Leishmania infections damage the feeding mechanism of the sandfly vector and implement parasite transmission by bite.

Abstract

Leishmania parasites are transmitted by the bites of infected female sandflles by a mechanism that has not been clarified. Leishmania infections in the vector develop only in the gut, and the parasites' exit is through the food channel in the proboscis. The problem is how during the bite, when blood flows in, parasites are emitted through the same channel in the opposite direction. It is well documented that infected sandfles maintained on sugar diets are potent vectors, whereas transmission fails after constant feeding on blood. Hence to study the mechanism of transmision, we fed these diets to Phkibotomus papatasi infected with L. maor. Histological examination demonstrated that only in the sugar-fed flies did the cuticle lining of the cardiac valve detach and other valve tissues degenerate gradually. The ijury of the main valve of the food pumps hindered gorging of most flies when force-fed from capillaries, and they regurgitated the gut contents with fluids from the capillaries. We suggest that infections are caused by parasites regurgitated from the stomach that are deposited in the host tissue. We found that secretion of chitinolytic enzymes by cultured L. major parasites is inhibited by blood or hemoglobin, and hence these enzymes are apparently absent from the blood-fed infected flies, where the cardiac valve appears undamaged. We therefore presume that lysis ofthe chitin in the cuticle lining of the valve leads to exposure and degeneration of the underlying tissues.Protozoa parasites of the genus Leishmania (Kinetoplastida: Trypanosomatidae) are causative agents of several diseases that are important public health problems in many countries. The vectors of these parasites are sandflies, and they infect humans and animal reservoirs of the diseases. The developmental cycle ofLeishmania in the sandfly is exclusively in the gut, and parasites reach the host tissue via the food channel in the proboscis. During the bite of infected sandflies the ingested blood is pumped into the gut while at the same time and through the same channel, parasites are deposited in the opposite direction. Evidently, in this system the transmission of the parasites is not implemented by the normal process of ingestion, and additional factors have to be involved. The common opinion was that transmission depends on the presence of parasites in part of the feeding system of the sandfly. The debate was whether parasites facilitate transmission by disturbing the flow of ingested blood or whether they are directly deposited from the proboscis by the act of probing (reviewed in refs. 1-7). These theories were not correlated to transmission experiments, and both the manner and the circumstances of transmission were (8) and still are (9) a major problem in the study of leishmaniasis. We have previously reported that Leishmania major infections in the vector Phlebotomus papatasi cause degeneration of the cardiac valve, the main valve of the feeding system, presum-

Quantification of the infectious dose ofLeishmania majortransmitted to the skin by single sand flies

“…This finding suggests that parasites in the foregut or associated with the anterior aspects of the open valve may have been more passively transmitted as a result of the backflow of the ingested meal rather then a more forceful regurgitation of parasites from behind the stomodeal valve. This may occur, as suggested by Schlein et al (13), when the parasites disrupt the coordinated action of the pharyngeal and esophygeal pumps or even when the feeding pumps are functioning normally. Thus, the source of low-dose inocula is expected to be flies that experience interrupted feeding and abandon their feeding attempts or that ultimately succeed in engorgement without dislodging parasites in the plug.…”

“…Each of these conditions is consistent with the ''blocked-fly'' hypothesis, proposed by Shortt and Swaminath in 1928 (9) and refined in the context of parasite-secreted molecules that contribute to the formation of a biological plug (4). It has been consistently noted that heavily infected sand flies experience difficulty in feeding (10)(11)(12), which is associated with the stomodeal valve being forced open by the pressure of the plug (4) and/or by direct damage to the valve as a consequence of a chitinase secreted by attached promastigotes (13)(14)(15). From the current data, it seems clear that an especially heavy anterior midgut infection promotes the conditions under which a substantial fraction of the parasites can become mobilized for egestion, possibly associated with a reflux of parasites during attempts by the fly to dislodge the plug.…”

Species Diversity and Flagellate Infections in the Sand Fly Fauna near Porto Grande, State of Amapá, Brazil (Diptera: Psychodidae. Kinetoplastida: Trypanosomatidae)

“…Evidence exists for at least two mechanisms for the transmission of Leishmania by bite in the absence of invasion of the vectors' salivary glands (Killick-Kendrick 1979, Schlein et al 1992). However, Killick-Kendrick et al (1996) obtained experimental salivary gland infections in Phlebotomus duboscqi that had been allowed to feed on a suspension of Le.…”

The Non-catalytic Chitin-binding Protein CBP21 from Serratia marcescens Is Essential for Chitin Degradation

“…Analogous processes are thought to occur in other protozoan parasites, e.g. Leishmania (19). A final example concerns insect viruses, which produce chitinases to disintegrate the peritrophic matrix of their target organism, thereby increasing virus infectiousness (20).…”