Transcript MALARIA Staining & identification Giemsa`s stain preferable to

UPDATE ON MALARIA
Dr. Ramamoorthy
Hon. Prof. of Medicine & Head
Dept. of Medicine
Bombay Hospital Institute of Medical Sciences
Mumbai
MALARIA
Incidence

200 to 300 million worldwide

1 to 2 million deaths
Resurgence

Resistance of anopheline vector to DDT

Increasing resistance of PI. Falciparum
to chloroquine & other drugs
TYPES OF RESISTANCE IN
MALARIA

S
Sensitive. Parasite clearance in 7
days no recurrence in 28 days

R1
Parasite clearance in 7 days.
Recurrence in 28 days

R2
> 75% clearance in 48 hrs.
Recurrence in 7 days

R3
< 75% clearance in 48 hrs.
Recurrence in 7 days
DISTRIBUTION OF RESISTANCE
IN INDIA
R1
35%
S
40%
R3
6%
R2
19%
R3 seen in Assam, Gujarat, Orissa & Rajasthan
MALARIA


Staining & identification

Giemsa’s stain preferable to Wright’s stain
thick smears about 20 times more sensitive
than thin smears because red cells have been
lysed (in thick smear identification of species
is difficult.)

Effect of parasite on red cell size or positive of
parasite within RBC cannot be judged
Hence thin smear is for species
identification of the parasite and thick
smear is for the presence of the parasite

Gametocytes take 7 to 10 days to develop
and hence to rely on the type of gametocyte
to diagnose the species of malaria is not
advisable

Gametocytes frequently present in blood of
semi-immune residents in an endemic area

Double infection with
Falciparum common

Parasitized red cells are lighter than non
parasitized cells and hence on centrifuging a
sample of blood in a capillary tube parasitized
cells are seen just below the buffy coat

DNA probes have also been used
PI.
Vivax
&
PI.
MORTALITY IN MALARIA

Vivax malaria


Rupture of spleen, immunocompromised state,
repeated attacks in malnourished patient
Falciparum malaria

Pathogenesis budding, rosette
cytoadherence and sequestration

Cerebral malaria, renal involvement, hepatic
involvement, pulmonary involvement, severe
anemia, shock, hyperthermia, gram negative
sepsis, pregnancy, metabolic acidosis, more
than 3% parasitemia, DIC, severe vomiting and
diarrhoea, infants and non immune subjects

Presence of trophozoites
peripheral blood smear
and
formation,
schizonts
in
CYTOKINES
 TNF
alpha increased in severe
falciparum malaria
 Good
correlation of increased
TNF alpha levels with incidence
of cerebral malaria, pulmonary
involvement and sepsis
ANTIMALARIA DRUGS

Chloroquine –
Amodiaquine

Quinine & Quinidine

Sulphonamides &
Pyrimethamine

Primaquine

Tetracycline,
Doxycycline,
Clindamycin,
Azithromycin &
Quinolones

Proguanil

Halofantrine &
Mefloquine

Artemisinin

Atovaquone

Benflumentol /
Hydroxypiperaquine

Desferixoamine
PRECAUTIONS


Prolonged QT

Mefloquine

Quinine / Quinidine

Halofantrine
Hypokaemia due to vomiting – dangerous
arrhythmias including Torsade Prolonged QT
also seen in B1 deficiency (vomiting in 1st
trimester)
Artemisin

Action rapid

Prevents parasite development

Prevents rosetting
sequestration

Reduction in gametocyte counts
cytoadherance
and
Atovoquone

Against MDR falciparum

High recrudescense rate rapid resistance

Combination with tetracycline / proguanil
prevents the problem
Estimated Stage Specificity of Antimalarial Action
of Artesunate & Other Antimalarials
RING FORM
SEQUESTRATION
R1
Late Trophozoite
Schizont
Hours
1. FSD 3 tab
1500 mg IV in 12 hrs
2. QN or MEF
Even though R1  6%,
1000 mg
T coma is avoidable
3. ART
Oral / TM
If R2  6%, T coma may occur
Even though high density of R1 or R2, T coma is avoidable
R1 = Width of cytoplasm / diameter of nucleus  ½
R2 = Width of cytoplasm / diameter of nucleus > ½ < 1
R3 = Width of cytoplasm / diameter of nucleus  1
FSD = ‘Fansidar’
QN = Quinine
MEF = Mefloquine
ART = Artesunate
Artemisinin

3.2 mgm / kgm stat. I.M.

1.6 mgm / kgm day
Artesunate

Unstable in aqueous soln.

Stable in 5% Na bicarb

2 mgm / kgm stat

1 mgm / kgm after 12 hrs

1 mgm / kgm subsequently

Total 8-12 mgm / kgm
TETRACYCLINES, CLINDAMYCIN
& COTRIMAXAZOLE
 Limited
 Two
antimalarial activity
slow when used alone
 Usually
with quinine, mefloquine etc.
DESFERRIOXAMINE

In uncomplicated falciparum

Decrease in duration of coma & parasite

Clearance time when added to quinine

Acts by deprivation of iron to the
parasite and also as a free oxygen
radical scavenger
PROPHYLAXIS

Mefloquine weekly 250 mgms in 1 trial
found to be safe in pregnancy

At present not recommended in pregnancy

Doxycline daily – not safe in children &
pregnancy

Chloroquine 300 mgm base weekly +
Proguanil 100-200 mgm daily

Found to be safe even in pregnancy
 Vaccine
immunity is species specific
and stage specific
 Sporozoite
vaccine to prevent infection
& development of liver stages
 Vaccines
against asexual
block transmission
stages
to
THE FUTURE

Mother nature gave us the cinchona alkaloids and
Qing Hao Su

World war II led to the discovery of Chloroquine,
Chloroguanide, Amodiaquine and Pyrimethamine

The Vietnam war brought Mefloquine and Halofantine

Little pharmaceutical industry interest are low. Much
of the malaria occurs in the developing countries.

Do we need another world war for developing newer
antimalarials ? Even now malaria is a challenging
problem and this may get out of control in the next
millenium
THANK YOU