Malaria

Introduction• Malaria is an infectious disease caused by the

parasites called Plasmodia. • It is transmitted by the female anopheles mosquito. • Before the link between malaria and female

anopheles mosquito was discovered( by Ronald Ross), the dreaded disease was attributed to supernatural influences such as angered deities, evil spirits or the black magic of sorcerers.

• Later on , with the observation that malaria occurred more often near the water logged areas, it was attributed to miasma and effluvia from swamps( hence its name mal aria= bad air).

Malaria Worldwide• Malaria is widely distributed throughout tropical

regions of the world in Africa, Hispaniola, Central and South America, Asia, the Middle East and Oceania.

• 41% of world’s population lives in malaria- endemic areas.

• An estimated 700,000-3 million persons die of malaria every year, 75% of them are African children.

• In areas of Africa with high transmission there are about 2700 deaths per day, 2 deaths per minute.

The Malaria ParasitePhylum: PROTOZOA Class: SPOROZOA

Order: COCCIDIIDA Family: PLASMODIIDAE

Genus: PLASMODIA Subgenera: PLASMODIUM

Species: P. falciparum, P. vivax, P. ovale, P. malariae

Classification of Malarial Parasite

• Only four species of the protozoan genus Plasmodium usually infect humans: P. falciparum, P. vivax, P. malariae, and P. ovale.

• P. falciparum and P. vivax account for the vast majority of cases.

• P. falciparum causes the most severe infection.

Pathogenesis• Malaria develops via two phases: an exoerythrocytic

and an erythrocytic phase.• An infected mosquito may pierce a person's skin to take

a blood meal. • The sporozoites, present in the saliva of the mosquito,

enter the bloodstream and migrate to the liver. • The sporozoites, in the liver cells, multiply asexually to

yield thousands of merozoites. This process is called exoerythrocytic schizogony.

• This exoerythrocytic or liver phase of the disease usually takes between 5 and 21 days, depending on the species of plasmodium.

Pathogenesis contd.• Following rupture of their host cells, thousands of

merozoites are released into the blood stream thus beginning the erthrocytic stage.

• Each merozoite can infect a red blood cell. Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their hosts to invade fresh red blood cells.

• Some merozoites turn into male and female gametocytes. If a mosquito pierces the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization of the parasite occurs in the mosquito's gut. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle.

Infected erythrocytes

Signs and Symptoms

• The general symptoms include fever , headache, sweating, tiredness, abdominal pain, diarrhoea, loss of appetite, jaundice, cough, vomiting etc.

• The time after which they develop depends on the type of plasmodium that caused the infection.

• Symptoms may appear and disappear in phases and may come and go at various time frames.

• Further serious complication involving the kidneys and brain may develop leading to delirium and coma.

Diagnosis

• Malaria is considered a potential medical emergency. Delay in diagnosis and treatment is a leading cause of death in malaria patients in the United States.

• Definitive diagnosis of malaria generally requires direct observation of malaria parasites in Giemsa-stained thick and thin blood smears.

• Other diagnostic methods include assays to detect malaria antibodies and antigens, and PCR/DNA and RNA probe techniques.

P. vivax P. ovale

P. falciparum P. malariae

Treatment

Treatment of malaria depends on the following factors:• Type of infection• Severity of infection• Status of the host• Associated conditions/ diseases

Treatment contd.Aims Causation Therapy Drugs

To alleviate symptoms

Symptoms are caused by blood forms of the parasite

Blood schizonticidal drugs

Chloroquine, quinine, artemisinin combinations

To prevent relapses

Relapses are due to

hypnozoites of P. vivax/ P.

ovale

Tissue schizonticidal

drugsPrimaquine

To prevent spread

Spread is through the gametocytes

Gametocytocidal drugs

Primaquine for P. falciparum, Chloroquine for all other

Prevention

• Most cases of malaria in Americans can be prevented by chemoprophylaxis and by avoiding the mosquito vector.

• The female Anopheles mosquito feeds from dusk until dawn. During these hours, individuals should avoid contact with the mosquito by wearing protective clothing, using an insect repellent and by sleeping under insecticide-impregnated bed nets.

Resistance• Resistance of P. falciparum to chloroquine, the cheapest

and most used drug, is spreading in almost all the endemic countries. Resistance to the combination of sulphur doxine- Pyrimethamine is also prevailing.

• Resistance occurs most commonly due to improper treatment and inadequate dosage of antimalarial drug.

• Possible mechanisms- The parasite does not allow the entry of drug or after the entry of drug the malarial parasite does not retain it and throws it out.

Molecular Tools

• Improved diagnostic tools, especially molecular biology- based tools, to support the clinical suspicion of malaria are developed.

• Nucleic acid-based diagnostic methods for parasitic infections have been developed over the past 12 years. PCR-hybridization assays, PCR-restriction fragment length polymorphism (PCR-RFLP) assays and random amplified polymorphic DNA (RAPD) analysis have proved valuable for epidemiological studies of parasites.

Molecular Tools contd.Species-specific PCR diagnosis of malaria:-• Detection and speciation of Plasmodium is done with

a two step nested PCR.• In the first step (PCR1), 1 µl of extracted DNA is

amplified using genus specific primers.• In the second step (PCR2), 1 µl of PCR1 amplification

product is further amplified using species specific primers.

• 10 µl of each PCR2 amplified DNA product is separated by 2% agarose gel electrophoresis, stained for 15 min with ethidium bromide and visualized by UV illumination.

Lane 1: P. vivax (size: 120 bp). Lane 2: P. malariae (size: 144 bp). Lane 3: P. falciparum (size: 205 bp). Lane 4: P. ovale (size: 800 bp).

Conclusion

• Each year, there are more than 225 million cases of malaria,

killing around 781,000 people which contributes to 2.23% of deaths worldwide.

• Its really a high time to overcome that “female” mosquito and accordingly taking measures to prevent its harmful effects on our lives.

References

• www.malariasite.com• www.wikipedia.org• www.cdc.gov• Google images

Any Questions?