eMedicine Specialties > Dermatology > Parasitic Infections
Leishmaniasis: Treatment & Medication
Updated: Sep 25, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Tailor treatment to the individual because leishmaniasis is caused by many species or subspecies of the Leishmania protozoa, all of which have different degrees of virulence and clinical predilections. Consider the clinical pattern of disease, the geographic region in which the infection occurs, the immunologic status of the patient, and the previous attempts at treatment when therapy is started.
Although treatment was previously recommended for every case of leishmaniasis, this is no longer the conventional practice. Treatment must be a balance of risk versus benefit, especially in the case of Leishmania major from Iraq, which is generally a self-limited cutaneous illness that heals within 12 months, leaving minimal scarring. For lesions caused by this species, treatment is not generally necessary unless the lesion is in a cosmetically or functionally sensitive site. Cases due to Leishmania tropica (another Old World species) and some L major from certain regions of Afghanistan may have a more aggressive or chronic course (up to years); this organism (ie, L tropica) has been implicated in occasional cases of recidivans or viscerotropic leishmaniasis. As such, treatment may need to be more involved in cases caused by this species.
In New World leishmaniasis, estimates of recurrence range from less than 5% to as many as 10% of untreated individuals experiencing chronic ulcers, recidivans lesions, or mucocutaneous involvement. Because of this, treatment is very often the standard of care and parenteral therapy is usually the treatment of choice.
Multiple treatment options are used throughout the world for cutaneous disease. In addition to parenteral and oral medications (see Medication), local therapies for some forms of cutaneous leishmaniasis include (1) cryotherapy, (2) infiltration of sodium stibogluconate at 0.3-0.8 mL, (3) local heat therapy at 40-42°C (One novel FDA-cleared device is called the ThermoMed device; see Thermosurgery Technologies.), and (4) various topical paromomycin preparations, typically 15% with 10% urea.
Surgical excision is not usually recommended because of the risk of relapse and the cosmetic disfigurement. In some areas of the world (eg, Russia, Middle East), live-attenuated L major promastigotes have been used preemptively to immunize against Old World cutaneous leishmaniasis. This practice produces a modified form of the disease and results in a scar at the injection site. Immunity to subsequent L major infections usually is good; however, as with natural infection, cross-reactive immunity to other Leishmania species does not occur. Many more universally useful and cosmetically acceptable Leishmania vaccine formulations are under investigation. To date, no vaccines are commercially available.
Of primary importance in dealing with leishmaniasis is the treatment of malnutrition, concurrent systemic illness (eg, HIV disease, tuberculosis), or local infection (secondary bacterial). Despite successful clinical outcomes, the question of whether the parasites are completely eradicated is unclear because reactivation of leishmaniasis with immunosuppression has been reported.9
The guideline summary Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America may be of interest.10
Consultations
Consult an infectious disease specialist.
Diet
Advise patients to eat a nutritious diet.
Medication
For 50 years, the mainstay of antileishmanial therapy has been pentavalent antimony (sodium stibogluconate or meglumine antimonate). This was previously used for all forms of the disease; however, recently, liposomal amphotericin B has replaced pentavalent antimony as the drug of choice for visceral disease. Pentavalent antimony is not marketed in the United States, but it can be obtained through the CDC under an Investigational New Drug application for civilian use and is also available at 2 medical centers in the US Department of Defense for military use, also under an Investigational New Drug application. Currently, however, efforts are underway to make this drug more widely available in the United States.
Originally, VioQuest Pharmaceuticals, a New Jersey–based biopharmaceutical company, partnered with the US Army, to receive orphan drug designation from the FDA with an eye toward licensure. Unfortunately, this has not materialized and other avenues are being sought, especially with the FDA's offer of priority review vouchers for the registration of badly needed drugs for certain diseases, such as leishmaniasis.
Cure rates for pentavalent antimony are 90-97% with 1-3 full intravenous treatment courses; however, the drawbacks are considerable. These drugs are expensive and difficult to obtain. They must be delivered parenterally, they have numerous adverse effects, they may have lot-to-lot variability, and they are becoming increasingly less effective because of the emergence of drug-resistant parasites (especially in certain countries such as India). In other parts of the world, intralesional injections have shown promise with less toxicity (although with much lower patient tolerability owing to the pain associated with the intralesional injections).
Alternative treatment regimens with acceptable cure rates are pentamidine, paromomycin, interferon-gamma plus antimony, and amphotericin B (and less toxic variations, eg, liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B colloidal dispersion). However, few of these options are used in the United States, except for on antimony-resistant organisms. While much has been made of the use of azoles for the Iraqi L major cutaneous disease, few practitioners in the field believe this is a prudent consideration for routine treatment of this disease. Recently, liposomal amphotericin B has been used with good success in the treatment of cutaneous disease from many parts of the world and is gaining increased acceptance with many practitioners.
Pentavalent antimonials
These are generally considered first-line therapy for cutaneous and mucocutaneous disease.
Sodium antimony gluconate (Pentostam)
DOC for leishmaniasis in United States. Manufactured by GlaxoSmithKline, London. No fixed chemical formulation; lot-to-lot variability. Storage optimal in dark at 4°C. Poorly understood antileishmanial mechanisms. Drug resistance well documented. Can be delivered locally into cutaneous lesions.
Adult
Sodium stibogluconate 100 mg/mL diluted 1:2 with lidocaine 1% (ie, 1 mL sodium stibogluconate plus 2 mL lidocaine); intralesionally, use 2-4 mL q8d, based on clinical response
Cutaneous disease: 20 mg/kg/d IV/IM for 20 d
Visceral or mucocutaneous disease: 20 mg/kg/d IV/IM for 28 d
Lesion borders: <1 mg/kg intralesional qwk
Pediatric
Administer as in adults
Avoid drugs with similar toxicities and adverse effects, including drugs that are hepatotoxic or cause QT prolongation
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse reactions include chemical pancreatitis, arthralgias, myalgias, nausea, abdominal pain, headache, anorexia, elevated serum transaminase levels, anemia, leukopenia, thrombocytopenia, cardiac conduction abnormalities, peripheral neuropathy, urticaria, acral vesicopustules, and fine papular truncal eruptions; reactions usually reversible upon cessation; inpatient monitoring throughout course of therapy is best
Antifungals
The major sterol in both Leishmania organisms and fungi is ergosterol. Antiergosterol agents, marketed as antifungals, have activity against Leishmania organisms.
Amphotericin B (Fungizone, Amphocin, Amphocil, Abelcet, AmBisome)
DOC in antimony-resistant infections (especially if contracted in India). To reduce renal toxicity (with deoxycholate), several formulations (lipid associated) are used (liposomal [AmBisome], lipid-complexed [Abelcet], colloidal-dispersion [Amphocil] preparations). Least toxic (infusion-related adverse effects) is AmBisome; most toxic, Amphocil. All expensive, but cure rates near 100%, except possibly in patients with HIV infection. AmBisome may be most studied lipid-associated preparation but not proven superior to other forms, including non–lipid-associated form.
Adult
Amphotericin B (with deoxycholate): 1 mg/kg IV for 20 d
AmBisome: 3 mg/kg IV days 1-5 and 10; total dose of 18 mg/kg (22 mg/kg in UK); alternatively for visceral leishmaniasis in immunocompetent patients, 3 mg/kg/d IV on days 1-5 and on days 14 and 21, infused over 120 min, or for visceral leishmaniasis in immunosuppressed patients, 4 mg/kg/d IV on days 1-5 and on days 10, 17, 24, 31, and 38, infused over 120 min
Abelcet: 3 mg/kg IV qod for 5 doses
Patients refractory to or intolerant of conventional amphotericin B: 5 mg/kg IV infusion qd; average duration about 4 wk
Amphocil: 2 mg/kg IV for 7 d
Pediatric
Administer as in adults
Antineoplastic agents and cyclosporine may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients receiving pentavalent antimony compounds within 10 d (risk of cardiac conduction abnormalities); monitor renal function, serum electrolyte levels (eg, Mg, K), liver function, CBC counts, and hemoglobin concentrations; resume at lowest level (0.25 mg/kg) when interrupted for >7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic and receiving leukocyte transfusions (separate time of infusion from time of leukocyte transfusion); fever and chills not uncommon after first few doses; rare acute reactions include hypotension, bronchospasm, arrhythmias, and shock
If severe respiratory distress occurs, discontinue infusion (do not re-treat)
Pentamidine (Pentam-300, Pentacarinat, NebuPent)
Inhibits growth of protozoa by blocking oxidative phosphorylation and incorporation of nucleic acids into RNA and DNA, inhibiting protein and phospholipid synthesis. Formulated as a sterile powder; must be reconstituted and administered as slow IV infusion or via IM route. Resistance common in India; high relapse rates reported.
Adult
Visceral disease: 2-4 mg/kg IV/IM qd until initial parasitologic cure (15-27 doses)
Cutaneous disease: 2-4 mg/kg IV/IM once or twice weekly until lesions resolve
Pediatric
Administer as in adults
Concurrent use with agents that prolong QT interval may increase toxicity; concurrent use of pentamidine (or other nephrotoxic drugs) and foscarnet may cause hypocalcemia and increase serum creatinine value
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in diabetes mellitus, hypertension or hypotension, hepatic dysfunction, hypoglycemia, leukopenia, and thrombocytopenia; adverse effects include myalgias, nausea, headache, local pain, metallic taste, numbness, hypotension, tachycardia, hypocalcemia, reversible hypoglycemia followed by hyperglycemia and diabetes mellitus, pancreatitis, neutropenia, thrombocytopenia, nephrotoxicity, and sterile abscess at IM injection site; prolongs QT interval
Amebicidals
Paromomycin has a relatively favorable adverse effect profile, but it is not as effective as antimony or amphotericin B for visceral disease when used as monotherapy. Paromomycin can be used in combination with sodium antimony gluconate to reduce the total time of therapy, and it has better cure rates.
Paromomycin (Aminosidine)
Amebicidal and antibacterial aminoglycoside obtained from Streptomyces rimosus grain; active in intestinal amebiasis. Recommended for treatment of Diphyllobothrium latum, Taenia saginata, Taenia solium, Dipylidium caninum, and Hymenolepis nana infections.
Adult
Effective in lowering duration of treatment when used adjunctively with antimonials (meglumine antimonate, sodium stibogluconate) for epidemic visceral leishmaniasis in southern Sudan
Because paromomycin acts synergistically with antimonials, an effective regimen against visceral leishmaniasis is paromomycin at 15-7 mg/kg/d plus pentavalent antimonial at 20 mg/kg/d for 14-20 d
Pediatric
Administer as in adults
Coadministration with other aminoglycosides, penicillins, cephalosporins, amphotericin B, and loop diuretics may increase nephrotoxic potential; may reduce digoxin effects if paromomycin added to therapy
Documented hypersensitivity; intestinal obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use for long-term therapy because of narrow therapeutic index and toxic hazards; caution in renal failure, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; renal and CN VIII toxicity possible, especially if use extended or combined with other agents
Ulcerative lesions of bowel (increased systemic absorption; potential renal toxicity) may occur; bacterial overgrowth of nonsusceptible organisms possible
Cytokines
Interferon-gamma a T-helper subtype 1 cytokine used to enhance host immunity to Leishmania parasites.
Interferon-gamma-1b (Actimmune)
Recombinant DNA product. Administered with sodium antimony gluconate (probably ineffective alone).
Adult
100 mcg/m2/d IV for 28 d (with 20 mg/kg/d sodium antimony gluconate)
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Assess platelet and CBC counts with differentials, blood chemistries (eg, renal and liver function), and urinalysis before and q3mo during therapy; adverse effects include significant flulike effects (eg, fever, chills, headache, myalgias, depression, and fatigue); caution in preexisting cardiac disease
More on Leishmaniasis |
| Overview: Leishmaniasis |
| Differential Diagnoses & Workup: Leishmaniasis |
 Treatment & Medication: Leishmaniasis |
| Follow-up: Leishmaniasis |
| Multimedia: Leishmaniasis |
| References |
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References
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Further Reading
Keywords
leishmaniasis, leishmaniosis, tropical disease, localized cutaneous leishmaniasis, diffuse cutaneous leishmaniasis, recidivans cutaneous leishmaniasis, post–kala azar dermal leishmaniasis, mucocutaneous leishmaniasis, visceral leishmaniasis, leishmanin skin test, sandfly,
