MALARIA

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MALARIA

Over view

Basic understanding of malaria

Epidemiology

Symptoms

Diagnosis

Treatment

Prevention

Malaria is a protozoan disease transmitted by the bite of

infected female Anopheles

mosquitoes.

Protozoan parasites of the genus

Plasmodium

Four species:

P

falciparum

P

vivax

P

ovale

P

malariae

characteristic

p.falciparum

p.vivax

p.ovulae

p.malariae

Severity of malaria

Severe may be fatal

Benign,

rarely same

Uncommon,

benign

Mild,occasional

Duration of intra

hepatic phase

5.5

8

9

15

Average incubation period

7-14 days

12-17 days

15-18 days

18-40days

Duration of

erythrocytic

cycle

48

48

50

72

Red cell

preference

Younger cells

Rbc

up to 14 days

recticuocytes

Older cells

Transmission

Man is the only important reservoir

Vector is female

Anopheles

mosquito

Temperature: below 86º F, above 68º F

Rainfall: thrive in tropical areas

Altitude: rarely exist above 2000 meters

Terrain: coastal areas and lowlands with

lots of freshwater breeding sites

Transmission

Mosquito vector:

ANOPHELES

Transmission also possible through:

Blood transfusion

Contaminated needle

Organ transplant

Congenital

Susceptibility

Universal susceptibility

No absolute immunity

Partial immunity in areas of high

endemicity

Pathogenesis

RBC destruction

Immune complexes and mediators

Capillary permeability

Tissue hypoxia

RBC Distruction

After invading an erythrocyte, the growing malarial parasite progressively consumes and degrades intracellular proteins, principally hemoglobin.

The potentially toxic

heme

is polymerized to biologically inert

hemozoin

, or malaria pigment.

The parasite also alters the RBC membrane by changing its transport properties, exposing cryptic surface antigens, and inserting new parasite-derived proteins.

The RBC becomes more irregular in shape, more antigenic, and less deformable.

In P.

falciparum

infections, membrane protuberances appear on

the erythrocyte's surface toward the end of the first 24 h of the

asexual cycle. These “knobs” extrude a high-molecular-weight,

antigenically

variant, strain-specific, adhesive protein

(PfEMP1) that mediates attachment to receptors on

venular

and

capillary endothelium—an event termed

cytoadherence

.

P.

falciparum

–infected RBCs may also adhere to uninfected

RBCs to form rosettes and to other parasitized erythrocytes

(agglutination). The processes of

cytoadherence

,

rosetting

, and

agglutination are central to the pathogenesis of

falciparum

malaria. They result in the sequestration of RBCs containing

mature forms of the parasite in vital organs (particularly the

brain), where they interfere with microcirculatory flow and metabolism.

P.

vivax

, P.

ovale

, and P.

malariae

show a marked predilection

for either young RBCs (P.

vivax

, P.

ovale

) or old cells (P.

malariae

) and produce a level of

parasitemia

seldom >2%, P.

falciparum

can invade erythrocytes of all ages and may be

associated with very high levels of

parasitemia

.

IMMUNE RESPONE

The specific immune response to malaria eventually controls the infection and, with exposure to sufficient strains, confers protection from high-level

parasitemia

and disease but not from infection.

As a result of this state of infection without illness (

premunition

), asymptomatic

parasitemia

is common among adults and older children living in regions with stable and intense transmission (i.e.,

holo

- or

hyperendemic

areas).

Immunity is mainly specific for both the species and the strain of infecting malarial parasite. Both

humoral

immunity and cellular immunity are necessary for protection, but the mechanisms of each are incompletely understood

Plasmodium Species

P.

falciparum

Most severe and prevalent

40-60% of cases

Widespread CHLOROQUINE resistance

Infects RBCs of all ages—Heavy

parasitemia

P.

vivax

30-40% of cases

Liver phase

INFECTS YOUNG RBCs: LESS SEVERE THAN FALCIPARUM

P.

ovale

Liver phase

INFECTS YOUNG RBCs

P.

malariae

Can persist SUBCLINICALLY for extended periods of time

INFECTS OLD RBCs

Presentation

Fever 96%

Chills 96%

Headache 79%

Muscle Pain 60%

Palpable liver 33%

Palpable Spleen 28%

Nausea or vomiting 23%

Abdominal pain

/diarrhea 06%

Complicated Malaria

Hyperparisitemia

: (>3%)

Hypoglycemia: (<60 mg/dl)

Severe anemia (

hct

< 21% or rapidly falling

hct

)

Renal failure

Hyponatremia

Cerebral malaria

Prolonged hypothermia

High output vomiting or diarrhea

Pregnancy

DIAGNOSIS

Gold standard: Multiple thick and thin smears

Dip stick tests

CBC

Anemia

Leukopenia

, or

leukocytosis

No

eosinophilia

Treatment

CHLOROQUINE sensitive infections:

CHLOROQUINE 600 mg (2 tabs) P.O. initially

300 mg (1 tab) in 6 hrs

300 mg (1 tab) QD for 2 days

Uncomplicated CHLOROQUINE-resistant infections:

Quinine 650 mg PO TID x 3 days and DOXYCYCLINE 100 mg PO bid x 7 days,

OR

MEFLOQUINE 1000-1500 mg PO once

Complicated or severe

infections

I.V. QUINIDINE or quinine

VIVAX

and

OVALE

therapy should include

PRIMAQUINE

15mg PO QD x 14 days

CDC now recommends:

PRIMAQUINE

30mg PO QD x 14 days

Treatment Options

For

chloroquine

sensitive

Chloroquuine

Primaquine

For

chloroquine

resistance

Sulfadoxine

Quinine

pyrimethamine

Doxycycline

Mefloquine

Artesunate

Artemether

WHO Guidelines For Malaria 2006

Treatment of uncomplicated malaria:

Vivax

malaria: (1)

chloroquine

600mg ( 10mg/kg) followed by 300mg ( 5mg/kg) after 8 hours and then for next 2 days.( total dose 25mg/kg over 3 days)+

primaquine

15mg (0.25mg/kg) daily for 14 days.

(2)Quinine 600mg (10mg/kg) 8 hourly for 7

days+doxycycline

100mg daily for 7

days+primaquine

(as above)

Chloroquine

sensitive

falciparum

malaria:

(1)

Chloroquine

(as above)+

primaquine

45mg(0.75mg/kg) single dose

(2)

Sulfadoxine

1500mg(25mg/kg)+

pyrimethamine

75mg(1.25mg/kg) single

dose+primaquine

0.75mg/kg single dose

Chloroquine

resistant

falciparum

malaria

(1)A75mg single dose

Or

artesunate

100mg BD for 3

days+mefloquine

750mg (15mg/kg) on 2

nd

day and 500mg (10mg/kg) on 3

rd

day

Or

artemether

80mg +

lumefantrine

480mg twice daily for 3 days.

or Quinine 600mg (10mg/kg) 8 hourly for 7 days +

doxycycline

100mg daily for 7 days

rtesunate

100mg BD for 3

days+sulfadoxine

1500mg +

pyrimethamine

Treatment of severe and complicated

falciparum

malaria:

(1)

Artemether

2.4mg/kg iv or

iM

followed by 2.4mg/kg after 12 and 24 hours and then once daily for 7 days

Or

artemether

3.2mg/kg

iM

on 1

st

day followed by 1.6mg/kg daily for 7 days

Or quinine loading dose: 20mg/kg and maintain 10mg/kg

ATC COMBINATIONS

1)

Artesunate-mefloquine

:

Artesunate

100mg BD (4mg/kg/day)for 3

days+Mefloquine

750mg(15mg/kg) on 2

nd

day and 500mg (10mg/kg)on 3

rd

day.(total dose 25mg/kg)

(2)

artemether-lumefantrine

(1:6)

Artemether

80mg

BD+lumefantrine

480mg BD for 3 days.

(3)

Artesunate-sulfadoxine+pyrimethamine

Artesunate

100mg BD for 3

days+sulfadoxine

1500mg &

pyrimethamine

75mg single dose