01Approach to the Critical Patient/attcp44

Immediate priorities

›Severity assessment on presentation

›Severe VL criteria

›Hemoglobin <5 g/dL or transfusion-dependent anemia

›Severe neutropenia with secondary bacterial infection

›Bleeding — epistaxis, petechiae, purpura from thrombocytopenia

›Hemodynamic instability

›SBP <90 mmHg or MAP <65 mmHg

›Tachycardia with signs of poor perfusion

›Features of HLH overlap

›Ferritin markedly elevated (>500 mcg/L)

›Hypertriglyceridemia

›Bicytopenia or pancytopenia

›If hemodynamically unstable, initiate IV fluid resuscitation immediately

›Isotonic crystalloid bolus 20–30 mL/kg

›Reassess after each bolus

Resuscitation targets

›Hemodynamic goals

›MAP target >65 mmHg

›Vasopressor support if unresponsive to fluids

›Norepinephrine first-line vasopressor

›Transfusion thresholds

›Packed red blood cells for Hb <7 g/dL or symptomatic anemia

›Platelet transfusion for active bleeding with thrombocytopenia

›Empiric antibiotics for secondary bacterial infection

›Broad-spectrum coverage within 1 hour if neutropenic fever

›Blood cultures before antibiotics when feasible

›Monitoring bundle

02History/hx75

Presenting symptoms

›Fever pattern

›Persistent fever >2 weeks unresponsive to antibiotics

›Irregular or remittent pattern with twice-daily spikes

›Duration can extend to months without treatment

›Fever in the context of relevant travel or exposure

›Even remote travel — latent infection can reactivate decades later

›Night sweats

Constitutional and abdominal symptoms

›Weight loss and wasting

›Anorexia, fatigue, malaise

›Cachexia as disease progresses

›Severity correlates with parasite burden

›Abdominal distension

›Massive splenomegaly crossing midline

›Hepatomegaly contributing to distension

›Hematologic symptoms

›Bleeding manifestations

›Epistaxis

›Gingival bleeding

›Easy bruising

›Pallor from progressive anemia

›Fatigue worsening over weeks to months

›Exertional dyspnea in severe anemia

›Skin changes

›Hyperpigmentation of face, hands, feet, abdomen (Indian subcontinent)

›"Kala-azar" means black fever in Hindi

›Post-kala-azar dermal leishmaniasis (PKDL) nodules or patches after treatment

Exposure and travel history

›Endemic area travel or residence

›Indian subcontinent (India, Nepal, Bangladesh)

›Historically highest global burden; now declining with DDT spraying

›Anthroponotic — human-to-sandfly-to-human transmission

›East Africa

›Ethiopia, Sudan, South Sudan — major epidemic burden

›Lymphadenopathy more prominent than in South Asia

›Brazil and South America

›Zoonotic reservoir in domestic dogs

›Urban transmission increasingly documented

›Mediterranean basin and Middle East

›L. infantum species; dog reservoir

›Immunocompromised adults especially at risk

›Transmission route risk factors

›Phlebotomine sandfly bite — primary route

›Dusk-to-dawn biting pattern

›Altitude and season dependent

›Needle sharing in PWID

›Southern Europe — documented outbreak clusters

›HIV coinfection common in this population

›Blood transfusion or organ transplant from infected donor

›Rare; always consider in immunocompromised recipients

›Congenital/perinatal transmission

›Rare but reported

Risk factors

›Immunocompromising conditions

›HIV/AIDS — most significant immunologic risk factor

›Atypical presentations with absent splenomegaly

›GI and mucosal involvement more common

›Organ transplant recipients on immunosuppression

›TNF-alpha antagonists (infliximab, adalimumab)

›HSCT recipients

›Chemotherapy or corticosteroid therapy

›Host and environmental risk factors

›Children <5 years in endemic areas — highest burden age group

›Diarrhea, cough, and growth retardation more prominent

›Higher mortality without treatment

›Malnutrition — bidirectional relationship with VL

›Poor cell-mediated immunity increases susceptibility

›VL worsens nutritional status

›Low socioeconomic status

›Mud walls and thatched roofs attract sandflies

›Poor housing proximity to sandfly habitat

Incubation and timeline

›Incubation period

›Typical range 2 weeks to 8 months

›Can be much longer — years to decades in latent reactivation

›Subacute to chronic onset in most patients

›Acute presentations

›More common in young children

›Immunocompromised patients may have accelerated course

03Physical Exam/exam43

Vital signs

›Fever and hemodynamic parameters

›Temperature typically >38.5 degrees C

›Irregular pattern — double daily spike characteristic

›Tachycardia often accompanying

›Weight and nutritional assessment

›Significant weight loss from cachexia

›Temporal wasting and generalized muscle loss

Abdominal examination

›Organomegaly findings

›Splenomegaly

›Often massive — can cross midline and reach pelvis

›Risk of spontaneous splenic rupture in severe cases

›Splenic rub may be audible or palpable

›Hepatomegaly

›Hepatomegaly with tender right upper quadrant

›Hepatic enlargement less striking than splenomegaly

Skin and lymph nodes

›Dermatologic findings

›Hyperpigmentation

›Face, hands, feet, abdomen — Indian subcontinent pattern

›Secondary to increased melanin deposition

›Pallor from anemia

›Conjunctival pallor

›Palmar pallor

›Bleeding stigmata

›Petechiae and purpura from thrombocytopenia

›Ecchymoses

04Differential Diagnosis/ddx52

Life-threatening mimics

›Hematologic malignancy

›Lymphoma — pancytopenia, hepatosplenomegaly, B symptoms

›ICD-10: C85.9 — Non-Hodgkin lymphoma, unspecified

›Distinguishing: bone marrow biopsy, PET-CT, LDH markedly elevated

›Acute leukemia

›ICD-10: C91.0, C92.0

›Blast cells on peripheral smear; flow cytometry

›Hemophagocytic lymphohistiocytosis

›VL can trigger or mimic HLH — critical diagnostic overlap

›ICD-10: D76.1

›Ferritin >500 mcg/L, hypertriglyceridemia, hemophagocytosis on marrow biopsy

›HLH-04 criteria: 5 of 8 criteria required for diagnosis

Infectious mimics

›Malaria

›Fever, splenomegaly, anemia in travelers from endemic areas

›ICD-10: B50-B54

›Distinguish: thick and thin blood smears, RDT, PCR

›Co-infection with VL possible

›Typhoid fever

›Prolonged fever, hepatosplenomegaly, relative bradycardia

›ICD-10: A01.0

›Blood culture remains gold standard

›Rose spots characteristic but often absent

›Miliary tuberculosis

›Fever, hepatosplenomegaly, pancytopenia

›ICD-10: A19.9

›AFB cultures, interferon-gamma release assay, biopsy

05Laboratory Tests/lt76

Initial hematologic and metabolic panel

›Complete blood count

›Pancytopenia — characteristic triad in VL

›Anemia: Hb often <100 g/L, normocytic or microcytic

›Leukopenia: WBC typically <2.4 x10^9/L with relative lymphocytosis

›Thrombocytopenia: platelets often <100 x10^9/L

›Eosinopenia

›Near-absent eosinophils characteristic of VL

›Useful distinguishing feature from other parasitic diseases

›Comprehensive metabolic panel

›Elevated transaminases (ALT, AST) from hepatic involvement

›Usually mild to moderate elevation

›Bilirubin may be mildly elevated

›Hypoalbuminemia

›Albumin <30 g/L in advanced disease

›Correlates with severity and nutritional status

›Renal function

›Creatinine and eGFR as baseline before amphotericin B

›Electrolytes: hypokalemia risk during amphotericin B therapy

Immunologic and protein studies

›Serum protein electrophoresis

›Polyclonal hypergammaglobulinemia

›Reversed albumin/globulin ratio characteristic

›IgG and IgM elevation from non-specific B-cell activation

›Elevated immunoglobulins may cause false-positive syphilis, ANA, rheumatoid factor

›Diagnostic confusion with autoimmune disease

›Inflammatory markers

›Ferritin markedly elevated

›>500 mcg/L raises HLH concern

›Very high ferritin (>10,000 mcg/L) strongly suggests HLH

›ESR and CRP elevated nonspecifically

›Useful for monitoring treatment response

›Triglycerides if HLH suspected

›Elevated triglycerides >3 mmol/l supports HLH diagnosis

Serologic and molecular diagnostics

›rK39 antigen rapid diagnostic test

›Immunochromatographic strip test — point-of-care

›Sensitivity 93–100% in Indian subcontinent

›Sensitivity 85–95% in East Africa

›Sensitivity variable and lower in immunocompromised patients

›Specificity >97% in endemic areas

›Cochrane review: rK39 RDT most validated rapid test for VL

›May remain positive years after treatment — cannot confirm active disease

›ELISA for anti-Leishmania antibodies

›High sensitivity (>90%) in immunocompetent patients

›Lower sensitivity in HIV-VL coinfection

›Useful as confirmatory serology

›Direct Agglutination Test (DAT)

›High sensitivity (>90%) with good specificity

›Labor intensive; less available than rK39

›Useful in settings where rK39 performs poorly

›PCR (quantitative)

›Highest sensitivity >95% on blood or bone marrow

›Available through CDC reference laboratory

›Useful for treatment response monitoring

›Buffy coat PCR preferred in HIV-coinfected patients

›HIV testing

›Mandatory in all VL patients

›Alters treatment regimen and secondary prophylaxis decisions

›CD4 count for staging and treatment planning

Parasitologic confirmation

›Bone marrow aspirate — preferred confirmatory test in North America

›Sensitivity 52–85% for amastigotes on Giemsa-stained smear

›Kinetoplast and nucleus visible within macrophages

›Culture of aspirate increases yield

›Risk profile lower than splenic aspirate

›Standard procedure in resource-adequate settings

›Splenic aspirate

›Highest sensitivity 93–99%

›Risk of hemorrhage — not recommended outside specialized centers

›Contraindicated with severe thrombocytopenia or coagulopathy

›Lymph node aspirate

›Sensitivity 52–58%

›Useful in East African VL where lymphadenopathy prominent

›Baseline safety labs before treatment

›ECG before pentavalent antimonial use

›QTc prolongation risk — arrhythmia and sudden cardiac death

›Not routinely required for liposomal amphotericin B

›Pregnancy test before miltefosine or pentavalent antimonials

›Both contraindicated in pregnancy

06Diagnostic Tests/dt69

Scoring Systems

›Severity stratification for VL

›Mild VL

›Ambulatory patient

›Moderate organomegaly

›Mild cytopenias without bleeding

›Severe VL

›Hb <50 g/L

›Severe neutropenia with secondary infection

›Bleeding secondary to thrombocytopenia

›HIV coinfection

›Malnutrition or cachexia

›Multi-organ dysfunction

›HLH-04 diagnostic criteria

›Five of eight criteria required for diagnosis

›Fever >38.5 degrees C

›Splenomegaly

›Bicytopenia in ≥2 cell lines

›Hypertriglyceridemia or hypofibrinogenemia

›Hemophagocytosis on bone marrow or lymph node biopsy

›Low or absent NK cell activity

›Ferritin >500 mcg/L

›Elevated soluble CD25 (sIL-2 receptor)

›VL can fulfill HLH criteria — treat underlying VL first

›HLH triggered by VL may resolve with antiparasitic therapy alone

›Consult hematology before initiating HLH immunosuppression

MRI

›Abdominal MRI indications in VL

07Disposition/dispo40

Admission criteria

›Indications for inpatient admission

›All confirmed or strongly suspected VL requiring IV therapy

›Liposomal amphotericin B administered only in monitored inpatient setting

›IV access, renal monitoring, infusion reaction management

›Severe anemia requiring transfusion

›Hb <70 g/L or symptomatic at higher levels

›Neutropenic fever or secondary bacterial infection

›Absolute neutrophil count <0.5 x10^9/L with fever

›Active bleeding from thrombocytopenia

›Platelet count <20 x10^9/L with bleeding

›HIV-VL coinfection

›Higher clinical complexity, different treatment regimen

›HLH features or multi-organ dysfunction

›ICU-level care if hemodynamically unstable

ICU indications

›ICU transfer criteria

›Hemodynamic instability requiring vasopressors

›MAP <65 mmHg despite fluid resuscitation

›Respiratory failure

›Requiring oxygen >4 L/min or non-invasive ventilation

›HLH with multi-organ failure

›Hepatic failure, renal failure, DIC

›Severe anemia with cardiac decompensation

›Angina or ischemic ECG changes with anemia

Outpatient management

›Conditions for outpatient miltefosine completion

›Immunocompetent patient, mild-moderate VL, stable cytopenias

08Treatment/t82

Initial stabilization

›Supportive measures before definitive therapy

›Blood transfusion for severe anemia

›Packed RBC if Hb <70 g/L or symptomatic at <90 g/L

›Leukodepleted products preferred in immunocompromised

›Platelet transfusion for active bleeding

›Target platelets >50 x10^9/L for active hemorrhage

›>20 x10^9/L for prophylactic threshold

›Empiric antibiotics for suspected secondary bacterial infection

›Broad-spectrum beta-lactam plus additional coverage based on suspected source

›Tailor to cultures and local resistance patterns

›Nutritional support

›High-calorie, high-protein diet to address cachexia

›Enteral nutrition preferred; parenteral if GI not functional

›Cochrane review found insufficient evidence for specific supplement protocols

First-line definitive therapy — immunocompetent patients

›Liposomal amphotericin B (AmBisome)

›FDA-approved regimen for VL in North America

›3 mg/kg/day IV on days 1–5, 14, and 21

›Total dose approximately 21 mg/kg

›Infuse over 2 hours; premedicate with paracetamol and diphenhydramine

›Alternative WHO single-dose regimen (Indian subcontinent)

›10 mg/kg IV single dose

›Cure rate >95% in India

›Not validated in East Africa or Americas — do not apply outside South Asia

›Monitoring requirements

›Renal function (creatinine, BUN) before each infusion

›Electrolytes: potassium and magnesium after each infusion

›CBC for response monitoring

›Infusion reactions

›Fever, rigors, hypotension — manage with rate reduction and premedication

›True anaphylaxis rare but test dose protocol recommended for first dose

›Miltefosine — oral alternative

›FDA-approved for L. donovani VL in patients ≥12 years and ≥30 kg

›Weight-based dosing: 2.5 mg/kg/day orally (maximum 150 mg/day)

›30–44 kg: 50 mg twice daily

›≥45 kg: 50 mg three times daily

›Duration: 28 days

›Adverse effects

›GI: nausea, vomiting — administer with food

›Potential renal and hepatic toxicity; monitor LFTs and creatinine weekly

›Teratogenic — absolute contraindication in pregnancy

›Limitations

›Not recommended as monotherapy for L. infantum (Mediterranean/Americas) — lower efficacy

›Not recommended in HIV-VL coinfection as monotherapy

HIV-VL coinfection treatment

›Preferred regimen — combination therapy

›Liposomal AmB plus miltefosine

›Liposomal AmB 30–40 mg/kg total dose IV over 10–20 days

›Miltefosine 2.5 mg/kg/day PO (max 150 mg/day) for 28 days concurrent

›WHO conditionally recommended for East Africa and South Asia

›Randomized trial evidence (Burza et al., 2022)

›Combination superior to AmB monotherapy in HIV-VL in India

›Better initial cure rates; relapse rates remain high in HIV coinfection

›Alternative — liposomal AmB monotherapy

›Total dose 20–60 mg/kg via extended schedule

›Example: 4 mg/kg IV on days 1–5, 10, 17, 24, 31, 38

›Higher total dose required due to impaired immune response

›IDSA/ASTMH guidelines support extended dosing in HIV-VL

Secondary prophylaxis — HIV-VL coinfection

›Relapse prevention in immunocompromised patients

›Liposomal AmB 3–5 mg/kg IV every 2–4 weeks

›Continue until immune reconstitution: CD4 count >200 cells/microL sustained

›ART initiation critical — without immune recovery, relapse is near-certain

›Monthly CBC and renal function monitoring during secondary prophylaxis

›Cumulative amphotericin B nephrotoxicity risk

›Consultation with HIV specialist required for prophylaxis planning

Alternative treatments

›Amphotericin B deoxycholate

›0.5–1.0 mg/kg/day IV over 4–6 hours

›Total dose 1.5–2.0 g

›Significant nephrotoxicity — inferior to liposomal formulation

›Reserved for resource-limited settings when liposomal form unavailable

›Rigorous renal monitoring required

›Pentavalent antimonials

›Meglumine antimoniate: 20 mg/kg/day IM or IV for 28 days

›Requires IND application in the US — not commercially available

›Cardiotoxicity risk: QTc prolongation, arrhythmia, sudden cardiac death

›Pancreatitis risk; hepatotoxicity

›Resistance now widespread in Indian subcontinent — no longer first-line

›Baseline and serial ECG required

›QTc >450 ms at baseline — do not initiate antimonials

›Paromomycin

›15 mg/kg/day IM for 21 days

›Low toxicity profile; ototoxicity and nephrotoxicity rare

›Inferior cure rate compared to liposomal AmB

›Used as combination partner in some regimens

09Special Populations/sp52

Pregnancy

›VL in pregnancy — high maternal and fetal risk

›Untreated VL is uniformly fatal — treatment risks must be weighed against disease severity

›Maternal mortality from untreated VL exceeds risk of treated disease

›Preterm birth, low birthweight, and perinatal mortality reported

›Treatment options in pregnancy

›Liposomal amphotericin B — preferred agent in pregnancy

›Crosses placenta but no established human teratogenicity

›Best-studied option with acceptable safety data

›Miltefosine — absolutely contraindicated

›Teratogenic in animal studies and human case reports

›Effective contraception required during therapy and for 5 months post-treatment

›Pentavalent antimonials — generally avoided in pregnancy

›Documented teratogenicity; use only if no alternatives

›Consult ID and maternal-fetal medicine for all pregnant VL patients

›Treatment individualized to gestational age and severity

Geriatric

›VL considerations in older adults

›Atypical presentation common

›Fever may be blunted

›Cognitive changes or delirium may predominate

›Splenomegaly less dramatic than in younger patients

›Renal function decline affects drug selection and dosing

›Liposomal AmB preferred — lower nephrotoxicity than deoxycholate

›Baseline creatinine clearance calculation required

›Aggressive pre-hydration with normal saline before each infusion

›Miltefosine in older patients

›No specific dose adjustment; GI tolerability may be worse

10Background/b84

Epidemiology

›Global burden

›VL is the second most lethal parasitic disease globally after malaria

›Approximately 50,000–90,000 new cases annually worldwide

›Concentrated in India/South Asia, East Africa, and Brazil

›Mortality without treatment exceeds 95%

›With appropriate treatment, case fatality rate <5%

›India has historically accounted for >50% of global burden

›Indoor residual spraying (IRS) with DDT has dramatically reduced Indian incidence

›Studies show IRS reduced sandfly density and VL incidence significantly in India 2016–2022

›East Africa carries high burden

›Sudan, Ethiopia, and South Sudan — epidemic outbreaks during conflict and displacement

›Brazil — major burden in the Americas

›Zoonotic transmission; urban expansion into endemic areas increasing cases

›Mediterranean and Middle East

›L. infantum species; sporadic cases with immunocompromised patients disproportionately affected

›Vulnerable populations

›Children <5 years — highest morbidity and mortality

›90% of pediatric cases in South Asia and East Africa

›HIV-coinfected adults — rising burden

›Bidirectional immunosuppression; VL accelerates HIV progression

›Transplant recipients and biologic therapy users — emerging risk group

Pathophysiology

›Causative organisms

›Leishmania donovani complex

›L. donovani — Indian subcontinent and East Africa (anthroponotic)

›L. infantum (= L. chagasi) — Mediterranean, Middle East, South America (zoonotic; dog reservoir)

›Transmitted by female Phlebotomus (Old World) or Lutzomyia (New World) sandflies

›Dusk-to-dawn feeding behavior

›Infective promastigote form inoculated during blood meal

›Host-parasite interaction

›Promastigotes phagocytosed by dermal macrophages and dendritic cells

›Transform to amastigote form within phagolysosomes

›Amastigotes resist oxidative killing and replicate intracellularly

›Systemic dissemination via lymphatics and bloodstream

›Bone marrow, spleen, liver, and lymph nodes primarily affected

›Splenic red pulp — major site of amastigote accumulation

›Immune evasion mechanisms

›Parasite downregulates MHC class II expression on macrophages

›Inhibits IL-12 production — impairs Th1 responses

›Promotes IL-10 and TGF-beta — immunosuppressive milieu

›Pathologic consequences

›Splenomegaly

›Massive reticuloendothelial hyperplasia with parasite accumulation

›Hypersplenism contributes to pancytopenia via increased splenic sequestration

›Pancytopenia mechanisms

›Bone marrow infiltration reducing hematopoiesis

›Hypersplenism from massive splenomegaly

›Autoimmune hemolysis from hypergammaglobulinemia

›Hypoalbuminemia

›Reduced hepatic synthesis from hepatic infiltration

›Protein loss from nutritional deficiency and increased catabolism

›Polyclonal hypergammaglobulinemia

›Non-specific B-cell hyperactivation

›Elevated IgG and IgM; reversed A/G ratio

Therapeutic Considerations

›Treatment selection framework

›Geographic region determines species and resistance patterns

›Indian subcontinent: liposomal AmB or miltefosine first-line

›East Africa: liposomal AmB preferred; combination regimens in HIV-VL

›Americas and Mediterranean: liposomal AmB preferred; miltefosine not recommended for L. infantum

›Immune status is the primary treatment stratifier

›Immunocompetent: standard 21-day liposomal AmB regimen

›HIV-coinfected: combination therapy plus secondary prophylaxis

›Transplant/immunosuppressed: individualized, higher doses often required

›Resistance and treatment failure

›Antimonial resistance widespread in Indian subcontinent

›Antimonials no longer first-line in South Asia

›Resistance not yet documented for liposomal AmB or miltefosine

›Miltefosine treatment failure increasing

›Pharmacokinetic variability — subtherapeutic levels in some patients

›Barrier to resistance lower than AmB

›Treatment failure definition

›Clinical deterioration after 7–10 days of appropriate therapy

›No parasitologic clearance at end of treatment

›Consult ID/tropical medicine; consider alternative agent

›Post-treatment surveillance

›PKDL risk after VL treatment

›Occurs in 5–10% of patients, months to years post-treatment

›Hypo- or hyperpigmented skin nodules; can serve as reservoir for transmission

›Requires additional treatment — often miltefosine or antimonials

›Test of cure

›Clinical response (defervescence, splenic regression) within 1–2 weeks

›Parasitologic confirmation at 6 months by PCR or bone marrow

›CDC reporting recommended for all VL cases in the US

›VL is reportable in most US states

›CDC provides consultation and diagnostic support

11Patient Discharge Instructions/pdi43

copy discharge instructions

›Diagnosis and recovery overview

›You have been diagnosed with visceral leishmaniasis (also called kala-azar)

›This is a serious parasitic infection transmitted by sandfly bites

›It is treatable and curable with proper medication

›Recovery timeline

›Fever typically resolves within 1–2 weeks of starting treatment

›Spleen and liver size return toward normal over weeks to months

›Blood counts improve gradually over weeks

›Medications

›Take all prescribed medications exactly as directed

›Miltefosine: take with food to reduce stomach upset

›Do not skip doses — incomplete treatment causes treatment failure

›Complete the full 28-day course even if you feel better

›Side effects to monitor

›Nausea and vomiting — manageable with antiemetics; contact clinic if severe

›Skin changes — report new spots, nodules, or discoloration

›Activity and diet

›High-protein, high-calorie diet to support recovery

›Protein-rich foods: eggs, meat, fish, legumes, dairy

›Adequate fluid intake daily

›Avoid strenuous activity until spleen size normalizes

›Risk of splenic rupture with trauma or contact sports during active disease

›No contact sports until cleared by your doctor

›Return to emergency department immediately for

›Red flags requiring urgent return

›Fever returning after initially resolving

›Sudden severe abdominal pain (may indicate splenic rupture)

12References/r38

Guidelines and key sources

›IDSA/ASTMH Clinical Practice Guidelines

›Aronson N et al. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by IDSA and ASTMH. Clin Infect Dis. 2016

›Foundational North American guideline for VL management

›Covers drug selection, dosing, HIV-VL, and follow-up

›IDSA/ASTMH guidelines recommend infectious disease consultation and CDC assistance for all US VL cases

›WHO and international guidance

›WHO control strategies: indoor residual spraying, active case detection, treatment access

›Combination therapy now conditionally recommended for HIV-VL coinfection

›van Griensven J et al. Status of Combination Therapy for VL: An Updated Review. Lancet Infect Dis. 2024

›Current evidence base for combination regimens

Key clinical studies

›Liposomal AmB and miltefosine evidence

›Burza S et al. AmBisome Monotherapy and Combination AmBisome-Miltefosine for VL in HIV Patients in India. Clin Infect Dis. 2022

›Randomized open-label phase 3 trial

›Combination superior to monotherapy in HIV-VL

›Sundar S et al. Short-Course Multidrug Treatment vs. Standard Therapy for VL in India. Lancet. 2011

›Non-inferiority RCT supporting combination approaches in South Asia

›Diagnostic studies

›Boelaert M et al. Rapid Tests for Diagnosis of VL in Patients With Suspected Disease. Cochrane Database Syst Rev. 2014

›rK39 RDT validated as best-performing rapid diagnostic tool

›Sensitivity varies by region and immune status

›Epidemiologic and surveillance

›Pareyn M et al. Leishmaniasis. Nature Reviews Disease Primers. 2025

›Comprehensive updated review of all forms of leishmaniasis

›Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet. 2018

›Seminal review with epidemiology, pathophysiology, and treatment

›Coffeng LE et al. Effect of Indoor Residual Spraying on VL Incidence in India 2016–2022. Lancet Infect Dis. 2024

Evidence & Review