Ferritin levels predict severe dengue

Rajendran, Senthilkumar; Agieshkumar, B.; Daisy, Mariya Samadanam; Jacob, Sherin; Cleetus, Cherupanakkal

doi:10.1007/s15010-014-0683-4

Cited by 63 publications

(81 citation statements)

References 30 publications

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“…For example, infections caused by the Dengue virus and Mycobacterium tuberculosis result in increased levels of ferritin 49,50 and increased host cell uptake of iron. Similarly, Chlamydia infection results in decreased ACO1 activity and thereby increased ferritin levels.…”

Section: Discussionmentioning

confidence: 99%

Ferritinophagy drives uropathogenicEscherichia colipersistence in bladder epithelial cells

Bauckman

Mysorekar

2016

Autophagy

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Autophagy is a cellular recycling pathway, which in many cases, protects host cells from infections by degrading pathogens. However, uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections (UTIs), persist within the urinary tract epithelium (urothelium) by forming reservoirs within autophagosomes. Iron is a critical nutrient for both host and pathogen, and regulation of iron availability is a key host defense against pathogens. Iron homeostasis depends on the shuttling of iron-bound ferritin to the lysosome for recycling, a process termed ferritinophagy (a form of selective autophagy). Here, we demonstrate for the first time that UPEC shuttles with ferritin-bound iron into the autophagosomal and lysosomal compartments within the urothelium. Iron overload in urothelial cells induces ferritinophagy in an NCOA4-dependent manner causing increased iron availability for UPEC, triggering bacterial overproliferation and host cell death. Addition of even moderate levels of iron is sufficient to increase and prolong bacterial burden. Furthermore, we show that lysosomal damage due to iron overload is the specific mechanism causing host cell death. Significantly, we demonstrate that host cell death and bacterial burden can be reversed by inhibition of autophagy or inhibition of iron-regulatory proteins, or chelation of iron. Together, our findings suggest that UPEC persist in host cells by taking advantage of ferritinophagy. Thus, modulation of iron levels in the bladder may provide a therapeutic avenue to controlling UPEC persistence, epithelial cell death, and recurrent UTIs.

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Section: Discussionmentioning

confidence: 99%

Ferritinophagy drives uropathogenicEscherichia colipersistence in bladder epithelial cells

Bauckman

Mysorekar

2016

Autophagy

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“…Additionally it is important to note that serum ferritin is a marker of macrophage activation in vivo , and is often elevated in dengue patients [7,8]. Level of serum ferritin in often higher in pediatric dengue patients as compared to adults [43].…”

Section: Discussionmentioning

confidence: 99%

“…Roughly 5% of clinically-apparent dengue cases will progress to severe dengue, which is characterized by plasma leakage leading to effusions, respiratory difficulty, hypovolemic shock, and hemorrhage [5]. Recent investigations have demonstrated that higher serum ferritin levels are associated with dengue as compared to other acute febrile illnesses, and that degree of elevation of ferritin is associated with disease severity and a pro-inflammatory cytokine profile [7, 8]. Similar to hemophagocytic syndromes, infection with either DENV or EBV results in a genetic immune response profile that is associated with uncontrolled inflammatory responses [9], and these immunologic pathways may be common to those that lead to the development of acquired HLH.…”

Section: Introductionmentioning

confidence: 99%

Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

Ellis¹,

Sharp²,

Pérez-Padilla³

et al. 2016

PLoS Negl Trop Dis

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BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness.Methodology/Principal FindingsAfter a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02).Conclusions/SignificanceDuring this cluster of dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.

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“…In addition, circulating ferritin in HIV patients ranges around a median of 487 μg/L and has been associated with HIV disease progression [54, 55]. The most striking elevation of circulating ferritin is seen in patients suffering from acute dengue infections, with median plasma ferritin levels up to 1,264 μg/L [56, 57]. Moreover, circulating levels of both IL-18 and ferritin show strong correlation with dengue disease severity and, therefore, may be considered as a tool to predict disease progression [57, 58].…”

Section: Plasma Inflammatory Profiles In Viral and Bacterial Infectionsmentioning

confidence: 99%

IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections

et al. 2016

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The host inflammatory response against infections is characterized by the release of pro-inflammatory cytokines and acute-phase proteins, driving both innate and adaptive arms of the immune response. Distinct patterns of circulating cytokines and acute-phase responses have proven indispensable for guiding the diagnosis and management of infectious diseases. This review discusses the profiles of acute-phase proteins and circulating cytokines encountered in viral and bacterial infections. We also propose a model in which the inflammatory response to viral (IL-18/ferritin) and bacterial (IL-6/CRP) infections presents with specific plasma patterns of immune biomarkers.

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Ferritin levels predict severe dengue

Abstract: On the basis of this diagnostic efficiency, we propose that ferritin may serve as a potential biomarker for an early prediction of disease severity.

Cited by 63 publications

References 30 publications

Ferritinophagy drives uropathogenicEscherichia colipersistence in bladder epithelial cells

Ferritinophagy drives uropathogenicEscherichia colipersistence in bladder epithelial cells

Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections

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