Visceral Leishmaniasis
Section snippets
Epidemiology and transmission
VL is transmitted through the bite of female hematophageous sand flies from the genus phlebotomus in the old world and Lutzomiya in the new world. At the global level, there are over 10 species of sand flies playing a role in the transmission of VL, with at least 1 species involved per geographic region.1, 2 The adult fly, about 2 to 4 mm long, is most active during dusk and night time. Resting sites are dark, moist places including soil cracks, termite hills, and other shady places. Whereas
Pathogenesis
The parasite exists in 2 distinct forms: a promastigote form found in the vector, and an amastigote form, which develops intracellularly in the susceptible mammalian host. Infection occurs after inoculation of promastigotes into the skin following the bite of an infected sand fly. Promastigotes are taken up by macrophages, where they develop into amastigotes and multiply within phagolysosomes (Fig. 2). Subsequently, the parasites can disseminate and infect cells of the reticuloendothelial
Clinical presentation
The incubation period for VL typically ranges from 2 to 6 months, but can vary from weeks to several years. Patients present with insidious onset fever, weight loss, and organomegaly that persists for months. Splenomegaly is prominent (Fig. 3). It is often soft on palpation and can complicate with infarction or spontaneous subcapsular bleeding. Hepatomegaly is less marked.2, 4 Lymphadenopathy is usually observed in Sudan but is rare in other endemic regions. Darkening of the skin is mainly
Parasitologic Diagnosis
The current gold standard for diagnosis relies on the visualization of the amastigote form of the parasite within macrophages by microscopic examination of tissue aspirates (spleen, bone marrow, or lymph nodes) after Giemsa staining (Fig. 5).1, 7 Whereas in Europe bone marrow aspiration is most commonly done, spleen aspiration is predominantly used in Africa and Asia, although the later is associated with a risk of life-threatening bleeding of around 0.1%. Specificity of microscopy is high, but
Treatment
Traditionally, treatment of VL has relied on the use of pentavalent antimonials (Sb5+), introduced in the 1940s.2, 13 From the 1980s on, conventional amphotericin B deoxycholate has been increasingly used in high-income countries. Subsequently, different lipid formulations of amphotericin B, most notably liposomal amphotericin B, have been developed, which combine a high efficacy with low toxicity.14 Liposomal amphotericin B is the only treatment approved by the US Food and Drug Administration
Preventive measures for travelers
No vaccine or chemoprophylaxis to prevent infection currently exists. Preventive measures are particularly important for individuals traveling in rural areas and in more primitive conditions, although the parasite has now also spread to peri-urban areas in some regions. Other people at risk include soldiers. Preventive measures aiming at reducing contact with sand flies include the use of (ideally insecticide-treated) bed nets and the use of insecticide sprays in the sleeping room. It is
VL-HIV coinfection
VL has emerged as an important opportunistic infection in VL-endemic areas in the era of HIV. The HIV epidemic has significantly influenced the epidemiology, the clinical manifestations, and course of VL. In return, VL also accelerates HIV disease progression by increasing the viral replication, leading to further immunosuppression. HIV contributed to the re-emergence of VL in Europe in the 1990s, with 50% to 60% of all VL cases coinfected at some point.3 Subsequently, VL-HIV coinfection was
Summary
VL is one of the major neglected infectious diseases. Whereas the development of rapid diagnostic tests has been a significant progress, non-invasive cheap tests to assess treatment response and diagnose relapse are currently lacking. Molecular testing is increasingly used in high-income countries. Significant progress has been made in terms of treatment, including the development of combination therapy. The emergence of drug resistance in disease-endemic countries is concerning and should be
References (36)
- et al.
Advances in leishmaniasis
Lancet
(2005) Leishmaniasis
Lancet
(1999)- et al.
Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda
Lancet Infect Dis
(2002) - et al.
Post-kala-azar dermal leishmaniasis
Lancet Infect Dis
(2003) - et al.
Diagnosis of visceral leishmaniasis
Trans R Soc Trop Med Hyg
(2011) - et al.
Chemotherapy in the treatment and control of leishmaniasis
Adv Parasitol
(2006) - et al.
Miltefosine–discovery of the antileishmanial activity of phospholipid derivatives
Trans R Soc Trop Med Hyg
(2006) - et al.
Unresponsiveness to AmBisome in some Sudanese patients with kala-azar
Trans R Soc Trop Med Hyg
(2007) - et al.
Paromomycin
Trans R Soc Trop Med Hyg
(2009) - et al.
Combination therapy for visceral leishmaniasis
Lancet Infect Dis
(2010)
Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment
Trans R Soc Trop Med Hyg
Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?
Nat Rev Microbiol
The relationship between leishmaniasis and AIDS: the second 10 years
Clin Microbiol Rev
Detection of leishmanial antigen in the urine of patients with visceral leishmaniasis by a latex agglutination test
Am J Trop Med Hyg
Molecular diagnosis of leishmaniasis: current status and future applications
J Clin Microbiol
Clinical use of polymerase chain reaction performed on peripheral blood and bone marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV-infected and HIV-uninfected patients: a single-center, 8-year experience in Italy and review of the literature
Clin Infect Dis
Reference values for Leishmania infantum parasitemia in different clinical presentations: quantitative polymerase chain reaction for therapeutic monitoring and patient follow-up
Am J Trop Med Hyg
Value of culture and nested polymerase chain reaction of blood in the prediction of relapses in patients co-infected with leishmania and human immunodeficiency virus
Am J Trop Med Hyg
Cited by (237)
Amphotericin B loaded nanoemulsion: Optimization, characterization and in-vitro activity against L. donovani promastigotes
2024, Parasitology InternationalPrevalence of HIV infection among visceral leishmaniasis patients in India: A systematic review and meta-analysis
2024, Clinical Epidemiology and Global HealthThe status of combination therapy for visceral leishmaniasis: an updated review
2024, The Lancet Infectious DiseasesMolecular-level strategic goals and repressors in Leishmaniasis – Integrated data to accelerate target-based heterocyclic scaffolds
2023, European Journal of Medicinal ChemistryHidden sources of bias in diagnostic studies: the example of visceral leishmaniasis in east Africa
2023, The Lancet Infectious Diseases
Conflict of interest: the authors have nothing to disclose.