Malaria remains a potent killer to the human inhabitants of
the tropical regions in the so-called “undeveloped world.” This disease results in approximately one
million deaths a year in Africa, alone. An
insect vector, the female Anopheles mosquito that requires blood to mature its
eggs, is responsible for its transmission to humans. There are a host of human maladies caused by
such diverse organisms as viruses, protozoans and even worms that infect humans
and that are carried by mosquitoes and other insects.
The causative agent for human malaria is a parasite referred
to as Plasmodium falciparum. The life cycle
of P. falciparum is quite complex and intriguing. When it is first inadvertently ingested by
the mosquito from an infected host, the parasite undergoes a progression of
transformations. The specialized sexual
precursor cells – male and female - are rapidly activated to form complete and
functional sex cells – gametes. Male and
female gamete pairs subsequently fuse to from the incipient new organism called
the zygote. Within 18 – 24 hours, this
zygote develops into a motile organism called the ookinete that is infectious
to the mosquito. This ookinete rapidly
enters the insect’s midgut and forms an oocyst.
Within the oocyst more than 10,000 sporozoites are created within ten
days. Once this oocyst ruptures, these
sporozoites navigate to the mosquito’s salivary glands where they are
transferred to the next human host upon the mosquito’s bite.
Given this information, the questions that comes to mind are the following –
- What are the mosquito’s natural defenses against this parasite?
- How does the P. falciparum successfully elude these defenses?
The investigations of Dr. Alvaro Molina-Cruz and colleagues
at the Laboratory of Malaria and Vector Research at the National Institute of
Allergy and Infectious Diseases at the National Institute of Health in
Rockville Maryland helped elucidate the mechanism by which the parasite escapes
the immune defenses of its host.
It has been well established that insects have a first line
of immune defense, as do vertebrates, referred to as the innate immune system
(IIR). IIR utilizes both humoral
(chemical) and cellular defense mechanisms; it is quite sophisticated. In spite of this ability to fend off foreign
invaders, P. falciparum manages to survive and propagate in this hostile environment.
Molina-Cruz and the team of collaborators were able to
identify a gene product from the parasite that enables the invading organism to
infect its host mosquito without activating the innate immune system described
earlier. The gene responsible for
producing this product was identified as Pfs47.
In fact when this gene was disrupted from its normal functionality, the
parasite’s survival within the host was greatly reduced.
This finding is significant, for it establishes the fact
that the Pfs47 gene contained within P. falciparum is essential for the
efficient transmission of the parasite responsible for malaria from the vector
to its human host.
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