Biology and Infection of Leishmania

Leishmania

The causative agent of leishmanioses

Leishmanias are transmitted by using sandflies (Phlebotomidal) and purpose the following most important kinds of leishmanioses in warm regions: visceral leishmanioses (VL), cutaneous leishmanioses (oriental sore) (CL), and mucocutaneous leishmanioses (MCL). In crucial Europe, leishmaniosis is of importance as an imported disorder and as an HIV-related contamination.

Occurrence

Diverse forms of leishmanioses arise within the hotter areas of 88 nations in Asia, Africa, Europe (Mediterranean countries!), and Latin the USA . The yearly quantity of latest instances is envisioned at 1.5–2 million (0.5 million VL, 1–1.5 million CL and MCL). Both geographic distribution and case numbers are stated to be at the growth (WHO, 2000). Parasites and life cycle. The various (about 15) species of the genus Leishmania pathogenic to people do now not show morphological differences. They can be differentiated on the premise of organic criteria, laboratory analyses (specifically isoenzyme styles and DNA analysis), the distinct clinical photographs, and epidemiological records .

In people and different vertebrates, leishmanias parasitize in mononuclear phagocytic cells (macrophages, monocytes, Langerhans cells) within the amastigote form. The Giemsa-stained organisms are recognizable under a light microscope as spherical-to-oval cells 2–five lm in diameter with a nucleus and a small, rod-shaped kinetoplast. A rudimentary flagellum, mitochondrion, and other cellular organelles also are rendered seen on the electron microscopic level.

The leishmania species are transmitted by female mosquitoes of the genera Phlebotomus (antique global) and Lutzomyia (New international) known as “sandflies”. The amastigote levels of the parasite ingested through the insect with a blood meal are converted in its intestine into slender, flagellated promastigote forms 10–15 cm long, which multiply and migrate returned into the proboscis. At tropical temperatures, this method takes five to eight days.When infected sandflies take some other blood meal the promastigote forms are inoculated into a new host (humans or other vertebrates). Inside the host, they bind host components to their surfaces (IgM, complement, erythrocyte receptor) and, for this reason ready, couple to macrophage receptors. They are then phagocytosed and enclosed in a phagolysosome, wherein they may be covered from the outcomes of lysosomal enzymes inter alia by substances in their cell membrane. The promastigotes quickly (inside 12–14 hours) remodel into amastigote stages, that are subsequently surrounded by using a parasitophorous vacuole within the phagolysosome and reproduce with the aid of binary fission. The amastigote form is then released in a procedure akin to exocytosis and can infect new cells.

Clinical manifestations and immunology

It's far essential to note that during CL and MCL the parasites usually remain restricted to the pores and skin or pores and skin and mucosa. CL lesions might also persist for lengthy durations, however, tend to heal spontaneously, while a greater tendency to destructive changes is visible in MCL infections. By way of contrast, in VL the leishmania organisms can invade the complete mononuclear phagocytic system in diverse organs (spleen, liver, lymph nodes, bone marrow, blood monocytes, and so forth.), causing infections that are commonly deadly with out treatment.

Fundamental studies the usage of animal models has supplied and reason behind these differences is the course of a contamination is outwardly depending on the activation of diverse T lymphocyte subpopulations with the aid of Leishmania antigens. Activation of TH1 cells involves the production of IFNc, which turns on macrophages that exert a defensive impact with the aid of killing Leishmania organisms via a nitric oxide-mediated mechanism. on the other hand, whilst TH2 cells are activated massive quantities of IL-four and IL-10 are produced, which inhibit NO pastime, hence reducing or maybe preventing elimination of the parasites. Production of antibodies is also significantly multiplied, however, they do no longer play a great position in immune protection. Findings in patients are according to with these interpretations: in CL, excessive concentrations of IFNc have been determined, but in extreme instances of VL the levels of IL-4 and IL-10 have been raised and IFNc concentrations were low. The state of affairs is comparable in excessive kinds of MCL.

It'd appear that the cell-mediated immune response in CL protects successfully, but the immune reaction in advanced VL and a few forms of MCL is more or less suppressed. In cases in which the immune defenses are moreover weakened via AIDS, a latent Leishmania infection may be activated and take a fulminant symptomatic direction. In endemic areas, the danger to collect a Leishmania contamination is multiplied for AIDS patients via one hundred–a thousand times. Most of the cases of AIDS-related leishmaniosis (about 50%) registered thus far (1990–1998) were stated from regions in which L. infant is endemic in southwestern Europe (Italy, France, Spain, Portugal) (others from India, Africa, Latin the us, and many others.) (WHO, 1999). except for L. infant, coinfections with different Leishmania species have additionally been discovered in AIDS sufferers (e.g., L. donovani, L. Brazilians is, L. tropical).

Epidemiology

In Europe, leishmaniosis merits interest as a travelers’ disease, especially the VL imported from Mediterranean countries. foremost VL epidemics have taken place lately in numerous elements of the sector, e.g., in southern Sudan with one hundred deaths in a populace of <1 million (WHO, 2000).

Prognosis

An etiological analysis of VL is made through direct parasite detection in aspirate cloth from lymph nodes or bone marrow (in HIV patients additionally within the enriched blood leukocyte fraction) in Giemsa-stained smears , in cultures (wherein promastigotes develop) or using PCR. Cultivation and PCR have approximately the identical high degree of sensitivity. Antibodies are detectable in almost all immunocompetent patients (round ninety-nine%), but 40–50% of HIV-coinfected patients are seronegative .

Analysis of a cutaneous leishmaniosis is commonly based totally on clinical evidence. Etiological verification calls for direct parasite detection (see above) in smears or excised specimens from the rims of the pores and skin lesions. Extra reliably, the parasites may be detected by using cultivation or PCR. Serological antibody checks are wonderful in simplest a small percentage of instances.

Therapy and prevention

Treatment of VL is usually completed with pentavalent antimonials (meglumine antimonate, sodium stibogluconate) pentamidine, or amphotericin B. The recurrence rate is exceptionally excessive, mainly in HIV patients. Miltefosine, a newly developed and nicely tolerated antitumor alkyl phospholipid for the oral drug , has proved powerful against VL. Numerous types of CL (as an example L. principal and L. tropical) can be inspired by injecting antimonial preparations into the lesions; mucocutaneous leishmaniosis (L. braziliensis) is dealt with systemically with antimonials (see above, amphotericin B, or pentamidine). A powerful chemoprophylaxis has now not but been advanced. It's miles consequently essential to prevent Phlebotome bites with finemeshed, insecticide-impregnated “mosquito nets” (p. 535). control of the vectors includes the use of pesticides and elimination of breeding locations.

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M Cheesbrugh.Medical laboratory manual for tropical countries.London, 2007