Malaria Transmission Biology & the Development of Novel Interventions

Overview

It has been estimated that more than 1-2 million individuals succumb to Malaria every year, a majority of whom are children under the age of five.  Plasmodium parasites, the causative agent of malaria, are transmitted to a vertebrate host by the infective bite of an Anopheles mosquito.  Our current understanding of the epidemiology of malaria is summarized below.

Malaria Epidemiology

  • 2-2.7 million deaths/year
  • Over 2,700 deaths per day, or approx. 2 deaths/min (majority of the burden is in Sub-Saharan Africa).
  • Cerebral malaria/Pregnancy
  • Plasmodium parasites: P. falciparum, P. vivax, P. ovale , P. malariae, P. knowlesi
  • No vaccine currently available
  • Drugs are available but resistance among parasite strains is spreading quickly
  • Obligate mosquito vector: Anopheles mosquito species

 

Male and female Plasmodium gametocytes are taken up into the mosquito midgut during blood feeding.  The male microgametes (8) and single female macrogamete fuse to form a motile zygote, called an ookinete.  The ookinete then makes its way to the periphery where it makes contact with the apical midgut microvilli surface.  It first attaches itself to the midgut surface prior to midgut cell invasion.  Once the ookinete makes it through the midgut, it transforms into an oocyst just beneath the basal lamina. Inside the oocyst, thousands of sporozoites develop, and upon oocyst rupture are released into the hemocoel of the mosquito.  The sporozoites make their way to the salivary glands.  Once the sporozoites have invaded the salivary gland tissue, the mosquito is rendered infectious throughout its remaining life span.  At this stage, once the mosquito feeds on another human, the sporozoites are transferred to that individuals to begin the life cycle of the parasite in the vertebrate host.

Development of Plasmodium in the mosquito vector.

Anopheles gambiae (KEELE) female mosquito bloodfeeding to repletion, ~1:30 (from Rhoel Dinglasan on Vimeo).

Initial Binding of the Ookinete to the Midgut Surface

A hypothesized working model for Plasmodium ookinete binding to the mosquito midgut epithelium surface (produced and rendered by Betsy Weissbrod from Rhoel Dinglasan on Vimeo).

Anopheles gambiae Midgut GPI-anchored Alanyl Aminopeptidase N (AgAPN1)

DINGLASAN LABORATORY

EMERGING PATHOGENS INSTITUTE

THE UNIVERSITY OF FLORIDA

Department of Infectious Diseases & Pathology
COLLEGE OF VETERINARY MEDICINE
2055 Mowry Road, Rm 375
Tel. +1 (352) 294-8448 (OFFICE) / Tel. +1 (410) 294-8470 (LAB Rm. 320-326)

 

 

 

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