Topic
Visceral leishmaniasis
About: Visceral leishmaniasis is a research topic. Over the lifetime, 7486 publications have been published within this topic receiving 184865 citations. The topic is also known as: Kala-Azar & viscus leishmaniasis.
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22 Apr 2016
TL;DR: Fexinidazole and PA-824 are new promising drugs which have shown encouraging results in preclinical studies and are being considered as potential treatments for visceral leishmaniasis.
Abstract: Limited therapeutic options in visceral leishmaniasis (VL) make the treatment of this neglected disease very challenging. In addition to this, long treatment duration and toxic adverse effects make it even more difficult. With no effective vaccine available to date, treatment of VL is based only on chemotherapy. In the Indian subcontinent, a single dose of liposomal amphotericin B (L-AmB) and multidrug therapy (L-AmB + miltefosine, L-AmB + paromomycin [PM], or miltefosine + PM) are the treatments of choice for VL. In East Africa, however, combination therapy of pentavalent antimonials (Sbv) and PM remains the treatment of choice, and in the Mediterranean region and South America, L-AmB is the recommended drug. Fexinidazole and PA-824 are new promising drugs which have shown encouraging results in preclinical studies.
95 citations
TL;DR: The results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-gamma production prior and after challenge.
95 citations
TL;DR: Polyclonal B‐cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention.
Abstract: In visceral leishmaniasis, the draining LN (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with Leishmania infantum. Although not unexpected, at early times post-infection there is a marked B-cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti-leishmania response. Although B-cell-deficient JhD BALB/c mice are relatively resistant to infection, neither B-cell-derived IL-10 nor B-cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JhD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non-specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JhD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to WT BALB/c mice as early as 2 days post-infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5a receptor (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL-10 or IFN-gamma). Overall these studies indicate that polyclonal B-cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention.
95 citations
TL;DR: Evidence is provided for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis and the data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients.
95 citations
TL;DR: Although there is an apparent lack of clinical symptoms in these dogs, asymptomatic animals harbor a chronic L. infantum infection and as such consist a ‘dangerous’ reservoir with regard to the spread of the disease.
Abstract: Leishmania (L.) infantum is the etiological agent of human and canine visceral leishmaniasis in the Mediterranean subregion. Domestic dogs are the main reservoir of the parasite in most urban areas. A survey of 1638 asymptomatic dogs registered in Greater Athens area was carried out in the Hellenic Pasteur Institute during the period 1986-1994 to investigate the prevalence of canine visceral leishmaniasis in apparently healthy dogs. Dog sera was tested using the indirect fluorescent antibody technique (IFAT). Of the 1638 dogs, 366 (22.4%) had anti-Leishmania infantum antibodies at titre greater than or equal to 1/200 which were considered positive; 53 (3.2%) had antibody titres of 1/100 and were considered uncertain; and 1219 (74.4%) dogs were seronegative. From the 366 seropositive dogs, 212 were positive at 1/1600 serum dilution, 57 at 1/800, 38 at 1/400 and 59 at 1/200. The results were plotted according the site of residence, breed and age. The rate of asymptomatic infections with L. infantum dogs in Greater Athens area appears to be significantly high. Although there is an apparent lack of clinical symptoms in these dogs, asymptomatic animals harbor a chronic L. infantum infection and as such consist a 'dangerous' reservoir with regard to the spread of the disease.
95 citations