1.

Life cycle
- Hepatic, erythrocytic, sexual (man & Anopheles female)
2. Clinical pathology and pathogenesis
- Acute malaria - cerebral, ARDS, hemolysis, shock,
uremia
-Chronic malaria- anemia, nephrosis, hypertrophic malarial
splenomegaly 3.. Treatment and prophylaxis
- Chloroquine
- Quinine
- Tetracyclines
- New drugs (halofantrin, arteminisin)
- Fansidar (pyrimethamine/sulfa)
- Malarone (proguanil/atovaquone)
-Primaquine
4. Diagnosis - Laboratory - thin, thick smears, antigen capture
EIA, PCR etc.
- Clinical - platelets, regularly intermittent fever
5. Prevention and control
- Removing breeding sites, larvacides, insecticides
- Chemoprophylaxis
- Avoidance (nets, clothing)

Malaria:

Phylum - Apicomplexa
Genus - Plasmodium Species - falciparum, vivax, ovale, malariae

MOST IMPORTANT SINGLE INFECTION OF

MANKIND
- more than 1 billion persons at risk
- mortality from malaria: 2.5 million/year in 1955
1 million/year in 1980

Definitions

Hepatic schizont The actively

dividing, multinucleated, parasite form
in hepatocytes; produces no
inflammatory response.

Trophozoite: Metabol
ically active form of
the malaria parasite
living within the RBC;
sometimes called the
ring form.
P. vivax

P. ovale

P. falciparum

Erythrocytic
schizont: multinucleated
stage in a RBC resulting
from asexual
multiplication of
trophozoite. Each
schizont contains a
species determined
number of meroziotes.
P. vivax

P. falciparum

Merozoite: the name given to infective schizont components (see within the
schizonts above) that break out of RBC or hepatocyte and then adhere to and
penetrate a new RBC.
Gametocyte: morphological
ly distinctive sexual (male
or female) form of the
parasite which develops
from some trophozoites in
RBCs. It is infective to
mosquito.

P. vivax

P. falciparum

Sporozoite: the morphological form

which develops in the mosquito salivary
gland and is injected when the mosquito
feeds, infecting humans.

Exoerythrocytic cycle: (hepatic cycle) asexual reproduction within hepatocytes

producing schizonts, which break out of the hepatocytes and invade other
hepatocytes; occurs as a complete cycle only in P. vivax and P. ovale.
Intraerythrocytic cycle: (erythrocytic cycle) asexual reproduction within RBC's.
Involves trophozoite to schizont, rupture of schizont, release of merozoites,
invasion of new RBC, and production of new trophozoite.

Life Cycle
- the incubation period
is both species and strain
dependent: e.g. P.
falciparum 8-42 days; P.
vivax 5 days to years
- only gametocytes
infect mosquito
- only
female Anopheles sp.
mosquitos are vectors
- no animal
reservoir

Diagnosis of
Malaria

a) clinical picture: fever, chills

travel history
fever pattern
b) examination of blood:

- thin
- thick smear
- buffy coat
- antigen
capture (ELISA)
- PCR

DIAGNOSIS OF SPECIES:
a) clinical

picture:

- P. falciparum: daily fever, rarely every 2 day fever

- other species: most of the time (but not necessarily) intermittent fevers
every 2 or 3 days
b) examination

of thin smear for characteristics of species

- use shape and size of: trophozoite, schizont and gametocyte

- % of RBCs with parasites (very rarely over >1% parasitemia in P. vivax,
ovale or malariae)
- metabolic debris in RBC around parasite (called Schuffner's
dots in P. vivax infection)

- size of RBCs which contain parasites (P. vivax and ovale

infect younger (larger) RBCs)

PATHOPHYSIOLOGY
- only RBC trophozoites and schizonts cause disease
- no liver pathology caused by hepatic schizonts or sporozoites
- disease caused by:
1. RBC destruction: - by parasite
- immune hemolysis
- splenic pooling
2. antigen-antibody complexes in kidney
3. schizonts of P. falciparum sticking to post-capillary venules' (esp. cerebral)
endothelial cells
4. cytokines and other ill-defined shock, proinflammatory and capillary leakage
producing products

apical complex of
merozoite attaching to
red cell membrane
receptors

malaria schizonts
adhered to endothelial
cells of retinal vessels
(same occurs in
brain) Lewallen S, Arch
Opthal 2000

sticky malarial protein

knobs on schizont
infected RBC surface
membrane

schizonts stuck in post-capillary venules in cerebral ma

Black water fever

Adult Respiratory Distress Syndrome (ARDS)

Table 10.52.2. Severe Malaria: Common Clinical Manifestations

Pathogenesis

Clinical Features

Cerebral

Sluggish flow caused by sticky

knobs on parasitized red cells
leading to stagnant hypoxia and
vascular damage.

Impaired level of consciousness.

Hyperpyrexia. Convulsions. Generalized
and localized neurological signs.

Anaemia

Destruction of parasitized and

Pallor and jaundice. High output cardiac
nonparasitized red cells by
state.
immune complexes, bone marrow
suppression and splenic pooling.

Renal

Acute tubular necrosis resulting

from sluggish blood flow and
hypotension. Hemoglobinuria.

Oliguria. Haemoglobinuria. Acute renal

failure.

Gastrointestinal

Unknown

Diarrhoea.

Respiratory

Increased pulmonary capillary

permeability.

Cough. Crepitations, pulmonary edema,

iatrogenic fluid overload,

bronchopneumonia.
Hepatic

Unknown. ? Partially due to

haemodynamic changes.

Jaundice (mainly attributable to

haemolysis). Elevated serum enzyme
levels, impaired elimination of drugs,
prolonged prothrombin time, bleeding.

Fluid and
electrolyte
balance

Unknown. ? Partially due to

inappropriate release of
antidiuretic hormone.

Increased intravascular volume.

Electrolyte changes, hypoglycemia,
hyperkalemia and hemolysis.

Obstetric

Sluggish blood flow in placental

vessels leading to vascular
damage.

Fetal death. Premature labour.

ACUTE CLINICAL PICTURE: COMPLICATIONS

- fever , headache, splenomegaly
cerebral malaria (P.falciparum only)
adult respiratory distress syndrome (ARDS)(P.falciparum)
black water fever (severe hemolysis)(P.falciparum only)
acute renal failure
CHRONIC CLINICAL PICTURE:
- nephrotic syndrome (P. malariae only)
- big spleen syndrome (hypertrophic malarial splenomegaly)

Epidemiology

- spread - Anopheles female

- blood transfusion
- vertical - transmission mother/child at time of
birth
- control:
- fogging and residual wall spray with variety of insecticides
(eg DDT)
- avoidance: screens, repellents, nets, insecticide
(permethrin) treated bed nets
- breeding site control: - fill in or cover water breeding sites
- larviciding of breeding water sites
- larva eating fish

- larva killing bacteria (e.g. Bacillus

thuringiensis israeliensis)

Drugs
a) chemoprophylaxis. A medication taken at regular
intervals to kill one or more of the morphological forms (life
stages) of the malaria parasite (eg chloroquine- trophozoites,
RBC schizonts) and therefore prevent the onset of clinical
illness.
b) treatment: - clinical cure - eradication of RBC trophoziotes and schizonts

- radical cure - eradication of RBC trophozoites and

schizonts and hepatic schizonts
- different drugs required for different stages of life cycle (eg.
primaquine and Malarone for hepatic schizonts and gametocytes)(mefloquine,
quinine and chloroquine for RBC schizonts and trophozoites).
quinine
4-aminoquinalines - eg. chloroquine, amodioquine etc.
8-aminoquinalines - eg. primaquine
antifolates - eg pyrimethamine, proquanil, sulfas, sulfones
antibiotics - tetracycline, doxycycline, clindamycin
combinations- Fansidar (sulfadoxine and pyrimethamine), Malarone (atovaquone
and paludrine)
miscellaneous- mefloquine, halofantrine, artemisinin
c) drug resistance.
1. Frequent P. falciparum resistance to chloroquine in most of world outside of
Central America and the Caribbean. P. vivax resistance to chloroquine in New
Guinea, SE Asia and Amazon.
2. P. falciparum multidrug resistance (to chloroquine, mefloquine, Fansidar) in
Myanmar-Thailand border and in Cambodia.