MALARIA

Plasmodium

1. P. vivax = benign tertian malaria

2. P. falciparum = aestivoautumnal malignant tertian or subtertian

malaria

3. P. malariae = quartan malariae

4. P. ovale
LIFE CYCLE

1. Schizogony - the asexual method of reproduction; occurs in

intermediate host (MAN)

2. Sporogony - the sexual method of reproduction; occurs in definitive

host (MOSQUITO)
 HUMAN CYCLE

* SPOROZOITES: infective form of the parasite found in the salivary

glands of the female ANOPHELES MOSQUITO (definitive host)

* Man gets infection by the bite of an infected ____ mosquito. During

the act of biting the proboscis of the mosquito pierces the skin & saliva
containing ____ is infected directly into the blood stream
 HUMAN CYCLE

* The cycle in man comprises of the following stages:

 Primary exoerythrocytic schizogony

 Erythrocyctic schizogony

Gametogony

 Secondary exoerythrocytic schizogony

1. Primary exoerythrocyctic schizogony
• Within 1 hour all the sporozoites leave the blood stream & enter into
the liver parenchyma cells (spindle-shaped bodies become rounded)
• They undergo a process of multiple nuclear division, followed by
cytoplasmic division & develop into primart exoerythrocytic schizont
• The duration of the cycle varies.
 P. falciparum - 6 days
 P. vivax - 8 days
 P. ovale - 9 days
 P. malariae - 13 to 16 days
• When primary shizogony is complete, the liver cell ruptures &
releases merozoites into the blood stream
2. Erythrocytic schizogony
• Merozoites enter the blood stream and invade RBCs where they
multiply at the expense of the host cells

• Passes thru the stages of trophozoites, schizonts & merozoites &

followed by cytoplasmic division, & RBCs rupture to release the
individual merozoites which then infect fresh RBCs

• The parasitic multiplication during this phase is responsible for

bringing on a clinical attack of malaria
3. Gametogony
• After malarial parasites have undergone erythrocytic schizogony for certain
period, some merozoites develop within red cells into male & female
gametocytes known as MICROGAMETOCYTES & MACROGAMETOCYTES
respectively. Only mature gametocytes are found in the peripheral blood.

• Although the longevity of mature gametocytes may exceed several weeks,

their half-life in the blood stream may only be 2 or 3 days, while waiting for
the mosquito to take them up.
 4. Secondary exoerythrocytic schizogony
• In case of P. vivax & P. ovale, some sporozoites on entering into hepatocytes enter into a
resting (dormant) stage before undergoing asexual multiplication while others undergo
multiplication w/o delay

• The resting stage of the parasite is called hypnozoite. After a period of weeks, months or
years (usually up to 2 years) hypnozoites are reactivated to become secondary
exoerythrocytic schizonts & release merozoites which infect RBCs producing RELAPSE of
malaria. The relapse therefore, is the situation in whih the erythrocytic infection is
eliminated & a relapse occurs later because of a new invasion of the RBCs from liver
merozoites
• Hypnozoites are not formed in case of P. falciparum & P. malariae.
Therefore, relapse does not occur in disease caused by these species.

• RECRUDESCENCE - the situation in which the RBC infection is not

eliminated by the immune system or by therapy & the numbers in the
RBCs begin to increase again with subsequent clinical symptoms
MOSQUITO CYCLE
• Sexual cycle actually starts in the human host itself by the formation
of gametocytes which are present in the peripheral blood.
• Asexual & sexual forms - ingested by female anopheles mosquito
during blood meal
• In the mosquito, only the mature sexual form is capable of further
development
• In order to infect mosquito, the blood of human carrier must contain
at least 12 gametocytes/uL & the number of female gametocytes
must be in excess of the number of males
MOSQUITO CYCLE

• In the stomach of the mosquito, microgametes are formed by the

process of EXFLAGELLATION

• It then develops into a Macrogamete - where a projection is formed

• Fertilization occurs when a microgamete penetrates this projection

called ZYGOTE (occurs in 20 minutes to 2 hours)
MOSQUITO CYCLE

• In the next 24 hours, the zygote lengthens & matures into OOKINETE
(a motile vermiculate stage)

• OOCYST develop in the stomach wall, where SPOROZOITES are

developed inside

• On the 10th day, the oocyst is fully mature, ruptures and releases
sporozoites in the body cavity of the mosquito
MOSQUITO CYCLE

• Through the body fluid, the Sporozoites are distributed to various

organs of the body except the ovaries

-- During this stage, the mosquito is capable of transmitting

infection to man
 FEBRILE PAROXYSM (Malarial Paroxysm)
• It generally begins in the early afternoon & comprises of 3 successive
stages:
1. COLD STAGE

- lasts for 15 to 60 minutes

- patient experience intense cold & shivering; inappropriate feeling of

coldnesss and apprehension

- teeth chattering, shaking of whole body

- peripheral vasoconstriction
 FEBRILE PAROXYSM (Malarial Paroxysm)
2. HOT STAGE

- lasts for 2 to 6 hours

- patient develops high fever (40 to 40.6 C), severe headache, nausea,
vomitting, palpitations and thirst

3. SWEATING STAGE

- occurs after fever

- temperature lowers & profuse sweating

- PERIODICITY OF THE ATTACK -
 P. vivax (benign tertian): 48 hour cycle of fever

 P. ovale (ovale tertian)

 P. malariae (quartan): 72 hour cycle of fever

 P. falciparum: every 36 hours

FORMS IN THE PERIPHERAL BLOOD
 P. vivax - trophozoites, schizonts & gametocytes

 P. falciparum - rings & crescents (gametocytes)

 P. malariae - trophozoites, schizonts & gametocytes

 P. ovale - trophozoites, schizonts & gametocytes

 P. falciparum
• RBC Infected: All stage
• Appearance of infected RBC: Normal
• Stages seen in peripheral blood: Gametocytes with banana/crescent shape
• Number of merozoites: 24
• Pathogenesis:
- Malignant tertian malaria (every 36 hours)
- Cerebral malaria
- Black water fever (Hemoglobinuria)
* G6PD-deficient individuals are resistant to P. falciparum
* Hgb S (sickle cell trait) - resistant because of a structurally &
functionally abnormal BAND 3 protein
 P. malariae
• RBC Infected: Old
• Appearance of infected RBC: Normal
• Stages seen in peripheral blood: rings, trophozoite, schizonts
• Number of merozoites: 8
• Pathogenesis:
- Quartan malaria (every 72 hours)
• Ring forms: “basket forms” or “band forms”
• Schizonts: “fruit pie”
• Gametocytes: “ovoid”
 P. ovale
• RBC Infected: young
• Appearance of infected RBC: enlarged
• Stages seen in peripheral blood: ALL STAGES
• Number of merozoites: 8
• Pathogenesis:
- Ovale malaria (every 48 hours)
- large pale red cell (oval/fimbriated)
 P. vivax
• RBC Infected: young
• Appearance of infected RBC: enlarged
• Stages seen in peripheral blood: ALL STAGES
• Number of merozoites: 16
• Pathogenesis:
- Benign tertian malaria (every 48 hours)
* Duffy negative blacks are resistant to P. vivax due to high prevalence
of Duffy negativity
• Morphology:
- appear as single large ring & amoeboid in form
 DIFFERENTIATION OF PLASMODIUM SPP.
SPECIES Type of RBC # of Merozoites Ring form Gametocyte
infected appearance

P. falciparum all stages 8-36 or 6-32 very delicate; crescent-shaped,

usually of 2 fine elongated, sausage-
chromatin fots shaped

P. vivax young or new rbc 14-24 or 12-24 delicate fine oval, compact and
chromatin dot rounded

P. malariae mature or adult rbc 6-12 (rosette -shaped, compact or dense compact and
fruit-pie, dairy head ring with chromatin rounded
arrangement mass often inside

P. ovale young or new rbc 4-8 or 6-14 dense ring of wall compact and
with defined rounded
chromatin mass
 SPECIES RBC appearance Trophozoite Stippling Relapse

P. falciparum normal; has smaller applique/accole shape Maurer's dots or No

& numerous rings cuneiform dots or
Garham's bodies

P. vivax enlarged; pale ameboid Schuffner's dots Yes

P. malariae normal compact-equatorial Ziemann's dots No

band form

P. ovale enlarged; pale; compact Schuffner's dots or Yes

ragged (fringed) Jame's dots
edges
 SPECIES Diseases Recrudescence

P. falciparum 1. Blackwater fever Yes

2. Cerebrial malaria
3. Acute renal failure
4. Acute respiratory distress
5. Malignant tertian malaria

P. vivax 1. Benign tertian malaria No

2. Splenomegaly

P. malariae 1. Quartan malaria Yes

2. Congenital or Transfusion malaria
3. Nephrotic syndrome

P. ovale 1. Benign tertian malaria or Oval malaria No