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1. Malaria Pathogenesis and
Reason for drug resistant

2. Plasmodium vivax (tertian)
Plasmodium ovale (tertian)
Plasmodium falciparum (tertian)
Plasmodium malariae (quartian)

3. Malaria Life Sporogony
Cycle Oocyst
Life Cycle Sporozoites
Mosquito Salivary
Zygote Gland
Hypnozoites
Exo- (for P. vivax
and P. ovale)
erythrocytic
(hepatic) cycle
Gametocytes
Erythrocytic
Cycle
Schizogony

4. Exo-erythrocytic (hepatic) Cycle:
Sporozoires injected Sporozoites infect liver cells and
into human host during develop into schizonts, which release
blood meal merozoites into the blood
Parasites
mature in
mosquito
midgut and HUMAN Dormant liver stages
MOSQUITO (hypnozoites) of P.
migrate to
salivary vivax and P. ovale
glands
Erythrocytic Cycle:
Merozoites infect red
blood cells to form
Some merozoites schizonts
Parasite undergoes
sexual reproduction in differentiate into male or
the mosquito female gametocyctes

5. Sporogonic cycle
Infective Period
Mosquito bites
uninfected
person Mosquito Vector
Parasites visible Human Host
Mosquito bites
gametocytemic
Prepatent Period Symptom onset
person
Recovery
Incubation Period
Clinical Illness

6.  Blood is infected with sporozoites about 30
minutes after the mosquito bite
 The sporozoites are eaten by
macrophages or enter the liver cells where
they multiply –
pre-erythrocytic schizogeny
 P. vivax and P. ovale sporozoites form
parasites in the liver called hypnozoites

7.  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

8.  P. vivax and P. ovale hypnozoites remain
dormant for months
 They develop and undergoes pre-
erythrocytic sporogeny
 The schizonts rupture, releasing
merozoites and produce clinical relapse

9. Malaria Life Sporogony
Cycle Oocyst
Life Cycle Sporozoites
Mosquito Salivary
Zygote Gland
Hypnozoites
Exo- (for P. vivax
and P. ovale)
erythrocytic
(hepatic) cycle
Gametocytes
Erythrocytic
Cycle
Schizogony

10.  P. vivax and P. ovale hypnozoites remain
dormant for months
 They develop and undergoes pre-
erythrocytic sporogeny
 The schizonts rupture, releasing
merozoites and producing clinical relapse

11.  Pre-patent period – interval between date of
infection and detection of parasites in peripheral
blood
 Incubation period – time between infection and
first appearance of clinical symptoms
 Merozoites from liver invade peripheral (RBC)
and develop causing changes in the RBC
 There is variability in all 3 of these features
depending on species of malaria

12.  Trophozoites are early stages with ring form the
youngest
 Tropohozoite nucleus and cytoplasm divide
forming a schizont
 Segmentation of schizont’s nucleus and
cytoplasm forms merozoites
 Schizogeny complete when schizont ruptures,
releasing merozoites into blood stream, causing
fever
 These are asexual forms

13.  Merozoites invade other RBCs and
schizongeny is repeated
 Parasite density increases until host’s
immune response slows it down
 Merozoites may develop into
gametocytes, the sexual forms of the
parasite

14.  Schizogenic periodicity is length of asexual
erythrocytic phase
 48 hours in P.f., P.v., and P.o. (tertian)
 72 hours in P.m. (quartian)
 Initially may not see characteristic fever pattern
if schizogeny not synchronous
 With synchrony, periods of fever or febrile
paroxsyms assume a more definite 3 (tertian)- or
4 (quartian)- day pattern

16.  Drug resistance is the ability of the parasite
species to survive and/or multiply despite the
administration and absorption of a drug given
in doses equal to or higher than those usually
recommended but within the limit of
tolerance.

17.  Longer half-life.
 Single mutation for resistance.
 Poor compliance
 Host immunity.
 Number of people using these drugs.

18.  a long terminal elimination half-life
 a shallow concentration-effect relationship
 mutations that confer marked reduction in
susceptibility.

19.  Drug resistance is most commonly seen in P.
falciparum.
 Only sporadic cases of resistance have been
reported in vivax malaria.
 Resistance to chloroquine is most prevalent

20.  WHO has developed a simple scheme for
estimating the degree of resistance that
involves studying the parasitemia over 28
days.
 Smears on day 2, 7 and 28 are done to grade
the resistance as R1 to R3. In a case of normal
response parasite count to fall to 25% of pre-
treatment value by 48 hours and smear
should be negative by 7 days.

21.  The asexual parasite count reduces to 25% of
the pre-treatment level in 48 hours after
starting the treatment and complete
clearance after 7 days, without subsequent
recrudescence - Complete Recovery.

22.  The asexual parasitemia reduces to < 25% of
pre-treatment level in 48 hours, but
reappears between 2-4 weeks.

23.  The asexual parasitemia reduces to < 25% of
pre-treatment level in 48 hours, but
reappears earlier.

24.  Marked reduction in asexual parasitemia
(decrease >25% but <75%) in 48 hours,
without complete clearance in 7 days.

25.  Minimal reduction in asexual parasitemia,
(decrease <25%) or an increase in parasitemia
after 48 hours.

26.  1. In endemic areas it is not easy to differentiate
recrudescence from re-infection.
 2. Recrudescence can occur beyond 28 days
also.
 3. Therapeutic failure could be due to other
causes also.
 4. RII is a very broad category.
 5. Practical difficulties in following the patient
for 28 days.
 6. Intermittent nature of parasitemia in the
blood

27. Resistance develops most rapidly when a
population of parasite encounters
subtherapeutic concentration of antimalarial
drugs.
.

28.  The following points will be helpful in
reducing the emergence of resistance:
 Selection of drugs - Use conventional drugs
first in uncomplicated cases. Greater the
exposure, higher will be the emergence of
resistance.
 Avoid drugs with longer half-life if possible
 Ensure compliance

29.  Avoid basic antimalarials for non-malarial
indications (e.g. Chloroquine for rheumatoid
arthritis in a malarial endemic area).
 Monitoring for resistance and early treatment
of these cases to prevent their spread.
 Clear policy of using newer antimalarials.
 Use of combinations to inhibit emergence of
resistance

30. THANK YOU