Effect of new diamidines against Leishmania donovani infection.

The impact of interamidine distance on antileishmanial activity of new aryldiamidines have been evaluated against amastigotes of L. donovani in hamster. Of the 20 compounds tested, only four (2,8-diamidino-9,10-dihydrodibenzoxepin; 2,7-diamidinoxanthone; 2,7-diamidinothioxanthone and 2,7-diamidinoxanthene) showed significant inhibition (more than 80%) of multiplication of amastigotes in spleen. The interamidine distance in the structure appears to have bearing on antileishmanial activity. The observations made are likely to evoke new understanding on the structure activity relationship of diarylamidines.

Studies on the infectivity of gametocytes of Plasmodium berghei (NK 65) in Anopheles stephensi.

The infectivity of gametocytes of Plasmodium berghei (NK 65) has been studied in laboratory bred Anopheles stephensi. Mosquitoes were fed daily on infected male and female Mastomys natalensis and subsequent development of the oocysts was monitored in the midguts. Maximum number of oocysts were found in mosquitoes which were fed on infected female mastomys on D8 and in male mastomys on D7 post-inoculation. During the next peak of gametocytaemia, very few oocysts developed. These findings suggest that gametocytes are maximally infective only during the first peak, later on their infectivity declines although having sufficient number of gametocytes in the circulation.

Reversal of T-cell unresponsiveness through serine-esterase inhibitors mediated enhanced lymphokine induced microbicidal activities in kala-azar.

After presenting processed glycoprotein of Leishmania donovani to T-cell, macrophage seeks the help of a panel of T-cells lymphokines to transform from a state that sustains intra cellular replication of parasite to an effector state for destructing parasites. But esterase and trypsin of macrophage membrane prevent T-cells to release MIF. Role of soya-bean trypsin inhibitor (STI) has been exposed in the present study with a view to alter esterase functional behaviour of macrophage for control of T-cell activation and also, if T-cells once made responsive to antigen by STI do alter macrophage response to T-cells or not. Results establish STI as potent effector molecule, which can serve as an adjuvant to candidate T-cell epitope and synthetic peptide for development of anti-Kala-azar vaccine protocol in future.

Epidemiology of kala-azar in rural Bihar (India) using village as a component unit of study.

It is assumed that some features like intra-macrophage habitat of the Leishmania parasites, rare availability of infected macrophages in peripheral blood for vector sandflies to suck in, short flight range of sandflies, non-availability of an animal reservoir encountered in visceral leishmaniasis indicate slow and limited transmission potential and even so epidemics occur every 15 to 20 yr. To verify if these assumptions are true, the natural history of kala-azar was studied, using an endemic village in Bihar (India) as an unit of study, over a period of 5 yr (1984-1988). Village Jethuli is bound by the river Ganga on the north and separated from neighbouring endemic villages on other three sides by agricultural land, is isolated entomologically (as regards sandflies). The village has a population of 3236 persons of different social status and depending on economic conditions have three types of dwellings, brick made with cement plaster, brick made with mud plaster and mud houses. The first case of kala-azar was reported in a migrant from district Vaishali on the other side of Ganga where kala-azar appeared in an epidemic form. Studies showed that the infection is built up slowly, first in the same house and then in the immediate neighbourhood. In this village, maximum number of cases occurred in 1984 and 1985, and they were treated by our Institute and cured. In subsequent years, only a few cases occurred (i.e., 6 in 1986 and 4 in 1987) while no case occurred in 1988.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative grading of Leishmania donovani amastigotes related to age of kala-azar patients.

Out of 370 Leishman Donovan bodies positive bone-marrow smears, maximum belonged to grade 1 + (42.4 per cent) and the least to grade 5 + (1.6 per cent). Persons belonging to 0-20 years age group were found in be statistically more susceptible to Leishmania infection as compared to persons above 20 years of age (P less than .01). The disease was least common in persons above 40 years (3.5 per cent) of age. Parasite load was found to be highest in 0-20 years group irrespective of grades of leishmania infection. Grade 5 + infection was found to be rare (1.6 per cent) and confined to 0-20 years age group. Males suffered from the disease predominantly (69.2 per cent) as compared to females (30.8 per cent).

In vitro culture of erythrocytic stages, including gametocytes of Plasmodium berghei (NK 65 strain) using candle jar method and a newly designed continuous medium flow apparatus.

Three methods have been described for cultivation of erythrocytic stages, specially gametocytes of P. berghei NK65 strain, (1) by using vial candle jar where the cultures were subcultured by addition of fresh erythrocytes, (2) a newly designed simple and compact continuous medium flow apparatus, where medium was continuously perfused but fresh erythrocytes were not added and (3) where the subcultures were also done using simple and compact continuous medium flow apparatus for comparison. The maximum percentage of parasitized erythrocytes obtained by these methods was 24.3, 27.1 and 26.4% respectively. Parasites in vials could survive for more than 10 days with 3 to 4 subcultures with maximum 1.96% gametocytaemia. However, the gametocytaemia in continuous medium flow apparatus, where subcultures were not made reached 2.2% compared to that of 2.7% in this apparatus where subcultures were done. The asexual as well as sexual stages of this parasite survived for about 16-18 days in compact continuous medium flow apparatus, where at least 7 subcultures were done.

Ontogeny of ookinete of Plasmodium berghei (NK 65): a scanning electron microscopic study.

The ontogeny of ookinete of Plasmodium berghei (NK 65) was studied in vector Anopheles stephensi fed on infected Mastomys natalensis. The round zygote transformed into an ookinete after passing through following stages-1 gram-seed shaped zygote, 2 comma-shaped stage, 3 semilunar and 4 banana shaped ookinete. Each fully formed ookinete had a 'Conule' at the anterior end of the body. In some ookinetes under SEM a depression was observed in the posterior half of the body. The function of the depression was not known.

Comparative analysis of surface components of adult, micro-filariae and infective larvae of Brugia malayi.

A comparative analysis of surface proteins of adult, microfilariae and infective larvae of Brugia malayi, the human filarial parasite, has been carried out using IODOGEN (1,3,4,6-tetrachloro-3,alpha 6 alpha-diphenyl-glycoluril) and lactoperoxidase methods. SDS-polyacrylamide gel electrophoretic and autoradiographic analyses revealed the presence of 9 proteins (15-200 kDa) in adults, while microfilariae and infective larvae showed 8 and 6 proteins (15-120 kDa), respectively. The pattern of proteins radiolabelled by IODOGEN method was very similar to that of proteins labelled by the lactoperoxidase method. Since these proteins are released by the protease treatment of whole parasites, they are likely to be present on the surface of the parasite.