The Burden of Malaria

Mosquito Proboscis at Higher Magnification

Eggs deposited by a female Anopheles
stephensi mosquito, a known vector of malaria.
D12548/Centers for Disease Control and
Prevention*

An Anopheles stephensi mosquito larva. Harry
Weinburgh/ID12554/Centers for Disease Control
and Prevention*

An Anopheles stephensi mosquito pupa.
Harry Weinburgh/ID12556/Centers for Disease
Control and Prevention*

Scanning electron micrograph depicting the head and
thoracic regions of an Anopheles gambiae mosquito. The
head contains a pair of compound eyes, a forward-projecting
proboscis and a pair of segmented antennae that are sensitive
to host odors. A pair of wings and three pairs of legs are
attached to the thorax. Photo credit: Janice Carr/ ID8759/Dr.
Paul Howell/Centers for Disease Control and Prevention*

Scanning electron micrograph depicting the anterior head
region of an Anopheles gambiae mosquito. The head contains
all the sensory organs the mosquito needs to detect and zero
in on its human prey. Photo credit: Janice Carr/ID8780/Dr.
Paul Howell/Centers for Disease Control and Prevention*

Scanning electron micrograph of an Anopheles gambiae
mosquito's proboscis --- a thin sheath that conceals the
actual razor-sharp stylets that the mosquito uses to pierce its
victim. Photo credit: Janice Carr/ ID8763/ Dr. Paul
Howell/Centers for Disease Control and Prevention*

Tip of an Anopheles gambiae mosquito's proboscis at
higher magnification. Once the mosquito has pierced the
skin of its prey, it injects a cocktail of saliva and
anticoagulant into the puncture site. If the mosquito is
infected, transmission of the malaria parasites (sporozoites)
occur at this stage. Photo credit: Janice Carr/ID8764/Dr.
Paul Howell/Centers for Disease Control and Prevention*

Anopheles quadrimaculatus, an important vector of
malaria in the central and eastern United States. Edward
McCellan/ ID3169/Centers for Disease Control and
Prevention*

A hungry female Anopheles freeborni taking a blood
meal to carry out egg production. Note the clear fluid
coming out of the mosquito's rear end. Anophelines
can excrete the water component of the blood
(prediuresis) to concentrate the number of red cells
ingested. Photo credit: James Gathany/ID6765/Centers
for Disease Control and Prevention*

Thin film Giemsa stained micrograph depicting
ring-form Plasmodium falciparum trophozoites. The
growing parasites feed on hemoglobin inside red blood
cells. Infected red cells eventually rupture, releasing
more parasites. Steven Glenn/ ID5861/Centers for
Disease Control and Prevention*

Thin film blood smear depicting a Plasmodium
falciparum microgametocyte. Gametocytes are sexual
forms of the parasite which, when picked up by a
feeding female Anopheline during a blood meal,
commence another cycle of growth and maturation
within the mosquito's digestive tract.Dr. Mae
Melvin/ID4918/Centers for Disease Control and
Prevention*

T H E F I N A L R A C E

*Image description may vary from original source. You can view the original source by visiting the CDC Public Health Image Library and entering the
corresponding ID in the search box.

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The Burden of Malaria

Malaria is a potentially fatal blood infection caused by a parasite of the genus Plasmodium that is transmitted to

humans

by the bite of

female mosquitoes of the

genus

Anopheles

Higher environmental temperatures not only allow the Anopheles mosquito to thrive and survive but also enable the

malaria

parasite to grow and complete part of its life

cycle within its insect host. Once the parasites develop and mature,

they are then

ready

to wreak havoc on humans

when the mosquito takes its next blood meal.

When the issue of climate change broke into the world's consciousness a couple of decades ago, the putative role

global warming

in the spread of malaria and other

mosquito-borne diseases was raised. (The possible ramifications

of such hypothetical

situation

are explored closely in the

book

Symptoms and signs of malaria include:

Fever
Shaking chills
Muscle aches
Headache
Nausea
Vomiting
Jaundice (yellowish discoloration of the eyes and skin)
Anemia (due to the loss and destruction of red blood cells)

Without prompt treatment, malaria may cause:

Severe anemia and shock
Kidney failure
Seizures
Coma
Death

There are more than 400 known Anopheles species, 30 to 40 of which transmit human

malaria.

Anophelines are found worldwide (except Antarctica).

In the United States, there are 3 important Anopheline vectors:

Anopheles freeborni in the west
Anopheles quadrimaculatus in the central and eastern regions
Anopheles pseudopunctipennis in the south

Although malaria has been eliminated in the United States since the 1950s, the mosquito vectors are still

on the loose --- alive and

well and breeding

great numbers.

This puts the country and other similar

regions in the

world

where malaria

been eliminated

at constant risk of re-introduction

of the

disease.

Malaria is a global killer:

Every 30 seconds, a child succumbs to malaria somewhere in Africa --- 3000 young lives lost

every single day.

Each year, there are 300 to 500 million clinical cases of malaria --- 90 percent of them in

Africa.

Endemic in more than 100 countries, malaria kills between 1 to 3 million people annually.

Unfortunately, there is no single antimalarial drug that is consistently effective against the malarial

parasite and there is

currently no

malaria vaccine approved for human use.

There are 5 species of human malarias:

Plasmodium falciparum

The most virulent of all human malarias
Found worldwide in tropical and subtropical regions
Causes severe malaria
Infection could be mitigated by the presence of certain hemoglobin disorders, such as

thalassemia (see

below)

and

sickle cell trait

Plasmodium vivax

Found mostly in Asia and Latin America
Less virulent than Plasmodium falciparum
Can lie dormant in the liver (hypnozoites) and activate several months or years after the initial

infecting mosquito bite

Historically, individuals who do not express the Duffy blood group protein on their red blood

cells were thought to be

resistant to

Plasmodium vivax

. However, recent studies have

shown

that such is no longer the case, suggesting that the

parasite is evolving into more virulent strains

that are able to

overcome host resistance and carve new invasion

pathways.

Plasmodium ovale

Found mostly in Africa and Asia
Like Plasmodium vivax, certain parasites can remain dormant in the liver as hypnozoites and

relapse several months or years

later.

Plasmodium malariae

Found worldwide
Tends to have milder clinical manifestations compared to falciparum, vivax and ovale malaria
Can cause chronic infection if not adequately treated

Plasmodium knowlesi

Predominantly found in Southeast Asia
Can cause severe disease

_______________________________________________________________________________

Plasmodium falciparum

and the Malaria Hypothesis

Malaria comes from the Italian mal and aria meaning "bad air." The ancient Romans believed that the

disease was caused by the

vapors emanating from

the swamps

around Rome where malaria

had

raged for

centuries.

The deadliest of all, Plasmodium falciparum has been around for thousands of years. But its incidence is

believed to have exploded

since the advent of

agriculture

about 10,000 years ago. Suddenly, age-old trees

were felled and vast

tracts of

forests were cleared

for farming --- providing sunlight and standing water

for the

Anopheles

mosquito vector to capitalize on.

In 1949, Italian investigators pointed out the strong geographic correlation between the high incidence of

thalassemia

and

endemic

falciparum

malaria in some

regions

of Italy.

Thalassemia is a type of hemoglobin disorder characterized by varying degrees of anemia. Individuals that are

heterozygous (those

who carry the trait) for

thalassemia

may be asymptomatic or experience only mild to moderate

anemia.

But those that

are

homozygous (those with full blown disease) suffer from severe

anemia and early

death without medical intervention.

To account for the high incidence of thalassemia in malarious regions in the Mediterranean despite its lethality in

the homozygous

state, a British-born biologist

and geneticist, J.B.S. Haldane, proposed what later became known as

the "

Malaria

Hypothesis

Essentially, Haldane hypothesized that while homozygotes succumbed to the complications of thalassemia or to the

ravages of

malaria, the heterozygotes on the

contrary not only had mild symptoms but could also be resistant to

falciparum

malaria itself,

which had exacted a very high death toll in southern Europe up until

the end of World War

II. And by

natural selection

, this

selective advantage

must have favored the persistence of the thalassemia

gene in the malaria-endemic

regions of the

Mediterranean.

However, since malaria had been eliminated in the Mediterranean countries after the Second World War, the

Malaria

Hypothesis could not be readily confirmed

among carriers of the thalassemia gene.

It was not until four years later when an actual systematic inquiry into the hypothesis was conducted. But this time,

it was in

connection with another

hemoglobin disorder:

sickle cell disease

In 1953, a British physician, Dr. Anthony Allison, carried out in-depth studies of the relationship between sickle cell

disease and

malaria in East Africa. He found

that the

incidence of parasitemia in children with the sickle cell trait was

significantly lower than a

comparable group without the trait. He further noted

that

the abnormal erythrocytes of

individuals with the trait were less easil

parasitized

Plasmodium falciparum

than were normal erythrocytes.

In 1954, Dr. Allison published "Protection afforded by sickle cell trait against subtertian malarial infection" in the

British Medical

Journal

. His work thus gave

further credence to the Malaria Hypothesis with respect to the sickle

gene --- that

despite the fact that

the homozygous state meant high morbidity and mortality,

those with sickle trait

appeared to possess a selective advantage and

innate

protection against a vicious global killer --- thus illustrating the

role of natural

selection and

survival of the fittest

ensuring the sickle gene's persistence

the gene pool,

especially in regions where malaria are hyperendemic.