Leishmaniasis medical therapy: Difference between revisions

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{{Leishmaniasis}}
{{Leishmaniasis}}
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{{CMG}}; {{AE}} {{AL}}


==Overview==
==Overview==
Treatment decisions should be individualized, with expert consultation. In general, all clinically manifest cases of visceral leishmaniasis and mucosal leishmaniasis should be treated, whereas not all cases of cutaneous leishmaniasis require treatment.  The treatment depends on the form of leishmaniasis, and this include medications such as [[Pentavalent antimonial (SbV) compounds]], [[liposomal amphotericin B]], [[miltefosine]], [[ketoconazole]], and [[fluconazole]].


==Medical Therapy==
==Medical Therapy==
There are two common therapies containing [[antimony]] (known as [[pentavalent antimonials]]), [[meglumine antimoniate]] (''Glucantim''®) and [[sodium stibogluconate]] (''Pentostam''®). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or [[trypanothione]] metabolism. Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis,<ref name="Soto2007">{{cite journal | author=Soto J, Toledo JT. | title=Oral miltefosine to treat new world cutaneous leishmaniasis | journal=Lancet Infect Dis | volume=7 | issue=1 | pages=7 }}</ref> but the level of resistance varies according to species.<ref>{{cite journal|author=Arevalo J, Ramirez L, Adaui V,''et al.''|title=Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis|journal=J Infect Dis|year=2007|volume=195|pages=1846&ndash;51|doi=10.1086/518041}}</ref> [[Amphotericin]] is now the treatment of choice<ref>{{cite journal|journal=Clin Infect Dis|year=2007|volume=45|pages=556&ndash;561|title=Amphotericin B Treatment for Indian Visceral Leishmaniasis: Response to 15 Daily versus Alternate-Day Infusions|author=Sundar S, Chakravarty J, Rai VK, ''et al.''|url=http://www.journals.uchicago.edu/CID/journal/issues/v45n5/50485/brief/50485.abstract.html}}</ref>; failure of [[amphotericin|AmBisome]]&reg; to treat visceral leishmaniasis (''Leishmania donovani'') has been reported in Sudan,<ref>{{cite journal | author=Mueller M, Ritmeijer K, Balasegaram M, Koummuki Y, Santana MR, Davidson R. | title=Unresponsiveness to AmBisome&reg; in some Sudanese patients with kala-azar | journal=Trans R Soc Trop Med Hyg | year=2007 | volume=101 | issue=1 | pages=19&ndash;24 | doi=10.1016/j.trstmh.2006.02.005 }}</ref> but this failure may be related to host factors such as co-infection with [[human immunodeficiency virus|HIV]] or [[tuberculosis]] rather than parasite resistance.
*The treatment approach depends in part on host and parasite factors.
*Some approaches/regimens are effective only against certain Leishmania species/strains and only in particular geographic regions.  
*Even data from well-conducted clinical trials are not necessarily generalizable to other settings. Of particular note, data from the many clinical trials of therapy for visceral leishmaniasis in parts of India are not necessarily directly applicable to visceral leishmaniasis caused by L. donovani in other areas, to visceral leishmaniasis caused by other species, or to treatment of cutaneous and mucosal leishmaniasis.
*Special groups (such as young children, elderly persons, pregnant/lactating women, and persons who are immunocompromised or who have other comorbidities) may need different medications or dosage regimens.
{| style="border: 0px; font-size: 85%; margin: 3px; width:400px;float:right" align=center
|valign=top|
|+<div style="font-size:130%">'''Indications for Therapy in Cutaneous Leishmaniasis'''</div>
! style="background: #4479BA; color:#FFF;" | Therapy of cutaneous leishmaniasis may be indicated to
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
*Decrease the risk for mucosal dissemination/disease (particularly for New World species in the Viannia subgenus)
|-
| style="padding: 5px 5px; background: #DCDCDC;" |
*Accelerate healing of the skin lesions
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
*Decrease the risk for relapse (clinical reactivation) of the skin lesions
|-
| style="padding: 5px 5px; background: #DCDCDC;" |  
*Decrease the local morbidity caused by large or persistent skin lesions, particularly those on the face or ears or near joints
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
*Decrease the reservoir of infection in geographic areas where infected persons (vs. non-human animals) serve as reservoir hosts <small> (such as in Kabul, Afghanistan, and other Leishmania tropica-endemic areas, where transmission is anthroponotic)</small>
|}


[[Miltefosine]] (Impavido®), is a new drug for [[visceral]] and [[cutaneous]] leishmaniasis. The cure rate of miltefosine in phase III [[clinical trials]] is 95%; Studies in Ethiopia show that is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs.
===Cutaneous Leishmaniasis===
Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by ''Leishmania braziliensis'' in Colombia,<ref name="Soto2007"/> and preliminary results are very promising.  It is now registered in many countries and is the first orally administered breakthrough therapy for visceral and cutaneous leishmaniasis.<ref name="Jha1999">{{cite journal | author=Jha TK, Sundar S, Thakur CP ''et al.'' | title=Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis | year=1999 | journal=New Engl J Med | volume=341 | pages=1795&ndash;800 }}</ref>(More, ''et al'', 2003). In October 2006 it received [[orphan drug]] status from the US Food and Drug administration.  
*Decisions about whether and how to treat should be individualized.  
The drug is generally better tolerated than other drugs. Main side effects are gastrointetinal disturbance in the 1-2 days of treatment which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative.  
*The treatment approach depends in part on the Leishmania species/strain and the geographic area in which infection was acquired; the natural history of infection, the risk for mucosal dissemination/disease, and the drug susceptibilities in the pertinent setting; and the number, size, location, evolution, and other clinical characteristics of the patient's skin lesions.
*In general, the first sign of a therapeutic response to adequate treatment is decreasing induration (lesion flattening).  
*The healing process for large, ulcerative lesions often continues after the end of therapy.  
*Relapse (clinical reactivation) typically is noticed first at the margin of the lesion.


The Institute for OneWorld Health has developed [[paromomycin]], results with which led to its approval as an [[orphan drug]]. The [[Drugs for Neglected Diseases Initiative]] is also actively facilitating the search for novel therapeutics.
<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font><ref name=CDC>{{cite web|url=http://www.cdc.gov/parasites/leishmaniasis/health_professionals/index.html#dx| title=CDC - Parasites - Leishmaniasis}}</ref></SMALL>
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<font color="#FFF">
'''Cutaneous Leishmaniasis'''
</font>
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Drug-resistant leishmaniasis may respond to [[immunotherapy]] (inoculation with parasite antigens plus an [[adjuvant]]) which aims to stimulate the body's own immune system to kill the parasite.<ref>{{cite journal | author=Immunotherapy for Drug-Refractory Mucosal Leishmaniasis | author=Badaro R, Lobo I, Munõs A, ''et al.'' | journal=J Infect Dis | year=2006 | volume=194 | pages=1151&ndash;59 | title=Immunotherapy for drug-refractory mucosal leishmaniasis | url=http://www.journals.uchicago.edu/JID/journal/issues/v194n8/36472/brief/36472.abstract.html }}</ref>
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<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''Systemic Therapy (Parenteral)'''
</font>
</div>


Several potential vaccines are being developed, under pressure from the [[World Health Organization]], but as of 2006 none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zürich are trying to design a carbohydrate-based vaccine [http://news.bbc.co.uk/1/hi/health/4930528.stm]. The genome of the parasite ''Leishmania major'' has been sequenced,<ref>{{cite journal | author=Ivens AC, ''et al.'' | title=The genome of the kinetoplastid parasite, Leishmania major | journal=[[Science (journal)|Science]] | volume=309 | issue=5733 | year=2005 | pages=436&ndash;42  | id=PMID 16020728}}</ref> possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments.
<div class="mw-customtoggle-table2" style="cursor: pointer; border-radius: 5px 5px 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 250px; background: #4479BA;">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''Systemic Therapy (Oral)'''
</font>
</div>
 
<div class="mw-customtoggle-table3" style="cursor: pointer; border-radius: 0 0 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 250px; background: #4479BA;">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''Local Therapy'''
</font>
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| valign=top |
{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table1" style="background: #FFFFFF;"
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{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Systemic Therapy (Parenteral)}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Preferred Regimen'''''
|-
| style="font-size: 90%; padding: 5px 5px; background: #DCDCDC" align=left | ▸ '''''[[Sodium stibogluconate]] 20 mg/kg IV/IM once daily for 10-20 days''''' <br> OR <br> ▸ '''''[[Meglumine antimoniate]] 20 mg/kg IV/IM once daily for 10-20 days'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Alternative Regimen'''''
|-
| style="font-size: 90%; padding: 5px 5px; background: #DCDCDC" align=left | ▸ '''''[[Liposomal amphotericin B]]<sup>†</sup> 3 mg/kg/day IV infusion for 6-10 days ''''' <br> OR <br> ▸ '''''[[Pentamidine]]<sup>‡</sup> 2-3 mg/kg/day IV/IM for 4-7 days '''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=left| <small>† Data supporting the use of amphotericin B for treatment of cutaneous (and mucosal) leishmaniasis are anecdotal; standard dosage regimens have not been established. <br>‡ In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness. </small>
|-
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{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Systemic Therapy (Oral)}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Preferred Regimen'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''Patients that weight 33-44 kg:'''''<br> ▸ '''''[[Miltefosine]] <sup>†</sup> 50 mg PO q12h for 28 days'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''Patients that weight >45 kg:'''''<br> ▸ '''''[[Miltefosine]] <sup>†</sup> 50 mg PO q8h for 28 days'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Alternative Regimen<sup>‡</sup>'''''
|-
| style="font-size: 90%; padding: 5px 5px; background: #DCDCDC" align=left | ▸ '''''[[Ketoconazole]] 600 mg daily for 28 days''''' <br> OR <br> ▸ '''''[[Fluconazole]] 200 mg daily for 6 weeks'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=left| <small>†The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis. <br> ‡ The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved</small>
|}
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{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Local Therapy}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''List of possible local therapies'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Cryotherapy]] (with [[liquid nitrogen]])'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Thermotherapy]] (use of localized current field radiofrequency heat)'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''Intralesional administration of [[SbV]] <sup>†</sup>''''' 
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''Topical application of [[paromomycin]] (such as an ointment containing 15% [[paromomycin]]/12% methylbenzethonium chloride in soft white paraffin)'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=left| <small>†To date, not covered by CDC's IND protocol for Pentostam® </small>
|}
|}
|}
<br>
 
===Visceral Leishmaniasis===
<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font><ref name=CDC>{{cite web|url=http://www.cdc.gov/parasites/leishmaniasis/health_professionals/index.html#dx| title=CDC - Parasites - Leishmaniasis}}</ref></SMALL>
{|
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<font color="#FFF">
'''Visceral Leishmaniasis'''
</font>
</div>
 
<div class="mw-customtoggle-table4" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 250px; background: #4479BA;">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''Systemic Therapy (Parenteral)'''
</font>
</div>
 
<div class="mw-customtoggle-table5" style="cursor: pointer; border-radius: 5px 5px 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 250px; background: #4479BA;">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''Systemic Therapy (Oral)'''
</font>
</div>
 
| valign=top |
{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table4" style="background: #FFFFFF;"
| valign=top |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Systemic Therapy (Parenteral)}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Preferred Regimen'''''
|-
| style="font-size: 90%; padding: 5px 5px; background: #DCDCDC" align=left | ▸'''''[[Liposomal amphotericin B]]<sup>†</sup> 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21  (Total dose: 21 mg/kg)''''' <br> OR <br> ▸ '''''[[Sodium stibogluconate]] 20 mg/kg IV/IM once daily for 28 days''''' <br> OR <br> ▸ '''''[[Meglumine antimoniate]] 20 mg/kg IV/IM once daily for 28 days'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Alternative Regimen'''''
|-
| style="font-size: 90%; padding: 5px 5px; background: #DCDCDC" align=left |▸'''''[[Amphotericin B]] deoxycholate 0.5-1 mg/kg IV once daily (Total dose: 15-20 mg/kg)'''''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=left| <small>† In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10,  17, 24, 31, and 38  (Total dose: 40 mg/kg)</small>
|}
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{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table5" style="background: #FFFFFF;"
| valign=top |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Systemic Therapy (Oral)}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''Preferred Regimen'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''Patients that weight 33-44 kg:'''''<br> ▸ '''''[[Miltefosine]] <sup>†</sup> 50 mg PO q12h for 28 days'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''Patients that weight >45 kg:'''''<br> ▸ '''''[[Miltefosine]] <sup>†</sup> 50 mg PO q8h for 28 days'''''
|}
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===Antimicrobial Regimen===
* ''' Leishmaniasis'''
:* 1. '''Cutaneous Leishmaniasis''' <ref>{{Citeweb|title=leishmaniasis | url=http://www.cdc.gov/parasites/leishmaniasis/health_professionals/index.html#tx}}</ref>
::*Different Leishmania species cause Old World versus New World (American) cutaneous leishmaniasis. In the Old World (the Eastern Hemisphere), the etiologic agents include Leishmania tropica, L. major, and L. aethiopica, as well as L. infantum and L. donovani. The main species in the New World (the Western Hemisphere) are either in the L. mexicana species complex (L. mexicana, L. amazonensis, and L. venezuelensis) or the subgenus Viannia (L. [V.] braziliensis, L. [V.] guyanensis, L. [V.] panamensis, and L. [V.] peruviana). The Viannia subgenus is also referred to as the L. (V.) braziliensis species complex.
::* 1.1 '''Systemic Therapy (Parenteral)'''
:::* Preferred Regimen (1): [[Sodium stibogluconate]] 20 mg/kg IV/IM q24h for 10-20 days 
:::* Preferred Regimen (2): [[Meglumine antimoniate]] 20 mg/kg IV/IM  q24h for 10-20 days
:::* Alternative Regimen (1): [[Liposomal amphotericin B]] 3 mg/kg/day IV infusion for 6-10 days
:::* Alternative Regimen (2): [[Pentamidine]] 2-3 mg/kg/day IV/IM for 4-7 days
:::* Note: Data supporting the use of amphotericin B for treatment of cutaneous (and mucosal) leishmaniasis are anecdotal; standard dosage regimens have not been established. In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.
::* 1.2 '''Systemic Therapy (Oral)'''
:::*  '''Adults and adolescents at least 12 years of age, who weigh from 33-44 kg'''
:::* Preferred Regimen:[[Miltefosine]] 50 mg PO q12h for 28 days
:::* '''Adults and adolescents at least 12 years of age, who weigh  >45 kg '''
 
:::* Preferred Regimen:[[Miltefosine]] 50 mg PO q8h for 28 days
:::* Alternative Regimen (1): [[Ketoconazole]] 600 mg qd for 28 days  {{or}}  qd for 6 weeks
:::* Alternative Regimen (2): [[Fluconazole]] 200 mg qd for 6 weeks
:::* Note:The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis.  The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved
::* 1.3 '''Local Therapy'''
:::* List of possible local therapies
:::* Cryotherapy (with [[liquid nitrogen]] {{or}} Thermotherapy (use of localized current field radiofrequency heat) {{or}} Intralesional administration of [[SbV]] {{or}} Topical application of [[Paromomycin]] (such as an ointment containing 15% [[Paromomycin]]/12% methylbenzethonium chloride in soft white paraffin)
:*2. '''Visceral Leishmaniasis'''
::* Visceral leishmaniasis usually is caused by the species L. donovani and L. infantum (L. chagasi generally is considered synonymous with L. infantum)
::*2.1 '''Systemic Therapy (Parenteral)'''
:::* Preferred Regimen (1): [[Liposomal amphotericin B]] 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21  (Total dose: 21 mg/kg) 
:::* Preferred Regimen (2): [[Sodium stibogluconate]] 20 mg/kg IV/IM q24h for 28 days
:::* Preferred Regimen (3): [[Meglumine antimoniate]] 20 mg/kg IV/IM q24h for 28 days
:::* Alternative Regimen: [[Amphotericin B]] deoxycholate 0.5-1 mg/kg IV  q24h (Total dose: 15-20 mg/kg)
:::* Note: In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10,  17, 24, 31, and 38  (Total dose: 40 mg/kg)
::* 2.2 '''Systemic Therapy (Oral)'''
:::* '''Adults and adolescents at least 12 years of age, who weigh from 33-44 kg'''
:::* Preferred Regimen: [[Miltefosine]] 50 mg PO q12h for 28 days
:::* '''Adults and adolescents at least 12 years of age, who weigh >45 kg'''
:::* Preferred Regimen: [[Miltefosine]] 50 mg PO q8h for 28 days


==References==
==References==
{{reflist|2}}
{{reflist|2}}
 
[[Category:Infectious Disease Project]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Infectious disease]]


[[Category:Zoonoses]]
[[Category:Parasitic diseases]]
[[Category:Parasitic diseases]]
[[Category:Tropical disease]]
[[Category:Tropical disease]]

Latest revision as of 18:09, 18 September 2017

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

Overview

Treatment decisions should be individualized, with expert consultation. In general, all clinically manifest cases of visceral leishmaniasis and mucosal leishmaniasis should be treated, whereas not all cases of cutaneous leishmaniasis require treatment. The treatment depends on the form of leishmaniasis, and this include medications such as Pentavalent antimonial (SbV) compounds, liposomal amphotericin B, miltefosine, ketoconazole, and fluconazole.

Medical Therapy

  • The treatment approach depends in part on host and parasite factors.
  • Some approaches/regimens are effective only against certain Leishmania species/strains and only in particular geographic regions.
  • Even data from well-conducted clinical trials are not necessarily generalizable to other settings. Of particular note, data from the many clinical trials of therapy for visceral leishmaniasis in parts of India are not necessarily directly applicable to visceral leishmaniasis caused by L. donovani in other areas, to visceral leishmaniasis caused by other species, or to treatment of cutaneous and mucosal leishmaniasis.
  • Special groups (such as young children, elderly persons, pregnant/lactating women, and persons who are immunocompromised or who have other comorbidities) may need different medications or dosage regimens.
Indications for Therapy in Cutaneous Leishmaniasis
Therapy of cutaneous leishmaniasis may be indicated to:
  • Decrease the risk for mucosal dissemination/disease (particularly for New World species in the Viannia subgenus)
  • Accelerate healing of the skin lesions
  • Decrease the risk for relapse (clinical reactivation) of the skin lesions
  • Decrease the local morbidity caused by large or persistent skin lesions, particularly those on the face or ears or near joints
  • Decrease the reservoir of infection in geographic areas where infected persons (vs. non-human animals) serve as reservoir hosts (such as in Kabul, Afghanistan, and other Leishmania tropica-endemic areas, where transmission is anthroponotic)

Cutaneous Leishmaniasis

  • Decisions about whether and how to treat should be individualized.
  • The treatment approach depends in part on the Leishmania species/strain and the geographic area in which infection was acquired; the natural history of infection, the risk for mucosal dissemination/disease, and the drug susceptibilities in the pertinent setting; and the number, size, location, evolution, and other clinical characteristics of the patient's skin lesions.
  • In general, the first sign of a therapeutic response to adequate treatment is decreasing induration (lesion flattening).
  • The healing process for large, ulcerative lesions often continues after the end of therapy.
  • Relapse (clinical reactivation) typically is noticed first at the margin of the lesion.

▸ Click on the following categories to expand treatment regimens.[1]

Cutaneous Leishmaniasis

  ▸  Systemic Therapy (Parenteral)

  ▸  Systemic Therapy (Oral)

  ▸  Local Therapy

Systemic Therapy (Parenteral)
Preferred Regimen
Sodium stibogluconate 20 mg/kg IV/IM once daily for 10-20 days
OR
Meglumine antimoniate 20 mg/kg IV/IM once daily for 10-20 days
Alternative Regimen
Liposomal amphotericin B 3 mg/kg/day IV infusion for 6-10 days
OR
Pentamidine 2-3 mg/kg/day IV/IM for 4-7 days
† Data supporting the use of amphotericin B for treatment of cutaneous (and mucosal) leishmaniasis are anecdotal; standard dosage regimens have not been established.
‡ In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.
Systemic Therapy (Oral)
Preferred Regimen
Patients that weight 33-44 kg:
Miltefosine 50 mg PO q12h for 28 days
Patients that weight >45 kg:
Miltefosine 50 mg PO q8h for 28 days
Alternative Regimen
Ketoconazole 600 mg daily for 28 days
OR
Fluconazole 200 mg daily for 6 weeks
†The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis.
‡ The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved
Local Therapy
List of possible local therapies
Cryotherapy (with liquid nitrogen)
Thermotherapy (use of localized current field radiofrequency heat)
Intralesional administration of SbV
Topical application of paromomycin (such as an ointment containing 15% paromomycin/12% methylbenzethonium chloride in soft white paraffin)
†To date, not covered by CDC's IND protocol for Pentostam®


Visceral Leishmaniasis

▸ Click on the following categories to expand treatment regimens.[1]

Visceral Leishmaniasis

  ▸  Systemic Therapy (Parenteral)

  ▸  Systemic Therapy (Oral)

Systemic Therapy (Parenteral)
Preferred Regimen
Liposomal amphotericin B 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21 (Total dose: 21 mg/kg)
OR
Sodium stibogluconate 20 mg/kg IV/IM once daily for 28 days
OR
Meglumine antimoniate 20 mg/kg IV/IM once daily for 28 days
Alternative Regimen
Amphotericin B deoxycholate 0.5-1 mg/kg IV once daily (Total dose: 15-20 mg/kg)
† In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10, 17, 24, 31, and 38 (Total dose: 40 mg/kg)
Systemic Therapy (Oral)
Preferred Regimen
Patients that weight 33-44 kg:
Miltefosine 50 mg PO q12h for 28 days
Patients that weight >45 kg:
Miltefosine 50 mg PO q8h for 28 days

Antimicrobial Regimen

  • Leishmaniasis
  • 1. Cutaneous Leishmaniasis [2]
  • Different Leishmania species cause Old World versus New World (American) cutaneous leishmaniasis. In the Old World (the Eastern Hemisphere), the etiologic agents include Leishmania tropica, L. major, and L. aethiopica, as well as L. infantum and L. donovani. The main species in the New World (the Western Hemisphere) are either in the L. mexicana species complex (L. mexicana, L. amazonensis, and L. venezuelensis) or the subgenus Viannia (L. [V.] braziliensis, L. [V.] guyanensis, L. [V.] panamensis, and L. [V.] peruviana). The Viannia subgenus is also referred to as the L. (V.) braziliensis species complex.
  • 1.1 Systemic Therapy (Parenteral)
  • Preferred Regimen (1): Sodium stibogluconate 20 mg/kg IV/IM q24h for 10-20 days
  • Preferred Regimen (2): Meglumine antimoniate 20 mg/kg IV/IM q24h for 10-20 days
  • Alternative Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV infusion for 6-10 days
  • Alternative Regimen (2): Pentamidine 2-3 mg/kg/day IV/IM for 4-7 days
  • Note: Data supporting the use of amphotericin B for treatment of cutaneous (and mucosal) leishmaniasis are anecdotal; standard dosage regimens have not been established. In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.
  • 1.2 Systemic Therapy (Oral)
  • Adults and adolescents at least 12 years of age, who weigh from 33-44 kg
  • Preferred Regimen:Miltefosine 50 mg PO q12h for 28 days
  • Adults and adolescents at least 12 years of age, who weigh >45 kg
  • Preferred Regimen:Miltefosine 50 mg PO q8h for 28 days
  • Alternative Regimen (1): Ketoconazole 600 mg qd for 28 days OR qd for 6 weeks
  • Alternative Regimen (2): Fluconazole 200 mg qd for 6 weeks
  • Note:The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis. The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved
  • 1.3 Local Therapy
  • List of possible local therapies
  • Cryotherapy (with liquid nitrogen OR Thermotherapy (use of localized current field radiofrequency heat) OR Intralesional administration of SbV OR Topical application of Paromomycin (such as an ointment containing 15% Paromomycin/12% methylbenzethonium chloride in soft white paraffin)
  • 2. Visceral Leishmaniasis
  • Visceral leishmaniasis usually is caused by the species L. donovani and L. infantum (L. chagasi generally is considered synonymous with L. infantum)
  • 2.1 Systemic Therapy (Parenteral)
  • Preferred Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21 (Total dose: 21 mg/kg)
  • Preferred Regimen (2): Sodium stibogluconate 20 mg/kg IV/IM q24h for 28 days
  • Preferred Regimen (3): Meglumine antimoniate 20 mg/kg IV/IM q24h for 28 days
  • Alternative Regimen: Amphotericin B deoxycholate 0.5-1 mg/kg IV q24h (Total dose: 15-20 mg/kg)
  • Note: In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10, 17, 24, 31, and 38 (Total dose: 40 mg/kg)
  • 2.2 Systemic Therapy (Oral)
  • Adults and adolescents at least 12 years of age, who weigh from 33-44 kg
  • Preferred Regimen: Miltefosine 50 mg PO q12h for 28 days
  • Adults and adolescents at least 12 years of age, who weigh >45 kg
  • Preferred Regimen: Miltefosine 50 mg PO q8h for 28 days

References

  1. 1.0 1.1 "CDC - Parasites - Leishmaniasis".
  2. Template:Citeweb


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