Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

cutaneous leishmaniasis (CL)

1st line – watchful waiting

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
simple: non-pregnant
1st line – 

watchful waiting

Simple CL is defined as: no mucosal involvement and parasite species not associated with mucosal leishmaniasis; 4 or fewer lesions <1 cm; location feasible for local therapy and/or non-exposed skin (not cosmetically important); immunocompetent host; lesions resolving without therapy.[8]

Most cases of CL, particularly among Old World species, will resolve spontaneously within 18 months; therefore, it is important to decide whether or not treatment is truly indicated.[107][128] This decision must be individualised considering factors such as whether healing has already begun, impairments of wound healing, risk of secondary infections, patient preference, whether there is evidence of impaired cell-mediated immunity, and availability/expertise in treatment.

Plus – wound management

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
simple: non-pregnant
Plus – 

wound management

Treatment recommended for ALL patients in selected patient group

Care should be taken to ensure proper wound management including washing the ulcer(s) and applying barrier ointment. The presence of warmth, redness, pain, and/or purulent discharge should prompt for the evaluation and management of a secondary bacterial infection. Evidence of healing often begins with flattening, and large ulcers may not be completely healed by the end of therapy. CDC: parasites – leishmaniasis Opens in new window

1st line – local therapy

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ACUTE
|
cutaneous leishmaniasis (CL)
|
simple: non-pregnant
1st line – 

local therapy

Simple CL is defined as: no mucosal involvement and parasite species not associated with mucosal leishmaniasis; 4 or fewer lesions <1 cm; location feasible for local therapy and/or non-exposed skin (not cosmetically important); immunocompetent host; lesions resolving without therapy.[8]

Local therapies may be used when watchful waiting is not recommended, or to accelerate cure. Any crust should be removed, if present, before local therapy is started.[8]

Cryotherapy: an option across all regions. Simple to administer: involves freezing the lesion and surrounding 1 to 2 mm of healthy skin with liquid nitrogen until it is white in appearance, allowing the area to thaw, and freezing again. Sessions are recommended every 3 weeks for up to three treatments. Adverse effects include transient pain and redness as well as hypopigmentation.[8]

Thermotherapy: an option across all regions. Size, location, and number of lesions influence the efficacy and efficiency of this modality. Highly effective against Leishmania tropica.[107] Local anaesthesia and topical antibiotics are recommended post-procedurally. A single treatment is often sufficient, and a specialised device is required. Adverse effects include cellulitis, redness, and pain at the treatment site.[8]

Topical paromomycin (15% in a complex base): effective for Old World disease, particularly Leishmania major, and New World disease caused by Viannia species.[131][132][133] Use in Viannia species may not be appropriate due to the risk for mucosal disease.[132] Local irritation is expected and is greater with some formulations. Commercial or compounded formulations may not be equivalent. A reasonable regimen is applying topically daily for 20 days. It may be used alone or in combination with methylbenzethonium chloride, urea, or gentamicin.[126]

Intralesional therapy: pentavalent antimonial compounds are most commonly used, when available. The combination of intralesional sodium stibogluconate and cryotherapy is very effective in Old World disease.[107] Meglumine antimonate is preferred in the New World.[135] Treatment can be administered one to five times every 3 to 7 days. Sodium stibogluconate is available for intralesional use in Europe. Pentamidine can also be used intralesionally.[136] Pain with injection can be significant.[8]

Plus – wound management

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
simple: non-pregnant
Plus – 

wound management

Treatment recommended for ALL patients in selected patient group

Care should be taken to ensure proper wound management including washing the ulcer(s) and applying barrier ointment. The presence of warmth, redness, pain, and/or purulent discharge should prompt for the evaluation and management of a secondary bacterial infection. Evidence of healing often begins with flattening, and large ulcers may not be completely healed by the end of therapy. CDC: parasites – leishmaniasis Opens in new window

2nd line – azole antifungal

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ACUTE
|
cutaneous leishmaniasis (CL)
|
simple: non-pregnant
2nd line – 

azole antifungal

Fluconazole, ketoconazole, and itraconazole are options where local therapies are not available but treatment (rather than watchful waiting) is preferred. All have gastrointestinal adverse effects and a risk of hepatotoxicity, but ketoconazole carries a warning related to the risk of life-threatening hepatotoxicity and QT prolongation that could lead to fatal arrhythmias.

A systematic review did not find enough evidence to recommend any of the azole antifungals routinely, but in the New World pooled efficacy for ketoconazole in the treatment of Leishmania mexicana was as high as 89%, suggesting this as a potential option in Mexico and parts of Central America with appropriate monitoring of adverse effects.[137]

Use of azole antifungals is off-label for this indication in Europe and the US.

Primary options

fluconazole: consult specialist for guidance on dose

OR

itraconazole: consult specialist for guidance on dose

Secondary options

ketoconazole: consult specialist for guidance on dose

Plus – wound management

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
simple: non-pregnant
Plus – 

wound management

Treatment recommended for ALL patients in selected patient group

Care should be taken to ensure proper wound management including washing the ulcer(s) and applying barrier ointment. The presence of warmth, redness, pain, and/or purulent discharge should prompt for the evaluation and management of a secondary bacterial infection. Evidence of healing often begins with flattening, and large ulcers may not be completely healed by the end of therapy. CDC: parasites – leishmaniasis Opens in new window

1st line – systemic anti-leishmanial therapy

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
complex: non-pregnant
1st line – 

systemic anti-leishmanial therapy

Complex CL is defined as: parasite species caused by species associated with mucosal leishmaniasis; local subcutaneous nodules; large regional adenopathy; >4 lesions generally >1 cm; individual lesion ≥5 cm; size or location makes local therapy infeasible and/or lesion of the face, fingers, toes, joints, or genitalia; immunocompromised host; failure of local therapy.[8]

Systemic therapy is preferred due to the extent or location of the lesion(s), prior failure of local therapy, and/or the risk of dissemination.

Miltefosine: the only oral anti-leishmanial. Effective in New World disease caused by Viannia species, although lower efficacy is seen in Guatemala.[138] Significant adverse effects such as nausea, vomiting, and abdominal pain are frequent.

Pentavalent antimonial compounds (sodium stibogluconate, meglumine antimonate): highly effective in Old World Leishmania major and widely used in the New World, when available, though may be less effective against Leishmania braziliensis and Leishmania mexicana in Guatemala.[138] Serious adverse effects can occur (e.g., pancreatitis, QT prolongation) and patients should be carefully monitored. Pentavalent antimonial compounds are not available in the US. Sodium stibogluconate is commercially available in Europe.

Amphotericin-B: less robust data, but likely useful globally. Higher efficacy seen in New World disease in Bolivia.[138] Liposomal amphotericin-B is the preferred formulation with improved safety, but expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative. Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Pentamidine: highly effective against Leishmania guyanensis in French Guiana and Suriname.[139][140] Intravenous administration is more effective than intramuscular.[141] In other settings, the adverse effects and relatively lower efficacy of pentamidine typically preclude its use. This may be due in part to underdosing based on the salt (isethionate) versus the base.[143] Serious adverse effects can occur (e.g., diabetes mellitus, pancreatitis, gastrointestinal symptoms, hypotension, QT prolongation, electrolyte disturbances, nephrotoxicity, hepatotoxicity, cytopenias, and rhabdomyolysis) and patients should be carefully monitored. These are mitigated with intralesional use.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

miltefosine: consult specialist for guidance on dose

OR

sodium stibogluconate: consult specialist for guidance on dose

OR

meglumine antimonate: consult specialist for guidance on dose

OR

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Secondary options

pentamidine: consult specialist for guidance on dose

Plus – wound management

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
complex: non-pregnant
Plus – 

wound management

Treatment recommended for ALL patients in selected patient group

Care should be taken to ensure proper wound management including washing the ulcer(s) and applying barrier ointment. The presence of warmth, redness, pain, and/or purulent discharge should prompt for the evaluation and management of a secondary bacterial infection. Evidence of healing often begins with flattening, and large ulcers may not be completely healed by the end of therapy. CDC: parasites – leishmaniasis Opens in new window

1st line – expert consultation

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
disseminated/diffuse disease or leishmaniasis recidivans: non-pregnant
1st line – 

expert consultation

Treatment of complex forms of CL including disseminated leishmaniasis, diffuse cutaneous leishmaniasis, and leishmaniasis recidivans should be guided by experts as treatment can be challenging and data are limited.

Disseminated leishmaniasis: liposomal amphotericin-B has been used with success (75% cure rate).[144]

Leishmaniasis recidivans: can be frustrating to treat.[8] One potential regimen combines a pentavalent antimonial compound with allopurinol for 30 days.[146] Liposomal amphotericin-B and miltefosine are often used.

1st line – deferred treatment or local therapy

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
pregnant
1st line – 

deferred treatment or local therapy

Treatment of simple and complex cutaneous disease in pregnant patients is highly individualised.

If possible, treatment should be deferred until after pregnancy, even exophytic lesions; however, there may be an increased risk of preterm birth and stillbirth in untreated CL patients.[147]

Local therapy options such as cryotherapy, thermotherapy, and topical paromomycin are often preferred to systemic therapies; however, there may be an increased risk of preterm delivery and stillbirth. Intralesional therapies can lead to systemic absorption and so are not recommended in pregnant women.

Treatment of complex forms of CL including disseminated leishmaniasis, diffuse cutaneous leishmaniasis, and leishmaniasis recidivans should be guided by experts as treatment can be challenging and data are limited.

Plus – wound management

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
pregnant
Plus – 

wound management

Treatment recommended for ALL patients in selected patient group

Care should be taken to ensure proper wound management including washing the ulcer(s) and applying barrier ointment. The presence of warmth, redness, pain, and/or purulent discharge should prompt for the evaluation and management of a secondary bacterial infection. Evidence of healing often begins with flattening, and large ulcers may not be completely healed by the end of therapy. CDC: parasites – leishmaniasis Opens in new window

2nd line – amphotericin-B

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
pregnant
2nd line – 

amphotericin-B

Liposomal amphotericin-B has the best overall safety data and has demonstrated safety in pregnancy. Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Treatment of complex forms of CL including disseminated leishmaniasis, diffuse cutaneous leishmaniasis, and leishmaniasis recidivans should be guided by experts as treatment can be challenging and data are limited.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Plus – wound management

Back
ACUTE
|
cutaneous leishmaniasis (CL)
|
pregnant
Plus – 

wound management

Treatment recommended for ALL patients in selected patient group

Care should be taken to ensure proper wound management including washing the ulcer(s) and applying barrier ointment. The presence of warmth, redness, pain, and/or purulent discharge should prompt for the evaluation and management of a secondary bacterial infection. Evidence of healing often begins with flattening, and large ulcers may not be completely healed by the end of therapy. CDC: parasites – leishmaniasis Opens in new window

mucosal leishmaniasis (ML)

1st line – systemic anti-leishmanial therapy

Back
ACUTE
|
mucosal leishmaniasis (ML)
|
non-pregnant
1st line – 

systemic anti-leishmanial therapy

Patients with ML should always receive treatment with systemic therapy. Robust data are limited and treatment efficacy varies requiring an individualised approach to therapy.

Pentavalent antimonial compounds (sodium stibogluconate, meglumine antimonate): reasonable first choice, when available, in patients able to tolerate the course with up to 88% efficacy seen with meglumine antimonate (lower with sodium stibogluconate). Some studies have added adjuncts such as pentoxifylline or interferon-gamma, but evidence for this is weak.[124] Serious adverse effects can occur (e.g., pancreatitis, QT prolongation) and patients should be carefully monitored. These are mitigated with intralesional use. Pentavalent antimonial compounds are not available in the US. Sodium stibogluconate is commercially available in Europe.

Amphotericin-B: data are limited compared with data for pentavalent antimonial compounds, but it has a better safety profile. It is an alternative, particularly for treatment failure, relapse, or intolerance of pentavalent antimonial compounds.[8] Retrospective data from Brazil show a 93% cure rate.[150] Liposomal amphotericin-B is the preferred formulation with improved safety, but expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative. Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Miltefosine: a potential option, but data are less robust and cure rates are low apart from clinically mild disease.[151] It is the only oral anti-leishmanial drug. Significant adverse effects such as nausea, vomiting, and abdominal pain are frequent.

Pentamidine: pentamidine is considered a lesser alternative.[8]

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

sodium stibogluconate: consult specialist for guidance on dose

OR

meglumine antimonate: consult specialist for guidance on dose

OR

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

OR

miltefosine: consult specialist for guidance on dose

Secondary options

pentamidine: consult specialist for guidance on dose

1st line – amphotericin-B

Back
ACUTE
|
mucosal leishmaniasis (ML)
|
pregnant
1st line – 

amphotericin-B

Treatment of ML should not be deferred in pregnant women.

Liposomal amphotericin-B has the best overall safety data and has demonstrated safety in pregnancy. Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

visceral leishmaniasis (VL)

1st line – amphotericin-B

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
1st line – 

amphotericin-B

Liposomal amphotericin-B is highly effective for Leishmania donovani in South Asia and Leishmania infantum (also known as Leishmania chagasi).[8][107][138]

Higher doses are required for L donovani in East Africa; therefore, this is a less preferred option in this region.[159][160]

Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

1st line – combination anti-leishmanial therapy

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
1st line – 

combination anti-leishmanial therapy

In East Africa, the combination of a pentavalent antimonial compound with paromomycin is highly effective for VL due to Leishmania donovani with cure rates of 90% to 95%.[160][163] This regimen is the preferred treatment in East Africa (over amphotericin-B) due to cost, availability, and regional efficacy. It should not be used in patients >50 years of age or those with HIV due to decreased cure rates in these patients.[163] This combination is not recommended in South Asia.

In South Asia, the combination of liposomal amphotericin-B with short courses of miltefosine or paromomycin, or miltefosine with paromomycin, are highly effective alternatives to amphotericin-B.[157][158][164]

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

sodium stibogluconate: consult specialist for guidance on dose

or

meglumine antimonate: consult specialist for guidance on dose

-- AND --

paromomycin: consult specialist for guidance on dose

OR

amphotericin B liposomal: consult specialist for guidance on dose

-- AND --

miltefosine: consult specialist for guidance on dose

or

paromomycin: consult specialist for guidance on dose

OR

miltefosine: consult specialist for guidance on dose

and

paromomycin: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

2nd line – miltefosine

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
2nd line – 

miltefosine

An alternative option for Leishmania donovani in South Asia, but emerging resistance has led to a decline in use. Efficacy in other regions is suboptimal for monotherapy.[138]

Significant adverse effects such as nausea, vomiting, and abdominal pain are frequent.

Dose depends on organism and geographic location; consult local guidance for drug selection and dose information.

Primary options

miltefosine: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

2nd line – pentavalent antimonial compound or paromomycin

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
2nd line – 

pentavalent antimonial compound or paromomycin

Pentavalent antimonial compounds (sodium stibogluconate, meglumine antimonate): can be used for Leishmania donovani in East Africa, or in Leishmania infantum with decent efficacy, but they are considered second-line when other options are not available. Drug resistance in South Asia precludes their use in the subcontinent.[107] Serious adverse effects can occur (e.g., pancreatitis, QT prolongation) and patients should be carefully monitored. Pentavalent antimonial compounds are not available in the US. Sodium stibogluconate is commercially available in Europe.

Paromomycin: safety and efficacy for monotherapy have been demonstrated in Leishmania donovani in South Asia, but other safer options with equal or greater efficacy are available.[165][166] Patients should be monitored for nephrotoxicity and ototoxicity. Systemic formulations of paromomycin are not available in the US.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

sodium stibogluconate: consult specialist for guidance on dose

OR

meglumine antimonate: consult specialist for guidance on dose

OR

paromomycin: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

1st line – amphotericin-B

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: pregnant
1st line – 

amphotericin-B

Treatment is essential because untreated VL can be fatal to both the mother and the fetus.

Limited data suggest that liposomal amphotericin-B is a safe and effective treatment option.[8][119]

Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information. Higher doses are required for Leishmania donovani in East Africa.[159][160]

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

2nd line – pentavalent antimonial compound or paromomycin

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: pregnant
2nd line – 

pentavalent antimonial compound or paromomycin

Use of pentavalent antimonial compounds in pregnancy should generally be avoided due to an increased risk of miscarriage or preterm delivery, and there is no safety data on paromomycin in pregnancy.[8] However, if no other options are available, treatment with these medications (alone or in combination), when available, may be an option under expert guidance only.

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompetent: pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

1st line – amphotericin-B

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
1st line – 

amphotericin-B

Liposomal amphotericin-B is generally regarded as the best option for patients with VL and HIV infection.[8]​​[169]​[170]

A higher total dose is used in immunocompromised patients. However, even with higher doses, treatment can be unsatisfactory and relapse is common. A published trial in East Africa showed only a 55% efficacy for liposomal amphotericin-B monotherapy among patients with a median CD4 count of 69 cells/microlitre.[171]

Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Plus – start or continue antiretroviral therapy

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Plus – 

start or continue antiretroviral therapy

Treatment recommended for ALL patients in selected patient group

Lifelong antiretroviral therapy should be initiated (or continued in patients already on it) in all patients with HIV infection according to current local guidelines. An improvement in immune function is essential to the treatment of VL. See HIV infection.

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

Consider – secondary prophylaxis

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Consider – 

secondary prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Secondary prophylaxis with an appropriate anti-leishmanial drug should be given to all patients with CD4 count <200 to 350 cells/microlitre (the higher CD4 cut-off is recommended by the Pan American Health Organization) due to the high risk of relapse.[8][145][169]​[170]

There is no consensus on the best regimen, but guidelines do recommend various options.[169] Consult local guidelines for further guidance.

It is unclear when secondary prophylaxis should end. Some guidelines suggest stopping after CD4 counts reach >200 to 350 cells/microlitre, whereas others recommend indefinite therapy as the risk for relapse continues. Regardless, careful monitoring for relapse is essential in all patients with HIV infection.[8][169]​

2nd line – combination anti-leishmanial therapy

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
2nd line – 

combination anti-leishmanial therapy

Combination therapy should be considered in this context. A combination of liposomal amphotericin-B and miltefosine showed an efficacy rate of 88% in East Africa among patients with a median CD4 count of 54 cells/microlitre.[171] In India, the combination of miltefosine and liposomal amphotericin-B was associated with 96% efficacy compared to miltefosine monotherapy at 85%.[172]

The World Health Organization (WHO) suggests liposomal amphotericin-B plus miltefosine over liposomal amphotericin-B monotherapy in people with HIV coinfection in East Africa and South East Asia.[62]

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

and

miltefosine: consult specialist for guidance on dose

Plus – start or continue antiretroviral therapy

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Plus – 

start or continue antiretroviral therapy

Treatment recommended for ALL patients in selected patient group

Lifelong antiretroviral therapy should be initiated (or continued in patients already on it) in all patients with HIV infection according to current local guidelines. An improvement in immune function is essential to the treatment of VL. See HIV infection.

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

Consider – secondary prophylaxis

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Consider – 

secondary prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Secondary prophylaxis with an appropriate anti-leishmanial drug should be given to all patients with CD4 count <200 to 350 cells/microlitre (the higher CD4 cut-off is recommended by the Pan American Health Organization) due to the high risk of relapse.[8][145][169]​[170]

There is no consensus on the best regimen, but guidelines do recommend various options.[169] Consult local guidelines for further guidance.

It is unclear when secondary prophylaxis should end. Some guidelines suggest stopping after CD4 counts reach >200 to 350 cells/microlitre, whereas others recommend indefinite therapy as the risk for relapse continues. Regardless, careful monitoring for relapse is essential in all patients with HIV infection.[8][169]​

3rd line – pentavalent antimonial compound

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
3rd line – 

pentavalent antimonial compound

Use in HIV co-infection has been associated with higher mortality and higher rates of severe adverse reactions and so other options should be used if possible.[173][174][175]

Serious adverse effects can occur (e.g., pancreatitis, QT prolongation) and patients should be carefully monitored.

Pentavalent antimonial compounds are not available in the US. Sodium stibogluconate is commercially available in Europe.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

sodium stibogluconate: consult specialist for guidance on dose

OR

meglumine antimonate: consult specialist for guidance on dose

Plus – start or continue antiretroviral therapy

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Plus – 

start or continue antiretroviral therapy

Treatment recommended for ALL patients in selected patient group

Lifelong antiretroviral therapy should be initiated (or continued in patients already on it) in all patients with HIV infection according to current local guidelines. An improvement in immune function is essential to the treatment of VL. See HIV infection.

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

Consider – secondary prophylaxis

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (HIV/AIDS): non-pregnant
Consider – 

secondary prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Secondary prophylaxis with an appropriate anti-leishmanial drug should be given to all patients with CD4 count <200 to 350 cells/microlitre (the higher CD4 cut-off is recommended by the Pan American Health Organization) due to the high risk of relapse.[8][145][169]​[170]

There is no consensus on the best regimen, but guidelines do recommend various options.[169]​

It is unclear when secondary prophylaxis should end. Some guidelines suggest stopping after CD4 counts reach >200 to 350 cells/microlitre, whereas others recommend indefinite therapy as the risk for relapse continues. Regardless, careful monitoring for relapse is essential in all patients with HIV infection.[8][169]​

1st line – amphotericin-B

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (other): non-pregnant
1st line – 

amphotericin-B

Other forms of immunosuppression include solid organ transplant, lymphatic or haematological malignancy, or treatment with immunosuppressants for other indications.

Treatment has been accomplished with multiple regimens, but liposomal amphotericin-B is recommended, particularly in solid organ transplant patients.[8][145][168]

Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (other): non-pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

Consider – discontinue immunosuppressant or decrease dose

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (other): non-pregnant
Consider – 

discontinue immunosuppressant or decrease dose

Additional treatment recommended for SOME patients in selected patient group

If patients are on immunosuppressants for other indications, consider decreasing the dose or stopping these medications, if possible, although this is based on expert opinion and not on strong data.[168] An improvement in immune function is essential to the treatment of VL.

Consider – secondary prophylaxis

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised (other): non-pregnant
Consider – 

secondary prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Consider secondary prophylaxis on an individual basis, especially among patients with a history of prior relapse for whom the immunosuppressive condition is ongoing. While relapse is common, particularly among solid organ transplant patients (approximately 25%), data are not clear on the role of secondary prophylaxis. The Infectious Diseases Society of America/American Society of Tropical Medicine and Hygiene guidelines recommend against secondary prophylaxis among those without a prior relapse, but in a small retrospective case-control study, risk of relapse decreased by 27% among those on secondary prophylaxis.[8][178]

1st line – amphotericin-B

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised: pregnant
1st line – 

amphotericin-B

Treatment is essential because untreated VL can be fatal to both the mother and the fetus.

Limited data suggest that liposomal amphotericin-B is a safe and effective treatment option.[8][119]

Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

Plus – supportive care

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised: pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Management must address frequent complications such as volume depletion, malnutrition, anaemia, and concomitant bacterial infections (e.g., pneumonia) or parasitic infections (e.g., malaria).

Plus – start or continue antiretroviral therapy

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised: pregnant
Plus – 

start or continue antiretroviral therapy

Treatment recommended for ALL patients in selected patient group

Lifelong antiretroviral therapy should be initiated (or continued in patients already on it) in all patients with HIV infection according to current local guidelines. A specific regimen recommended for pregnant women should be used. An improvement in immune function is essential to the treatment of VL. See HIV infection in pregnancy.

Consider – discontinue immunosuppressant or decrease dose

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised: pregnant
Consider – 

discontinue immunosuppressant or decrease dose

Additional treatment recommended for SOME patients in selected patient group

If patients are on immunosuppressants for other indications, consider decreasing the dose or stopping these medications, if possible, although this is based on expert opinion and not on strong data.[168] An improvement in immune function is essential to the treatment of VL.

Consider – secondary prophylaxis

Back
ACUTE
|
visceral leishmaniasis (VL)
|
immunocompromised: pregnant
Consider – 

secondary prophylaxis

Additional treatment recommended for SOME patients in selected patient group

Secondary prophylaxis with an appropriate anti-leishmanial drug should be given to patients with HIV infection and a CD4 count <200 to 350 cells/microlitre (the higher CD4 cut-off is recommended by the Pan American Health Organization) due to the high risk of relapse.[8][145][169]​[170]

In patients with other forms of immunosuppression, consider secondary prophylaxis on an individual basis, especially among patients with a history of prior relapse for whom an immunosuppressive condition is ongoing.

ONGOING

post-kala-azar dermal leishmaniasis (PKDL)

1st line – systemic anti-leishmanial therapy

Back
ONGOING
|
post-kala-azar dermal leishmaniasis (PKDL)
|
non-pregnant
1st line – 

systemic anti-leishmanial therapy

Treatment is indicated in East African patients with severe or non-self-healing PKDL, in Indian PKDL, and in immunocompromised patients.[6]

Miltefosine: recommended first-line treatment in South Asia.[185] It is the only oral anti-leishmanial drug. Significant adverse effects such as nausea, vomiting, and abdominal pain are frequent. Combination therapy with liposomal amphotericin-B and miltefosine was associated with 100% efficacy in South Asia.[184]

Amphotericin-B: considered a second-line option in South Asia.[170] Liposomal amphotericin-B has shown some efficacy in limited studies in the region.[182][181] Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative. Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Pentavalent antimonial compounds: commonly used in East Africa for severe or persistent disease.[186] Serious adverse effects can occur (e.g., pancreatitis, QT prolongation) and patients should be carefully monitored. Pentavalent antimonial compounds are not available in the US. Sodium stibogluconate is commercially available in Europe.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

miltefosine: consult specialist for guidance on dose

OR

sodium stibogluconate: consult specialist for guidance on dose

OR

sodium stibogluconate: consult specialist for guidance on dose

-- AND --

paromomycin: consult specialist for guidance on dose

Secondary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

1st line – amphotericin-B

Back
ONGOING
|
post-kala-azar dermal leishmaniasis (PKDL)
|
pregnant
1st line – 

amphotericin-B

Limited data in this setting, but the recommendation is guided by relative safety and the contraindication of miltefosine in pregnancy.

Liposomal amphotericin-B has the best overall safety data and has demonstrated safety in pregnancy.

Expense and cold chain may limit availability globally and so amphotericin-B deoxycholate is an alternative.

Generally well tolerated; however, patients require monitoring for nephrotoxicity, electrolyte disturbances, and anaemia.

Dose depends on organism and geographical location; consult local guidance for drug selection and dose information.

Primary options

amphotericin B liposomal: consult specialist for guidance on dose

OR

amphotericin B deoxycholate: consult specialist for guidance on dose

relapse

1st line – retreatment

Back
ONGOING
|
relapse
1st line – 

retreatment

Relapses are uncommon with appropriate treatment in immunocompetent hosts. Patients should be monitored for signs of relapse, particularly patients with HIV/AIDS or who are immunocompromised.

An expert should be consulted to determine the best regimen for retreatment if necessary.

Amphotericin-B formulations are an option in mucosal leishmaniasis, particularly for treatment failure or relapse.[8]

Immunocompetent patients with visceral leishmaniasis (VL) who do not respond to, or who relapse after, initial therapy should receive full treatment with an anti-leishmanial drug (or a combination of anti-leishmanial drugs) from a different class. However, if the initial treatment was with liposomal amphotericin-B, retreatment with amphotericin-B, potentially at higher total doses, is appropriate.[8][107]

Among immunocompromised patients with VL who relapse, treatment with liposomal amphotericin-B is reasonable, even among those who received it as primary therapy as failure in this setting is thought to be immunological rather than a result of drug resistance. Alternatively, other options or combination therapies can be tried.[8]

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