Leishmaniasis — fellow's quick read

Personal study digest for a new ID fellow. Recommendations are drawn from the IDSA/ASTMH 2016 guideline (Aronson et al., CID 2016;63:e202–64) updated with the 2026 NEJM review by the same lead author (Aronson, Musa, Satoskar. N Engl J Med 2026;394:2026–2039). The “What’s changed since 2016” section is reviewer synthesis of newer evidence, each claim cited. Not a substitute for the full guideline.

In one line

Leishmaniasis treatment is species- and geography-dependent. Not every CL lesion needs treatment, but every VL does. Liposomal amphotericin B is the treatment of choice for VL and the safest option in pregnancy; miltefosine is the only oral agent (FDA-approved for CL/ML/VL by species) but is teratogenic.

◆When to suspect / diagnose

CL: Chronic, painless, indurated skin lesion (papule → nodule → ulcer) at an exposed site in a person with travel to or residence in an endemic area (Latin America, Middle East, Central/South Asia, East Africa, Mediterranean). Incubation ≥2–4 weeks. Satellite lesions, sporotrichoid spread, and regional adenopathy are clues. IDSA rec 1–2, strong/moderate
ML: Persistent nasal congestion, epistaxis, septal perforation, or oropharyngeal/laryngeal lesions — especially with a history of prior CL caused by L. (V.) braziliensis or related Viannia spp acquired in the “mucosal belt” (Bolivia, Peru, Brazil south of the Amazon). Can appear years to decades after CL. IDSA rec 3–9, strong/low
VL: Chronic fever, weight loss, hepatosplenomegaly, pancytopenia, hypergammaglobulinemia in a person from an endemic area (East Africa, Indian subcontinent, Mediterranean, Latin America). Mortality 75–95% untreated; 3–10% with treatment. VL is an opportunistic infection in HIV/AIDS. IDSA rec 10–13
Diagnostic approach: Use multiple methods — smear/histopath for amastigotes, culture, and PCR (most sensitive single test, strong/moderate). Species identification by molecular methods guides therapy (weak, moderate). Serology (rK39) is useful for VL but not for CL. Newer: CL Detect Rapid Test (immunochromatographic antigen detection), MALDI, metagenomic sequencing, Karius cfDNA for VL. IDSA rec 14–22; NEJM 2026
Contact a reference lab before collecting specimens — CDC (Atlanta), McGill, or WRAIR (for military beneficiaries). IDSA rec 15, strong/low

◆Workup the fellow drives

Classify the CL: Simple vs complex (Table 1 in the guideline). Complex = ML-risk species, >4 lesions, ≥5 cm, face/ears/genitals, immunocompromised, or failure of local therapy → systemic treatment indicated. IDSA rec 32–34
Species identification: Attempt in all CL cases. It determines ML risk, drug choice, and expected healing time. Send to a reference lab. IDSA rec 18, weak/moderate
Mucosal exam in New World CL: All patients at risk for ML need a thorough naso-oropharyngeal exam at initial and all follow-up visits, even if asymptomatic. Refer for fiber-optic endoscopy if symptoms develop. IDSA rec 5–9, strong/low
VL workup: Bone marrow aspirate (preferred) for smear, culture, PCR. Serum for rK39. In immunocompromised patients, buffy coat exam and molecular testing of blood. Assess for HIV coinfection. IDSA rec 10–13
PKDL: Occurs in 10–50% of treated L. donovani VL (higher in East Africa). Characteristic facial distribution; macular, maculopapular, or nodular. Diagnose by biopsy PCR. NEJM 2026

◆Empiric & definitive therapy

Cutaneous leishmaniasis

Scenario	Drug / dose / route	Notes / strength
Simple OWCL (non-ML-risk)	Local therapy preferred: cryotherapy (freeze 15–20 s, repeat q3 wk ×3), thermotherapy (ThermoMed, 1 session), intralesional SbV (0.2–5 mL q3–7 d ×5–8), topical paromomycin 15%/gentamicin 0.5% cream (qd ×20 d). Observation without treatment is acceptable if simple, healing, immunocompetent patient concurs.	Strong, moderate. No universally applicable treatment for CL. Individualize by species/host.
Complex CL or ML-risk species	Miltefosine ~2.5 mg/kg/day (30–44 kg: 50 mg bid; ≥45 kg: 50 mg tid) × 28 d. L-AmB 3 mg/kg/day days 1–5 and 10, or days 1–7 (total 18–21 mg/kg). SbV 20 mg/kg/day × 20 d (via CDC IND). Pentamidine 3–4 mg/kg q2d × 3–4 doses.	Strong, moderate. Systemic treatment recommended for complex CL: ML-risk Viannia spp, immunocompromised, large/multiple/facial lesions, or failed local therapy. Miltefosine is FDA-approved for CL caused by Viannia spp.
L. major / L. mexicana	Fluconazole 200 mg PO daily × 6 weeks	Weak. Azoles have poor efficacy against other species, especially Viannia spp. Off-label.

Mucosal leishmaniasis

Scenario	Drug / dose / route	Notes / strength
All ML (systemic required)	AmB deoxycholate 0.5–1.0 mg/kg/dose daily or q2d, cumulative 20–45 mg/kg. L-AmB ~3 mg/kg/day, cumulative 20–60 mg/kg. Miltefosine 2.5 mg/kg/day × 28 d (FDA-approved for ML from L. (V.) braziliensis). SbV 20 mg/kg/day × 28 d.	Strong, moderate. No single treatment of choice — individualize. Better outcomes with mild-to-moderate disease. Systematic reviews: cure rates ~59–79% (L-AmB/AmB), ~63% (SbV), ~53% (miltefosine). Prophylactic corticosteroids if laryngeal disease risks airway obstruction.

Visceral leishmaniasis

Scenario	Drug / dose / route	Notes / strength
VL, immuno- competent	L-AmB 3 mg/kg/day IV on days 1–5, 14, 21 (total 21 mg/kg)	Strong, high. FDA-approved regimen. Treatment of choice. East Africa: may need ≥40 mg/kg total (higher parasite burden). ABLC not considered interchangeable — less well studied.
VL, immuno- suppressed (incl. HIV)	L-AmB 4 mg/kg/day IV on days 1–5, 10, 17, 24, 31, 38 (total 40 mg/kg)	Strong, low. FDA-approved regimen. Secondary prophylaxis until CD4 >200–350 × ≥6 months + viral suppression. ART critical — initiate during or soon after VL treatment. WHO also endorses L-AmB + miltefosine combo for HIV/VL.
VL, alternative (L. donovani, Indian subcontinent)	Miltefosine 2.5 mg/kg/day × 28 d	Strong, moderate. FDA-approved for VL caused by L. donovani. Not as effective for L. infantum. Age ≥12, weight ≥30 kg, not pregnant.
VL, alternative (low SbV resistance)	SbV 20 mg SbV/kg/day IV/IM × 28 d	Strong, high. Only where antimony resistance <10%. Do NOT use for India-acquired VL (widespread resistance). Available via CDC IND or USAMMDA for military.
East Africa VL (combination)	Paromomycin + SbV or paromomycin + miltefosine	Post-2016 Shorter course, cost-effective. Paromomycin + miltefosine: lower toxicity and death vs paromomycin + SbV. Paromomycin not available in North America.

How to get pentavalent antimonials (SbV) in North America

Sodium stibogluconate (Pentostam) is available in the US only under a CDC-sponsored IND protocol — contact CDC Drug Service (404-639-3670, drugservice@cdc.gov). For military beneficiaries, contact USAMMDA Force Health Protection (301-401-2768). In Canada: Health Canada Special Access Program.

◆Key decisions a fellow owns

Does this CL need treatment at all? Simple OWCL in an immunocompetent patient that is spontaneously healing can be observed (strong, moderate). Reassess periodically — reconsider if healing stalls. IDSA rec 24–27
Is this patient at risk for mucosal disease? New World CL caused by Viannia spp (especially L. (V.) braziliensis) from the mucosal belt (Bolivia, Peru, Brazil) → systemic treatment even for healing CL (weak, low). Monitor naso-oropharynx for ≥2 years. IDSA rec 26, 30
Species identification drives the treatment plan — attempt it in all CL cases. It determines ML risk, drug choice, and prognosis. Contact a reference lab before collecting specimens.
L-AmB dosing varies by region for VL — standard 21 mg/kg total works in the Indian subcontinent and Mediterranean; East Africa may require ≥40 mg/kg.
VL in an immunosuppressed host (HIV, transplant, biologics) — use the 40 mg/kg L-AmB regimen. Start ART. Plan for secondary prophylaxis and lifelong monitoring. Reduce immunosuppressive drugs when possible. IDSA rec 61–66, 70–76
Know the CDC consult service: parasites@cdc.gov for treatment guidance on refractory or complicated cases.

◆Special populations

Pregnancy: Miltefosine is contraindicated (teratogenic; requires negative pregnancy test, contraception during + 5 months after). SbV and pentamidine are not recommended. L-AmB is the safest option (FDA pregnancy category B). Defer CL treatment if feasible until after delivery; treat VL and ML. IDSA rec 78–79; NEJM 2026
HIV coinfection: VL is an opportunistic infection. L-AmB is first-line (40 mg/kg regimen). WHO also endorses L-AmB + miltefosine for first-episode HIV/VL coinfection with L. donovani. Secondary prophylaxis (pentamidine or L-AmB) until CD4 >200–350 for ≥6 months with suppressed viral load. Monitor indefinitely for relapse. Immune reconstitution inflammatory syndrome (IRIS) with CL/PKDL reported. IDSA rec 61–69; NEJM 2026
Transplant / biologics: L-AmB is treatment of choice for VL (40 mg/kg). Decrease immunosuppressive drugs during treatment. TNF-α antagonists are a risk factor for VL reactivation — consider withdrawal during treatment (case-by-case). IDSA rec 70–77
Children: Miltefosine is not FDA-approved for <12 years or <30 kg. L-AmB can be used. SbV dosing is weight-based (no upper-limit cap in mg).
Renal impairment: L-AmB is less nephrotoxic than AmB deoxycholate but still requires monitoring. Minimize concomitant nephrotoxins. Saline loading, electrolyte supplementation as needed.

◆Duration & stopping

CL: Monitor healing clinically (not parasitologically) for 6–12 months after treatment. First sign of healing: flattening by 4–6 weeks; full re-epithelialization by ~3 months. Failure = new lesions, worsening, or incomplete healing by 3 months → additional therapy (strong, low). IDSA rec 40–44
ML: Nasopharyngeal/laryngeal visualization every 3–6 months for ≥2 years after treatment, then lifelong symptom monitoring. Relapses are common. Elective surgery on prior lesion sites should wait ≥1 year after treatment. IDSA rec 45–48; NEJM 2026
VL response markers: Fever should decrease within 7 days. Cytopenias improve within 1 month (anemia may lag to 6 months). Splenomegaly resolves over 6–12 months. Relapse is most common in the first 6 months. Clinical monitoring — repeat bone marrow is NOT needed if responding well. IDSA rec 55–56
VL + HIV: Secondary prophylaxis until CD4 >200–350 and viral suppression for ≥6 months. Monitor indefinitely for relapse even after immune reconstitution. Periodic PCR of blood can detect early relapse. IDSA rec 65–66; NEJM 2026

What’s changed since 2016

Reviewer synthesis of newer evidence — not the guideline. Each claim cited; the NEJM 2026 review by the same lead author (Aronson) serves as the primary 10-year update.

Combination therapy for East African VL is now standard practice. Paromomycin + SbV and paromomycin + miltefosine are both effective, shorter, and more cost-effective than monotherapy. Paromomycin + miltefosine has lower toxicity and mortality than paromomycin + SbV. The 2016 guideline noted combinations “may be considered” (weak, low); they are now established first-line in East Africa. Aronson et al., NEJM 2026;394:2026–2039 (PMID 42202321; doi:10.1056/NEJMra2403309)
WHO endorses L-AmB + miltefosine for HIV/VL coinfection (first episode, L. donovani), followed by secondary prophylaxis with pentamidine or L-AmB. This was not in the 2016 guideline. NEJM 2026
Molecular diagnostics are now the standard. The 2016 guideline called PCR “emerging as the most sensitive”; in 2026 it is the established standard for diagnosis and species identification. CL Detect Rapid Test (immunochromatographic antigen detection in ulcer tissue), MALDI, and the Karius cfDNA test (identifies L. infantum/L. donovani from blood) have entered practice. NEJM 2026
Five oral anti-trypanosomatid compounds are in the clinical pipeline — DNDI-6148, GSK3186899/DDD853651, GSK3494245/DDD01305143, LXE408, and DNDI-0690. None are approved yet. Recency-sensitive — verify status before citing in clinical decisions. NEJM 2026 (ref 78)
CRISPR-attenuated L. major vaccine was safe and effective in preclinical testing and is expected to enter human testing in 2026. Modeling suggests a vaccine with 50% efficacy could eliminate VL in 8–10 years. NEJM 2026 (refs 79–81)
New topical CL agents — lefleuganan and LSH 001 are emerging topical therapies for CL, added to the armamentarium alongside the established paromomycin/gentamicin cream (WR 279,396). NEJM 2026 (refs 54–62)
Host-directed therapies for CL are emerging: glyburide, anakinra, maraviroc, and tofacitinib treat clinical manifestations but do not kill parasites. NEJM 2026 (ref 64)
VL elimination in Bangladesh — the WHO elimination target of <1 case per 10,000 has been reached. East Africa now reports the highest burden globally. NEJM 2026
Still current: L-AmB remains the treatment of choice for VL worldwide. Miltefosine indications, SbV dosing, and the CL treatment algorithm are unchanged. The core framework of individualizing CL therapy by species and geography holds.

◆Anki cards minted this run

VL L-AmB dosing: immunocompetent vs immunosuppressed vs East Africa — the specific day-by-day schedule and total doses. [core actionable, must-know dosing]
Miltefosine: FDA-approved indications, dosing, and contraindication in pregnancy — the only oral antileishmanial; species-specific approval. [board-relevant, discriminating]
When to treat CL vs observe: simple vs complex, ML-risk species — the treatment decision algorithm. [fellow-level decision framework]
Combination VL therapy in East Africa (post-2016) — paromomycin + miltefosine or SbV is now standard; marks where the guideline lags practice. [currency layer, practice-changing]

Anki MCP unavailable this run (device bridge disconnected) — cards staged as TSV for manual import.

Sources: IDSA/ASTMH 2016 leishmaniasis guideline — Aronson N et al., Clin Infect Dis 2016;63(12):e202–e264 (doi:10.1093/cid/ciw670); NEJM 2026 review — Aronson NE, Musa AM, Satoskar AR. Leishmaniasis. N Engl J Med 2026;394:2026–2039 (PMID 42202321; doi:10.1056/NEJMra2403309).