Malaria: For Students

Malaria
for students
Dr.T.V.Rao MD
Malaria Early History
The symptoms of
malaria were described in
ancient Chinese medical
writings. In 2700 BC,
several characteristic
symptoms of what would
later be named malaria
were described in the Nei
Ching,
Hippocrates and Malaria
Hippocrates, a physician
born in ancient Greece,
today regarded as the
"Father of Medicine",
was the first to describe
the manifestations of the
disease, and relate them
to the time of year and to
where the patients lived.

Malaria

Name is derived from Italian
Mal aria or bad air
Malaria continues to be most important cause of
fever and morbidity in the Tropical world
Malaria has been eradicated from Europe, Most
of North America, USA South America Korea
and Japan,
Malaria-endemic Areas 2000
Why it is important in Medicine
Malaria remains the world's most
devastating human parasitic infection.
Malaria affects over 40% of the world's
population. WHO, estimates that there are
350 - 500 million cases of malaria worldwide,
of which 270 - 400 million are Falciparum
malaria, the most severe form of the disease.
Malaria Kills more people than AIDS
Malaria kills in one year what AIDS kills in
15 years. For every death due to HIV/AIDS
there are about 50 deaths due to malaria. To
add to the problem is the increasing drug
resistance to the established drug.

History Events on Malaria
1880 - Charles Louis Alphose Lavern discovered
malarial parasite in wet mount
1883 - Methylene blue stain - Marchafava
1891 - Polychrome stain- Romanowsky
1898 - Roland Ross - Life cycle of parasite
transmission, wins Nobel Prize in 1902
1948 - Site of Exoerythrocytic development in Liver by
Shortt and Garnham

Major Developments in 20
th
Century
1955 - WHO starts world wide malaria
eradication programme using DDT
1970 Mosquitos develop resistance to DDT
Programme fails
1976 Trager and Jensen in vitro cultivation of
parasite
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Charles Louis Alphonse Laveran,
Charles Louis Alphonse
Laveran, a French army
surgeon stationed in
Constantine, Algeria, was the
first to notice parasites in
the blood of a patient
suffering from malaria.
This occurred on the 6th of
November 1880. For his
discovery, Laveran was
awarded the Nobel Prize in
1907.
Doctortvraos e learning series

Ronald Ross
In August 20th, 1897, Ronald
Ross, a British officer in the
Indian Medical Service, was
the first to demonstrate that
malaria parasites could be
transmitted from infected
patients to mosquitoes For
his discovery, Ross was
awarded the Nobel Prize
in 1902.

Nobel Prizes in Malaria
The discovery of this parasite
in mosquitoes earned the
British scientist Ronald Ross
the Nobel Prize in
Physiology or Medicine in
1902. In 1907, Alphonse
Lavern received the Nobel
prize for his findings that the
parasite was present in
human blood.
Chloroquine (Resochin) (1934, 1946)

Chloroquine was discovered by a German, Hans
Andersag, in 1934 at Bayer I.G. Farbenindustrie A.G.
laboratories in Eberfeld, Germany. He named his
compound resochin. Through a series of lapses and
confusion brought about during the war, chloroquine
was finally recognized and established as an effective
and safe antimalarial in 1946 by British and U.S.
Malaria a vector borne Disease
Malaria is a vector-
borne infectious disease
caused by protozoan
parasites. It is widespread
in tropicl and subtropical
regions, including parts
of the Americas, Asia,
and Africa.
Female Anopheles Mosquitos
transmit Malaria
Parasites Cause of Malaria
Malaria is caused by an infection by one
of four single celled Plasmodia species,
they are: falciparum, vivax, malariae,
and ovale. The most dangerous
of the four is.P.falciparum
Newer species
A fifth species,
Plasmodium knowlesi,
causes malaria in
macaques but can also
infect humans.

SPOROZOA

SPOROZOA belong to phylum Apicomplexa
contains two classes
1 Haematozoea
2 Coccidea
Belong to class Haematozoea occur in the blood of the
vertebrate hosts
contain two orders Haemosporidia (genus
Plasmodium Malaria )
Piroplasmidia (containing genus Babesia)

Structure of Malarial parasite
Falciparum most Dangerous
Falciparum accounts for 90% of deaths due to
malaria and vivax is the most widely spread
species because it exists in both temperate and
tropical climates (Encarta). The malaria life cycle
is a complex system with both sexual and
asexual aspects .


A complex Life cycle
Human Cycle

1 Pre erythrocytic
schizogony
2 Erythrocytic
Schizogony
3 Gametogony
4 Exoerythrocytic
schizogony
Events in Humans start with Bite of Mosquito
Man Intermediate host.
Mosquito Definitive host
Sporozoites are infective
forms
Present in the salivary gland
of female anopheles
mosquito
After bite of infected
mosquito sporozoites are
introduced into blood
circulation.
Period of Pre erythrocytic cycle

1 P.vivax 8 days
2 P.falciparum 6 days
3 P.malariae - 13 16 days,
4 P.ovale 9 days
On maturation Liver cells ruputure
Liberate Merozoites into blood stream
Pre erythrocytic cycle
Sprozoites undergo
developemtnal phase in the
liver cell
Sprozoites are elongated and
spindle shaped become
rounded inside the liver
parenchyma
Multiple nuclear divisions
develop to Schozonts
A Schizont contains 20,000
50,000 merozoites.
Exo-
erythrocytic
(hepatic) cycle
Sporozoites
Mosquito Salivary
Gland
Malaria Life
Cycle
Life Cycle
Gametocytes
Oocyst
Erythrocytic
Cycle
Zygote
Schizogony
Sporogony
Hypnozoites
(for P. vivax
and P. ovale)
Exo-erythrocytic (tissue) phase
P. malariae or P. falciparum sporozoites
do not form hypnotizes, develop directly
into pre-erythrocytic schizonts in the liver
Pre-erythrocytic schizogeny takes 6-16 days
post infection
Schizonts rupture, releasing merozoites which
invade red blood cells (RBC) in liver
Affinity of Parasite to Erythrocytes

P.vivax
P.malariae Infectes only young or
P.ovale Old Erythocytes

P.falciparum Infects all age groups
Also adhere to the endothelial lining of Blood vessesl
Causes the obstruction, Thrombosis and Local
Ischemias
Erythrocyte cycle
Merozoites released invade red cells
P.vivax infects young erythrocytes
P.malariae Infects old erythrocytes
P.falciparum infects RBC of all ages
The Merozoites are pear shaped 1-5 microns in
length
The receptors for Merozoites are on red cells in
the glycoprotein

Erythrocytic Schizogony
Liberated Merozoites
penetrate RBC
Three stages occur
1 Trophozoites
2 Schizont
3 Merozoite
Erythrocytic cycle
Ruptured red cells release
Merozoites which attack new
red cells
Continue with Schizogony
Repeated cycles will continue
In P.falciparum - infected
erythrocytes with Schizonts
aggregate in the capillaries of
brain and other internal organs
Only ring forms are seen in the
blood smears
Trophozoites
After invasion grow and
feed on hemoglobin
Blue cytoplasm and red
nucleus, Called as Signet
ring appearance
Hence called ring form
Schizont

When the Trophozoite is fully developed
becomes compact.
Malarial pigments are scattered through the
cytoplasm
The Nucleus is large and lies at the periphery
starts dividing.
Becomes Schizont
Plasmodium vivax
Number of merozoites 12 to 24
arranged in grape like clusters
RBC enlarged
Schuffners dots present
Yellowish brown fine granules
Schizont 9-10 microns fills and
enlarged Red cell
Gametocytes spherical or
globular
Size much larger than red cell
Male 9 microns
Female 10 11 microns

Plasmodium falciparum
RBC is normal size
Maurers dots 9 large red
spots sometimes basophilic
stippling
Dark brown or blackish one
or two solid blocks
Gametocytes Crescentric,
larger than a red cell 9 -10
microns, male and female 12-
14 microns
Plasmodium malaria
RBC Normal size
Contain Ziemanns stippling
Contain dark brown coarse
granules
Schizont 6 7 microns
almost fills a normal sized
red cell.
Gametocytes Spherical or
globular
Size much larger than a red
cell

Plasmodium ovale
Infected RBC slightly larger
Contain Schuffners dots coarse
granules
Schizont 6.2 microns fills three
quarters
Merozoites 6 -12 fills three
quarters
Gametocytes Spherical or globular,
much larger than a red cell
Exo-erythrocytic (tissue) phase
P. malariae or P. falciparum sporozoites do not
form hypnozites, develop directly into pre-
erythrocytic schizonts in the liver
Pre-erythrocytic schizogeny takes 6-16 days
post infection
Schizonts rupture, releasing merozoites which
invade red blood cells (RBC) in liver
Exo Erythrocytic Schizogony
Some Sprozoites do not undergo sporogony in
the first instance
But go into resting stage called as Hypnozoites,(
hibernation )
Within 2 years reactivate to form Schizonts
release Merozoites and attack red cell and
produce relapses
Absent in P falciparum
Gametogony
Merozoites differentiate into Male and female
gametocytes
Macrogametocytes also called female gametocytes
Microgametocyte also called as male gametocytes
They develop in the red cells
Found in the peripheral blood smears
Microgametocyte of all species are similar in size
Macro gametocytes are larger in size.

Mosquito cycle
A definitive Host Mosquito
Mosquito cycle
Sexual cycle
Sexual cycle will be initiated in the Humans by the
formation of Gametocytes
Develop further in the female Anopheles Mosquito
Only mature sexual forms are capable of further
development in Mosquito
In midgut one Microgametocyte develops into 4-8
thread like filamentous structures named Micro gametes
From one macrogametocyte only one macrogamete is
formed
Events in Mosquitos
Fertilization occurs when a Microgametocyte
penetrate into Macrogametocyte
Fertilized macrogametocyte is known as
ZYGOTE
ZYGOTE matures into OOKINETE
OOKINETE to OOCYST

Formation of Sporozoites in Mosquitos.
OOCYST matures with large number of Sporozoites (
A few hundred to thousands.)
OOCYST ruptures and release SPOROZOITES in
the body cavity of Mosquito
There is a specific predilection for salivary glands
Now capable to transmit the infection to new Host


Pathology and Pathogenesis

Sporozoites result from sexaul and sporogenic
cycle of development in mosquitoes and injected
into human blood serum.
Events start with bite of Infected Anopheles
Mosquitoes
Sporoozoites enter liver, in 1 hour infect the
parenchymal cell.

Pathology and Pathogenesis

Sporozoites result from sexaul and sporogenic
cycle of development in mosquitoes and injected
into human blood serum.
Events start with bite of Infected Anopheles
Mosquitoes
Sporoozoites enter liver, in 1 hour infect the
parenchymal cell.

Pathogenesis in Pre Erythrocyte cycle
Numerous asexual progeny Merozoites ruputure and
leave from liver cells
Enter the Blood and invade Erythrocytes
Erythrocytic cycle starts Multiply in species specific
fashion
Broods of Merozoites appearing at 48 hour interval in
P.ovale, P.vivax , P.falciparum
P.malariae appear in 72 hour cycles,
Chooses to enter the RBC
Specific for each species
They pit on red cells
By endocytosis enters the
RBC
Becomes a Trophozoites
Schizont

When the Trophozoite is fully developed
becomes compact.
Malarial pigments are scattered through the
cytoplasm
The Nucleus is large and lies at the periphery
starts dividing.
Becomes Schizont
Cycles differs in Different species

Cycle repeats every 48 hours in
1 P.falciparum
2 P.ovale
3 P.vivax
Repeats every 72 hours In
P.malariae
Incubation period varies according to species
Which includes Exo eythrocytic cycle time and
one or two erythocytic cycles,
P.vivax and P.falciparum 10 15 days (can vary
from weeks to months)
P.malariae infection can start after 28 days.


Clinical Features of
Malaria
Clinical Manifestations are related to cycle of
events in relation to RBC
How Malaria present Clinically
Stage 1
Chills for 15 mt to 1 hour
Caused due to rupture from the host red cells
escape into Blood
Preset with nausea, vomitting,headache
Stage 2
Fever may reach upto 40
0
c may last for several
hours starts invading newer red cells.
Clinical Malaria
Stage 3
Patent starts sweating, concludes the episode
Cycles are frequently Asynchronous
Paroxysms occur every 48 72 hours
In P.malariae pyrexia may lost for 8 hours or
more and temperature my exceed 41
0
c
More commonly, the patient presents with a
combination of the following symptoms
Fever
Chills
Sweats
Headaches
Nausea and vomiting
Body aches
General malaise.

Doctortvraos e learning

Early symptoms
The common first symptoms fever,
headache, chills and vomiting usually
appear 10 to 15 days after a person is
infected. If not treated promptly with
effective medicines, malaria can cause
severe illness and is often fatal.
What are the characteristics of a malaria attack

Fever and shivering. The attack begins with fever, with
the temperature rising as high as 40C and falling again
over a period of several hours.
A poor general condition, feeling unwell and having
headaches like influenza.
Diarrhea, nausea and vomiting often occur as well.

Malaria the disease
9-14 day
incubation period
Fever, chills,
headache, back and
joint pain
Gastrointestinal
symptoms (nausea,
vomiting, etc.)
Clinical events
The symptoms often associated with malaria are
due to bursting red blood cells and clogged
capillaries of major organs. Infection occurs
when an infected anopheles mosquito feeds on
an individual releasing sporozites into the blood
stream. Mosquitos can carry more than one
species and thus can infect peoples with more
than one species

Malaria stages of the disease
Malaria intensifies
Symptoms intensify
Irregular high fever
Anxiety, delirium and other
mental problems
Sweating, increased pulse
rate, severe exhaustion
Worsening GI symptoms
Enlarged spleen and liver
Broad clinical manifestations of Malaria
Fever
Sweating
Anemia
Splenomagaly (enlarged spleen)
Irratability
Coma, Retinal Hemorrages
Algid Malaria ( a shocklike syndrome)
Respiratory distress syndrome

Periodicity can be clue in Diagnosis and
species relation
Malaria tertiana: 48h
between fevers (P.
vivax and ovale)

Malaria quartana: 72h
between fevers (P.
malariae)

Malaria tropica:
irregular high fever (P.
falciparum)
Malaria the disease
Pathogenesis of Malaria
In highly endemic areas:
high mortality among
children due to severe
anemia, children who
survive beyond the first
years show decreasing
parasitemia and disease
(this immunity is not
sterile and depends on
constant exposure)

Cytokines & toxins
Hatched=chill
Black=rigor
Clear=sweating
Malaria produces a strong
Th-1 type response
Elevated serum levels of
IFNg and TNFa
Cytokines can induce
(mimic) many of the
symptoms and signs of
malaria (shivering,
headache, chills, spiking
fever, sweating,
vasodilation, hypoglycemia)

Cerebral Malaria

Malignant malaria can
affect the brain and the
rest of the central
nervous system. It is
characterized by changes
in the level of
consciousness,
convulsions and
paralysis.
Cerebral Malaria

Present with
Hyperpyrexia
Can lead to Coma
Paralysis and other
complications.
Brain appears congested
Pathogenesis of Cerebral
malaria
High cytokine levels could be toxic on their own
High levels of cytokine also enhance the second process
thought to be responsible for cerebral malaria: sequestration
of infected RBCs
Sequestration & cytoadherence
Rosetting (adhesion of
infected RBCs to other RBCs)
and clumping (adhesion
between infected cells) was
first observed in in vitro
culture
Rosetting was also found in
50% of field isolates and
correlated strongly with the
severity of the observed
disease
Sequestration & cytoadherence
How do parasite proteins travel to
the surface of the RBC?
This is a considerable challenge as
RBC lack functional secretory
apparatus
Why do patients fail to mount an
effective immune response against
antigens that are presented this
prominently?
Black Water Fever
In malignant malaria a large
number of the red blood corpuscles
are destroyed. Haemoglobin from
the blood corpuscles is excreted in
the urine, which therefore is dark
and almost the colour of cola
How long Malaria infection can lost in Man
Without treatment P.falciparum will terminate in less
than 1 year.
But in P.vivax and P.ovale persist as hypnozoites after
the parasites have disppeared from blood.
Can prodce periodic relapses upto 5 years
In P.malariae may last for 40 years
( Called as recrudescence X relapse )
Parasites survive in erythrocytes Liver ?
Why Falciparum Infections are Dangerous
Can produce fatal complications,
1.Cerebral malaria
2.Malarial hyperpyrexia
3.Gastrointestinal disorders.
4.Algid malaria
5 Black water fever can lead to death

Complication of P.malariae

Can produce Nephrotic
syndrome
Affects mainly children
of years age
Pernicious Malaria
Carries a High Mortality

On few occasions life
threading complications can
occur.
Occurs in infections with
P.falciparum
Associated with Heavy
parasitaztion
Grouped into three types
1. Cerebral Malaria
2 Algid malaria
3 Black water fever
Uncomplicated Malaria

The classical (but rarely observed) malaria attack
lasts 6-10 hours. It consists of:
a cold stage (sensation of cold, shivering)
a hot stage (fever, headaches, vomiting; seizures
in young children)
and finally a sweating stage (sweats, return to
normal temperature, tiredness)


Malaria A Major Health problem of
Tropical countreis
Pernicious Malaria
Is a life threatening complication in acute falciparum
malaria
It is due to heavy parasitization
Manifest with
1 Cerebral malaria it presents with hyperpyrexia, coma
and paralysis. Brain is congested
2 Algid malaria presents with clammy skin leading to
peripheral circulatory failure.
Complication in Malaria
Pulmonary edema (fluid buildup in the lungs) or
acute respiratory distress syndrome (ARDS),
which may occur even after the parasite counts
have decreased in response to treatment
Abnormalities in blood coagulation and
thrombocytopenia (decrease in blood platelets)
Cardiovascular collapse and shock
Black water Fever
It is a manifestation of infection with P.falciparum
occuring in persons who have been previously infected
and have had been inadequate dose of quinine
It is characterized by intravascular hemolysis fever, and
Haemoglobunuria
Cardiovascular collapse and shock
Abnormalities in blood coagulation and
thrombocytopenia (decrease in blood platelets)
Other Complications In Malaria
Acute kidney failure
Hyperparasitemia, where more than 5% of the
red blood cells are infected by malaria parasites
Metabolic acidosis (excessive acidity in the blood
and tissue fluids), often in association with
hypoglycemia
Immunity
Influenced by
Genetics
Age
Health condition
Pregnancy status
Intensity of transmission in region
Length of exposure
Maintenance of exposure
Immunity
Innate
Red cell polymorphisms associated with some protection
Hemoglobin S sickle cell trait or disease
Hemoglobin C and hemoglobin E
Thalessemia and
Glucose 6 phosphate dehydrogenase deficiency
(G6PD)
Red cell membrane changes
Absence of certain Duffy coat antigens improves resistance
to P.v.
Immunity
Acquired
Transferred from mother to child
3-6 months protection
Then children have increased susceptibility
Increased susceptibility during early childhood
Hyper- and holoendemic areas
By age 5 attacks usually < frequent and severe
Can have > parasite densities with fewer symptoms
Meso- or hypoendemic areas
Less transmission and repeated attacks
May acquire partial immunity and be at higher risk for
symptomatic disease as adults

Immunity
Acquired
No complete immunity
Can be parasitemic without clinical disease
Need long period of exposure for induction
May need continued exposure for maintenance
Immunity can be unstable
Can wane as one spends time outside endemic area
Can change with movement to area with different
endemicity
Decreases during pregnancy, risk improves with increasing
gravidity
Laboratory Diagnosis of
Malaria
Diagnostic Tools
for Human Infections with
Malaria
Blood film
examination
Serology - IFA
PCR
Blood collected with sterile technique

Making the smears
Making of Thick smear

Thin and Thick smear
Appearance of Thick and Thin
Smears
Microscopy
Malaria parasites can be identified by examining
under the microscope a drop of the patient's
blood, spread out as a "blood smear" on a
microscope slide. Prior to examination, the
specimen is stained (most often with the Giemsa
stain) to give to the parasites a distinctive
appearance. This technique remains the gold
standard for laboratory confirmation of malaria
How parasites appear
QBC system has evolved as rapid and precise
method in Diagnosis
The QBC Malaria method is the simplest and most
sensitive method for diagnosing the following diseases.
Malaria
Babesiosis
Trypanosomiasis (Chagas disease, Sleeping Sickness)
Filariasis (Elephantiasis, Loa-Loa)
Relapsing Fever (Borreliosis)


QBC system
Appearance of Malarial parasite in QBC
system
Antigen Detection Methods are Rapid and
Precise
Antigen Detection
Various test kits are available to detect antigens derived
from malaria parasites. Such immunologic
("immunochromatographic") tests most often use a
dipstick or cassette format, and provide results in 2-15
minutes. These "Rapid Diagnostic Tests" (RDTs) offer
a useful alternative to microscopy in situations where
reliable microscopic diagnosis is not available. Malaria
RDTs are currently used in some clinical settings
Serology

Serology detects antibodies
against malaria parasites,
using either indirect
immunofluorescence (IFA)
or enzyme-linked
immunosorbent assay
(ELISA). Serology does not
detect current infection but
rather measures past
experience.
Newer Diagnostic methods
Molecular Diagnosis

Parasite nucleic acids are detected using
polymerase chain reaction (PCR). This technique
is more accurate than microscopy. However, it is
expensive, and requires a specialized laboratory
(even though technical advances will likely result
in field-operated PCR machines).
Types of Serological Assays
Malaria
Antibody Detection
Indirect Fluorescent Antibody
Enzyme immunoassays
Antigen Detection
Immunochromatographic
Antibody Detection
=
Antigen-antibody
complex
Patients serum
contains specific
and non-specific
antibodies
+
Antigen
Antibody Detection
*-labeled antibody to
human antibody
+
Antigen-antibody-
*antibody
complex
=
Antigen-
antibody
complex
Indirect Fluorescent Antibody (IFA)
Microscope slide
Enzyme Immunoassay
(EIA/ELISA)
_
+
enzyme
substrate
ELISA
Antigen Detection
Monoclonal
antibody
=
Antigen-antibody
complex
+
Antigen in
patients serum
Antigen Detection
=
Antibody-antigen-
antibody
complex
+
Immobiliz
ed
monoclon
al
antibody
Antigen-antibody
complex
Antigen Detection
Malaria Immunochromatographic
Dipstick
Optimal Assay
P. falciparum
specific
monoclonal
antibody
Malaria IFA Test
Sensitivity = 98%
Specificity = 99.5%

Sulzer et al, Am J Trop Med Hyg 1969;18:199-205
Sulzer et al, Bull Wld Hlth Org 1971;45:375-379
P malaria
Malaria IFA Test
Initial detection of antibodies

Parasitemia precedes antibody
P. vivax 2-6 days
P. falciparum and P. malariae 4-6
days
If parasitemia is suppressed by
treatment, may develop
detectable antibody
Malaria IFA Test
Determination of Infecting Species
Non-Immune
Samples drawn 0-14 days post
onset: Highest titer was to the
infecting species in 81%
Samples drawn 15-60 days
post onset: Highest titer was to
the infecting species in 96%
Malaria IFA Test
Determination of Infecting Species
Is possible in non-immune
individuals with primary
infection.
Is NOT possible in immune
individuals because their antibody
response reflects multiple
infections with multiple species.

Malaria IFA Test

Antibody Persistence after Treatment
Non-Immunes (Vietnam Vets with
Pv)

53% IFA negative at 6 mo.
post-Rx
post-Rx

Wilson et al, Am J Trop Med Hyg 1970;19:401-404
Malaria IFA Test

Antibody Persistence after Treatment
Non-Immunes (Vietnam Vets with
Pv)

post-Rx
post-Rx

Wilson et al, Am J Trop Med Hyg 1970;19:401-404
Sensitivity of Tools for
Diagnosis of Malarial
Infection
1. Most sensitive:
Antibody detection
2. PCR
3. Blood film
examination
Diagnosis of
Untreated Acute Malaria
Blood film
examination
PCR
Diagnosis of
Chronic Malaria
Screen with serology
If IFA positive:
May do blood film examination
May do PCR

Diagnosis of
Treated Recent Malaria
Serology
Blood film
examination
PCR
Malaria Relapses

In P. vivax and P. ovale infections, patients having
recovered from the first episode of illness may suffer
several additional attacks ("relapses") after months or
even years without symptoms. Relapses occur because
P. vivax and P. ovale have dormant liver stage parasites
("hypnozoites") that may reactivate. Treatment to
reduce the chance of such relapses is available and
should follow treatment of the first attack.
Treatment
Over view of Treatment options in
Malaria
Most drugs used in treatment are active against the parasite
forms in the blood (the form that causes disease) and include:
Chloroquine
Sulfadoxine-pyrimethamine (Fansidar)
Mefloquine (Lariam)
Atovaquone-proguanil (Malarone)
Quinine
Doxycycline
Artemisin derivatives (not licensed for use in the United States,
but often found overseas)

In endemic areas, the World Health
Organization recommends that treatment be
started within 24 hours after the first symptoms
appear. Treatment of patients with
uncomplicated malaria can be conducted on an
ambulatory basis (without hospitalization) but
patients with severe malaria should be
hospitalized if possible.
What is presumptive treatment?
Presumption - In an area with high transmission of malaria, it
should be presumed that ALL cases of fever are due to malaria.
Treatment - First loading dose of Chloroquine should be
administered immediately after collecting the blood specimen,
even without waiting for its report.
If the fever is indeed malaria, this treatment alleviates symptoms
early, may be well before the test result is available.
If it is malaria, Chloroquine also prevents the spread of malaria
by destroying the gametocytes of P. vivax (the more common
malaria).
If it is not malaria, nothing is lost, for Chloroquine at this dose is
safe and has no adverse effects!
Radical treatment
Radical treatment is administration of Primaquin to all
confirmed cases of malaria.
In P. vivax malaria, 2 weeks' therapy with Primaquin
completely cures the infection in the host by its tissue
schizonticidal activity and thereby prevents relapses.
In P. falciparum malaria, a single dose of primaquine
destroys the gametocytes, thereby prevents the spread
of the infection into the mosquito.
Use of Primaquin
Primaquine is active against the dormant parasite
liver forms (hypnozoites) and prevents relapses.
Primaquine should not be taken by pregnant
women or by people who are deficient in G6PD
(glucose-6-phosphate dehydrogenase). Patients
should not take primaquine until a screening test
has excluded G6PD deficiency.
Drug Resistance
Choroquine Resistance
Chloroquine resistant P. falciparum (CRPF) first
developed independently in 3 to 4 foci in
Southeast Asia, Oceania , and South America in
the late 1950's and early 1960's. Since then,
Chloroquine resistance has spread to nearly all
areas of the world where falciparum malaria is
transmitted
Chloroquine Resistance
Chloroquine resistant P. vivax (CRPV) malaria
was first identified in 1989 among Australians
living in or travelling to Papua New Guinea.
CRPV has also now been identified in Southeast
Asia, on the Indian subcontinent, and in South
America. Vivax malaria, particularly from
Oceania, also exhibits decreased susceptibility to
primaquine.
Testing Drug Resistance
There are 4 basic methods for testing malaria for drug
resistance: in vivo tests, in vitro tests, molecular
characterization, and animal models. Of these, only the
first 3 are routinely done
In vivo tests: In these tests, patients with clinical malaria
are given a treatment dose of an antimalarials drug
under observation and are monitored over time for
either failure to clear parasites or for reappearance of
parasites.
In vitro Testing
In vitro tests: In these tests, blood samples from
malaria patients are obtained and the malaria
parasites are exposed to different concentrations
of antimalarials drugs in the laboratory. Some
methods call for adaptation of parasites to
culture first, while others put blood directly
from patients into the test system.
Molecular Methods
Molecular characterization: For some drugs
(Chloroquine, SP and similar drugs,
atovaquone), molecular markers have been
identified that confer resistance. Molecular
techniques, such as polymerase chain reaction
(PCR) or gene sequencing can identify these
markers in blood taken from malaria-infected
patien
Resistance to Chloroquine - 1960

Resistance to Chloroquine - 1970
Resistance to Chloroquine -
1980
Resistance to Chloroquine -
2000
Antimalarials Resistance - 1998
(excluding CQ)
SP, Mefloquine, Halofantrine,
Quinine
SP
Mefloquine
SP, Mefloquine
Reports of Chloroquine Resistance
in P.vivax
1989
1990
1995
1995
1991
1995
World Malaria Day, April 25
April 25 is World Malaria
Day, which commemorates
the date in 2000 when 44
African leaders committed to
cutting malaria deaths in half
by 2010. This year's World
Malaria Day theme is
"Counting Malaria Out."
How does CDC contribute?
CDC's malaria Web site offers telediagnosis and treatment
strategies

You can e-mail a digital
image to the Centres for
Disease Control and
Prevention for
telediagnosis, and if
necessary download
guidelines for treatment
from its new malaria
Web site,
Tele Net Working
Images of other suspected
parasitic infections can be e-
mailed to the CDC's
Laboratory Identification of
Parasites of Public Health
Concern program
(www.dpd.cdc.gov/dpdx).

Development of Vaccines
Malaria vaccines in development include: pre-
erythrocytic or liver-stage vaccines that aim to
protect against the early stage of malaria
infection; blood-stage vaccines that aim to
reduce the severity of disease; and transmission-
blocking vaccines that are intended to prevent
mosquitoes that fed on an infected person from
spreading malaria to new hosts.
Future Ambitions
The malaria vaccine community aims to licenseby
2015a first-generation vaccine that has 50 percent
efficacy against severe disease and death, with
protection lasting at least one year without the need for
boosting. They also aim to licenseby 2025a
second-generation malaria vaccine that has a protective
efficacy of at least 80 percent against clinical disease
and with protection lasting for many years without a
booster.
Why vaccines are Difficult
No licensed vaccine against malaria currently exists
The parasite has evolved a series of strategies that
allow it to confuse, hide, and misdirect the human
immune system.
The parasite changes through several life stages even
while in the human host, presenting a different subset
of molecules for the immune system to combat at each
stage.
Simple protective Measures
There's no reason only poor people should get malaria':
The moment Bill Gates released jar of mosquitoes at
packed conference

Bill and Melinda Gates Foundation that announced last year it was
donating 115 million to help develop a vaccine for the deadly
disease.
Goal of Medical Humanity
Created for Medical and
Paramedical students in
Developing World
Dr.T.V.Rao MD
Email
doctortvrao@gmail.com

Malaria: For Students

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