptomatic Malaria ◽  
Severe Anemia ◽  
Iron Availability ◽  
Community Based ◽  
Increased Risk ◽  
Life Threatening ◽  
The Relationship

Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged ≤5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a two-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10 [IQR 0.03, 0.19]) than those with CM (0.24 [0.14, 0.69]; P=0.006) or asymptomatic malaria (0.19 [0.09, 0.46]; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL [4.7, 49.8]) and hepcidin/ferritin ratios (0.03 [0.01, 0.22]) than those with NTS alone (105.8 ng/mL [17.3, 233.3]; P=0.02 and 0.31 [0.06, 0.66]; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole (SCV), we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidinferroportin axis might mediate susceptibility to NTS in severely anemic children.

Abstract P254: Daytime Napping is Associated With Incident Stroke in Community

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Xuting Jin ◽  
Bin Yan ◽  
Ruohan Li ◽  
Ya Gao ◽  
Jingjing Zhang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Life Quality ◽  
Health Study ◽  
Sleep Habits ◽  
Community Based ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Registration Number ◽  
The Relationship

Introduction: There are conflicting reports regarding whether daytime napping is a risk factor for cardiovascular events. The purpose of this study was to investigate the relationship between daytime napping and incident stroke within a community-based cohort study. Hypothesis: We assessed the hypothesis that the duration and the frequency of daytime napping may be associated with incident stroke. Methods: Participants without previous stroke were enrolled in the present prospective study from the Sleep Heart Health Study (registration number, NCT00005275). Daytime napping were assessed with a self-reported Sleep Habits Questionnaire. Duration of daytime napping was divided into the following categories: no naps, 0-30 min, 31-60 min, or >60 min. Frequency of naps were categorised as: no naps, 1-2 times/week, 3-4 times/week, 5-6 times/week, or daily. After combining nap duration and frequency, participants were further divided into groups with regular long naps (≥5 times per week and >30 min), regular short naps (≥5 times per week and ≤30 min), irregular naps or no naps. Subsequently, participants were followed up until the first stroke occurred between the date of the completed questionnaire and the final censoring date. Cox regression analysis was used to estimate the relationship between daytime napping and incident stroke. Results: The present study enrolled 4757 participants, of which 220 participants (4.6%) experienced incident stroke during an average follow-up of 10.6 years. There was a higher rate of stroke among participants taking longer and more frequent naps than others. Multivariate Cox regression analysis indicated that, when compared with participants with no naps, those with a nap duration of ≥60 min or of 31-60 min had a higher risk of stroke (HR, 2.182; 95% CI, 1.443-3.301; HR, 1.594; 95% CI, 1.003-2.531, respectively). Moreover, there was an increased risk of stroke among participants taking daily daytime naps (HR, 1.563; 95% CI, 1.059-2.307) or napping 5-6 times per week (HR, 1.548; 95% CI, 1.026-2.335) than those with no naps. And after combining nap duration and frequency, regular long naps and regular short naps were also associated with higher risk of incident stroke (HR, 1.903; 95% CI, 1.182-3.065; HR, 1.451; 95% CI, 1.010-2.084, respectively). Conclusions: In conclusion, daytime napping of long duration and high frequency may increase the risk of incident stroke in community. Modification of sleep habits may improve the life quality among those elderly community-based population.

Abstract P539: The Association Between Social Isolation and Metabolic Syndrome in Japanese Adults: The Tohoku Medical Megabank Project

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Yuka Kotozaki ◽  
Kozo Tanno ◽  
Kotaro Otsuka ◽  
Ryouhei Sasaki ◽  
Nobuyuki Takanashi ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Social Isolation ◽  
Group Versus ◽  
Current Smoker ◽  
Community Based ◽  
Japanese Adults ◽  
Increased Risk ◽  
The Social ◽  
History Of ◽  
The Relationship

Metabolic syndrome (MetS) and its components are well established as risk factors for cardiovascular disease (CVD). On the other hand, it has also been reported that social isolation is associated with an increased risk of CVD. However, the relationship between social isolation and MetS and its components is not clear. Thus, the purpose of this study is to investigate the association between social isolation and the number of MetS components in Japanese adults. Participants were 28,917 individuals (male/female = 10,226/18,691, age = 59.9±11.6 years) from the Iwate area of the Tohoku Medical Megabank Organization Community-based cohort study (TMM CommCohort study). They had no history of coronary heart disease or stroke. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6). The participants were classified into two groups, the social isolation group and the non-isolation group, based on a cutoff point of 11/12 on the LSNS-6. An assessment of MetS used the criteria defined by the Japanese societies’ committee. The multivariate-adjusted odds ratios (95% confidence intervals) [AORs (95% CIs)] of the social isolation group versus the non-isolation group were calculated using ordered logistic analyses and compared to the number of MetS components. We used gender, age, education, current smoker, current alcohol drinker, total physical activity, current job status, and depression as covariates. AORs (95% CIs) of social isolation against non-isolation were 1.02 (0.95-1.09) for one component of MetS, 1.09 (1.01-1.19) for two components of MetS, and 1.16 (1.06-1.28) for three or more components of MetS, when compared to 0 component of MetS. In conclusion, Japanese adults who experience social isolation might have a greater number of MetS components.

scholarly journals Identifying the Components of Acidosis in Patients With Severe Plasmodium falciparum Malaria Using Metabolomics

2018 ◽  
Vol 219 (11) ◽  
pp. 1766-1776 ◽  
Author(s):  
Stije J Leopold ◽  
Aniruddha Ghose ◽  
Erik L Allman ◽  
Hugh W F Kingston ◽  
Amir Hossain ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Intestinal Barrier ◽  
Plasmodium Falciparum Malaria ◽  
Intestinal Barrier Function ◽  
Life Threatening ◽  
Plasma Marker ◽  
Severe Falciparum Malaria

AbstractBackgroundAcidosis in severe Plasmodium falciparum malaria is associated with high mortality, yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of metabolic acids contributing to acidosis in patients with severe falciparum malaria.MethodsA prospective observational study was conducted to characterize circulating acids in adults with P. falciparum malaria (n = 107) and healthy controls (n = 45) from Bangladesh using high-resolution liquid chromatography–mass spectrometry metabolomics. Additional in vitro P. falciparum culture studies were performed to determine if parasites release the acids detected in plasma from patients with severe malaria acidosis.ResultsWe identified previously unmeasured plasma acids strongly associated with acidosis in severe malaria. Metabolomic analysis of P. falciparum parasites in vitro showed no evidence that these acids are released by the parasite during its life cycle. Instead, 10 of the plasma acids could be mapped to a gut microbial origin. Patients with malaria had low L-citrulline levels, a plasma marker indicating reduced gut barrier integrity. Longitudinal data showed the clearance of these newly identified acids was delayed in fatal cases.ConclusionsThese data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria.Clinical Trials RegistrationNCT02451904.

scholarly journals Loneliness, health and mortality

2017 ◽  
Vol 28 (2) ◽  
pp. 234-239 ◽  
Author(s):  
J. Henriksen ◽  
E. R. Larsen ◽  
C. Mattisson ◽  
N. W. Andersson
Keyword(s):  
Mortality Risk ◽  
Structured Interviews ◽  
Community Based ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Relative Risk Of Death ◽  
The Relationship ◽  
Health And Mortality

Aims.Literature suggests an association between loneliness and mortality for both males and females. Yet, the linkage of loneliness to mortality is not thoroughly examined, and need to be replicated with a long follow-up time. This study assessed the association between loneliness and mortality, including associations to gender, in 1363 adult swedes.Methods.This community-based prospective cohort study from the Swedish Lundby Study included 1363 individuals of whom 296 individuals (21.7%) were identified as lonely with use of semi-structured interviews in 1997. The cohort was followed until 2011 and survival analyses were used to estimate the relative risk of death.Results.Death occurred with an incidence rate of 2.63 per 100 person-years and 2.09 per 100 person-years for lonely and non-lonely individuals, respectively. In crude analysis, loneliness was associated with a significant increased mortality risk of 27% compared with non-lonely individuals [hazard ratio (HR) 1.27; 95% CI 1.01–1.60]. Unadjusted, lonely females had a significant increased risk (HR 1.76; 95% CI 1.31–2.34) and adjusted insignificant increased mortality risk of 27% (HR 1.27; 95% CI 0.92–1.74), compared with non-lonely females. Lonely males were found to have an adjusted significant decreased risk of mortality (HR 0.50; 95% CI 0.32–0.80), compared with non-lonely males.Conclusions.Findings suggest an association between loneliness and increased risk of mortality and that gender differences may exist, which have not been previously reported. If replicated, our results indicate that loneliness may have differential physical implications in some subgroups. Future studies are needed to further investigate the influence of gender on the relationship.

scholarly journals Malaria infection and severe disease risks in Africa

Science ◽  
2021 ◽  
Vol 373 (6557) ◽  
pp. 926-931 ◽  
Author(s):  
Robert S. Paton ◽  
Alice Kamau ◽  
Samuel Akech ◽  
Ambrose Agweyu ◽  
Morris Ogero ◽  
...  
Keyword(s):  
East Africa ◽  
Severe Malaria ◽  
Hospital Admissions ◽  
Severe Disease ◽  
Parasite Prevalence ◽  
Admission Rates ◽  
Wide Range ◽  
Life Threatening ◽  
Disease Risks ◽  
The Relationship

The relationship between community prevalence of Plasmodium falciparum and the burden of severe, life-threatening disease remains poorly defined. To examine the three most common severe malaria phenotypes from catchment populations across East Africa, we assembled a dataset of 6506 hospital admissions for malaria in children aged 3 months to 9 years from 2006 to 2020. Admissions were paired with data from community parasite infection surveys. A Bayesian procedure was used to calibrate uncertainties in exposure (parasite prevalence) and outcomes (severe malaria phenotypes). Each 25% increase in prevalence conferred a doubling of severe malaria admission rates. Severe malaria remains a burden predominantly among young children (3 to 59 months) across a wide range of community prevalence typical of East Africa. This study offers a quantitative framework for linking malaria parasite prevalence and severe disease outcomes in children.

scholarly journals CLINICAL ASPECTS OF UNCOMPLICATED AND SEVERE MALARIA

2012 ◽  
Vol 4 (1) ◽  
pp. e2012026 ◽  
Author(s):  
Alessandro Bartoloni ◽  
Lorenzo Zammarchi
Keyword(s):  
Severe Malaria ◽  
Falciparum Malaria ◽  
Plasmodium Knowlesi ◽  
Gastrointestinal Symptoms ◽  
Plasmodium Falciparum Malaria ◽  
Clinical Findings ◽  
Clinical Aspects ◽  
Appropriate Treatment ◽  
Life Threatening ◽  
Wrong Diagnosis

The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed to look for early signs of systemic complications.In fact, severe malaria is a life threatening but treatable disease.  The protean and nonspecific clinical findings occurring in malaria (fever, malaise, headache, myalgias, jaundice and sometimes gastrointestinal symptoms of nausea, vomiting and diarrhoea) may lead physicians who see malaria infrequently to a wrong diagnosis, such as influenza (particularly during the seasonal epidemic flu), dengue, gastroenteritis, typhoid fever, viral hepatitis, encephalitis. Physicians should be aware that malaria is not a clinical diagnosis but must be diagnosed, or excluded, by performing microscopic examination of blood films. Prompt diagnosis and appropriate treatment are then crucial to prevent morbidity and fatal outcomes. Although Plasmodium falciparum malaria is the major cause of severe malaria and death, increasing evidence has recently emerged that Plasmodium vivax and Plasmodium knowlesi can also be severe and even fatal.

scholarly journals The Association between Metabolic Syndrome and Elevated Alanine Aminotransferase Levels in an Indigenous Population in Northern Taiwan: A Community-Based and Cross-Sectional Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yi-Fang Chen ◽  
Yen-An Lin ◽  
Wei-Chung Yeh ◽  
Yu-Chung Tsao ◽  
Wen-Cheng Li ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Enzyme ◽  
Indigenous Population ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Community Based ◽  
Cross Sectional ◽  
Increased Risk ◽  
The Relationship ◽  
Northern Taiwan

Our study aims to determine the prevalence of metabolic syndrome (MetS) among the Northern Taiwanese indigenous population and to explore the relationship between MetS and liver enzyme, especially serum alanine transaminase (ALT). This is an observational and cross-sectional study that was conducted in remote villages of an indigenous community in Northern Taiwan between 2010 and 2015. MetS was defined based on the revised NCEP/ATPIII criteria from Taiwan Health Promotion Administration. A total of 454 participants were included in the analysis. There were 277 people with MetS and 177 people without. The prevalence of MetS was 61.01%. The average age was 49.50 years. People with MetS had a significantly higher liver enzyme (ALT) level than those without MetS. In addition, the study showed that participants with higher ALT had a tendency towards a higher prevalence of MetS (76.7% vs. 57.3%, p  = 0.001). The adjusted odds ratio (OR) of ALT levels >36 U/L for MetS was 2.79 (95% CI = 1.24–6.27, p  = 0.01). The area under the ROC curve (AUC) of the ALT level was 0.63 (95% CI = 0.58–0.68, p  < 0.001), which showed that the ALT level was positively associated with MetS. The overall prevalence of MetS was 61.01% in the highland indigenous population in Northern Taiwan; this study indicated that higher serum ALT levels were associated with an increased risk of MetS.

ABO In Morbidity and Mortality of Plasmodium Falciparum malaria

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 666-666
Author(s):  
Christine Cserti-Gazdewich ◽  
Charles Musoke ◽  
Aggrey Dhabangi ◽  
Deborah Nakiboneka-Ssenabulya ◽  
Henry Ddungu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Blood Groups ◽  
Abo Blood Groups ◽  
Significant Difference ◽  
Group A ◽  
The Relationship

Abstract Abstract 666 Background: Plasmodium falciparum malaria has been called the greatest force in human evolution as a result of its disproportionate lethality among children and its longstanding presence in human history. Malaria's complex pathogenesis is based in part on cytoadhesion, which is mediated by a parasite-derived surface protein (PfEMP1) expressed on infected erythrocytes. PfEMP1 binds with ligands on red cells, platelets, and endothelium, and through the lectin-like DBL1α domain, binds preferentially to blood Group A. This contributes to the obstruction of microvascular perfusion and to cerebral malaria, lactic acidosis, and death. Initial studies demonstrated increased cytoadhesion to Group A RBC in vitro, suggesting that Group A hosts may be at risk of greater morbidity with P falciparum. Subsequently, retrospective clinical studies demonstrated a higher proportion of Group A individuals among those with severe disease. Recently, attention has focused on malaria pathogenesis and von Willebrand factor, which is elevated in Group A individuals. While the cumulative evidence suggests a central role for ABO in malaria, proof for a driving effect on the evolutionary distribution of ABO blood groups has awaited definitive study of the relationship between ABO and P falciparum malaria mortality. We report here initial findings from the Cytoadherence in Pediatric Malaria (CPM) Study (clinicaltrials.gov, NCT 00707200) which was designed to examine associations between malaria outcomes and host blood groups implicated in erythrocyte cytoadhesion. Methods: We performed a 2 year prospective observational study of children with acute malaria (age 6 mo – 12 yr) presenting for care at Mulago Hospital, Uganda. HIV positive patients were excluded from analysis. We enrolled children who met pre-study WHO criteria for either Uncomplicated Malaria (UM) or Severe Malaria (SM). Patients were followed from the time of presentation to discharge or death. ABO blood groups were determined by standard hemagglutination. The study was approved by the Uganda National Council on Science and Technology and all participating institutions. Results: At the study's conclusion (October 2009), 2092 children were enrolled. Children with HIV (n=45), those whose blood smears lacked species-confirmed P falciparum parasitemia on review by an external, blinded reference parasitology laboratory (n=35), and one child outside of the pre-defined study age range were excluded, leaving 2011 for analysis. Of these, 1078 had UM and 855 had SM, with 48 of the SM (5.6%) being fatal cases. Among those with SM, 850 had either cerebral malaria (CM, n=174), severe malaria anemia (SMA, hemoglobin < 5g/dL, n=558), or lactic acidosis (LA, lactate >5mM, n=482) in an overlapping distribution. The proportion of individuals with Group A or AB increased with categories of increasing disease severity (UM = 28%, SM = 37.1%; fatal = 47.9%). Group O correspondingly decreased (UM = 49.9%, SM = 40.6%, fatal = 37.5%). There was a highly statistically significant difference in the distribution of A, B, AB and O between UM and SM, χ2 =29.57, p=0.000002. Importantly, we observed a significant difference between UM and fatal cases for the distribution of all four ABO groups (χ2 = 4.624, p=0.0315) which was especially significant for Group A or AB versus O (χ2 = 5.946, p=0.0147). A significant difference in ABO distribution was also observed for specific severe malaria syndromes, with Group O enriched for UM and Group A or AB enriched among those with CM (χ2= 12.18, p=0.006791) and SMA (χ2 = 34.24, p<10−5). Conclusions: This is the largest prospective study on the relationship between ABO blood groups and P falciparum malaria and the first report sufficiently powered to demonstrate the effect of ABO on survival in P falciparum malaria. We report a statistically significant and clinically important advantage among group O hosts and a corresponding disadvantage for group A or AB hosts. Our results confirm clinically the findings of in vitro studies on ABO and cytoadhesion as well as prior retrospective studies on ABO and disease severity. Because our study was conducted in children, the results have direct bearing on the effect of malaria on genetic selection. The results have implications for the pathogenesis of P falciparum malaria, for new treatment strategies aimed at interrupting cytoadhesion, and for our understanding of the worldwide distribution of ABO blood groups. Disclosures: No relevant conflicts of interest to declare.

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