eMedicine Specialties > Infectious Diseases > Parasitic Infections

Leishmaniasis: Differential Diagnoses & Workup

Author: Craig G Stark, MD, Regional Medical Director, Northern Europe and Russia Regions, Tricare Medical Director for Western Hemisphere, International SOS Assistance UK, Ltd
Contributor Information and Disclosures

Updated: Mar 27, 2008

Differential Diagnoses

Acute Lymphoblastic Leukemia
Paracoccidioidomycosis
Acute Myelogenous Leukemia
Pinta
Basal Cell Carcinoma
Sarcoidosis
Blastomycosis
Sporotrichosis
Chronic Lymphocytic Leukemia
Staphylococcal Infections
Chronic Myelogenous Leukemia
Streptococcus Group A Infections
Histoplasmosis
Syphilis
HIV Disease
Systemic Lupus Erythematosus
Impetigo
Tuberculosis
Leprosy
Tularemia
Lymphoma, Cutaneous T-Cell
Typhoid Fever
Malaria
Yaws
Metastatic Cancer, Unknown Primary Site
Mycobacterium Avium-Intracellulare
Mycobacterium Marinum

Other Problems to Be Considered

Cutaneous leishmaniasis

Fungal – Paracoccidioidomycosis, chromoblastomycosis, sporotrichosis, blastomycosis

Bacterial – Staphylococcal and streptococcal infections, pinta, yaws, syphilis, tuberculosis, leprosy, cutaneous diphtheria, tularemia, tropical pyoderma, and other mycobacterioses

Viral -Orf

Inflammatory - Sarcoidosis, pyogenic granuloma, lupus

Neoplastic - Cutaneous T-cell lymphoma, basal cell carcinoma, squamous cell carcinoma, metastases, Psoriasis, Keloids

Mucocutaneous leishmaniasis

Paracoccidioidomycosis
Sporotrichosis
Histoplasmosis
Blastomycosis
Lethal midline granuloma
Carcinoma
Tuberculosis
Tertiary syphilis
Yaws
Rhinoscleroma

Visceral leishmaniasis

Leukemia
Lymphoma
Bacterial, fungal, parasitic, and viral infections, including HIV, malaria, tuberculosis, and typhoid fever

Workup

Laboratory Studies

  • Historically, the diagnosis of leishmaniasis has been confirmed by isolating, visualizing, and culturing the parasite from infected tissue. Over recent years, significant advances in polymerase chain reaction (PCR) techniques have allowed for the highly sensitive and rapid diagnosis of specific Leishmania species. Although currently limited to military and reference laboratories, leishmania PCR diagnosis is becoming more widely available in developing-world laboratories and field sites.
  • Serological detection of antibodies to recombinant K39 antigen using a direct agglutination test, immunofluorescence assay, or enzyme-linked immunosorbent assay (ELISA) have been shown to be highly sensitive and specific in diagnosing visceral leishmaniasis.4 Recombinant K39 reactivity appears to correlate with active visceral disease caused by L donovani, L chagasi, and L infantum and is absent in cutaneous and mucocutaneous infections. Recent studies have confirmed its diagnostic utility in India and Brazil but have showed limited utility in Sudan because of regional species variance.5,6,7
  • Cutaneous and mucocutaneous forms generally display normal laboratory values.
  • Visceral leishmaniasis 
    • Complete blood cell (CBC) count: Normocytic normochromic anemia, leukopenia with decreased neutrophils, and thrombocytopenia may occur due to parasitic bone-marrow infiltration. The severity of pancytopenia may vary with only 1 or 2 cell lines decreased.
    • Serum plasma electrophoresis (SPEP): An elevated serum immunoglobulin level with polyclonal spike may be present. Visceral leishmaniasis was traditionally diagnosed based on the addition of formaldehyde to a serum sample, which would increase the viscosity secondary to excessive immunoglobulins.
    • Liver function tests (LFTs): The patient may exhibit mild elevations in alkaline phosphatase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels.
    • Coagulation panel: Prothrombin and partial thromboplastin times are generally normal.

Other Tests

  • Additional investigational diagnostic techniques include monoclonal antibody immunofluorescence, molecular analysis of kinetoplast DNA, rapid diagnostic antibody detection dipstick against rK39 antigen, and ELISA identification of exoantigens. Novel recombinant DNA-derived leishmania proteins are currently under intense review for their use in future rapid diagnostic kits.
  • The Montenegro skin test is similar to the purified protein derivative (PPD) and has been used in the developing world to determine delayed-type hypersensitivity reactions. Injected intradermally, a 5-mm area of induration suggests past infection. In most cases, it is made locally from killed promastigotes. It is not approved for use in the United States.

Procedures

  • For cutaneous leishmaniasis, take a punch or wedge biopsy sample from a cutaneous sore from the raised edge of an active lesion where parasites are present. Avoid samples from the necrotic center. Additional tissue can be obtained through saline aspiration, tissue scrapings, or slit incisions.
  • For mucocutaneous leishmaniasis, tissue can be obtained through dental scrapings or mucosal granuloma biopsy, although parasites may be difficult to isolate.
  • For visceral leishmaniasis, the safest way to obtain tissue is through bone-marrow aspiration, although splenic aspiration may be used in cases that are difficult to diagnose. Splenic aspiration has a higher sensitivity but should be attempted only by experienced physicians. Contraindications include low platelet count, abnormal prothrombin time, and a spleen palpable 4 cm or less below the costophrenic angle. Additional tissue can be obtained through liver biopsy and lymph node dissection.
  • Once tissue is obtained, send touch preparations, tissue impression slides, and formalin-fixed paraffin sections for hematoxylin and eosin staining. Send touch preparations and aspirations for Giemsa staining, as well. Direct visualization of amastigotes with their red rodlike cytoplasmic kinetoplast is diagnostic and helps distinguish them from other parasites. Brown-Hopps staining has a higher sensitivity than other staining techniques.
  • Culture tissue samples and aspirates to aid further in diagnosis and speciation. Specimens may be cultured on Nicolle-Novy-MacNeal (NNN) medium, rabbit blood agar, Schneider Drosophila medium, or a multitude of specialized media to induce promastigote growth. Additional cultures can be performed by inoculating tissue into the footpad and nose of hamsters. Cultures usually take a few days to 2 weeks to demonstrate growth. In animal models, growth may take months. Positive culture results occur approximately 75% of the time.
  • With successful culture, the parasite can be sent to specialized facilities or the CDC for PCR, isoenzyme electrophoresis, or monoclonal antibody speciation.

More on Leishmaniasis

Overview: Leishmaniasis
Differential Diagnoses & Workup: Leishmaniasis
Treatment & Medication: Leishmaniasis
Follow-up: Leishmaniasis
Multimedia: Leishmaniasis
References
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Further Reading

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Keywords

leishmaniasis, cutaneous leishmaniasis, mucosal leishmaniasis, visceral leishmaniasis, dermal leishmaniasis, post-kala-azar dermal leishmaniasis, leishmaniasis recidivans, mucocutaneous leishmaniasis, viscerotropic leishmaniasis, black fever, kala-azar, forest yaws, Aleppo evil, Baghdad sore, Biskra button, Chiclero ulcer, Delhi boil, Oriental sore, Rose of Jericho, Uta, dumdum fever, Assam fever, infantile splenomegaly

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Contributor Information and Disclosures

Author

Craig G Stark, MD, Regional Medical Director, Northern Europe and Russia Regions, Tricare Medical Director for Western Hemisphere, International SOS Assistance UK, Ltd
Craig G Stark, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, International Society of Travel Medicine, Phi Beta Kappa, and Society of US Army Flight Surgeons
Disclosure: Nothing to disclose.

Medical Editor

Pranatharthi Haran Chandrasekar, MD, Director of Infectious Disease Fellowship, Professor, Department of Internal Medicine, Harper Hospital, Wayne State University School of Medicine
Pranatharthi Haran Chandrasekar, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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