Malaria
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Transcript of Malaria
MALARIA
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.
Quartan malaria
Falciparum malaria
Blackwater fever
Tertian malaria
Alternative names:
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.
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.
TRANSMISSION
• Blood tranfusions
• Organ transplants
• Shared use of needles and syrings
• Mother to fetus brfore or during delivery
Malaria can also be transmitted through
PATHOPHYSIOLOGY
2 Phases
- Human host
- Mosquito inhabitation
Animated lifecycle of the malaria parasite
1
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
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)
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.
DIR
EC
T D
IAG
NO
SIS
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.
B) THE DIRECT ACRIDINE ORANGE
STAINING
sensitive microscopic test based on the ability
of acridine orange to stain nucleic acid
containing cells.
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.
IND
IRE
CT
DIA
GN
OS
IS
(IM
MU
NO
DIA
GN
OS
IS)
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.
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.
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.
MANAGEMENTGOALS 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).
NON PHARMACOLOGICAL
Fluid therapy
Blood transfusion
Iron rich food
PH
AR
MA
CO
LO
GIC
AL
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,hematologicaldiseases,eye impairment.
S/E:loss of hearing ,rashes, photo allergy,mentaldisturbances,myopathy …etc.,
CHLOROQUINE
MOA
Drug taken
up in the
erythrocyte
Concentrates in
the acidic
vacuoles of the
parasiteParasite digests the host haemoglobin
Transports it
into their
acidic food
vacuole
Toxic product
HAEM
HAEM HAEMOZOIN
(non-toxic)
HAEM POLYMERASE
CHLOROQUINE
Also inhibits
digestion of HB
Thus disrupts
parasites amino
acid supply
ATOVAQUONE
DOSE:250 mg
MOA: inhibits ETC leading to collapse of mitochondrial membrane .
C/I:Hypersensitivity.
S/E:insomnia, rash, weakness,abdominalpain.
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.
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.
ARTESUNATEDose: 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.
PYRIMETHAMINE
DOSE:25 mg
MOA: inhibits the conversion of dihydrofolicacid to tetrahyrofolic by blockade of dihydrofolate reductase
C/I:Hypersensitivity,anaemia,renal dysfunction,breastfeeding.
S/E:Anorexia,maliase,seizures,leucopenia,thrombocytopenia.
TREA
TMEN
T AL
GO
RITH
M
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
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.
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
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 artemisininderivatives can be given to save the life of the mother
Second trimester and third trimester: Parenteral artemisinin derivatives—AS is the drug of choice.
CHEMOPROPHYLAXIS
Short-term Prophylaxis (< 6 Weeks)
Doxycycline: 100 mg/day (1.5 mg/kg of bodyweight per day) to be started 2 days before andcontinued 4 weeks after leaving a malarias area.
Long-term Prophylaxis (> 6 Weeks)
Mefloquine: 250 mg weekly (5 mg/kg of bodyweight/week) to be started 2 weeks before goingto the affected area and continued for 4 weeksafter leaving the affected area.
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
PREVENTION
Use mosquito repellants.
Sleep under mosquito nets – especially
effective if they have been treated with
insecticides
Use window screens
•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.
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