MALARIA…

FAHAD

Some Imp.Terminologies

• Incubation Period: From the injection of sporozoite to the point of first manifestation of clinical illness.

• It varies from 8 to 40 days in its four diff. species

• Microscopic threshold: The minimum level of parasitaemia necessary for their detection in the blood

• Fever threshold: Clinical disease develop only after further multiplication .

• Primary Attack: First Clinical illness that marks the end of incubation period.

Pathogenesis

• Malaria is initiated by the bite of an infected female anopheline mosquito & injects the malaria parasite into blood.

• Sporozoite multiply in the parenchymal cells of liver

• After maturation averg. 1- 2 weeks, merozoites are released and invade the erythrocytes. Microscopic threshold.

• The infected erythrocytes rupture and release gametocytes, merozoites, pyrogens and toxins. Fever threshold

• The febrile paroxysm comprises three successive stages.

• Cold stage : the patient experiences intense cold & uncontrollable shivering, lasting 15 to 60 minutes.

• Hot stage : the patient feels intensely hot fever mounts to 41C, lasting 2 to 6 hours.

• Headache, Nausea and vomiting are common during this period.

• Sweating stage : the patient is drenched in profuse sweat, the temp. drops rapidly and patient usually falls into deep sleep.

The paroxysm usually begins in early afternoon and lasts 8 to 12 hrs

• P. malariae have afebrile period of 72hours while it is 48 hours for P. falciparum, vivax and ovale

• During the second blood meal , the RBCs infected with gametocyte are taken up by the mosquito from infected human.

• The male & female gametes fertilize, to ultimately form the sporozoite, in the gut.

• From the gut parasite reach the Anophele’s Salivary glands.

• When such a Anopheles mosquito bites a human, these sporozoites repeat the Plasmodium life cycle.

What are the Reasons behind Clinical Manifestations ?

• All clinical manifestations are due to:

1 ) The products of Erythrocytic schizogony, following completion of erythrocytic schizogony.

2) The host’s reaction to them.

What are these Products?

• Red cell fragments • Merozoites• Malarial pigments.• Parasitic debris.• Macrophage and polymorph release endogenous pyrogens..• Cytokines

MALIGNANT TERTIANIt is because….. this is the most highly pathogenic of all plasmodia. P. Falciparum • The erythrocytic schizogony occurs in deeper capillaries of various organs..

• In acute falciparum malaria , following heavy infection of RBCs the RBCs becomes Deformed & sticky and adhere to one another & the capillaries of internal organs

• Thus the infected cells are held back in the capillaries and block them leading to blockage, congestion and hypoxia related necrosis of tissues.

• In severe cases the rate of parasitized cells may even be up to 50%

• The cycle completes in 2- 3 weeks.. COMPLICATIONS• CEREBRAL MALARIA hyperpyrexia, coma, paralysis.• ALGID MALARIA circulatory collapse, cold clammy skin.• SEPTICAEMIC MALARIA Alveolar, coronary & renal capillaries are

congested.

• Occurs in all types of malaria.• Anemia is hemolytic.• Decreased erythropoiesis.

SPLENOMEGALY• Spleen is always enlarged in malaria.• Cellular hyperplasia, dilated sinusoids &

accumulation of macrophages accentuate enlargement.

ANAEMIA

Some Major Complications

BLACK WATER FEVER

• Massive intravascular haemolysis caused by antierythrocytic antibodies

• Mostly associated with repeated attacks of Falciparum

• Inadequate treatment with quinine..• Manifestation : • Bilious vomiting, • prostration,• dark red or blackish urine..

TSS ( Tropical Splenomegaly syndrome)

• A Chronic mild condition….

• Results from abnormal immunological response to malaria.

• Features :

• High titres of circulating antimalarial antibody.

• Absence of malaria parasites,

• Hyper Ig aemia, cryoglobulinemia.

MEROZOITE-INDUCED MALARIA• Malaria is sporozoite induced • Injection of merozoites can directly lead to infection of

RBCs.• Its self limiting.

• This may occur in:

• Transfusion Malaria • Therapeutic Malaria• Congenital Malaria

What is the Role of Immune system in MALARIA ?

• Innate -• It seems to play a very obscure role !• For e.g. – Does not multiply in sickle cell, Individuals

lacking Duffy blood group Ag are resistant

• Acquired –• Immune System induces specific immunity with a clinical

cure.• the parasite is continuously prevalent in blood at

subclinical levels, premunition.• Immunity is strain specific thus infection by diff. strain of

the same species is not protective.

IMMUNOPATHOLOGY

• Malaria is known to produce some depression of the immune system.

• For e.g : Responsible for conditions such as – Burkitt’s lymphoma a Lymphoma due to EBV

• Autoimmunity –

• Erythrocytes undergo antigenic changes due to infection leading to auto immune phenomena.

WHY IS IT THAT PLASMODIUM

AFFECTS ONLY HUMANS AND NOT

MOSQUITOES ?

Manifestations of Severe Malaria

• Prostration• Impaired consciousness/coma• Multiple convulsions• Circulatory shock• Jaundice• Severe anemia• Acute renal failure• Disseminated intravascular coagulation• Hemoglobinuria