this ppt tells about the basic pathology and mechanisms and etiology of malaria

1. M.S. (Pharm)- PHARMACOLOGY & TOXICOLOGY
CHEMOTHERAPY OF PARASITIC & MICROBIAL
INFECTIONS
(PC- 540)
NIPER-Guwahati

2. What was the first Synthetic
compound
used as a medicine?
Methylene Blue
1876 - Heinrich Caro – a German chemist
1891 - Paul Guttmann & Paul Ehrlich – used as a
antimalarial drug

3.  Malaria or a disease resembling malaria has been noted for more than
4,000 years.
 Detection of malaria antigen in skin and lung sample of mummies proved
the prevalence of malaria in Egypt around 3000 years ago.
 2700 BC, the Chinese medico Nei Ching described several characteristic
symptoms
 Hippocrates (460 BC – 370 BC), the “father of medicine”
mentioned the principal symptoms of malaria in his writings
 Sushruta, Indian medical treatise described the fever
caused by bites of certain insects
 200 BC- Roman medical literature described the causes
and symptoms
History of Malaria

4. Charles Louis Alphonse Laveran (1880)
French army surgeon
Malaria to Pathogenesis: Landmark Discoveries
Sir Ronald Ross (1897)
1907 1902

5. 1890- the Italian investigators Giovanni Batista Grassi and
Raimondo Filetti first introduced the names P. malariae and
Plasmodium vivax for two of the malaria parasites that affect humans.
1897- William H. Welch, named the malignant tertian malaria
parasite P. falciparum.
1922 - John William Watson Stephens- described Plasmodium ovale.
1931- Robert Knowles and Brij Mohan Das Gupta described
Plasmodium knowlesi in a long-tailed macaque.
Malaria to Pathogenesis: Landmark Discoveries

6.  Sir Ronald Ross (1902) - for identifying the oocyst of malaria
parasite in the gut wall of mosquito (a cyst containing a zygote
formed by a parasitic protozoan such as the malaria parasite.)
 Alphonse Laveran (1907) - for the observation of parasites in the
blood of a patient suffering from intermittent fever
 Julius Wagner- Jauregg (1927) for treating dementia paralytica
by deliberate infection of malaria parasites
 Paul Hermann Müller (1948) - for the discovery of DDT, which
was used for malaria vector control
 Tu Youyou (2015) - for the isolation of antimalarial drug
Artemisinin.
Noble Prizes for malaria related research

7. Female Anopheles -Vector
• transmitted through the bites of female Anopheles mosquitoes.
• more than 400 different species
• 30 to 40 Anopheles species commonly transmit malaria parasites
• Anopheles gambiae- transmits of the deadly species Plasmodium
falciparum

8. Taxonomic classification
Kingdom Protista
Subkingdom Protozoa
Phylum Apicomplexa
Class Aconoidasida
Order Haemosporida
Family Plasmodiidae
Genus Plasmodium
Malaria parasite
 more than 100 species of Plasmodium
 5 species infect Human
 29 species infect non-human
primates, rodents, bats, porcupines
and squirrels
 ~70 species infect Birds
P. falciparum
P. vivax
P. malariae.
P. ovale
P. knowlesi

9. Clinical manifestations + Symptoms
 Fever
 Sweating
 Anemia
 Splenomegaly (enlarged spleen)
 Irritability
 Coma
 Retinal Hemorrhages
 Algid Malaria (a shock like syndrome)
 Respiratory distress syndrome
 Cerebral Malaria
 Black water fever
 Malaria nephropathy

10. Laboratory Diagnosis
• Laboratory diagnosis of malaria is confirmed by the
demonstration of malarial parasites in the blood film
under microscopic examination.
• Antigen detection methods- HRP-II, Aldose, LDH
• Serology
• Molecular Diagnosis - PCR

11.  National Malaria Control Program-1953
 National Malaria Eradication Program- 1958
 Resurgence of Malaria - 1967 to 1976
 Urban Malaria Scheme - 1971
 Modified Plan of Operation - 1977
 Malaria Action Program- 1995
 Enhanced malaria control Project - 1997
 National Anti-Malaria Program- 1999
 National Vector Borne Disease Control Program- 2004
 Intensified Malaria Control Project - 2005
 WHO Global Malaria Programme (GMP)
Malaria control programs in India

12. Global Distribution and Impact of Malaria
219 million malaria cases
435 000 associated deaths
In India - 8760000 cases/17400 deaths

13. PLASMODIUM LIFE CYCLE

17. HUMAN STAGE FROM MOSQUITOE’S BITETO DEVELOPMENT OF
GAMETES

21. Etiology of Malaria parasite
■P. falciparum, found worldwide in tropical
and subtropical areas.
■P. falciparum can cause severe malaria
because it multiples rapidly in the blood,
and can thus cause severe blood loss
(anemia). It has Malignant tertian cycle
■In addition, the infected parasites can clog
small blood vessels – rosette formation
■When this occurs in the brain, cerebral
malaria results, a complication that can be
fatal.
Ring-form trophozoites of
P. falciparum
in a thin blood smear

22. • P. vivax, which is found mostly in Asia,
Latin America, and in some parts of
Africa.
• Because of the population densities
especially in Asia it is probably the
most prevalent human malaria
parasite.
• Benign tertian cycle
• P. vivax (as well as P. ovale) has dormant
liver stages ("hypnozoites") that can
activate and invade the blood
("relapse") several months or years
after the infecting mosquito bite.
Ring-form trophozoites of
P. Vivax in a thin blood smear.
Etiology of Malaria parasite

23. ■ P. ovale is found mostly in Africa (especially
West Africa) and the islands of the western
Pacific.
■ It is biologically and morphologically very
similar to P. vivax.
■ Benign tertian cycle
■ However, differently from P. vivax, it can infect
individuals who are negative for the Duffy
blood group, which is the case for many
residents of sub-Saharan Africa.
■ This explains the greater prevalence of P.
ovale (rather than P. vivax ) in most of Africa.
Trophozoites of P. ovale
in a thin blood smear.
Etiology of Malaria parasite

24. • P. malariae, found worldwide, is
the only human malaria parasite
species that has a quartan cycle
(three-day cycle).
• If untreated, P. malariae causes a
long-lasting, chronic infection
that in some cases can last a
lifetime.
• In some chronically infected
patients P. malariae can cause
serious complications such as the
nephrotic syndrome.
Band-form trophozoites of P.
malariae in a thin blood smear.
Etiology of Malaria parasite

25. ■P. knowlesi is found throughout
Southeast Asia as a natural pathogen
of long-tailed and pig-tailed
macaques.
■It has recently been shown to be a
significant cause of zoonotic malaria
in that region, particularly in
Malaysia.
■P. knowlesi has a 24-hour
replication cycle and so can
rapidly progress from an
uncomplicated to a severe
infection; fatal cases have been
reported.
Schizonts and ring-form
trophozoites of
P. knowlesi in a thin blood smear.
Etiology of Malaria parasite

26. Species
Ring forms Growing forms Mature schizonts Gametocytes
Stippling
(later stages)
P. falciparum Unaltered (0.15–0.5
diameter size)
cytoplasm very fine in
young rings; thick,
irregular in old rings.
Marginal (accole)
forms, forms with two
chromatin dots and
multiple infections
common.
RBC unaltered in
size, sometimes
spotted, pale,
parasite compact;
pigment dense
brown or black
mass
Not usually seen in
peripheral blood.
RBC unaltered in
size, sometimes
spotted, pale,
parasites about 0.6 of
RBC, nuclei or
merozoites 8–24.
Pigment clumped
black.
RBC distorted,
parasite
crescentic.
Maurer’s
clefts.
P. vivax 0.3–0.5 diameter of
RBC which is
unaltered in size:
cytoplasm, circle,
thin.
RBC enlarged,
stippled, parasite
amoeboid,
vacuolated,
pigment fine and
scattered, golden
brown.
RBC much enlarged,
stippled, parasite large
filling enlarged RBC.
merozoites 12- 24,
pigment,
a golden-brown
central loose mass.
RBC enlarged,
stippled, parasite
large, rounded,
filling enlarged
RBC.
Schuffner’s
dots
P. ovale 0.3–0.5 diameter of
RBC which is
unaltered in size:
cytoplasm circle,
thicker.
RBC unaltered or
slightly enlarged;
stippled, may be
oval and
fimbriated.
Parasite compact,
rounded, pigment
fine brown grains.
RBC frequently oval,
fimbriated, stippled.
Parasite as for P.
malariae but does not
fill the RBC. Pigment
brown central clump.
RBC slightly
enlarged,
stippled, parasite
round.
James’s dots.
Morphological differences between human Plasmodium species in
blood smears

27. P. malariae 0.3–0.5 diameter of
RBC which is
unaltered in size:
cytoplasm circle,
thicker.
RBC unaltered or
shrunk, parasite
compact, rounded
/band-shaped,
dark brown or
black pigment,
often concentrates
in a line along
one edge of band.
Parasite fills
unaltered RBC
completely. Nuclei or
merozoites 6–12,
usually 8, sometimes
forming a rosette.
Pigment brown or
yellowish, central
clump
RBC unaltered,
parasite small,
round, filling
RBC.
None (fine dots
when
overstained).
P. knowlesi 0.3–0.5 diameter of
RBC which is
unaltered in size:
cytoplasm circle,
thicker
Elongated
trophozoites
stretching across
the erythrocyte,
called band
forms.
Typically have 8-10
merozoites, arranged
in a rosette pattern
with a clump of
pigment in the center.
RBC unaltered,
parasite small,
round, filling
RBC.
None (fine dots
when
over stained).
Morphological differences between human Plasmodium species in blood
smears