The document provides a historical overview of malaria. Some key points: - Malaria symptoms have been described as early as 2700 BC in China and 400 BC by Hippocratic writings. - In 1880, Charles Louis Alphonse Laveran discovered the malaria parasite in blood samples. - In 1897, Ronald Ross demonstrated that malaria can be transmitted from infected patients to mosquitoes. - In 1898, it was shown that the human malaria parasites Plasmodium falciparum, P. vivax, and P. malariae complete their life cycle within mosquitoes. - Major developments in the 20th century included the 1955 WHO malaria eradication program using DDT and

1. RAM NAIK. M
5th Sem
AMC

2. INTRODUCTION
¥ Otherwise known as AGUE
¥ Derived from Italian: Mal’ aria= bad’ air (Horace Walpole in 1740)
¥ Malaria continues to be most important cause o
fever and morbidity in the Tropical world.

4. HISTORY

5. 2700 BC: China- Huang Di Nei Jing
Described one form of intermittent fever recurring
every one, two or three days
Hippocratic corpus (400 B.C.) was the first to describe the manifestations of the
disease and to relate them to the time of the year and where the patient lived.

6. • The periodic fever episodes characteristic for
malaria have been described by physician early
on in human history.
• People recognized a connection between
malaria and swamps.
• It was thought that swamps exude a miasma
or poison which causes the disease
Giovanni Maria Lancisi (1654-1720)
☺He first described a characteristic black pigmentation of
the brain and spleen in the victims of malaria.
☺Lancisi linked malaria with poisonous vapors of swamps
or stagnant water on the ground.

7. Discovery of the Malaria Parasite (1880)
6th of November 1880.
Charles Louis Alphonse Laveran, a French army surgeon concluded
that “Swamp fevers are due to a germ”
Parasites in the blood of a patient suffering from malaria.
Unable to identify the species.

8.  1883 - Methylene blue stain - Marchafava
1891 - Polychrome stain- Romanowsky

9. Discovery that mosquitoes transmit malaria
On august 20th, 1897, RONALD ROSS, a
British officer in the Indian medical service,
demonstrated that malaria parasites could be
transmitted from infected patients to mosquitoes.
In further work with bird malaria, Ross showed that
mosquitoes could transmit malaria parasites from bird
to bird.
The mystery of malaria transmission was solved.

10. Discovery of the transmission of the human malaria
parasites
• In 1898, led by Giovanni Batista Grassi, a team of Italian
investigators, collected Anopheles claviger mosquitoes and fed them
on malaria patients.
• The complete sporogonic cycle of Plasmodium falciparum, P. vivax,
and P. malariae was demonstrated.
• In 1899, mosquitoes infected by feeding on a patient in Rome were
sent to London where they fed on two volunteers, both of whom
developed malaria.

11. Camillo Golgi
An Italian neurophysiologist, established that
there were at least two forms of the
disease
-one with tertian periodicity (fever
every other day) and one with quartan
periodicity (fever every third day).
He prepared high quality micrographs and
described the asexual replication of the
parasite within the RBC.
He observed that fever coincided with the
rupture and release of merozoites into the
blood stream.

12. 1948 - Site of Exoerythrocytic development in Liver by Shortt and Garnham

13. Major Developments in 20th Century
• WHO
1955 • Malaria eradication programme using DDT
• Resistance to DDT
1970 • Programme fails
• Trager & Jensen
1976 • Invitro-cultivation of the parasite

14. PAUL
ROSS MULLER
• High efficient of
• Oocyst of Plasmodium
DDT as a contact
in gut-wall of mosquito
poison against
• 1897-Aug-20
several arthropods
• 1902
NOBLE
LAVERAN LAURETES GOLGI
• Noticed parasite • Asexual
in the blood of a reproduction of
patient Plasmodium in
RBC
• 1880-Nov-6
• 1907

15. Why is it important…..?????
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.

16. 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.

17. TRANSMISSION
• Mosquito Bite (Female Anopheles)
• Blood
– Maximum with fresh blood up to 5 days.
– No infection - stored blood > 5 days.
– No infection - Plasma Transfusion
• Syringes
– Drug Addict / Iatrogenic.
• Congenital Malaria
– Mother to Child ( Rare ) ( AIDS )

18. Factors affecting the transmission
• Anopheles mosquito- species of the mosquito
• Environment:
Temperature between 16-33 oC
Rainfall provides breeding site for mosquito.
Humidity favors mosquito survival.
At low altitudes
• Vector resistance to insecticides
• Parasitic resistance to drugs
• Man-made:
• War and migrations

19. Mosquito serves as a vector of human malaria because……
Susceptible to infection by malarial parasite.
Repeatedly bite humans rather than animals for their blood-
meal.
Present in adequate number near human habitats.
Live long enough for the development into sporozoits in the
midgut

20. FACT FILES
Affects >2400 million people, over 40% of the world's population, in more than
100 countries
• About 1.5 million to 3 million people die of malaria every year (85% of these
occur in Africa)
One child dies of malaria somewhere in Africa every 20 sec., and one malarial
death every 12 sec somewhere in the world
• Estimated annual expenditure on malaria research, prevention and
treatment: $ 84 million.
Eradicated in Europe, USA, Korea, japan, Most of N&S America
In India, Orissa constitutes 25% of cases

22. TAXONOMIC CLASSIFICATION
Kingdom Protista
Subkingdom Protozoa
Phylum Apicomplexa
Class Haematozoea
Order Haemosporida
Family Plasmodiidae
Genus Plasmodium {sub genera- lavarania and plasmodium}
Species falciparum, malariae, ovale, vivax
There are 165 known species of Plasmodium- may infect reptiles, birds and
mammals
Of these, 4 were known to infect humans.
A new species- Plasmodium knowlesi- causes malaria in macaques but can also infect
humans.

24. Malaria
72 species of anopheles mosquito (♀)
90% cases
Plasmodium Plasmodium Plasmodium Plasmodium
Falciparum vivax Ovale Malariae
95%
malarial
Death

25. Plasmodium falciparum:-Welch
falx=cresent/sickle + parere=to bring forth.
Malignant tertian or Estivo-autumnal or falciparum malaria
Plasmodium vivax:-Grassi&Feletti,1890
vivax or tertian malaria.
Occurrence of true relapses in characteristic.
Described by Laveran- but not as a distinct species in 1880
Golgi described it as a distinct species.
Plasmodium malariae:-Laveran,1881
malariae malaria or quartan malaria.
Natural parasite of chimpanzee
synonym= Pl.rodhaini
Plasmodium ovale:-Stephans,1922
relatively restricted distribution.
Ovale malaria

26. The morphological characteristics and features of the life cycle
acts a major criteria in GARNHAM’S CLASSIFICATION.
These include:
 Shape of the tropozoite
 Gametocyte
 Oocyst
 Number of nuclei in erythrocytic & exo-erythrocytic
schizonts
 Aspect and distribution of pigment
 Nature of damage induced in host cell

27. General characteristics:
 Alternation of generation accompanied by
alternation of hosts.
 Schizogony(asexual) takes place in humans
 Sporogony(sexual) takes place in mosquito
 Typically, pigment is produced during the
developing stages parasite in RBC

29. PARASITE FORMS
Blood forms: merozoites,
Merozoite: invades erythrocytes
rings, trophozoite, schizonts
Sporozoite invades mosquito salivary glands and liver cells
Mosquito forms:
Ookinete invades mosquito gut epithelial cells Oocyst, ookinete,
gametocytes,
sporozoite

30. There is a Plant inside Malaria !
(secondary endosymbiosis)
Plasmodium- contains a broken down old chloroplast (an Apicoplast)
that doesn't do any photosynthesizing.
The Apicoplast is however, needed for the parasite to invade new cells.
Even more fascinating- common herbicides that are generally pretty
non-toxic to humans seem to stop the Apicoplast from working.
O =Apicoplast

32. Plasmodium blood forms: the ring stage
1st 14-16 hours spent as ring
stage, or young trophozoite
little to no Hb degradation
only form seen in blood films of P.
falciparum
A ring stage of the cup-like
form showing the nucleus
(n), surrounded by
ribosomes and some
endoplasmic reticulum.

33. THE TROPHOZOITE
• It is the form found inside the erythrocyte after 10-18 hours post-infection
• It interact with the host cell in a very sophisticated way:
•1) it takes up the red blood cell hemoglobin and digests it inside a food
vacuole. Many of the drugs in use target this compartment;
•2) it transports proteins from the parasite to the surface of the erythrocyte for
its own benefit.

34. THE SCHIZONT
• Schizogony: form of asexual reproduction in which multiple
mitoses take place, followed by cytokinesis resulting in
multiple daughter cells
• multiple mitoses produce 20-24 nuclei
• once nuclei & organelles replicated cytokinesis occurs
• rupture of RBC membrane releases merozoites
Schizont from Plasmodium falciparum

35. P.Falciparum
Why is it important……????
• Sticky knobs - obstruction to blood flow
• Rosettes - clogs microcirculation
• Secondary organ dysfunction
• Pregnancy - adhere to placenta, so maternal
anemia & low birth weight

36. Character P.falciparum P.vivax P.ovale P.malariae
Relative age of May infect cells of Only those are Only those are Only mature cells
infected RBC all ages young &immature young &immature
Appearance of Normal size, no Enlarged, distorted Oval enlarged, Normal size, no
infected RBC distortion distorted with distortion
ragged cell walls
Stippling infected Maurer’s dots Schuffner James’s dots Ziemann’s dots
RBC dots

37. Character P.falciparum P.vivax P.ovale P.malariae
Ring form Circle configuration/ head- Delicate cytoplasmic Similar to P.vivax Smaller than P.vivax
phone configuration ring measuring 1/3 RBC Ring larger than Occupies 1/6th RBC
Scanty cytoplasm&small Single chromatin dot P.vivax Heavy chromatin dot
vacuole Ring surrounds a Often Pigment forms early
Multiple rings common vacuole thick&amoeboid
Accole forms are seen

38. Character P.falciparum P.vivax P.ovale P.malariae
Trophozoite Heavy rings common Irregular, Ring appearance Non-amoeboid
with fine pigment amoeboid usually maintained solid cytoplasm
granules Ring remnants until late In Coarse dark brown
Mature forms seen only common development pigment that
in severe infections Brown Amoeboid tendencies masks chromatin
pigment not as evident as No vacuoles in
P.vivax mature forms

39. Maurer's clefts can be seen Maurer's clefts resemble the
in P. falciparum infections Schüffner's dots seen in P.
containing older ring-form vivax and P. ovale, but are
trophozoites and asexual usually larger and more
coarse.
stages.
Visualization of these Like Schüffner's dots,
structures is dependent on the Maurer's clefts appear to
quality of the smear play a role in the metabolic
preparation and the pH of the pathways of the infected
Giemsa stain. RBCs.

42. Character P.falciparum P.vivax P.ovale P.malariae
Immature Multiple chromatin Mature Progressive Similar to P.vivax,
schizont bodies surrounded chromatin bodies dividing only smaller and may
by cytoplasm Brown pigment chromatin contain large dark
Only detected in surrounded by peripheral granules
severe infection cytoplasmic
material
Mature 8-36 merozoites. 12-24 merozoits Parasites occupy 6-12 merozoites in
schizont in clusters Surrounded by ¾ RBC rosettes
Only in severe cytoplasmic 8-12 merozoites Central arrangement
infections material Rosettes of an of brown green
average of pigment
8merozoites

43. Character P.falciparum P.vivax P.ovale P.malariae
Micro Sausage/cresent shaped Large pink to purple Similar to P.vivax, Similar to P.vivax,
Gametocyte Dispersed central chromatin mass smaller in size smaller in size
chromatin with nearly surrounded by colorless
black pigment visible to pale halo.
Brown pigment present
Macro Sausage/cresent shaped Round to oval cytoplasm Similar to P.vivax, Similar to P.vivax,
gametocyte Compact chromatin Eccentric chromatin mass smaller in size smaller in size
Black pigment visible Light brown pigment

45. schuffers amoeboid
P. vivax
Rings and accole maurers
P. falciparum
Band forms Undotted RBC
P.malariae
James dots
P.ovale

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