INFECTIOUS PROTOZOAL INFECTION

1. MALARIA

2. INTRODUCTION
 Malaria is an infectious disease caused by
protozoan of the genus Plasmodium
(P.falciparum, P.vivax, P.malariae or
P.ovale), which is transmitted by the bite
of an infected female Anophelus
mosquito. Malaria is characterised by
recurrent episodes of chills, fever,
sweating and anaemia.

3.  Quartan malaria
 Falciparum malaria
 Blackwater fever
 Tertian malaria
Alternative names:

4. EPIDEMIOLOGY
 Malaria is typically found in warmer regions of the
world. In tropical and subtropical climates.
 Plasmodium vivax is more prevalent in India,
Pakistan, Bangladesh, Sri Lanka, and Central
America
 P. falciparum is predominant in Africa, Haiti,
Dominican Republic, the Amazon region of South
America, and New Guinea.
 Plasmodium ovale occur in Africa, and the
distribution of Plasmodium malariae is considered
worldwide.

6. ETIOLOGY
 Malaria is caused by the bite of an infected
female anopheles mosquito that introduces
the sporozoites of the following:
i. Plasmodium falciparum,
ii. Plasmodium vivax
iii. Plasmodium ovale
iv. Plasmodium malariae
 It can also be caused by blood transfusion in
rare cases.

7. TRANSMISSION

8. • Blood tranfusions
• Organ transplants
• Shared use of needles and syrings
• Mother to fetus brfore or during
delivery
Malaria can also be transmitted
through

9. PATHOPHYSIOLOGY
2 Phases
- Human host
- Mosquito inhabitation

10. Animated lifecycle of the malaria parasite
TRANSMISSION
TO MAN
TRANSMISSION
TO MAN
LIVER
Sporozoites
Nucleus
Hypnozoite
Infected
Hepatocyte
Schizont
Merozoites
Erythrocyte
Ring
Trophozoite
Schizont
43 – 48 h
Cycle leading
to clinical
symptoms
P. vivax
dormant stage
Gametocytes
TRANSMISSION
TO MOSQUITO
Macro-
gametocyte
Macro-
gametocyte
(Exflagellation)
Diploid
Zygote
Ookinete
Oocysts
Sporozoites
15-30 mins
5.4 days
9 days
15 mins
1h
12-36h
9-12 days

12. DIAGNOSIS
The diagnosis of malaria may in fact into two
ways:
 Direct diagnosis: Direct demonstration of the
parasite whole cell or of parasite’s nucleic
acid or products in the blood.
 Indirect Diagnosis: The demonstration of the
patient’s immune response to the infection
(immunodiagnosis)

13. A)LIGHT MICROSCOPIC
OBSERVATION(LMO)
1) THIN FILM TEST
 Observation of malarial parasites are optimal when
parasites are fixed and observed in RBCs after
appropriate staining.
 Thin film has a low sensitivity and is thus
inadequate for low parasitaemic infection.
DIRECTDIAGNOSIS

14. 2) THICK FILM TEST
 An adequate parasite concentration method
obtained by osmotic lysis of the RBCs
releasing the parasites.
 The sensitivity is more than thin film.

15. B) THE DIRECT ACRIDINE ORANGE
STAINING
 sensitive microscopic test based on the ability
of acridine orange to stain nucleic acid
containing cells.

16. C) DETECTION OF P. FALCIPARUM
ANTIGEN
The production of histidine rich protein II
(HRP-II) antigen by blood stages of
Plasmodium falciparum forms the basis for the
development of ELISA antigen test.

17. INDIRECTDIAGNOSIS
(IMMUNODIAGNOSIS)
1) IMMUNOFLUORESCENT ASSAY
TEST (IFAT)
First serological test used for malarial
antibodies was immunofluorescence
(IFAT), which may give quantitative
results for both G and M specific
immunoglobulin.

18. 2) Indirect Haemoagglutination Test (IHA)
 Simple and suitable for field studies but its
sensitivity and specificity are poor.
3) Radioimmuno Assay (RIA)
 Sometimes used but needs well equipped
research laboratories and personnel.

19. Known quantity of
antigen is made
radioactive frequently by
labelling it with gama
radio active isotopes of
iodine(125-i)
Radio labelled antigen is
mixed with known
amount of antibody for
the antigen and they
bind.
Sample serum from a patient
containing an unknown of that same
antigen is added. This causes the
unlabelled antigen(cold) from the
serum to compete with the radio
labelled antigen(hot) for antibody
binding site.
As the concentration of the cold
antigen increases ,more of it
binds to the antibody ,displacing
the radio labelled variant and
reduces the ratio of the antibody
bound radio labelled antigen to
free radio labelled antigen.
The bound antigens are then
seperated from the unbound
and the radio activity of the free
antigen remaining in the
supernatant is measured using
a gamma counter.

20. MANAGEMENT
GOALS OF THERAPY
 Releive the signs and symptoms of a disease
 Decrease morbidity and mortality associated with
the infection.
 To prevent the clinical attack of malaria
(prophylactic)
 To treat the clinical attack of malaria (clinical
curative)
 To completely eradicate the parasite from the
patients body (radical curative).
 To cut down human to mosquito transmission
(gametocidal).

21. NON PHARMACOLOGICAL
 Fluid therapy
 Blood transfusion
 Iron rich food

22. PHARMACOLOGICAL
Dose: 1gm stat followed by 500 mg after 6 hours and 500 mg
daily for next 2 days
C/I:pregnancy,liver damage,severe GI,hematological
diseases,eye impairment.
S/E:loss of hearing ,rashes, photo allergy,mental
disturbances,myopathy …etc.,
CHLOROQUINE

23. MOA
Drug taken
up in the
erythrocyte
Concentrates in
the acidic
vacuoles of the
parasite Parasite
digests the
host
haemoglobin
Transports it
into their
acidic food
vacuole
Toxic product
HAEM

24. HAEM HAEMOZOIN
(non-toxic)
HAEM POLYMERASE
CHLOROQUINE
Also inhibits
digestion of HB
Thus disrupts
parasites amino
acid supply

25. ATOVAQUONE
DOSE:250 mg
MOA: inhibits ETC leading to collapse of
mitochondrial membrane .
C/I:Hypersensitivity.
S/E:insomnia, rash, weakness,abdominal
pain.

26. MEFLOQUINE
Dose:15-25mg /kg
MOA: Same as that of chloroquine.
C/I: hypersensitivity
S/E: psychological changes (depression
, confusion ,anxiety ,hallucination)
INT: quinidine and quinine, beta blocker,
ty phoid vaccine and sodium valproate.

27. QUININE SULPHATE
Dose:15 mg daily for 14 days.
MOA: inhibits haem polymerase
C/I: patient is suffering from systemic
disease
S/E:abdominal cramp ,epigastric distress
,anaemia, cyanosis and leukocytosis.

28. ARTESUNATE
Dose: parenteral 120 mg on 1st day followed by 60 mg daily
for next 4 days.Oral 100 mg twice on 1st day followed by 50
mg twice daily for next 4 days.
MOA: Interacts with haem and generates free radicals that
binds with membrane protein and damages.
S/E: Reticulocytopenia,bradycardia ,elevation of serum
transaminases
INT:antimalarial action potentiated by oxidant drugs.

29. PYRIMETHAMINE
DOSE:25 mg
MOA: inhibits the conversion of dihydrofolic
acid to tetrahyrofolic by blockade of
dihydrofolate reductase
C/I:Hypersensitivity,anaemia,renal
dysfunction,breastfeeding.
S/E:Anorexia,maliase,seizures,leucopenia,thr
ombocytopenia.

30. TREATMENTALGORITHM

31. GUIDELINES
TREATMENT OF UNCOMPLICATED
PLASMODIUM FALCIPARUM MALARIA
 Artemisinin combination therapy (ACT) is the
drug of choice for all confirmed cases of
uncomplicated PF. This should be combined with
primaquine (PQ) (0.75 mg/kg body weight or 45
mg) on day-2. There are several ACTs

33. TREATMENT OF UNCOMPLICATED
PLASMODIUM VIVAX MALARIA
 Chloroquine is the drug of choice of
Plasmodium vivax (PV) cases. It is given at a
dose of 10 mg/kg (600 mg) on day-1 and day-2
and 300 mg on day-3.
 Primaquine at a dose of 0.25 mg/kg (15
mg/day) for 14 days is to be added to prevent
relapse. Primaquine is contraindicated in
G6PD deficiency cases, infants and pregnant
women.

34. TREATMENT OF SEVERE PLASMODIUM
FALCIPARUM MALARIA
 Artesunate: It is the drug of choice. It should be
given in a dose of 2.4 mg/kg IV on admission (0
hour), then at 12 hours and 24 hours and then
once daily till the patient takes orally or for 7
days. Then, they should get full course of ACT
for 3 days
 Quinine: Alternative to AS. It should be given at
a dose of 20 mg /kg of body weight in 5%
dextrose/ dextrose saline, over 4 hours. It is
followed by 10 mg/kg of body weight 8 hourly
infusions which should be started 8 hours after
the 1st loading dose

35. TREATMENT OF SEVERE PLASMODIUM VIVAX
MALARIA OR MIXED MALARIAL INFECTION
 It should be treated as severe PF malaria cases.
TREATMENT OF SEVERE PLASMODIUM
FALCIPARUM MALARIA CASES IN PREGNANCY
 First trimester: Parenteral quinine is the drug of
choice. If it is not available, parenteral artemisinin
derivatives can be given to save the life of the mother
 Second trimester and third trimester: Parenteral
artemisinin derivatives—AS is the drug of choice.

36. CHEMOPROPHYLAXIS
 Short-term Prophylaxis (< 6 Weeks)
Doxycycline: 100 mg/day (1.5 mg/kg of body
weight per day) to be started 2 days before and
continued 4 weeks after leaving a malarias area.
 Long-term Prophylaxis (> 6 Weeks)
Mefloquine: 250 mg weekly (5 mg/kg of body
weight/week) to be started 2 weeks before going
to the affected area and continued for 4 weeks
after leaving the affected area.

37. COMPLICATIONS
Cerebral malaria
Destruction of blood cells(hemolytic anemia)
Kidney failure
Hypoglycaemia
Fluid ,electrolyte and acid –base disturbance
Circulatory collapse
Hyperpyrexia
Acidosis
Pulmonary edema
Rupture of the spleen

38. PREVENTION
Use mosquito repellants.
Sleep under mosquito nets – especially
effective if they have been treated with
insecticides
Use window screens

39. •Spray insecticides on your home’s
walls.
•Wear insect repellant and long sleeve
clothing when outdoors at night.
•Eliminate places around your home
where mosquitoes breed.

40. REFERENCES
 Guidelines for the Treatment of Malaria 2010 (2nd
edition). World Health Organization, 20, Avenue
Appia-CH-1211 Geneva 27.
 Guidelines for Diagnosis and Treatment of Malaria in
India 2011 (2nd edition). Government of India,
National Institute of Malaria Research, New Delhi.
 Handbook of pharmacotherapy 7th edition by Joseph
T Dipiro
 Drug today
 Essentials of medical pharmacology 7th edition KD
Tripathi