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.

The diagnostic accuracy of serologic and molecular methods for detecting visceral leishmaniasis in HIV infected patients: meta-analysis.

Abstract: Background Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising. Objective This work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients. Methods Two independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). Results Thirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95–130.29) and Blot 27.51 (9.27–81.66) than for IFAT 7.43 (3.08–1791) and ELISA 3.06 (0.71–13.10). PCR in whole blood had the highest DOR: 400.35 (58.47–2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92–0.97, which means good overall performance. Conclusion Based mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup.

Visceral leishmaniasis control: a public health perspective.

Abstract: Visceral leishmaniasis (VL), also known as kala-azar, is a vector-borne disease caused by a protozoan of the Leishmania donovani complex. A phlebotomine sandfly transmits the parasite from person to person or via an animal reservoir. VL is a severe, debilitating disease, characterized by prolonged fever, splenomegaly, hypergammaglobulinaemia and pancytopenia. Patients become gradually ill over a period of a few months, and nearly always die if untreated. Case-fatality ratios are high even in treated patients. Worldwide an estimated 500 000 VL cases occur each year. This study reviews clinical, epidemiological and public health aspects of the disease and shows how critical adequate case detection is for the success of VL control. Examination of the issue of VL diagnosis with respect to the global challenges in VL control leads to the observation that a sound diagnostic-therapeutic algorithm for the health services in endemic areas is badly needed. Serological tests could be an alternative to parasitological diagnosis and the direct agglutination test (DAT) was found to fulfil many criteria for a ‘field test’, including cost effectiveness. Although research needs on vaccine and better drugs continue to be high on the agenda, a VL test-treatment strategy based on currently available highly sensitive serological tests, such as the DAT, should be introduced in the health services in endemic areas.

Successful Therapy of Lethal Murine Visceral Leishmaniasis with Cystatin Involves Up-Regulation of Nitric Oxide and a Favorable T Cell Response

Abstract: The virulence of Leishmania donovani in mammals depends at least in part on cysteine proteases because they play a key role in CD4 + T cell differentiation. A 6-fold increase in NO production was observed with 0.5 μM chicken cystatin, a natural cysteine protease inhibitor, in IFN-γ-activated macrophages. In a 45-day BALB/c mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by cystatin in synergistic activation with a suboptimal dose of IFN-γ. In contrast to the case with promastigotes, cystatin and IFN-γ inhibited the growth of amastigotes in macrophages. Although in vitro cystatin treatment of macrophages did not induce any NO generation, significantly enhanced amounts of NO were generated by macrophages of cystatin-treated animals. Their splenocytes secreted soluble factors required for the induction of NO biosynthesis, and the increased NO production was paralleled by a concomitant increase in antileishmanial activity. Moreover, splenocyte supernatants treated with anti-IFN-γ or anti-TNF-α Abs suppressed inducible NO generation, whereas i.v. administration of these anticytokine Abs along with combined therapy reversed protection against infection. mRNA expression and flow cytometric analysis of infected spleen cells suggested that cystatin and IFN-γ treatment, in addition to greatly reducing parasite numbers, resulted in reduced levels of IL-4 but increased levels of IL-12 and inducible NO synthase. Not only was this treatment curative when administered 15 days postinfection, but it also imparted resistance to reinfection. These studies provide a promising alternative for protection against leishmaniasis with a switch of CD4 + differentiation from Th2 to Th1, indicative of long-term resistance.

Evaluation of a newly developed direct agglutination test (DAT) for serodiagnosis and sero-epidemiological studies of visceral leishmaniasis: comparison with IFAT and ELISA

Abstract: A newly developed direct agglutination test (DAT) for visceral leishmaniasis, IFAT and ELISA were applied to sera of patients with visceral leishmaniasis, African and American trypanosomiasis, other parasitic infections and healthy controls. The sensitivities of the 3 tests were comparable (96.3% to 100%); excluding patients with African and American trypanosomiasis, the specificities of DAT and IFAT were 100% and ELISA 87.3%. When trypanosomiasis sera were included, the specificities were 72.6%, 94.3% and 79.4% in DAT, IFAT and ELISA respectively. In 273 sera from a leishmaniasis endemic area (Baringo District, Kenya), the sensitivity was 80% in DAT and IFAT and 60% in ELISA, specificities being 99.6% (DAT), 98.5% (IFAT) and 62.5% (ELISA). As the new DAT is economical and easy to perform, it is recommended for sero-epidemiological field work on visceral leishmaniasis.

Antileishmanial drug discovery: comprehensive review of the last 10 years

Abstract: Leishmaniasis, a group of diseases caused by hemoflagellate obligate intracellular protozoa (trypanosomatids) from the genus Leishmania, has not received the attention it deserves and has developed into a major health problem in developing countries. No effective vaccine is available against leishmaniasis, so chemotherapy is the only effective way to treat all forms of the disease. However, the drugs currently used for treatment of human cutaneous and visceral leishmaniasis are toxic, having severe adverse reactions which limit their use. Therefore, development of novel, effective, and safe antileishmanial agents, with reduced side effects, is a major priority for health researchers, and large numbers of research reports have been published on antileishmanial agents in the last 10 years. Herein, we comprehensively review the developments of the last decade, covering all aspects of leishmaniasis including clinically used drugs, various new classes of antileishmanial agents (synthetic as well as natural), patented antileishmanial agents, and possible drug targets.