Fever in children: Difference between revisions

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==Overview==
==Overview==
[[Fever]] can be defined as any elevation of body [[temperature]] above 38°C, it is a normal [[physiological]] response as a result of the encounter of an [[infectious]] agent producing [[exogenous]] and [[endogenous]] pyrogenes affecting the central set point of body temperature. It is mostly caused by a [[benign]] [[viral infection]], but it can be an indicator of a serious [[sickness]] such as [[meningitis]], [[septicaemia]], [[pneumonia]]. The risk for severe change depends on the clinical condition and the age of the infant. Most predictive for serious sickness are situations in which infants are younger than 3 months with body temperature > or = 38°C, infants between 3 and 6 months with body temperature > or = 39°C, and children of any ages with critical clinical signs. Uncomplicated [[fever]] is [[benign]] and should not be treated.


==Historical Perspective==
==Historical Perspective==


*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
*The history of [[fever]] are briefly reviewed by the Greeks as well as the views brought up in the Bible and widespread throughout the Middle Ages where [[fever]] and [[disease]] were interpreted as punishment for misbehavior.
*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
*Later views are introduced, based on the rise of science and Harvey's discovery of the [[circulation]] of the [[blood]] which produced two rival camps, [[iatrochemists]] and [[iatrophysicists]].
*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
*Next are brought up as the contributions of [[tissue]] [[pathology]], experiments defining the role of the [[CNS]] in regulating [[body]] [[temperature]], the old correlation of fever with [[inflammation]] and the discovery of [[microbial]] agents of disease and [[bacterial]] [[pyrogens]] in the late nineteenth and early twentieth century
*Finally, work in the last 30 years is summarized, starting with the discovery of [[endogenous]] [[pyrogen]] ([[EP]]) and the recent finding that [[EP]] is probably similar to [[lymphocyte activating factor]] ([[LAF]]) and [[leukocytic endogenous mediator]] ([[LEM]]) which collectively as [[interleukin-1]] ([[IL-1]]) play a major role in both [[inflammation]] and [[immunity]].<ref name="pmid2029820">{{cite journal| author=Stein MT| title=Historical perspective on fever and thermometry. | journal=Clin Pediatr (Phila) | year= 1991 | volume= 30 | issue= 4 Suppl | pages= 5-7 | pmid=2029820 | doi=10.1177/0009922891030004S02 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2029820  }} </ref>
 
==Classification==
==Classification==


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**'''Chronic fever''': (>2 weeks), typical of [[chronic]] [[bacterial infections]] ([[tuberculosis]] [[TB]]), [[viral infections]] ([[HIV]]), [[cancers]] and [[connective tissue diseases]].
**'''Chronic fever''': (>2 weeks), typical of [[chronic]] [[bacterial infections]] ([[tuberculosis]] [[TB]]), [[viral infections]] ([[HIV]]), [[cancers]] and [[connective tissue diseases]].


*[[Fever]] also can be classified based on height of body temperature into:
*[[Fever]] also can be classified based on height of body [[temperature]] into:
**Low grade fever
**[[Low grade fever]]
**Moderate grade fever
**[[Moderate grade fever]]
**High grade fever (attributes to Serious [[bacterial infections]] in [[infants]])  
**[[High grade fever]] (attributes to Serious [[bacterial infections]] in [[infants]])  
**Hyperpyrexia
**[[Hyperpyrexia]]


*The height of fever may correlate with [[severity]] of [[illness]], such as in [[dengue fever]], [[shigellosis]], and [[acute]] [[falciparum malaria]].  
*The height of [[fever]] may correlate with [[severity]] of [[illness]], such as in [[dengue fever]], [[shigellosis]], and [[acute]] [[falciparum malaria]].  
*There are three major [[fever]] type: [[Sustained]]/[[continuous]] [[fever]], [[intermittent]] fever and [[remittent]] fever.  
*There are three major [[fever]] type: [[Sustained]]/[[continuous]] [[fever]], [[intermittent]] fever and [[remittent]] fever.  
**[[Continuous]] or [[sustained]] [[fever]] does not [[fluctuate]] more than about 1°C (1.5°F) during 24hours, but never touches normal, characteristics of [[lobar]] and [[gram negative]] [[pneumonia]], [[typhoid]], [[acute]] [[bacterial]] [[meningitis]], and [[urinary tract infection]].
**[[Continuous]] or [[sustained]] [[fever]] does not [[fluctuate]] more than about 1°C (1.5°F) during 24hours, but never touches normal, characteristics of [[lobar]] and [[gram negative]] [[pneumonia]], [[typhoid]], [[acute]] [[bacterial]] [[meningitis]], and [[urinary tract infection]].
**Fever with bradycardia (Faget’s sign or sphygmothermic dissociation)is characteristic of untreated typhoid, leishmaniasis, brucellosis, Legionnaire’s disease and psittacosis, and Yellow Fever.
**[[Fever]] with [[bradycardia]] ([[Faget’s sign]] or [[sphygmothermic dissociation]])is characteristic of untreated [[typhoid]], [[leishmaniasis]], [[brucellosis]], [[Legionnaire]]’s disease and [[psittacosis]], and [[Yellow Fever]].
**[[Intermittent]] [[fever]] is defined as fever present only for several hours during the day. It can be seen in [[malaria]], [[pyogenic infections]], [[tuberculosis (TB)]], [[schistosomiasis]], [[lymphomas]], [[leptospira]], [[borrelia]], [[kala-azar]], or [[septicemia]].  
**[[Intermittent]] [[fever]] is defined as fever present only for several hours during the day. It can be seen in [[malaria]], [[pyogenic infections]], [[tuberculosis (TB)]], [[schistosomiasis]], [[lymphomas]], [[leptospira]], [[borrelia]], [[kala-azar]], or [[septicemia]].  
**Sources of continuous, [[intermittent]] or [[transient]] [[bacteraemia]] may lead to continuous, [[intermittent]] or  transient fevers respectively. Inmalaria, depending on the specie of parasite, fever can occur with a periodicity of 24h (quotidian-due to plasmodium falciparum), 48h (tertian plasmodium ovale and vivax), or 72h (quartan Plasmodium malaria). The Pel-Epstein’s feveris an intermittent low grade fever characterised by3—10 days of fever with subsequent a febrile peri-ods of 3—10 days[31,40]. It is thought to be a typical but rare manifestation of Hodgkin’s lymphoma.
**Sources of [[continuous]], [[intermittent]] or [[transient]] [[bacteraemia]] may lead to [[continuous]], [[intermittent]] or  [[transient]] fevers respectively. In [[malaria]], depending on the specie of [[parasite]], fever can occur with a periodicity of 24h (quotidian-due to plasmodium falciparum), 48h (tertian plasmodium ovale and vivax), or 72h (quartan Plasmodium malaria). The [[Pel-Epstein’s fever]] is an [[intermittent]] [[low grade fever]] characterised by 3—10 days of [[fever]] with subsequent a [[febrile periods]] of 3—10 days. It is thought to be a typical but rare manifestation of [[Hodgkin’s lymphoma]].
**[[Remittent]]  [[fever]]  is  defined  as  fever  with  daily fluctuations exceeding 2◦C but at no time touches normal. Remittent  fevers  are  often  associated  with  infectious  diseases such as infective endocarditis, rickettsiae infections, and brucellosis. Relapsing fevers refer to those that are recurring  and  separated  by  periods  with low-grade fever or no fever. Periodic orrelapsing fevers are seen in malaria, lymphoma,borrelia, cyclic  neutropenia, and rat-bite fever. Fever  associated  with  night  sweats  has been described in infectious diseases such as TB, Nocardia, brucellosis, liver or lung abscess and sub-acute infective endocarditis, as well as in non-infectious diseases such as polyarteritis nodosa and cancers such as lymphomas.
**[[Remittent]]  [[fever]]  is  defined  as  fever  with  daily fluctuations exceeding 2◦C but at no time touches normal. [[Remittent]] [[fevers]] are  often  associated  with  [[infectious  diseases]] such as [[infective endocarditis]], [[rickettsiae]] infections, and [[brucellosis]]. Relapsing fevers refer to those that are recurring  and  separated  by  periods  with [[low grade fever]] or no fever. [[Periodic]] or [[relapsing]] fevers are seen in [[malaria]], [[lymphoma]], [[borrelia]], cyclic  [[neutropenia]], and [[rat-bite fever]]. [[Fever]] associated  with  [[night  sweats]] has been described in [[infectious diseases]] such as [[TB]], [[Nocardia]], [[brucellosis]], [[liver]] or [[lung]] [[abscess]] and [[sub-acute]] [[infective endocarditis]], as well as in [[non-infectious]] [[diseases]] such as [[polyarteritis nodosa]] and [[cancers]] such as [[lymphomas]].


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==Pathophysiology==
==Pathophysiology==


*The development of the pyrexia is similar to the normal thermoregulatory processes that follow exposure to cold temperatures.<ref name="pmid21843857">{{cite journal| author=Ogoina D| title=Fever, fever patterns and diseases called 'fever'--a review. | journal=J Infect Public Health | year= 2011 | volume= 4 | issue= 3 | pages= 108-24 | pmid=21843857 | doi=10.1016/j.jiph.2011.05.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21843857  }} </ref>  
*The development of the [[pyrexia]] is similar to the normal [[thermoregulatory]] processes that follow exposure to [[cold]] [[temperatures]].<ref name="pmid21843857">{{cite journal| author=Ogoina D| title=Fever, fever patterns and diseases called 'fever'--a review. | journal=J Infect Public Health | year= 2011 | volume= 4 | issue= 3 | pages= 108-24 | pmid=21843857 | doi=10.1016/j.jiph.2011.05.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21843857  }} </ref>  
*The thermal balance point in fever is reset to a higher level such that normal peripheral and central body temperatures are now sensed as cold temperature signals by the thermoregulatory circuitry.
*The [[thermal]] balance point in [[fever]] is reset to a higher level such that normal [[peripheral]] and [[central]] [[body]] [[temperatures]] are now sensed as cold temperature signals by the thermoregulatory circuitry.
*Fever is different from heat stroke and hyperthermia where body temperature is increased without an equivalent increase of the thermal balance point.  
*Fever is different from [[heat stroke]] and [[hyperthermia]] where body [[temperature]] is increased without an equivalent increase of the [[thermal]] [[balance]] point.  


'''The role of pyrogens and cryogens'''
'''The role of pyrogens and cryogens'''
*The initiation, manifestations and regulation of pyrexia are dependent on the pyrogenic and anti-pyretic properties of numerous exogenous and endogenous substances.  
*The initiation, manifestations and regulation of [[pyrexia]] are dependent on the [[pyrogenic]] and [[anti-pyretic]] properties of numerous [[exogenous]] and [[endogenous]] [[substances]].  
*Pyrogens directly or indirectly lead to pyrexia and cryogens prevent extortionate temperature elevation.  
*[[Pyrogens]] directly or indirectly lead to [[pyrexia]] and [[cryogens]] prevent [[extortionate]] [[temperature]] elevation.  
*The balance in the interactivity between pyrogens and cyrogens is control the height and duration of the pyrexia.  
*The [[balance][] in the [[interactivity]] between [[pyrogens]] and [[cryogens]] is control the [[height]] and [[duration]] of the [[pyrexia]].  


'''Pryogens'''
'''Pryogens'''
*Pyrogens are classified into exogenous and endogenous pyrogens based on their site of production.  
*[[Pyrogens]] are classified into [[exogenous]] and [[endogenous]] [[pyrogens]] based on their site of production.  
*Exogenous pyrogens are part or whole micro organisms (lipopolysaccharide (LPS) in gram negative cell wall) or products of micro organisms as toxins.  
*Exogenous pyrogens are part or whole [[micro]] [[organisms]] ([[lipopolysaccharide]] ([[LPS]]) in [[gram negative]] [[cell wall]]) or products of [[micro]] [[organisms]] as [[toxins]].  
*Endogenous pyrogens include muramyl dipeptidase and enterotoxins of Staphylococcus aureus and group A and B Streptococcus (superantigens).  
*[[Endogenous]] [[pyrogens]] include [[muramyl dipeptidase]] and [[enterotoxins]] of [[Staphylococcus aureus]] and group A and B [[Streptococcus]] (superantigens).  
*Endogenous pyrogens are mainly pyrogenic cytokines including interleukins (IL-6, IL-1), interferon gamma (INF-a) and ciliary neurotropic factor(CNTF) and tumor necrosis factor (TNFa).
*[[Endogenous]] [[pyrogens]] are mainly [[pyrogenic]] [[cytokines]] including [[interleukins]] ([[IL-6]], [[IL-1]]), [[interferon gamma]] ([[INF-a]]) and [[ciliary neurotropic factor]] ([[CNTF]]) and [[tumor necrosis factor]] ([[TNFa]]).


'''Cryogens'''
'''Cryogens'''
*Cyrogens include cytokines(IL10), hormones (a-melanocyte stimulating hormone, corticotrophin and corticotrophin releasing hormone) and neuroendocrine products (neuropeptide Y, bombesin, and thyroliberin), and cytochrome P-450.
*[[Cyrogens]] include [[cytokines]]([[IL-10]]), [[hormones]] ([[a-melanocyte stimulating hormone]], [[corticotrophin]] and [[corticotrophin releasing hormone]]) and [[neuroendocrine]] products ([[neuropeptide Y]], [[bombesin]], and [[thyroliberin]]), and [[cytochrome P-450]].
*The antipyretic effect induced by inhibiting synthesis of pyrogenic cytokines (glucocorticoids), cytokine receptors blockade (IL-1 receptor antagonist), and increasing heat loss by enhancing sensitivity of warm sensitive neurons (bombesin).  
*The [[antipyretic]] effect induced by [[inhibiting]] [[synthesis]] of [[pyrogenic]] [[cytokines]] ([[glucocorticoids]]), [[cytokine]] [[receptors]] [[blockade]] ([[IL-1]] [[receptor]] [[antagonist]]), and increasing [[heat]] loss by enhancing [[sensitivity]] of warm [[sensitive]] [[neurons]] ([[bombesin]]).  






The pathophysiological mechanisms for the injurious effects of a fever, classified as follows:<ref name="pmid27411542">{{cite journal| author=Walter EJ, Hanna-Jumma S, Carraretto M, Forni L| title=The pathophysiological basis and consequences of fever. | journal=Crit Care | year= 2016 | volume= 20 | issue= 1 | pages= 200 | pmid=27411542 | doi=10.1186/s13054-016-1375-5 | pmc=4944485 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27411542  }} </ref>
The [[pathophysiological]] [[mechanisms]] for the [[injurious]] effects of a [[fever]], classified as follows:<ref name="pmid27411542">{{cite journal| author=Walter EJ, Hanna-Jumma S, Carraretto M, Forni L| title=The pathophysiological basis and consequences of fever. | journal=Crit Care | year= 2016 | volume= 20 | issue= 1 | pages= 200 | pmid=27411542 | doi=10.1186/s13054-016-1375-5 | pmc=4944485 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27411542  }} </ref>
*Direct cellular damage:
*Direct [[cellular]] [[damage]]:
**Membrane, mitochondrial and DNA damage
**[[Membrane]], [[mitochondrial]] and [[DNA]] [[damage]]
**Stimulation of excitotoxic mechanisms  
**[[Stimulation]] of [[excitotoxic]] [[mechanisms]]
**Protein denaturation
**[[Protein]] [[denaturation]]
**Cell death
**[[Cell death]]
*Local effects:
*Local effects:
**Cytokine stimulation
**[[Cytokine]] [[stimulation]]
**Inflammatory response
**[[Inflammatory]] response
**Vascular stasis
**[[Vascular]] [[stasis]]
**Extravasation
**[[Extravasation]]
**Oedema
**[[Oedema]]
*Systemic effects:
*Systemic effects:
**Endotoxaemia
**[[Endotoxaemia]]
**Gut bacterial translocation
**[[Gut]] [[bacterial]] [[translocation]]


==Causes==
==Causes==
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Causes of undiagnosed [[fever]] in children include:<ref name="pmid14218464">{{cite journal| author=BREWIS EG| title=CHILD CARE IN GENERAL PRACTICE. UNDIAGNOSED FEVER. | journal=Br Med J | year= 1965 | volume= 1 | issue= 5427 | pages= 107-9 | pmid=14218464 | doi= | pmc=2165027 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14218464  }} </ref>
Causes of undiagnosed [[fever]] in children include:<ref name="pmid14218464">{{cite journal| author=BREWIS EG| title=CHILD CARE IN GENERAL PRACTICE. UNDIAGNOSED FEVER. | journal=Br Med J | year= 1965 | volume= 1 | issue= 5427 | pages= 107-9 | pmid=14218464 | doi= | pmc=2165027 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14218464  }} </ref>
*'''Infection'''
*'''Infection'''
**Viruses
**[[Viruses]]
**Pyogenic Inection
**[[Pyogenic]] [[Infection]]
**Salmonella Infection
**[[Salmonella]] [[Infection]]
**Brucellosis
**[[Brucellosis]]
**Tuberculosis
**[[Tuberculosis]]
*'''Collagen Vascular Diseases'''
*'''Collagen Vascular Diseases'''
*'''Neoplasm'''
*'''Neoplasm'''


==Differentiating [disease name] from other Diseases==
==Differential diagnoses for fever in children==


For further information about the differential diagnosis, click [[Disease_Name differential diagnosis|here]].
{| border="2" cellpadding="4" cellspacing="0" style="margin: 1em 1em 1em 0; background: #f9f9f9; border: 1px #aaa solid; border-collapse: collapse;" width="75%"
! Cause !! Differential Diagnosis
|-
|<nowiki>Infectious; Bacterial or mycobacterial</nowiki>
| [[Brucellosis]], [[dental abscess]], [[endocarditis]], non-[[tuberculous]] [[mycobacteria]] (eg, [[Mycobacterium chelonae]]), [[occult]] [[bacterial infection]], recurrent [[bacterial infections]], relapsing [[fever]] ([[Borrelia]] spp other than [[Borrelia burgdorferi]]), [[Yersinia enterocolitica]]
|-
|<nowiki>Parasitic</nowiki>
| [[Malaria]] (eg, [[Plasmodium vivax]], [[Plasmodium ovale]])
|-
|<nowiki>Inflammatory or Immunologic</nowiki>
| [[Behçet syndrome]], [[inflammatory bowel disease]] (eg, [[Crohn disease]]), [[hereditary]] [[fever]] [[syndromes]] (eg, [[FMF]]), [[juvenile]] [[dermatomyositis]], [[PFAPA]] [[syndrome]], [[sarcoidosis]], [[systemic lupus erythematous]], [[systemic]] [[juvenile idiopathic arthritis]] ([[Still disease]]), [[vasculitis]] (eg, [[polyarteritis nodosa]])
|-
|<nowiki>Malignant</nowiki>
|[[Leukemia]], [[lymphoma]]
|-
|<nowiki>Other</nowiki>
|[[Benign]] [[giant]] [[lymph node]] [[hyperplasia]] ([[Castleman disease]]), [[CNS]] [[abnormalities]] (eg, [[hypothalamic dysfunction]]), [[drug fever]], [[factitious fever]], [[IgG4-related disease]], [[immunodeficiency]] [[syndromes]] with [[recurrent]] [[infections]]
|}<br clear="left" />
 
*[[CNS]]—[[central nervous system]]; [[FMF]]—[[familial Mediterranean fever]]; [[IgG4]]—[[immunoglobulin G4]]; [[PFAPA]]—[[periodic fever]], [[aphthous stomatitis]], [[pharyngitis]], and [[adenitis]].<ref name="pmid29025800">{{cite journal| author=Soon GS, Laxer RM| title=Approach to recurrent fever in childhood. | journal=Can Fam Physician | year= 2017 | volume= 63 | issue= 10 | pages= 756-762 | pmid=29025800 | doi= | pmc=5638471 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29025800  }} </ref>


==Epidemiology and Demographics==
==Epidemiology and Demographics==


*Following the widespread use of immunizations against Streptococcus pneumoniae and Haemophilus influenzae b, incidence of fever caused by infection due to these organisms has been decreased.
*Following the widespread use of [[immunizations]] against [[Streptococcus pneumoniae]] and [[Haemophilus influenzae]] b, incidence of fever caused by [[infection]] due to these [[organisms]] has been decreased.
*Since 1990, rates of invasive Hib infection (including meningitis) in children 5 years and younger have declined by more than 99%.
*Since 1990, rates of invasive [[Hib]] [[infection]] (including [[meningitis]]) in children 5 years and younger have declined by more than 99%.
*In 2005, the incidence of fever caused by invasive pneumococcal infection in children declined by 77% from 1998.
*In 2005, the incidence of fever caused by [[invasive]] [[pneumococcal]] [[infection]] in children declined by 77% from 1998.


===Age===
===Age===


*Fever caused by urinary tract infections (UTIs) are the most common source of serious bacterial infection in children younger than 3 months, commonly from E.coli or Klebsiella species.
*[[Fever]] caused by [[urinary tract infections]] ([[UTI]]s) are the most common source of serious [[bacterial infection]] in children younger than 3 months, commonly from [[E.coli]] or [[Klebsiella]] species.
*According to a case series, fever caused by pneumonia is the most common serious bacterial infection in children 3 to 36 months of age, followed by UTI.
*According to a case series, [[fever]] caused by [[pneumonia]] is the most common serious [[bacterial infection]] in children 3 to 36 months of age, followed by [[UTI]].
 
==Risk Factors==
 
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].


==Natural History, Complications and Prognosis==
==Prognosis==
 
*The prognosis of [[fever]] depends on the underlying cause.
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*There is an association with a greater likelihood of serious [[bacterial infection]] ([[SBI]]) for [[temperatures]] >39 °C.  
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*In a prospective cohort study on more than 12,800 children presenting with [[febrile illness]], [[fever]] >39 °C was associated with an increased risk of SBI, especially in [[infants]] under 6 months.  
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*In a prospective series of 103 children with a [[temperature]] >41 °C, almost 50% had an SBI.
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*[[Temperatures]] above 41 °C have also been associated with a higher risk of [[meningitis]].
*Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].
*[[Children]] with SBI may also have a normal [[temperature]] or be [[hypothermic]].


==Diagnosis==
==Diagnosis==
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
:*[criterion 1]
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]
   
   
===Symptoms===
===Symptoms===


*[Disease name] is usually asymptomatic.
*[[Fever]] is often characterised by:<ref name="pmid21843857">{{cite journal| author=Ogoina D| title=Fever, fever patterns and diseases called 'fever'--a review. | journal=J Infect Public Health | year= 2011 | volume= 4 | issue= 3 | pages= 108-24 | pmid=21843857 | doi=10.1016/j.jiph.2011.05.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21843857  }} </ref>
*Symptoms of [disease name] may include the following:
**[[Chills]]
**[[Rigors]]
**[[Sweating]]
**[[Headache]]
**[[Malaise]]
**[[Anorexia]]


:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]
===Physical Examination===
===Physical Examination===


*Initial history and physical examination in infants and young children with fever is aim to identify serious illness. Immunocompromised patients (cancer, asplenia, or HIV infection) need more evaluation and treatment.  
*Initial [[history]] and [[physical examination]] in [[infants]] and [[young children]] with [[fever]] is aim to identify serious [[illness]]. [[Immunocompromised]] patients ([[cancer]], [[asplenia]], or [[HIV infection]]) need more [[evaluation]] and [[treatment]].  
*Benign causes of fever such as vaccination in the past 24 hours are reassuring. Teething is rarely associated with a fever of more than 100.4°F
*[[Benign]] causes of [[fever]] such as [[vaccination]] in the past 24 hours are reassuring. [[Teething]] is rarely associated with a [[fever]] of more than 100.4°F
*A meta-analysis of febrile children older than one month has identified red flags associated with a high likelihood of serious infection.
*A meta-analysis of [[febrile]] [[children]] older than one month has identified red flags associated with a high likelihood of serious [[infection]].


*Clinical Red Flags for Serious Infection in Children Older than One Month<ref name="pmid20132979">{{cite journal| author=Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D, European Research Network on Recognising Serious Infection investigators| title=Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review. | journal=Lancet | year= 2010 | volume= 375 | issue= 9717 | pages= 834-45 | pmid=20132979 | doi=10.1016/S0140-6736(09)62000-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20132979  }} </ref>
*Clinical Red Flags for Serious [[Infection]] in Children Older than One Month<ref name="pmid20132979">{{cite journal| author=Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D, European Research Network on Recognising Serious Infection investigators| title=Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review. | journal=Lancet | year= 2010 | volume= 375 | issue= 9717 | pages= 834-45 | pmid=20132979 | doi=10.1016/S0140-6736(09)62000-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20132979  }} </ref>
*'''Global assessments'''
*'''Global assessments'''
**Parental concerns
**Parental concerns
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*'''Child behavior'''
*'''Child behavior'''
**Changes in crying pattern
**Changes in crying pattern
**Drowsiness
**[[Drowsiness]]
**Inconsolability
**[[Inconsolability]]
**Moaning
**[[Moaning]]
*'''Circulatory/respiratory'''
*'''Circulatory/respiratory'''
**Crackles
**[[Crackles]]
**Cyanosis
**[[Cyanosis]]
**Decreased breath sounds
**Decreased [[breath sounds]]
**Poor peripheral circulation
**Poor peripheral [[circulation]]
**Rapid breathing
**Rapid [[breathing]]
**Shortness of breath
**[[Shortness of breath]]
*'''Other factors'''
*'''Other factors'''
**Decreased skin elasticity
**Decreased [[skin]] elasticity
**Hypotension
**[[Hypotension]]
**Meningeal irritation
**[[Meningeal irritation]]
**Petechial rash
**[[Petechial rash]]
**Seizures
**[[Seizures]]
**Unconsciousness
**[[Unconsciousness]]


===Laboratory Findings===
===Laboratory Findings===


*History and physical examination cannot identify all children with serious bacterial infections, hence sensible use of imaging and laboratory testing is valuable.
*[[History]] and [[physical examination]] cannot identify all children with serious [[bacterial infections]], hence sensible use of imaging and laboratory testing is valuable.


'''Urinalysis and urine culture'''
'''Urinalysis and urine culture'''


*Urinalysis is a key factor in the evaluation of fever in infancy and early childhood because UTI is a common cause of serious bacterial infection.                                     *Urine sample should be obtained for all children younger than 24 months with unexplained fever. It may be obtained by catheterization or suprapubic aspiration.  
*[[Urinalysis]] is a key factor in the evaluation of [[fever]] in [[infancy]] and early [[childhood]] because [[UTI]] is a common cause of serious [[bacterial infection]].
*In children with voluntary urine control, a clean catch method (urination into a specimen container after cleaning the area around the urethra) may be used.  
*Urine sample should be obtained for all children younger than 24 months with unexplained fever. It may be obtained by [[catheterization]] or [[suprapubic aspiration]].  
*In [[children]] with [[voluntary urine control]], a [[clean catch]] method (urination into a specimen container after cleaning the area around the urethra) may be used.  
*Cultures of specimens collected in a urine bag may have an 85 percent false-positive rate, and urine dipstick testing has a 12 percent false-negative rate.  
*Cultures of specimens collected in a urine bag may have an 85 percent false-positive rate, and urine dipstick testing has a 12 percent false-negative rate.  
*All specimens should be sent for formal urinalysis and culture.  
*All specimens should be sent for formal urinalysis and culture.  
*UTI rates vary with patient sex and age.  
*[[UTI]] rates vary with patient sex and age.  
*In the first three months of life, UTIs are more common in boys than in girls, and much more common in uncircumcised boys. After three months of age, UTIs are more common in girls.
*In the first three months of life, [[UTIs]] are more common in boys than in girls, and much more common in [[uncircumcised]] boys. After three months of age, [[UTIs]] are more common in girls.


'''Blood cell counts and blood culture'''
'''Blood cell counts and blood culture'''


*White blood cell (WBC) counts and absolute neutrophil counts have been used to point out serious bacterial infection, including occult bacteremia.  
*[[White blood cell]] ([[WBC]]) counts and absolute [[neutrophil]] counts have been used to point out serious [[bacterial infection]], including occult [[bacteremia]].  
*Blood cell counts have higher value in neonates than in older children.
*[[Blood cell]] counts have higher value in neonates than in older children.
*WBC counts lower than 5,000 per mm3 (5 × 109 per L) or more than 15,000 per mm3 (15 × 109 per L) had a PPV of 44% for serious bacterial infection, and an absolute neutrophil count of more than 10,000 per mm3 (10 × 109 per L) had a PPV of 71% according to a study of neonates up to 28 days of age.
*[[WBC]] counts lower than 5,000 per mm3 (5 × 109 per L) or more than 15,000 per mm3 (15 × 109 per L) had a PPV of 44% for serious [[bacterial infection]], and an [[absolute neutrophil count]] of more than 10,000 per mm3 (10 × 109 per L) had a PPV of 71% according to a study of neonates up to 28 days of age.
*Current guidelines recommend a complete blood count with differential and blood culture for infants three months or younger with fever.
*Current guidelines recommend a [[complete blood count]] with differential and [[blood culture]] for infants three months or younger with [[fever]].


'''Stool testing'''
'''Stool testing'''


*Diarrhea with fever in neonates and young infants submit systemic illness therefore stool culture and fecal WBC counts are supported.
*[[Diarrhea]] with [[fever]] in neonates and young infants submit [[systemic illness]] therefore [[stool culture]] and [[fecal]] [[WBC]] counts are supported.


'''Inflammatory markers'''
'''Inflammatory markers'''


*The clinical value of C-reactive protein levels in recognizing serious infection in neonates, infants, and young children is being explored.
*The clinical value of [[C-reactive protein]] levels in recognizing serious infection in neonates, infants, and young children is being explored.
*C-reactive protein (CRP) level of 2 mg per dL (19 nmol per L) or greater has better sensitivity, specificity, and predictive value than a WBC count of greater than 15,000 per mm3 or less than 5,000 per mm3.
*[[C-reactive protein]] ([[CRP]]) level of 2 mg per dL (19 nmol per L) or greater has better [[sensitivity]], [[specificity]], and predictive value than a [[WBC]] count of greater than 15,000 per mm3 or less than 5,000 per mm3.
*Elevated levels of procalcitonin (another marker of inflammation and bacterial infection) also appear to have better sensitivity, specificity, and predictive value than WBC counts.
*Elevated levels of [[procalcitonin]] (another marker of [[inflammation]] and [[bacterial infection]]) also appear to have better [[sensitivity]], [[specificity]], and predictive value than [[WBC]] counts.


'''Lumbar puncture'''
'''Lumbar puncture'''
*Vaccination against S. pneumoniae and Hib has greatly reduced the incidence of meningitis limiting the need for lumbar puncture.
*[[Vaccination]] against [[S. pneumoniae]] and [[Hib]] has greatly reduced the [[incidence]] of [[meningitis]] limiting the need for [[lumbar puncture]].
*Fever with clinical signs of meningitis such as nuchal rigidity, petechiae, or abnormal neurologic findings in neonates, infants and young children is indication for lumbar puncture.
*[[Fever]] with clinical signs of [[meningitis]] such as [[nuchal rigidity]], [[petechiae]], or abnormal [[neurologic]] findings in neonates, infants and young children is indication for [[lumbar puncture]].
*In children older than 3 months, the test is not suggested unless neurologic signs are present.
*In children older than 3 months, the test is not suggested unless [[neurologic]] signs are present.
*Two guidelines recommended a lumbar puncture for well-appearing, previously healthy young infants with no focal signs of infection, a WBC count between 5,000 and 15,000 per mm3, and no pyuria or bacteriuria on urinalysis.
*Two guidelines recommended a [[lumbar puncture]] for well-appearing, previously healthy young infants with no focal signs of infection, a [[WBC]] count between 5,000 and 15,000 per mm3, and no [[pyuria]] or [[bacteriuria]] on [[urinalysis]].
*Although low peripheral WBC counts (less than 5,000 per mm3) are more often associated with meningitis than with bacteremia, WBC counts should not be used alone to determine which infants need lumbar puncture.
*Although low peripheral [[WBC]] counts (less than 5,000 per mm3) are more often associated with [[meningitis]] than with [[bacteremia]], [[WBC]] counts should not be used alone to determine which infants need [[lumbar puncture]].


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
There are no [[ECG]] findings associated with [[fever]] in children.
 
OR
 
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR


There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
*[[Chest X ray]] is recommended in all neonates with unexplained [[fever]].
*[[Chest X ray]] is also recommended for young children older than one month revealing [[respiratory]] symptoms and for patients with a [[fever]] of more than 102.2°F (39°C) and a [[WBC]] count of more than 20,000 per mm3 (20 × 109 per L).


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with [disease name].
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[fever]] in [[children]].
 
OR
 
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
There are no [[CT scan]] findings associated with [[fever]] in children.
 
OR
 
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
There are no [[MRI]] findings associated with [[fever]] in children.
 
OR
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
===Other Diagnostic Studies===
 
*[Disease name] may also be diagnosed using [diagnostic study name].
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===


*Fever plays a physiologic role in response to infection, inhibiting bacterial growth and viral replication, and enhancing the immune response.
*[[Fever]] plays a [[physiologic]] role in response to [[infection]], [[inhibiting]] [[bacterial growth]] and [[viral replication]], and [[enhancing]] the [[immune]] response.
*There is no evidence that use of antipyretics prolongs illness in children
*There is no evidence that use of [[antipyretics]] prolongs [[illness]] in children.
*Antipyretic treatment should be reserved for distressed children, aiming at improving the child’s wellbeing rather than achieving normothermia.
*[[Antipyretic]] treatment should be reserved for distressed children, aiming at improving the child’s wellbeing rather than achieving normothermia.
*Antipyretic treatment has not been shown to prevent recurrence of febrile seizures.
*[[Antipyretic]] treatment has not been shown to prevent recurrence of [[febrile]] [[seizures]].
*Response to antipyretics cannot predict the severity of the underlying illness, since children with bacterial and viral illnesses have a similar response to antipyretics [134]. However, evaluating if the child’s conditions markedly improve with antipyretic treatment may be useful to discern whether it was related to fever or to the severity of the underlying illness.  
*Response to [[antipyretics]] cannot predict the severity of the underlying [[illness]], since children with [[bacterial]] and [[viral]] [[illnesses]] have a similar response to [[antipyretics]]. However, evaluating if the child’s conditions markedly improve with [[antipyretic]] treatment may be useful to discern whether it was related to fever or to the severity of the underlying illness.  
*In children with inherited metabolic and mitochondrial diseases, catabolic stressors should be avoided, and both fever and underlying infections should be treated
*In children with [[inherited]] [[metabolic]] and [[mitochondrial]] diseases, [[catabolic]] [[stressors]] should be avoided, and both [[fever]] and underlying [[infections]] should be treated
*Fever may increase metabolic and oxygen consumption; therefore, aggressive treatment may be more important in children with a limited cardiopulmonary or metabolic reserve, and it is recommended in patients recovering from cardiac arrest.
*[[Fever]] may increase [[metabolic]] and [[oxygen]] [[consumption]]; therefore, aggressive treatment may be more important in children with a limited [[cardiopulmonary]] or [[metabolic]] reserve, and it is recommended in patients recovering from [[cardiac arrest]].
*Ibuprofen and acetaminophen are the only drugs approved for treatment of fever in children and they are generally considered to be equally safe and effective for reducing temperature and relieving discomfort.  
*[[Ibuprofen]] and [[acetaminophen]] are the only drugs approved for [[treatment]] of [[fever]] in children and they are generally considered to be equally safe and effective for reducing temperature and relieving discomfort.  
*Combination therapy with acetaminophen plus ibuprofen seems to be slightly more effective in reducing body temperature compared with monotherapy alone<ref name="pmid28862659">{{cite journal| author=Barbi E, Marzuillo P, Neri E, Naviglio S, Krauss BS| title=Fever in Children: Pearls and Pitfalls. | journal=Children (Basel) | year= 2017 | volume= 4 | issue= 9 | pages=  | pmid=28862659 | doi=10.3390/children4090081 | pmc=5615271 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28862659  }} </ref>
*Combination therapy with [[acetaminophen]] plus [[ibuprofen]] seems to be slightly more effective in reducing body [[temperature]] compared with monotherapy alone<ref name="pmid28862659">{{cite journal| author=Barbi E, Marzuillo P, Neri E, Naviglio S, Krauss BS| title=Fever in Children: Pearls and Pitfalls. | journal=Children (Basel) | year= 2017 | volume= 4 | issue= 9 | pages=  | pmid=28862659 | doi=10.3390/children4090081 | pmc=5615271 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28862659  }} </ref>


==References==
==References==

Latest revision as of 00:32, 28 March 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zaida Obeidat, M.D.

Synonyms and keywords: Fever in kids

Overview

Fever can be defined as any elevation of body temperature above 38°C, it is a normal physiological response as a result of the encounter of an infectious agent producing exogenous and endogenous pyrogenes affecting the central set point of body temperature. It is mostly caused by a benign viral infection, but it can be an indicator of a serious sickness such as meningitis, septicaemia, pneumonia. The risk for severe change depends on the clinical condition and the age of the infant. Most predictive for serious sickness are situations in which infants are younger than 3 months with body temperature > or = 38°C, infants between 3 and 6 months with body temperature > or = 39°C, and children of any ages with critical clinical signs. Uncomplicated fever is benign and should not be treated.

Historical Perspective

Classification

Body temperature °C °F
Normal 37-38°C 98.6-100.4°F
Mild/low grade fever 38.1-39°C 100.5-102.2°F
Moderate grade fever 39.1-40°C 102.2-104.0°F
High grade fever 40.1-41.1°C 104.1-106°F
Hyperpyrexia >41.1°C >106.0°F

Pathophysiology

The role of pyrogens and cryogens

Pryogens

Cryogens


The pathophysiological mechanisms for the injurious effects of a fever, classified as follows:[3]

Causes

Common conditions that can cause fevers include:

Fever in children can sometimes associated with more serious signs and symptoms, such as:

Serious bacterial infections include:

Causes of undiagnosed fever in children include:[4]

Differential diagnoses for fever in children

Cause Differential Diagnosis
Infectious; Bacterial or mycobacterial Brucellosis, dental abscess, endocarditis, non-tuberculous mycobacteria (eg, Mycobacterium chelonae), occult bacterial infection, recurrent bacterial infections, relapsing fever (Borrelia spp other than Borrelia burgdorferi), Yersinia enterocolitica
Parasitic Malaria (eg, Plasmodium vivax, Plasmodium ovale)
Inflammatory or Immunologic Behçet syndrome, inflammatory bowel disease (eg, Crohn disease), hereditary fever syndromes (eg, FMF), juvenile dermatomyositis, PFAPA syndrome, sarcoidosis, systemic lupus erythematous, systemic juvenile idiopathic arthritis (Still disease), vasculitis (eg, polyarteritis nodosa)
Malignant Leukemia, lymphoma
Other Benign giant lymph node hyperplasia (Castleman disease), CNS abnormalities (eg, hypothalamic dysfunction), drug fever, factitious fever, IgG4-related disease, immunodeficiency syndromes with recurrent infections


Epidemiology and Demographics

Age

Prognosis

Diagnosis

Symptoms

Physical Examination

Laboratory Findings

Urinalysis and urine culture

  • Urinalysis is a key factor in the evaluation of fever in infancy and early childhood because UTI is a common cause of serious bacterial infection.
  • Urine sample should be obtained for all children younger than 24 months with unexplained fever. It may be obtained by catheterization or suprapubic aspiration.
  • In children with voluntary urine control, a clean catch method (urination into a specimen container after cleaning the area around the urethra) may be used.
  • Cultures of specimens collected in a urine bag may have an 85 percent false-positive rate, and urine dipstick testing has a 12 percent false-negative rate.
  • All specimens should be sent for formal urinalysis and culture.
  • UTI rates vary with patient sex and age.
  • In the first three months of life, UTIs are more common in boys than in girls, and much more common in uncircumcised boys. After three months of age, UTIs are more common in girls.

Blood cell counts and blood culture

Stool testing

Inflammatory markers

Lumbar puncture

Electrocardiogram

There are no ECG findings associated with fever in children.

X-ray

  • Chest X ray is recommended in all neonates with unexplained fever.
  • Chest X ray is also recommended for young children older than one month revealing respiratory symptoms and for patients with a fever of more than 102.2°F (39°C) and a WBC count of more than 20,000 per mm3 (20 × 109 per L).

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with fever in children.

CT scan

There are no CT scan findings associated with fever in children.

MRI

There are no MRI findings associated with fever in children.

Treatment

Medical Therapy

References

  1. ↑ Stein MT (1991). "Historical perspective on fever and thermometry". Clin Pediatr (Phila). 30 (4 Suppl): 5–7. doi:10.1177/0009922891030004S02. PMID 2029820.
  2. ↑ 2.0 2.1 2.2 Ogoina D (2011). "Fever, fever patterns and diseases called 'fever'--a review". J Infect Public Health. 4 (3): 108–24. doi:10.1016/j.jiph.2011.05.002. PMID 21843857.
  3. ↑ Walter EJ, Hanna-Jumma S, Carraretto M, Forni L (2016). "The pathophysiological basis and consequences of fever". Crit Care. 20 (1): 200. doi:10.1186/s13054-016-1375-5. PMC 4944485. PMID 27411542.
  4. ↑ BREWIS EG (1965). "CHILD CARE IN GENERAL PRACTICE. UNDIAGNOSED FEVER". Br Med J. 1 (5427): 107–9. PMC 2165027. PMID 14218464.
  5. ↑ Soon GS, Laxer RM (2017). "Approach to recurrent fever in childhood". Can Fam Physician. 63 (10): 756–762. PMC 5638471. PMID 29025800.
  6. ↑ Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D, European Research Network on Recognising Serious Infection investigators (2010). "Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review". Lancet. 375 (9717): 834–45. doi:10.1016/S0140-6736(09)62000-6. PMID 20132979.
  7. ↑ Barbi E, Marzuillo P, Neri E, Naviglio S, Krauss BS (2017). "Fever in Children: Pearls and Pitfalls". Children (Basel). 4 (9). doi:10.3390/children4090081. PMC 5615271. PMID 28862659.
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