Falciparum malaria

1. FALCIPARUM MALARIA
AN OVER VIEW


DR.C.K.TALUKDAR
MD.,DRM,FICP,FICN,FICC
PRAGATI NURSING HOME
NALBARI

2. MALARIA
Basic considerations and clinical
features
Malaria in man is caused by four distinct
speciesofmalaria parasite:
* P.vivax,P.falciparum,P.malariae,P.ovale
* P.Vivax & P.falciparum are resposible for most of the
infections found throughout the malarial belt.
*P.malariae is widely distributed but is less common.
*P.ovale is rare but in West Africa it seems to have
replaced P.vivax.
*Malaria is estimated to kill between 1.5 and 2.7 million
people each year.
*In an average one person, often a child below 5yrs. Of
age die in every 12 seconds.
*Additional 300-500 million people contact the disease
each year(Butlon,1997)

3. MALARIA
MILESTONES
1600 B.C. References can be found in the writings
400 Hippocrates’ description of malaria.Charaka
and Sushrutha gave vivid descriptions of malaria
& even associated it with the bites of the mosquitoes.
1640 A.D. Huan del Vego – Cinchona bark for malaria treatment
1696 Morton first detailed picture of Malaria.
1717 Lanicsi Links malaria to bad air in swamps and thus
originates the name malaria.


1816 Gize-Extraction of quinine from cinchona bark
1820 Pelletier and Caventou – extraction of pure quinine alkaloids
1880 Laveran identifies malarial parasite under microscope.
1895 Golgi-Identification of P.vivax & P.malariae
1889-90 Sakharov,Marchiafava,Celli-identification of P.falciparum
cont…….

4. 1897 Ronald Ross–Demonstration on malarial oocysts
in gut of female anopheles mosquito
1934 Chloroquine synthesized by Germans.


 1939 Paul Miller – Insecticidal properties of DDT
 1944 Curd, Davey, Rose – Synthesis of Proguanil for
treatment.
 1950 Elderfield– Synthesis of primaquine.
 1967 WHO- emphasis on control of malaria rather than global
eradication of the disease.
1990’s Synthesis of quinine analogue mefloquine.
Artemesinins obtained from Quinghaosu introduced
for resistant malaria.
 1994 Sequencing of P.Falciparum Genome begun
1999 WHO Recommends – Combined therapy to delay
resistance development to anti-malarials
Including Artemesinin.
 2000 Chloroquine resistance gene identified as PfeRTK767

5. PLASMODIUM VIVAX
1. Red cells containing parasites are usually
enlarged.
2. Schuffner”s dots are frequently present in the red
cells as shown.
3. The mature ring forms tend to be large and
coarse.
4. Developing forms are frequently present.
PLASMODIUM FALCIPARUM

1. Red cells are not enlarged.
2. Rings appear fine and delicate & there maybe
several in one cell.
3. It is unusual to see developing forms in peripheral
blood films.
4. Gametocytes have a characteristic crescent
shape appearance.

6. PLASMODIUM
MALARIAE
1.Ring forms may have a squarish appearance.
2.Band forms are a characteristic of this species.
3.Mature schizonts may have a typical daisy head
appearance with up to ten merozoites.

PLASMODIUM OVALE
1. Only found in Africa.
2. Red cells enlarged.
3. Comet forms common.
4. Rings large and coarser.

7. MALARIA PATHOLOGY
* * Pigmentation of various organs with haemozoin giving a
characteristic “SLATE GREY” Or “BLACK COLOUR”.
* * Hyperplasia of the Reticulo-Endothelial system resulting
from increased activity in order to deal with parasite and
their product.
* * Parasitized erythrocytes filling the Lumina of the
capillaries of the internal organs. This is particularly seen in
P.falciparum infection.
* * Vascular changes-dilatation of sinusoidal vessels,
perivascular haemorrhages are seen in falciparum malaria.
* * Degenerative changes of parenchyma cells due to
hypoxia [ seen in falciparum malaria].
* * Effects of anaemia.
* * Immunosupression has been observed in malarial
infection and this may lead to secondary bacterial infection.

8. THE SPLEEN
Spleen is enlarged,colour varies from slate gray to black,
capsule is thin & stretched, consistency soft in acute cases
while firm in chronic cases. “AGUE CAKE SPLEEN ”
THE LIVER
The Liver is uniformly enlarged due to vascular
congestion and proliferation of reticuloendothelial cells.
The colour varies from chocolate red to slate gray or
even black depending upon the stage of congestion and
deposition of the haemozoin pigment.
BONE MARROW
KIDNEYS

9. Does the Patient Need
Hospitalization ?
Seriously ill patients needing Hospitalization-
Include:-
Continuous vomiting andinability to retain oval drugs.
Increasing Headache.
Severe Dehydration.

Poor general condition.
Alteration of sensorium.
Suspected cerebral malaria with unarousable Coma.

Hyper pyrexia, convulsion.
Pregnancy Oedema.
Bleeding disorders.

10. COMPLICATIONS :
Cerebral malaria and coma.
Hyperpyrexia.
Haemolytic Anaemia.
Non cardiogenic pulmonary oedema
(ARDS ) ;
Acute tubular necrosis and renal
failure ;
Acute Hepatomegaly and centrilobular
necrosis ;
Hypoglycaemia ;
An adrenal insufficiency like syndrome
;
Cardiac dysrhythmias ;
Lactic acidosis .

11. Pathophysiology :
of complicated malaria
Pathology associated with all malarial species is related to the
rupture of the infected RBC and release of haemozoin
(Malarial pigment).
An increased in reticulo-endothelial system is fond causing
hepato-splenomegaly.
Cytoadhence of infected red cells to the vascular endothelium &
RBC’s causing rossetting-compromises microcirculatory flow.
In cerebral malaria-due to sequestration of the infected
erythrocyles in the cerebral microcirculation.
Sequestration in cytiadherence of trophozoite and schizont infected
erythrocytes to the endothelial cells of the deeper vascular beds of
the vital organs-specially the brain,liver,gut,heart & placenta,

12. Table 1= Anti-malarial Drug
DRUG Indications Dosage
Side effects/
Precautions
Chloroquine
Tabs: 150/300mg
Syp:50mg/ml
Inj.:50mg/ml
Treatment
Prophylaxis
Adults:
Oral :
Day 1=600mg stat
300mg after 6 hrs
Day 2 = 300mg OD
Day 3 = 300mg OD
Injectable
IM = 10ml stat,
5ml after 6 hrs.,
5ml daily for 2 days
Children:
Oral : 10mg/kg stat,
5mg/kg after 6 hrs.
Then 5mg/kg/day for 2 days
300 mg OD weekly,2 wks
Before entering endemic
Area continue for 4 wks after
leaving
Hepatic and/or
renal
dysfunction,
Vision
problems,
Psoriasis,
Epilepsy,
Porphyria.

13. Contd….
Table 1:- Anti-malarial Drugs
Drug IndicationsDosage
Side effects/
precautions
Sulphadoxine
Pyrimethamine
Tablets
500mg
sulphadoxine+
25mg pyrimethamine
Liquid:
250mg
sulphadoxine+
12.5mg
pyrimethamine/5ml.
Treatment
Prophylaxis
Adults :<50 kg 2 tabs.
>50 kg 2 tabs.
Children 0.5-0.75 mg/kg
per dose.
Adults : 1 tab. Once wkly.
Unusual bleeding,
Bruising rash,
Fever, sore throat
Quinine
300mg,600mg
tabs,
300mg/ml inj.
Adults :
300-600mg TID 5-7 days
Children :
25mg/kg/day div. Every 8 hrs for
7 days,
Disturbed vision,
tinnitus,nausea,
headache,
rash,
Special Precaution
Renal dysfunction,
optic neuritis,
myasthenia gravis,
cardiac dysfunction

14. Contd.
Drug IndicationsDosage Side effects/
precautions
Primaquine
2.5,7.5,15mg
tabs.
Radical cure
of vivax
malaria
Adults :
15mg/day x 14 days
Along with standard
Chloroquine treatment
Children :
25mg/kg/day div.
Every 8 hrs for 7 days
Nausea,vomiting,weakness
abd.pain,
Methhaemoglobinaemia,
Anemia,
Leucopaemia,
G6PD test
Mefloquine
250 mg tabs.
Resistant
malaria
Adults :
15mg/kg single dose
Max.1259-1500mg or 750mg stat
followed by another 250mg 6-8 hrs.
Later
Children :
15-25mg/kg, single oral dose
Prophylaxis
5mg/kg/wk
Nausea,vomiting,diarrhoe
a,dizziness,rash,
Somnolescence,
Neuro-psychiatric
symdrome,
neuropathy,
vestibulopathy,
circulatory disease

15. Contd….
Artemether
40mg tabs.
80mg/ml inj.
Resistant
falciparum
malaria,
Severe
falciparum
malaria
IM 3.2mg/kg initially then
1.6mg/kg 12-24 hrs. for 3-7 days
Adults : Oral tab.Day 1=80mg BD
Then, 80mg OD for 2-5 days.
Children : Day 1=1.6mg/kg BD
1.6 mg/kg OD for 2-5 days
Cardio toxicity,
Blood changes,
Raised liver
Enzymes,
Neurotoxicity.
Artesunate
50mg tab.
60mg inj.
Resistant
Falciparum
Malaria,
Severe
malaria.
Oral:Day 1 : 100mg BD
Day2-5 : 50mg BD
Parenteral : 2mg/kg stat ,
1mg/kg 12 hrly. Till oral
treatment possible
Drug fever,rash
Cardio toxicity,
Raised liver
enzymes,
Arteether
150mg in 2ml
amp.
Resistant
Falciparum
malaria
Adult :
150mg inj. IM once daily for 3
days.
Children :
3mg/kg/day IM x 3 days.
Neurotoxicity
Nausea,
Dizziness,
Depressed GIT
activity

16. Treatment of Resistant Malaria
(Uncomplicated Resistant)
1.Sulphadoxine-Pyrimethamine :-
patients weighing >50kg. 3 tablets stat,
patients weighing <50kg. 2 tablets stat,
(provided patient has no sulpha allergy)
+ quinine 600mg TDS for 2 days.
2.Quinine 600mg TDS or Quinine sulphate 10mg/kg/8 hrly for 7
days + Doxycycline 100mg BD or Tetracycline 500 mg BD for 7
days.
3.Mefloquine 750 mg stat, followed by 750 mg after 6 hrs. (Pts.
Weighing > 50 kg) or 500mg stat followed by 500mg after
6hrs. (Pts. Weighing < 50 kg.)

17. Treatment of Resistant
Malaria
(Complicated Resistant)
Ideally all patients with complicated should be
hospitalized.
Inj. Quinine IV slowly in Dextrose.
Higher loading dose is preferred relative to
maintenance dose.
In patients requiring more than 48 hours parenteral
therapy, reduce the maintenance dose by ½ rd.
In presence of renal failure; quinine dose should be
halved after 48 hours.
Inj. Artemether 160mg IM, then 80mg daily for 4 days

18. Artemether Dosage regimen
Rezart Route Adults Pediatric
Day 1Days 2-5 Day 1Days 2-5
80 mg/
Ampoule
60mg cap
IM
Oral
1.6mg/kg
twice
1.6mg/kg
twice
1.6 mg/kg
once
1.6mg/kg
once
1.6
mg/kg
twice
1.6
mg/kg
twice
1.6
mg/kg
Once
1.6mg/kg
once

19. Comparative Efficacy :
In Cerebral Malaria
Parameter Arteether Quinine
Coma recovery time
(hrs.)
Mortality (%)
24.33
6.67
38.87
27.27

20. Arteether Dosage RegimenArteether Dosage Regimen
Rezart-E Route Adults Pediatric
150 mg/
ampoule


IM
Day 1
150 mg
Days
2 –3
150mg/
day
Day 1
3mg/kg
Days
2-3
3mg/kg/
day

21. Bulaquine : A New generation Anti-malarial drug
Bulaquine a derivative of primaquine developed by the

Central Drug research Institute in collaboration with
W.H.O.,
Advantage :-

Bulaquine has a biological activity against
the tissue schizont forms of
Plasmodium Vivax having :-

a. A better therapeutic window.

b. Lesser side effects,
c. A better therapeutic index as compared to
current treatment available.

22. Mechanism of action of :
Bulaquine
In contrast to current Drugs, 8-Aminoquinolones are the
only drug which act on the liver stage and prevent
infection by killing liver stages of the parasite before
merozoites reach blood Stream. Thus prevents
emergence of either primary or secondary attacks.
Bulaquine Inhibits protein synthesis in protozoa and
indirectly inhibits Polymerisation of Amino acids by the
Plasmodia.
It has also high gametocidal action.

23. Dosage of Bulaquine :-
** 25 mg once daily for 5 days.
** Should be given with
chloroquine for complete
cure
of Vivax malaria.
INDICATION : For the treatment of Vivax malaria
Contra-indications:
1. Rheumatoid Arthritis.
2. Systematic Lupus erythematosus.

Concurrent use of Drugs known to cause Haemolysis

24. Future of Malarial
Treatment
I. Gene Therapy.
II. Malarial Vaccine.
III. Genetic Mapping
Plasmodium falciparum.

IV. Low Interleukin-12
Activity in severe
Plasmodium falciparum
malaria.