2. Presentation Layout:
1. Introduction
2. Evolution and Origin
3. Epidemiology
4. Life Cycle Of Malarial Parasite
5. Mode of transmission
6. Pathophysiology and pathogenesis
7. Clinical presentation of malaria
8. Diagnostic Test
9. Antimalarial Drugs and treatment guideline
Sunday, August 2, 2020 2
3. Introduction:
• Malaria is derived from Italian word; mal (= bad) and aria (= air).
• It is caused by protozoan parasites called Plasmodium.
• More than 200 species of the genus Plasmodium (=plasma + eidos,
form) have been identified that are parasitic to reptiles, birds, and
mammals.
• There are five identified species of this parasite causing human
malaria, namely, Plasmodium vivax, P. falciparum, P. ovale, P.
malariae and P. knowlesi.
Sunday, August 2, 2020 3
4. • The infection is transmitted between humans by the female
anopheles mosquito.
• It is a disease that can be treated in just 48 hours, yet it can cause
fatal complications if the diagnosis and treatment are delayed.
Evolution And Origin:
• Man and Malaria seem to have evolved together.
• It is believed that most, if not all, of today’s populations of human
malaria may have had their origin in West Africa (P. falciparum) and
West and Central Africa (P. vivax).
Sunday, August 2, 2020 4
5. Epidemiology:
• Globally, an estimated 3.2 billion people continue to be at risk of being
infected with malaria and developing disease, and 1.2 billion are at
high risk (>1 in 1000 chance of getting malaria in a year).
• According to World Malaria Report 2018, in 2017, an estimated 219
million cases of malaria occurred worldwide, compared with 239
million cases in 2010 and 217 million cases in 2016.
• Fifteen countries in sub-Saharan Africa and India carried almost 80%
of the global malaria burden.
Sunday, August 2, 2020 5
6. • Five countries accounted for nearly half of all malaria cases
worldwide: Nigeria (25%), Democratic Republic of the Congo (11%),
Mozambique (5%), India (4%) and Uganda (4%).
• According to the World Malaria Report 2017, India accounted for
6% of all malaria cases in the world, 6% of the deaths, and 51% of
the global P. vivax cases. The Report estimates the total cases in
India at 1.31 million (0.94-1.83 million) and deaths at 23990.
• Nepal has achieved a significant reduction in its malaria; 3900
cases in 2010 down to 585 cases in 2018.
Epidemiology cont’d…
Sunday, August 2, 2020 6
7. Anopheles Mosquito:
Why does a mosquito need human blood?
The female mosquito lays 30-150 eggs every 2-3 days.
Human blood is needed to nourish these eggs and Anopheles
shows the most regular cycles of blood feeding and egg
laying.
How long do they live?
The average life span of a mosquito is 2-3 weeks. It can be
longer in ideal living conditions.
Sunday, August 2, 2020 7
8. Life Cycle Of Malarial
Parasite
Sunday, August 2, 2020 8
9. Life Cycle Of Malarial Parasite
• The malaria parasite has a complex, multistage life cycle occurring
within two living beings, the vector mosquitoes (sexual phase or
sporogony) and the vertebrate hosts (asexual phase or schizogony).
• The parasite passes through several stages of development such as
the sporozoites (Gr. Sporos = seeds; the infectious form injected by the
mosquito), merozoites (Gr. Meros = piece; the stage invading the
erythrocytes), trophozoites (Gr. Trophes = nourishment; the form
multiplying in erythrocytes), and gametocytes (sexual stages) and all
these stages have their own unique shapes and structures and protein
complements.
• The surface proteins and metabolic pathways keep changing during
these different stages, that help the parasite to evade the immune
clearance, while also creating problems for the development of drugsSunday, August 2, 2020 9
10. Pre-erythrocytic Phase – Schizogony in the Liver:
• The entire pre-erythrocytic phase lasts about 5–16 days depending on
the parasite species: on an average 5-6 days for P. falciparum, 8
days for P. vivax, 9 days for P. ovale, 13 days for P. malariae and 8-9
days for P. knowlesi.
• The pre-erythrocytic phase remains a “silent” phase, with little
pathology and no symptoms, as only a few hepatocytes are affected.
• This phase is also a single cycle, unlike the next, erythrocytic stage,
which occurs repeatedly.
Sunday, August 2, 2020 10
11. • The erythrocytic cycle occurs every 24 hours in case of P. knowlesi,
48 h in cases of P. falciparum, P. vivax and P. ovale and 72 h in case
of P. malariae.
• During each cycle, each merozoite grows and divides within the
vacuole into 8–32 (average 10) fresh merozoites, through the stages
of ring, trophozoite, and schizont.
• At the end of the cycle, the infected red cells rupture, releasing the
new merozoites that in turn infect more RBCs. With unbridled growth,
the parasite numbers can rise rapidly to levels as high as 1013 per
host.
Erythrocytic Phase
Sunday, August 2, 2020 11
12. Mode of transmission:
1.Bite from infected female anopheles mosquito (principal cause)
2.Transplacental
3.Transfusion
4.Needle stick injury
Sunday, August 2, 2020 12
13. Pathophysiology:
Sunday, August 2, 2020 13
• At the completion of the
schizogony within the red cells,
newly developed merozoites
are released by the lysis of
infected erythrocytes and along
with them, numerous known
and unknown waste
substances, such as red cell
membrane products, hemozoin
pigment, and other toxic factors
such as
glycosylphosphatidylinositol
(GPI) are also released into the
blood.
15. Incubation Period:
• P. vivax: 10-17 days
• P. ovalae: 1o-17 days
• P. malariae: 18-40 days
• P. falciparum: 8-11 days
Symptoms:
• Fever
• Chills
• Sweats
• Headaches
• Nausea and vomiting
• Body aches
• General malaise
• Diarrhoea
Sunday, August 2, 2020 15
16. Clinical type of malaria:
1. Uncomplicated malaria
2. Complicated malaria
Uncomplicated malaria
The classical malaria attack last 6-10 hours. It consist of;
1. A Cold Stage:
• Sensation of cold
• Shivering
• 15 minutes to 1 hours
• Onset is less with lassitude, headache, nausea and chilly sensation
• Pulse is rapid but weak
Sunday, August 2, 2020 16
17. 2. A Hot Stage:
• Fever, headache, vomiting
• Seizure in young children
• Last for 2-6 hour
• Patient feels burning hot with intense headache and nausea diminished
• Pulse is full and respiration is rapid
3. A Sweating Stage:
• Sweats
• Return to normal temperature
• Patient feel tiredness
• It last for 2-4 hours
• Fever come down with profuse
sweating
• Body temperature drops
rapidly to normal
• Pulse rate become slower
• Patient feels relieved and fall
asleep
Sunday, August 2, 2020 17
18. • These malaria attack
occur classically every
second day week with
P. falciparum, P. vivax,
P. ovalae and every
third day in P. malariae.
Sunday, August 2, 2020 18
19. • Severe/ complicated
malaria is defined by
the demonstration of
asexual forms of the
malaria parasites in
the blood in a patient
with a potentially fatal
manifestation or
complication of
malaria in whom other
diagnoses have been
excluded.
2. Complicated Malaria
Sunday, August 2, 2020 19
20. Cerebral Malaria:
• most common complication and cause of
death in severe P. falciparum infection.
• A strict definition of cerebral malaria has
been recommended for sake of clarity and
this requires the presence of unarousable
coma, exclusion of other encephalopathies
and confirmation of P. falciparum infection.
• Manifestations of cerebral dysfunction include
any degree of impaired consciousness,
delirium, abnormal neurological signs, and
focal and generalized convulsions, seizures.
Sunday, August 2, 2020 20
22. Causes of neurological manifestations in malaria:
1. High-grade Fever
2. Antimalarial Drugs
3. Hypoglycemia
4. Hyponatremia,
5. Severe Anaemia And Hypoxemia
6. Vascular Disease, Other Neurological Infections And
Diseases.
Investigations: Lumbar puncture and CSF analysis may have to be
done in all doubtful cases and to rule out associated meningitis. In
malaria, CSF pressure is normal to elevated, fluid is clear and WBCs
are fewer than 10/µl; protein and lactic acid levels are elevated.
EEG may show non-specific abnormalities. CT scan of the brain is
usually normal.Sunday, August 2, 2020 22
24. Microscopic Tests
• The microscopic tests involve staining
and direct visualization of the parasite
under the microscope.
• Thick smear: The thick smear of correct
thickness is the one through which newsprint is
barely visible. It is dried for 30 minutes and not
fixed with methanol. This allows the red blood
cells to be hemolyzed and leukocytes and any
malaria parasites present will be the only
detectable elements. However, due to the
hemolysis and slow drying, the plasmodia
morphology can get distorted, making
differentiation of species difficult. Thick smears
are therefore used to detect infection, and to
estimate parasite concentration.
Sunday, August 2, 2020 24
25. • Thin smear: Air dry the thin smear for 10
minutes. After drying, the thin smear
should be fixed in methanol. This can be
done by either dipping the thin smear into
methanol for 5 seconds or by dabbing the
thin smear with a methanol-soaked
cotton ball. While fixing the thin smear, all
care should be taken to avoid exposure
of the thick smear to methanol.
• Staining: Giemsa’s, Wright’s and
Leishman’s are suitable for staining
the smears.
Sunday, August 2, 2020 25
29. Classification Of Anti Malarial Drugs Based On Anti
Malarial Activity:
1. Tissue schizonticides for causal prophylaxis:
• These drugs act on the primary tissue forms of the plasmodia which
after growth within the liver, initiate the erythrocytic stage.
• By blocking this stage, further development of the infection can be
theoretically prevented.
• Pyrimethamine and Primaquine have this activity.
• However since it is impossible to predict the infection before clinical
symptoms begin, this mode of therapy is more theoretical than
practical.Sunday, August 2, 2020 29
30. • These drugs act on the hypnozoites of P. vivax and P. ovale in the
liver that cause relapse of symptoms on reactivation.
• Primaquine is the prototype drug; pyrimethamine also has such
activity.
2. Tissue schizonticides for preventing
relapse:
3. Blood schizonticides:
• These drugs act on the blood forms of the parasite and thereby
terminate clinical attacks of malaria.
• These are the most important drugs in anti malarial chemotherapy.
• These include chloroquine, quinine, mefloquine, halofantrine,
pyrimethamine, sulfadoxine, sulfones, tetracyclines etc.Sunday, August 2, 2020 30
31. 4. Gametocytocides:
• These drugs destroy the sexual forms of the parasite in the blood and
thereby prevent transmission of the infection to the mosquito.
• Chloroquine and quinine have gametocytocidal activity against P. vivax
and P. malariae, but not against P. falciparum.
• Primaquine has gametocytocidal activity against all plasmodia,
including P. falciparum.
Thus in effect, treatment of malaria would include a blood schizonticide,
a gametocytocide and a tissue schizonticide (in case of P. vivax and P.
ovale). A combination of chloroquine and primaquine is thus needed in
ALL cases of malaria.Sunday, August 2, 2020 31
32. The Artemisinin Derivatives
• Artemisinin or Qinghaosu (“ching-how-soo”) is the active principal of
the Chinese medicinal herb Artemisia annua.
• Artemisinin derivatives are used for the treatment of cerebral
malaria as well as for the control of multi-drug resistant P.
falciparum malaria.
• It is the fastest acting anti malarial available. It inhibits the
development of the trophozoites and thus prevents progression of
the disease. Young circulating parasites are killed before they
sequester in the deep microvasculature. These drugs starts acting
within 12 hours.
• Availability: Artemisinin is available as its derivatives, Artemether,
Artesunate And Arteether.Sunday, August 2, 2020 32