Lassa fever medical therapy: Difference between revisions

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Latest revision as of 18:08, 18 September 2017

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

Overview

Management of Lassa fever includes supportive care and administration of intravenous (IV) ribavirin. Data on the efficacy of antiviral agents in Lassa fever are scarce. IV ribavirin was previously evaluated for treatment of Lassa fever and demonstrated a reduction in mortality when administered anytime during the course of the disease, especially early within the first 6 days of symptom-onset. Ribavirin is administered intravenously for a total of 10 days using the following regimen: first, loading dose of 30 mg/kg (max. 2g) followed by a dose of 16 mg/kg (max. 1g) IV q6h for 4 days, followed by a dose of 8 mg/kg (max. 500mg) IV q8h for 6 days.^[1] In addition to antiviral therapy, management includes supportive care to adequately maintain respiratory status, as well as fluid and electrolyte balance.

Medical Therapy

Supportive Care

All hospitalized individuals with suspected Lassa fever should be isolated with proper disposal of body fluids and excreta.
Supportive care, including adequate fluid and electrolyte replacement and blood transfusions, may also be required.

Antiviral Therapy: Ribavirin

Intravenous (IV) ribavirin, an antiviral agent with an effect on viral replication, is associated with a reduction in mortality among patients with Lassa fever, especially when administered within the first 6 days of symptom-onset.^[1]
Although ribavirin is more effective when administered early in the course of the disease (first 6 days of symptom onset) than when administered late, the benefit of ribavirin outweighs the risk of its adverse effects at any point during the illness, and administration of ribavirin is recommended at any time during the infection.^[1]^[2]
Compared with oral ribavirin, intravenous (IV) ribavirin is almost twice as effective. It is thought, however, that the efficacy of IV ribavirin may, at least in part, be attributed to the decreased tolerance for oral intake among high-risk symptomatic groups (e.g. patients with gastrointestinal or neurological disease).^[3]
The efficacy of ribavirin is more pronounced among symptomatic patients with signs of Lassa fever-related liver injury (i.e. AST > 150 IU/L)^[1]
Use of IV followed by oral ribavirin may be considered.^[1]
The efficacy of ribavirin for the post-exposure prophylaxis is unknown.^[1]

Optimal Treatment

Ribavarin^[1]^[4]

Loading dose: 30 mg/kg (max. 2g) IV
Concentration dose: 16 mg/kg (max. 1g) IV q6h for 4 days, then 8 mg/kg (max. 500mg) IV q8h for 6 days

Pregnancy

There are no randomized data on the efficacy of ribavirin among pregnant women.
For 3rd-term pregnant women with Lassa fever, the risk of death is very high. Among these patients, emergent evacuation of the uterus (by induction or surgically) has been demonstrated to decrease the risk of death.^[5]
It is hypothesized that evacuating the uterus decreases the viral load significantly as the virus has high affinity for the placenta and other highly vascular tissues.
Observational studies have demonstrated that the fetus has only a one in ten chance of survival irrespective of the therapies used or the interventions attempted.
The main focus is on reducing the risk of death in the mother. Following active obstetrical intervention, treatment with ribavirin should be initiated immediately.

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM; et al. (1986). "Lassa fever. Effective therapy with ribavirin". N Engl J Med. 314 (1): 20–6. doi:10.1056/NEJM198601023140104. PMID 3940312.
↑ Fact sheet N°179: Lassa Fever. World Health Organization. Accessed on June 09, 2015.
↑ Fisher-Hoch SP, McCormick JB (2004). "Lassa fever vaccine". Expert review of vaccines. 3 (2): 189–97. doi:10.1586/14760584.3.4.S189. PMID 15056044.
↑ Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM, Jahrling PB; et al. (2002). "Hemorrhagic fever viruses as biological weapons: medical and public health management". JAMA. 287 (18): 2391–405. PMID 11988060.
↑ Price ME, Fisher-Hoch SP, Craven RB, McCormick JB (1988). "A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy". BMJ. 297 (6648): 584–7. PMID 3139220.

Template:WikiDoc Sources

[pmid3940312-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM; et al. (1986). "Lassa fever. Effective therapy with ribavirin". N Engl J Med. 314 (1): 20–6. doi:10.1056/NEJM198601023140104. PMID 3940312.

[who-2] Fact sheet N°179: Lassa Fever. World Health Organization. Accessed on June 09, 2015.

[3] Fisher-Hoch SP, McCormick JB (2004). "Lassa fever vaccine". Expert review of vaccines. 3 (2): 189–97. doi:10.1586/14760584.3.4.S189. PMID 15056044.

[pmid11988060-4] Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM, Jahrling PB; et al. (2002). "Hemorrhagic fever viruses as biological weapons: medical and public health management". JAMA. 287 (18): 2391–405. PMID 11988060.

[5] Price ME, Fisher-Hoch SP, Craven RB, McCormick JB (1988). "A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy". BMJ. 297 (6648): 584–7. PMID 3139220.

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@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Lassa fever}}
-{{CMG}}
+{{CMG}}; {{AE}} {{YD}}; {{SSK}}; {{Ammu}}
+==Overview==
+Management of Lassa fever includes supportive care and administration of intravenous (IV) [[ribavirin]]. Data on the efficacy of antiviral agents in Lassa fever are scarce. IV [[ribavirin]] was previously evaluated for treatment of Lassa fever and demonstrated a reduction in mortality when administered anytime during the course of the disease, especially early within the first 6 days of symptom-onset. Ribavirin is administered intravenously for a total of 10 days using the following regimen: first, loading dose of 30 mg/kg (max. 2g) followed by a dose of 16 mg/kg (max. 1g) IV q6h for 4 days, followed by a dose of 8 mg/kg (max. 500mg) IV q8h for 6 days.<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref> In addition to antiviral therapy, management includes supportive care to adequately maintain respiratory status, as well as [[fluid]] and [[electrolyte]] balance.
 ==Medical Therapy==
-All persons suspected of Lassa fever infection should be admitted to [[Isolation (health care)|isolation]] facilities and their [[body fluids]] and [[excretion|excreta]] properly disposed of.
+===Supportive Care===
+* All hospitalized individuals with suspected Lassa fever should be isolated with proper disposal of [[body fluids]] and [[excretion|excreta]].
+* Supportive care, including adequate f[[Fluid replacement|luid]] and electrolyte replacement and [[blood transfusions]], may also be required.
+===Antiviral Therapy: Ribavirin===
+* Intravenous (IV) [[ribavirin]], an antiviral agent with an effect on viral replication, is associated with a reduction in mortality among patients with Lassa fever, especially when administered within the first 6 days of symptom-onset.<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref>
+*Although ribavirin is more effective when administered early in the course of the disease (first 6 days of symptom onset) than when administered late, the benefit of ribavirin outweighs the risk of its adverse effects at any point during the illness, and administration of ribavirin is recommended at any time during the infection.<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref><ref name="who">Fact sheet N°179: Lassa Fever. World Health Organization. [http://www.who.int/mediacentre/factsheets/fs179/en/ Accessed on June 09, 2015.] </ref>
+*Compared with oral ribavirin, intravenous (IV) ribavirin is almost twice as [[effective dose|effective]]. It is thought, however, that the efficacy of IV ribavirin may, at least in part, be attributed to the decreased tolerance for oral intake among high-risk symptomatic groups (e.g. patients with gastrointestinal or neurological disease).<ref>{{cite journal |author=Fisher-Hoch SP, McCormick JB |title=Lassa fever vaccine |journal=Expert review of vaccines |volume=3 |issue=2 |pages=189-97 |year=2004 |pmid=15056044 |doi=10.1586/14760584.3.4.S189}}</ref>
+*The efficacy of ribavirin is more pronounced among symptomatic patients with signs of Lassa fever-related liver injury (i.e. AST > 150 IU/L)<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref>
+*Use of IV followed by oral ribavirin may be considered.<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref>
+*The efficacy of ribavirin for the post-exposure prophylaxis is unknown.<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref>
-After extensive testing, it was determined that early administration of [[ribavirin]] is critical to success. Additionally, Ribavirin is almost twice as [[effective dose|effective]] when given [[intravenous]]ly as when taken by mouth.<ref>{{cite journal |author=Fisher-Hoch SP, McCormick JB |title=Lassa fever vaccine |journal=Expert review of vaccines |volume=3 |issue=2 |pages=189-97 |year=2004 |pmid=15056044 |doi=10.1586/14760584.3.4.S189}}</ref> Ribavirin is a [[prodrug]] which appears to interfere with [[viral replication]] by inhibiting [[RNA]]-dependent [[DNA Replication|nucleic acid synthesis]], although the precise [[mechanism of action]] is disputed.<ref>{{cite journal |author=Crotty S, Cameron C, Andino R |title=Ribavirin's antiviral mechanism of action: lethal mutagenesis? |journal=J. Mol. Med. |volume=80 |issue=2 |pages=86-95 |year=2002 |pmid=11907645 |doi=10.1007/s00109-001-0308-0}}</ref> The drug is relatively inexpensive, but the cost of the drug is still very high for many of those in poverty-stricken West African states. Thanks to treatment with [[Ribavirin]], fatality rates are continuing to decline. [[Fluid replacement]], [[blood transfusion]] and fighting [[hypotension]] are usually required. [[Intravenous]] [[interferon]] [[therapy]] has also been used.
+{| style="border: 0px; font-size: 90%; margin: 3px;"
+|-
+| align="center" style="background:#4479BA; padding: 3px;" |{{fontcolor|#FFF|'''Optimal Treatment'''}}
+|-
+| align="left" style="background:#efefef; padding: 10px;" |'''Ribavarin'''<ref name="pmid3940312">{{cite journal| author=McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM et al.| title=Lassa fever. Effective therapy with ribavirin. | journal=N Engl J Med | year= 1986 | volume= 314 | issue= 1 | pages= 20-6 | pmid=3940312 | doi=10.1056/NEJM198601023140104 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3940312  }} </ref><ref name="pmid11988060">{{cite journal| author=Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM, Jahrling PB et al.| title=Hemorrhagic fever viruses as biological weapons: medical and public health management. | journal=JAMA | year= 2002 | volume= 287 | issue= 18 | pages= 2391-405 | pmid=11988060 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11988060  }} </ref>
+*{{fontcolor|#4479BA|''Loading dose:''}} 30 mg/kg (max. 2g) IV<br>
+*{{fontcolor|#4479BA|''Concentration dose:''}} 16 mg/kg (max. 1g) IV q6h for 4 days, then 8 mg/kg (max. 500mg) IV q8h for 6 days
+|-
+|}
-When Lassa fever infects [[pregnant]] women late in their [[third trimester]], it is necessary to abort the pregnancy for the mother to have a good chance of survival.<ref>{{cite journal |author=Price ME, Fisher-Hoch SP, Craven RB, McCormick JB |title=A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy |journal=BMJ |volume=297 |issue=6648 |pages=584–7 |year=1988 |pmid=3139220 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=3139220}}</ref>  This is due to the fact that the virus has an affinity for the [[placenta]] and other highly [[vascular]] tissues.  The [[fetus]] has only a one in ten chance of survival no matter what course of action is taken; hence focus is always on saving the life of the mother. Following [[abortion]], women should receive the same treatment as other Lassa fever patients.
+==Pregnancy==
+*There are no randomized data on the efficacy of ribavirin among pregnant women.
-;Shown below is a table summarizing the preferred treatment for Lassa fever<ref name="pmid11988060">{{cite journal| author=Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM, Jahrling PB et al.| title=Hemorrhagic fever viruses as biological weapons: medical and public health management. | journal=JAMA | year= 2002 | volume= 287 | issue= 18 | pages= 2391-405 | pmid=11988060 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11988060  }} </ref>.
+* For 3rd-term pregnant women with Lassa fever, the risk of death is very high. Among these patients, emergent evacuation of the uterus (by induction or surgically) has been demonstrated to decrease the risk of death.<ref>{{cite journal |author=Price ME, Fisher-Hoch SP, Craven RB, McCormick JB |title=A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy |journal=BMJ |volume=297 |issue=6648 |pages=584–7 |year=1988 |pmid=3139220 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=3139220}}</ref>
+*It is hypothesized that evacuating the uterus decreases the viral load significantly as the virus has high affinity for the [[placenta]] and other highly [[vascular]] tissues.
-{| class="wikitable" border="1" style="background:FloralWhite"
+*Observational studies have demonstrated that the [[fetus]] has only a one in ten chance of survival irrespective of the therapies used or the interventions attempted.
-|- align="center"
+*The main focus is on reducing the risk of death in the mother. Following active obstetrical intervention, treatment with ribavirin should be initiated immediately.
-|'''Optimal Treatment'''
-|'''Duration of Treatment'''
-|- align="center"
-|'''Ribavarin'''
-Loading dose: 30 mg/kg (max. 2g) IV
-Concentration dose: 16 mg/kg (max. 1g) IV Q6H X 4 days, then 8 mg/kg (max. 500mg) IV Q8H X 6 days
-|10 days
-|- align="center"
-|}
 ==References==
 {{Reflist|2}}
 [[Category:Disease]]
-[[Category:Needs overview]]
 [[Category:Viral diseases]]
 [[Category:Viruses]]
@@ Line 38: / Line 43: @@
 [[Category:Tropical disease]]
 [[Category:Biological weapons]]
-[[Category:Infectious disease]]
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