Bioactivity guided fractionation of Moringa oleifera Lam. flower targeting Leishmania donovani.

Leishmaniases is a group of diseases caused by the protozoan parasite belonging to the genus Leishmania. At least 20 species of Leishmania are known to infect humans transmitted by female sandflies, Phlebotomus spp. Leishmania donovani causes visceral leishmaniasis, considered most lethal among the common three forms of leishmaniasis. Lack of appropriate vaccines, emergence of drug resistance and side effects of currently used drugs stress the need for better alternative drugs, particularly from natural sources. Here, we conducted in vitro and in vivo experiments to study the efficacy of different parts of Moringa oleifera Lam. against Leishmania donovani promastigotes. The flower extract of M. oliefera (MoF) was found to be the most potent antileishmanial agent when compared to other parts of the plant like leaf, root, bark and stem. It imparted significant reduction in parasite number in infected macrophages. The bioactivity guided fractionation of MoF showed ethyl acetate fraction (MoE) as the most active and gave significant parasite reduction in the infected macrophages. Further, growth kinetics studies revealed loss of L. donovani promastigotes viability in the presence of MoE in both time and dose dependent manner. In vivo experiment in Balb/c mouse model of leishmaniasis supported the in vitro findings with a remarkable reduction of the parasite burden in both liver and spleen.

Antileishmanial efficacy of Boerhaavia diffusa L. and Ocimum sanctum L. against experimental visceral leishmaniasis.

The chemotherapy of visceral leishmaniasis (VL) has several limitations including resistance and toxicity of the existing drugs. Down regulation of immune system further aggravates the problems. To combat this situation we evaluated the leishmanicidal efficacy of Boerhaavia diffusa and Ocimum sanctum through oral route in L. donovani infection in BALB/c mice. Results have demonstrated maximum clearance of the parasites from infected animals treated with combination of B. diffusa and O. sanctum (@ 100 and 400 mg/kg body wt., respectively 5 days) as depicted through Leishman Donovan Units in liver. Up-regulation of cell-mediated immunity was also observed in animals of this group as heightened delayed type hypersensitivity responses and increased IgG2a levels were observed. Moreover, increased levels of SGOT, SGPT, serum urea, blood urea nitrogen and serum creatinine were brought down to normal levels. Since VL is associated immunosuppression, the above treatment is a good option as it helps in the up-regulation of Th1 responses and reduction in parasite load in L. donovani infected mice. These findings suggest a new option for antileishmanial chemotherapy at lower cost and nil toxicity.

Identification and glycobiological characterization of circulating immune complexes in patients with visceral leishmaniasis and post kala azar dermal leishmaniasis.

Here, we investigated the quantitative and qualitative differences in antibody classes and subclasses in serum immune complexes (ICs) of Visceral Leishmaniasis (VL), Post Kala-azar Dermal Leishmaniasis (PKDL) and different cross reactive diseases like Malaria, Leprosy, Vitiligo as compared to control subjects. IC levels were measured through a newly developed PEG ELISA, using L. donovani promastigote membrane antigen coated plate. Antibody classes and subclasses were identified using polyspecific sera and monoclonal antibodies, respectively. ICs were purified using polyethylene glycol (PEG) precipitation. Conditional logistic regression showed an association between IgG1-containing ICs and increased risk of PKDL (OR=75, P <0.05) and an association of IgG-containing ICs with VL (OR=621, P=0.001). PEG ELISA demonstrated almost 13-15 fold higher IgG containing ICs titers in VL as compared to control (P <0.001). The assay further established a significant (P <0.05) difference in the IgG containing ICs titers between VL and PKDL. The isolated ICs were further analyzed by subjecting them to one-dimensional PAGE and subsequently stained with combination of periodic acid schiff (PAS) with silver. A differential banding pattern between VL and PKDL was obtained. Four distinct bands with carbohydrate rich glycoconjugates were identified in PKDL ICs, which were absent in VL and control group. It suggests the scope for developing a novel differential diagnostic assay.

Visceral Leishmaniasis (Kala Azar) Elimination from Indian Sub-continent by 2015.

Objective: To review the progress towards the goal of elimination of visceral leishmaniasis (Kala azar) from the Indian sub-continent by 2015. Method: Both electronic and print databases were searched for studies related to Kala azar. Finding: The burden of Kala azar is grossly underestimated by the health systems in the Indian sub-continent due to over-reliance on passive surveillance. Poly-parasitism and co-infections are the major emerging problems in the world of Kala azar. Resistance has been reported for DDT indoor residual spraying. Treatment drugs are not ideal, and supplies of these drugs are irregular as well. Conclusion: Achievement of elimination of Kala azar from Indian sub-continent is still unpredictable. To improve the elimination of Kala azar it should be classified as a notifiable disease. There is a need to refocus current strategies and monitor the program more closely. Furthermore, there is a need to assess alternative vector control methods. Policies to control Kala azar will have to include health education and behaviour change. Kala azar may not affect the national economy or the national GDP, but it devastates the families affected.

A evolução do conhecimento sobre as hepatites virais na região amazônica: da epidemiologia e etiologia à prevenção / The evolution of knowledge about viral hepatitis in Amazon region: from epidemiology and etiology to the prophilaxy

Desde os anos cinqüenta uma doença similar a febre amarela, porém considerada como nova doença, ocorre em áreas dos vales dos Rios Juruá, Purus e Madeira. Temida pelos residentes locais pela alta letalidade, sendo clinicamente uma hepato-encefalopatia de evolução fulminante (média de 5 a 6 dias). Dos que apresentam manifestações neurológicas 90% evoluem a óbito. A doença é popularmente conhecida como febre negra de Lábrea e pelos patologistas como hepatite de Lábrea pela histopatologia hepática mostrar o aspecto vacuolar dos hepatócitos, daí considerarem-na uma nova doença. Incide principalmente em crianças e adolescentes do sexo masculino. O achado do HBsAg e de marcadores de vírus da hepatite D no soro e fígado dos pacientes, levaram os pesquisadores a considerarem a febre negra de Lábrea como uma superinfecção ou coinfecção do HDV. Na falta de vacina específica contra o HDV, a vacinação contra hepatite B aplicada após o nascimento é a prevenção recomendada.

Since the 1950 years a disease similar to yellow fever but thought to be a new disease with unknown etiology has been described to health and researcher authorities. This disease occurs in Jurua, Purus and Madeira Rivers valleys. It´is feared by local people by its high lethality. It´is clinically a hepato-encephalopathy (Average survival time of 5-6 days) About 90% of sick people with typical symptoms go to death. The disease is popularly known as black fever of Lábrea and by pathologist as Lábrea hepatites after the city where the first cases were observed. The specifc histopatologic picture of vesicular degeneration of hepatocytes like spider cells motivate the local pathologist to think as a new disease: Lábrea hepatitis. The finding of HBsAg and marker of hepatites D vírus (HDV) in the serum motivate the researchers to think the disease as a superinfection of HDV in chronic carriers of HBV. In absence of a specific vaccine against HDV, the vaccine against HBV, must be given soon after the birth is the recommended prevention.