Visceral leishmaniasis pathophysiology

Jump to navigation Jump to search

Visceral leishmaniasis Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Visceral Leishmaniasis from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Visceral leishmaniasis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Visceral leishmaniasis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Visceral leishmaniasis pathophysiology

CDC on Visceral leishmaniasis pathophysiology

Visceral leishmaniasis pathophysiology in the news

Blogs on Visceral leishmaniasis pathophysiology

Directions to Hospitals Treating Visceral leishmaniasis

Risk calculators and risk factors for Visceral leishmaniasis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Pathophysiology

Life-cycle of the parasite

Kala-azar is spread through an insect vector, the sandfly of the Phlebotomus genus in the Old World and the Lutzomyia genus in the New World. Leishmania are tiny creatures, 3-6 micrometers long by 1.5-3 micrometers in diameter, and found in tropical or temperate regions throughout the world. Sand fly larvae grow in warm, moist organic matter, so old trees, house walls or garbage are their most common breeding centers — making them hard to eradicate.

The adult female sand fly is a bloodsucker, usually feeding at night on sleeping prey. When the fly bites an animal infected with L. donovani, the pathogen is ingested along with the prey’s blood. At this point the protozoan is in the smaller of its two forms, called an amastigote — round, non-motile, and only three to seven micrometers in diameter.

Taken into the stomach of the sandfly, the amastigotes quickly transform into a second L. donovani form, called the promastigote. This form is spindle-shaped, triple the size of the amastigote, and has a single flagellum that allows for motility. The promastigotes live extracellularly in the sandfly’s alimentary canal, reproducing asexually, then migrate to the proximal end of the gut where they become poised for a regurgitational transmission. This is their means of transmission back into a mammalian host, as the fly injects its saliva into prey when it bites. The promastigotes are introduced locally at the bite site along with the fly’s saliva.

Once inside the new host, promastigotes invade macrophages. Once inside, they transform back into the smaller amastigote form. As an amastigote, L. donovani can only reproduce intracellularly — and the amastigotes replicate in the most hostile part of the macrophage cell, inside the phagolysosome, whose normal defensive response they are able to prevent. After they have reproduced to a certain extent, the L. donovani lyse their host cell by sheer pressure of mass, but there is some recent speculation that they are able to leave the cell by triggering the exocytosis response of the macrophage. The daughter cell protozoans then migrate through the bloodstream to find new macrophage hosts. In time, L. donovani becomes a systemic infection, spreading to all the host’s organs, particularly the spleen and liver.

Disease progression

In human hosts, response to infection by L. donovani varies a great deal, not only by the strength but also by the type of the patient’s immune reaction. Patients whose immune systems produce large numbers of TH1-type T-Cells, which strengthen cell defenses but do not encourage antibody formation, often recover easily from infection on their own, and after recovery are immune to reinfection. Patients whose systems produce more TH2-type cells, which prompt antibody formation but do nothing for cellular health, are likely to quickly succumb to leishmaniasis. Sadly, some of the stronger strains of L. donovani appear to be able to force a switch in the host from a TH1 to a TH2-type immune response as the infection progresses.

References


Template:WikiDoc Sources