Lassa fever natural history, complications and prognosis: Difference between revisions

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{{Lassa fever}}
{{Lassa fever}}
{{CMG}}; {{AE}} {{Ammu}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
Following exposure, infected patients remain asymptomatic for approximately 3 to 21 days. The majority of patients experience no or mild clinical manifestations. Typically, patients first develop persistent [[high-grade fever]] and other non-specific signs and symptoms. If left untreated, the majority of cases self-resolve without intervention. However, in the minority of cases, clinical manifestations may progress to [[hemorrhage]], [[deafness]], [[abdominal pain|abdominal]]/[[chest pain]], [[pleural effusion|pleural]]/[[pericardial effusion|pericardial]] effusions and [[ascites]], and [[facial edema]]. Eventually, manifestations progress to include [[convulsions]], [[hypovolemic shock]], [[coma]], and eventually [[death]]. The most common complications of Lassa fever are [[deafness|neurosensory deafness]] and [[hepatitis|hepatic injury]], which may be a mild [[hepatitis]] or [[fulminant hepatic necrosis]]. Although prognosis of Lassa fever is generally good, development of complications, [[pregnancy]], [[infancy]], are associated with poorer prognosis and increased risk of death.


{{SK}} Lassa hemorrhagic fever; LHF
==Overview==
The most common [[complication]] of Lassa fever is [[deafness]]. Various degrees of deafness occur in approximately one-third of cases, and in many cases [[hearing loss]] is permanent. [[Spontaneous abortion]] is another serious complication. Approximately 15%-20% of patients hospitalized for Lassa fever die from the illness. However, overall only about 1% of [[infection]]s with Lassa virus result in death. The death rates are particularly high for women (greater than 80%) in the [[third trimester]] of [[pregnancy]], and for [[fetus]]es, about 95% of which die in the uterus of infected pregnant mothers.
==Natural History==
==Natural History==
* Signs and symptoms of Lassa fever typically occur 1-3 weeks after the [[patient]] comes into contact with the [[virus]]. For the majority of Lassa fever virus infections (approximately 80%), symptoms are mild and are undiagnosed<ref name=CDC>{{cite web | title = The Centers for Disease Control and Prevention | url =http://www.cdc.gov/vhf/virus-families/arenaviridae.html }}</ref>.
===Incubation Period===
* Mild symptoms include slight [[fever]], general [[malaise]] and weakness, and [[headache]]. In 20% of infected individuals, however, [[disease]] may progress to more serious symptoms including [[hemorrhaging]] (in [[gums]], [[eyes]], or [[nose]], as examples), respiratory distress, repeated [[vomiting]], [[facial swelling]], [[pain]] in the [[chest]], [[back]], and [[abdomen]], and [[shock]].
*Infected patients remain asymptomatic for 3 to 21 days following exposure.<ref name="pmid15487592">{{cite journal| author=Günther S, Lenz O| title=Lassa virus. | journal=Crit Rev Clin Lab Sci | year= 2004 | volume= 41 | issue= 4 | pages= 339-90 | pmid=15487592 | doi=10.1080/10408360490497456 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15487592  }} </ref>
* Neurological problems have also been described, including [[hearing loss]], [[tremors]], and [[encephalitis]]. Death may occur within two weeks after symptom onset due to [[multi-organ failure]].
 
* Clinical stages of Lassa fever <SMALL>(adapted from McCarthy)<ref name="pmid12296302">{{cite journal| author=McCarthy M| title=USA moves quickly to push biodefence research. | journal=Lancet | year= 2002 | volume= 360 | issue= 9335 | pages= 732 | pmid=12296302 | doi=10.1016/S0140-6736(02)09938-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12296302  }} </ref></SMALL>
===Development of Clinical Manifestations===
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
*The majority of patients experience no or mild symptoms. Only a minority (approximately 15-20%) of patients experience multiorgan dysfunction, and typically 5-15% of infected patients die of Lassa fever.
| align="center" style="background:#4479BA; padding: 5px 5px;"|{{fontcolor|#FFF|'''Stage'''}}
*Patients typically first develop persistent high-grade [[fever]] (39 °C to 41 °C) and other non-specific symptoms, such as [[muscle aches]], [[conjunctival injection]], [[headache]], [[sore throat]], [[nausea]], and [[vomiting]].
| align="center" style="background:#4479BA; padding: 5px 5px;"|{{fontcolor|#FFF|'''Symptoms'''}}
*If left untreated, the majority of patients self-resolve without any intervention.
| align="center" style="background:#4479BA; padding: 5px 5px;"|{{fontcolor|#FFF|'''Days'''}}
*In a minority of cases, patients may develop worsening abdominal/chest pain, temporary/permanent deafness, facial edema, mucosal bleeding and hemorrhage, pulmonary edema, pleural/pericardial effusions or ascites, multi-organ failure, and shock.
*Prolonged and worsening symptoms are usually associated with worsening prognosis, typically resulting in convulsions, encephalitis, seizures, coma and finally death.  
 
*The following table demonstrates the 4 clinical stages of Lassa fever <SMALL>(adapted from McCarthy et al. 2002<ref name="pmid12296302">{{cite journal| author=McCarthy M| title=USA moves quickly to push biodefence research. | journal=Lancet | year= 2002 | volume= 360 | issue= 9335 | pages= 732 | pmid=12296302 | doi=10.1016/S0140-6736(02)09938-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12296302  }} </ref> and Richmond et al. 2003<ref name="pmid14644972">{{cite journal| author=Richmond JK, Baglole DJ| title=Lassa fever: epidemiology, clinical features, and social consequences. | journal=BMJ | year= 2003 | volume= 327 | issue= 7426 | pages= 1271-5 | pmid=14644972 | doi=10.1136/bmj.327.7426.1271 | pmc=PMC286250 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644972  }} </ref>)</SMALL>
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
| align="center" style="background:#4479BA; width: 50px;" |{{fontcolor|#FFF|'''Stage'''}}
| align="center" style="background:#4479BA; width: 400px;" |{{fontcolor|#FFF|'''Typical Symptoms'''}}
| align="center" style="background:#4479BA; width: 80px;" |{{fontcolor|#FFF|'''Days Since Symptom-onset'''}}
|-
|-
| style="padding: 5px 5px; background: #EBEBEB;"| Stage 1||style="padding: 5px 5px; background: #EBEBEB;"|High [[fever]] of 39°C with peaks of 40°C-41°C, [[malaise]], [[weakness]] ||style="padding: 5px 5px; background: #F2F2F2;"|Day1 -day 3
| style="padding: 5px 5px; background: #EBEBEB;" | Stage 1|| style="padding: 5px 5px; background: #EBEBEB;" |High-grade [[fever]] (39-41 °C), [[malaise]], [[weakness]] || style="padding: 5px 5px; background: #F2F2F2;" |day-1 to day-3
|-
|-
| style="padding: 5px 5px; background: #EBEBEB;"| Stage 2||style="padding: 5px 5px; background: #EBEBEB;"|[[Headache]], [[backache]], [[chest pain]], exudative [[sore throat]] with white [[patches]], [[abdominal pain]], [[diarrhea]], [[nausea]], [[vomiting]], low [[blood pressure]], [[anemia]], [[proteinuria]], [[conjunctivitis]]||style="padding: 5px 5px; background: #F2F2F2;"|Day4 -day 7
| style="padding: 5px 5px; background: #EBEBEB;" | Stage 2|| style="padding: 5px 5px; background: #EBEBEB;" |[[Headache]], [[backache]], [[chest pain]], [[sore throat]] with exudation, [[abdominal pain]], [[diarrhea]], [[nausea]], [[vomiting]], [[hypotension]], [[anemia]], [[proteinuria]], [[conjunctivitis]]|| style="padding: 5px 5px; background: #F2F2F2;" |day-4 to day-7
|-
|-
| style="padding: 5px 5px; background: #EBEBEB;"| Stage 3||style="padding: 5px 5px; background: #EBEBEB;"|[[Mucosal bleeding]], internal [[bleeding]], [[facial edema]], [[confusion]], [[disorientation]] and [[convulsion]]||style="padding: 5px 5px; background: #F2F2F2;"|>7 days
| style="padding: 5px 5px; background: #EBEBEB;" | Stage 3|| style="padding: 5px 5px; background: #EBEBEB;" |[[Mucosal bleeding]], internal [[bleeding]], [[facial edema]], [[confusion]], [[disorientation]] and [[convulsion]]|| style="padding: 5px 5px; background: #F2F2F2;" |Beyond day-7
|-
|-
| style="padding: 5px 5px; background: #EBEBEB;"| Stage 4||style="padding: 5px 5px; background: #EBEBEB;"|[[Coma]], [[death]] ||style="padding: 5px 5px; background: #F2F2F2;"|>14 days
| style="padding: 5px 5px; background: #EBEBEB;" | Stage 4|| style="padding: 5px 5px; background: #EBEBEB;" |[[Coma]], [[death]] || style="padding: 5px 5px; background: #F2F2F2;" |Beyond day-14
|}
|}
[[File:Signs and symptoms Lassa.png|thumb|center|800 px|Clinical signs and symptoms Lassa Fever CDC<SMALL><SMALL>''[http://www.cdc.gov/NCIDOD/dvrd/spb/mnpages/lassaslides.htm]''</SMALL></SMALL>]]


==Complications==
==Complications==
* Approximately 15%-20% of patients hospitalized for Lassa fever die from the [[illness]]. However, only 1% of all Lassa virus infections result in death. The death rates for women in the [[third trimester]] of pregnancy are particularly high. Other complications include the following.
Complications of Lassa fever include the following:
===Sensorineural Deafness===
*[[Sensorineural Deafness]]
* The most common complication of Lassa fever is [[deafness]].
** The most common complication of Lassa fever is [[deafness]] (1/3 of patients)
* Occurs in 1/3rd of the cases.
** Deafness may be either temporary or permanent and may either by unilateral or bilateral.  
* Various degrees of [[deafness]] occur in approximately one-third of [[infections]], and in many cases [[hearing loss]] is permanent.  
** Deafness does not seem to be associated with the severity of disease and may develop equally among patients with mild or severe infections.
* As far as is known, severity of the disease does not affect this complication: deafness may develop in mild as well as in severe cases.
*[[Spontaneous abortion]] among pregnant women
* It could be unilateral or bilateral.
*[[Hepatitis]] and [[hepatic necrosis]]
===Lassa Fever in Pregnancy===
*[[Splenic necrosis]]
* Increased mortality in 3rd trimester of more than 30% to the mother.
*[[Adrenocortical necrosis]]
* Increased [[viremia]] in [[pregnant]] woman.
*[[Pulmonary alveolar edema]]
* Evacuation of the [[uterus]] improves mother's chance of survival.
*[[Interstitial pneumonitis]]
* Placental infection of the [[fetus]].
*Lymph node [[histiocytosis]]
* [[Spontaneous abortion]] is a serious complication of infection with an estimated 95% mortality in fetuses of infected pregnant mothers.
*Mucosal (e.g. GI) bleeding
* Increased fetal and neonatal mortality of more than 85%.
*[[Renal tubular injury]] and [[interstitial nephritis]]
===Lassa Fever in Children===
*[[Swollen baby syndrome]] (edema and bleeding among fetuses)
====Swollen Baby Syndrome====
* [[Edema]].
* [[Abdominal distention]].
* [[Bleeding]].
* Poor prognosis.


==Prognosis==
==Prognosis==
* Prognosis of lassa fever is poor if its associated with following features<ref name=CDC>{{cite web | title = The Centers for Disease Control and Prevention | url =http://www.cdc.gov/NCIDOD/dvrd/spb/mnpages/lassaslides.htm }}</ref>.
* Approximately 5-15% of patients hospitalized for Lassa fever die from the [[illness]]. The following factors are associated with poorer prognosis of Lassa fever:<ref name="CDC">{{cite web | title = The Centers for Disease Control and Prevention | url =http://www.cdc.gov/NCIDOD/dvrd/spb/mnpages/lassaslides.htm }}</ref>
:* Increased [[viremia]].
** Infection during the t[[Third trimester of pregnancy|hird trimester of pregnancy]] or during [[infancy]]
:* Serum [[AST]] level > 150 IU/L
** Increased [[viremia]] concentration
:* [[Bleeding]].
** Serum [[AST]] level > 150 IU/L
:* [[Encephalitis]].
** [[Bleeding]], [[hypotension]], and [[shock]]
:* [[Edema]]
** Development of [[encephalitis]], [[confusion]], or [[coma]]
:* [[Third trimester of pregnancy]].
** [[Edema]] ([[facial edema]], [[Pleural effusion|pleural]]/[[pericardial effusion]], [[ascites]])


==References==
==References==
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[[Category:Tropical disease]]
[[Category:Tropical disease]]
[[Category:Biological weapons]]
[[Category:Biological weapons]]
[[Category:Infectious disease]]
 


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Latest revision as of 18:08, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

Following exposure, infected patients remain asymptomatic for approximately 3 to 21 days. The majority of patients experience no or mild clinical manifestations. Typically, patients first develop persistent high-grade fever and other non-specific signs and symptoms. If left untreated, the majority of cases self-resolve without intervention. However, in the minority of cases, clinical manifestations may progress to hemorrhage, deafness, abdominal/chest pain, pleural/pericardial effusions and ascites, and facial edema. Eventually, manifestations progress to include convulsions, hypovolemic shock, coma, and eventually death. The most common complications of Lassa fever are neurosensory deafness and hepatic injury, which may be a mild hepatitis or fulminant hepatic necrosis. Although prognosis of Lassa fever is generally good, development of complications, pregnancy, infancy, are associated with poorer prognosis and increased risk of death.

Natural History

Incubation Period

  • Infected patients remain asymptomatic for 3 to 21 days following exposure.[1]

Development of Clinical Manifestations

  • The majority of patients experience no or mild symptoms. Only a minority (approximately 15-20%) of patients experience multiorgan dysfunction, and typically 5-15% of infected patients die of Lassa fever.
  • Patients typically first develop persistent high-grade fever (39 °C to 41 °C) and other non-specific symptoms, such as muscle aches, conjunctival injection, headache, sore throat, nausea, and vomiting.
  • If left untreated, the majority of patients self-resolve without any intervention.
  • In a minority of cases, patients may develop worsening abdominal/chest pain, temporary/permanent deafness, facial edema, mucosal bleeding and hemorrhage, pulmonary edema, pleural/pericardial effusions or ascites, multi-organ failure, and shock.
  • Prolonged and worsening symptoms are usually associated with worsening prognosis, typically resulting in convulsions, encephalitis, seizures, coma and finally death.
  • The following table demonstrates the 4 clinical stages of Lassa fever (adapted from McCarthy et al. 2002[2] and Richmond et al. 2003[3])
Stage Typical Symptoms Days Since Symptom-onset
Stage 1 High-grade fever (39-41 °C), malaise, weakness day-1 to day-3
Stage 2 Headache, backache, chest pain, sore throat with exudation, abdominal pain, diarrhea, nausea, vomiting, hypotension, anemia, proteinuria, conjunctivitis day-4 to day-7
Stage 3 Mucosal bleeding, internal bleeding, facial edema, confusion, disorientation and convulsion Beyond day-7
Stage 4 Coma, death Beyond day-14

Complications

Complications of Lassa fever include the following:

Prognosis

References

  1. ↑ Günther S, Lenz O (2004). "Lassa virus". Crit Rev Clin Lab Sci. 41 (4): 339–90. doi:10.1080/10408360490497456. PMID 15487592.
  2. ↑ McCarthy M (2002). "USA moves quickly to push biodefence research". Lancet. 360 (9335): 732. doi:10.1016/S0140-6736(02)09938-5. PMID 12296302.
  3. ↑ Richmond JK, Baglole DJ (2003). "Lassa fever: epidemiology, clinical features, and social consequences". BMJ. 327 (7426): 1271–5. doi:10.1136/bmj.327.7426.1271. PMC 286250. PMID 14644972.
  4. ↑ "The Centers for Disease Control and Prevention".


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