DEEPA BABINASST PROF,MICROBIOLOGY,TMC

Malaria is a major public health problem in warm climates especially in developing countries.

It is a leading cause of disease and death among children under five years, pregnant women and non-immune travellers/immigrants.

Malaria

Name means “bad air”-A life-threatening parasitic disease 40% of the world’s population is at risk90% of the deaths due to Malaria occur

in Sub-Sahara Africa, mostly among young children.

Around 400-900 million people are affected

At least 2.7 million deaths annually.

What is malaria ?

Malaria is a disease caused by the protozoan parasites of the genus Plasmodium. The 4 species that commonly infect man are:

Consists of 4 species:P. vivax

P. falciparum P. malariae

P. ovale

• Plasmodium parasites are highly specific with female Anopheles mosquitoes

Benign tertian malaria = Vivax Malaria

Malignant tertian Malaria = Falciparum Malaria

Quartian Malaria = P.Malaria

Ovale malaria -P. ovale

Landmarks in the evolution of Malaria

• 1880 – Laveran identified the malarial parasite in

an unstained smear• 1885 – Golgi described the blood stage (erythrocytic schizogony) of

malarial parasite – Golgi cycle• 1898 – Amigo & Grassi described the life

cycle• 1891 – Romanowsky introduced the staining method• 1897 – Ronald Ross while in Calcutta, India,

demonstrated Anopheles sp. of

mosquitoes as vectors of malaria. Got Nobel prize for his work in 1902

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Transmission & Life Cycle

Definitive host Female Anopheles

mosquito

Intermediate host Man

Infective form Sporozoites

Portal of entry Skin

Mode of transmission Bite of an infected

mosquito

Site of localization First in liver cells &

then in

RBCs

Malaria parasites are transmitted from one person to another by the bite of a female anopheles mosquito.

The female mosquito bites during dusk and dawn and needs a blood meal to feed her eggs.

Male mosquitoes do not transmit malaria as they feed on plant juices and not blood.

There are about 60 species of anopheles are able to transmit malaria.

Like all mosquitoes, anopheles breed in water - hence accumulation of water favours the spread of the disease.

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Incubation period

• P. vivax • P. ovale 10 to 14 days• P. falciparum

• P. malariae 18 days to 6 weeks

Infection Sporozoites

Liver

Asexualcycle

Gametocytes

Merozoites

Transmissionto mosquito

Click on the diagram to explore different areas of

the life cycle

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Clinical Features• Series of febrile paroxysms –

fever is caused by the release of merozoites & toxins from ruptured erythrocytic schizont which in turn causes the release of cytokines.

Quartan malaria – every 72 hrs

Tertian malaria - every 48 hrs

* each paroxysm has 3 stages - cold stage (rigors), hot stage (high temp., body & joint pains, vomiting & diarrhoea) and perspiration stage (fall in temp.)

Erythrocytic schizogony is the time taken for trophozoites to mature into merozoites before release when the cell ruptures.

It is shortest in P. falciparum (36 hours), intermediate in P. vivax and P. ovale (48 hours) and longest in P. malariae (76 hours).

Note how the frequency of spikes of fever differ according to the Plasmodium species. In practice, spikes of fever in P. falciparum, occur irregularly - probably because of the presence of parasites at various stages of development.

o Vomitingo Diarrhoea – more commonly seen in young children and, when vomiting also occurs,

may be misdiagnosed as viral gastroenteritiso Convulsions – commonly seen in young children. Malaria is the leading cause of

convulsions with fever in African children. o Pallor – resulting mainly from the lysis of red blood cells. Malaria also reduces the

synthesis of red blood cells in the bone marrow. o Jaundice – mainly due to haemolysis.Malaria is a multisystem disease. Other common clinical features are: o Anorexiao Cougho Headacheo Malaiseo Muscle acheso Splenomegalyo Tender hepatomegaly These clinical features occur in “mild” malaria. However, the infection

requires urgent diagnosis and management to prevent progression to severe disease.

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Falciparum Malaria

• Most widespread• Accounts for 80% of malaria cases

worldwide• Most pathogenic of human malaria

species• Untreated infections - severe disease

& even death, particularly in young children, pregnant woman & non immune adults.

1. Cerebral malaria2. Severe malaria anaemia3. Hypoglycaemia4. Metabolic acidosis

5. Acute renal failure 6. Pulmonary oedema7. Circulatory collapse,

shock or “algid malaria”8. Blackwater fever

Nearly all severe disease and the estimated >1 million deaths from malaria are due to P. falciparum. Although severe malaria is both preventable and treatable, it is frequently a fatal disease.

The following are 8 important severe manifestations of malaria:Click on each severe manifestation for details

Note: It is common for an individual patient to have more than one severe manifestation of malaria!

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Pernicious Malaria

• Def: refers to a series of phenomenon occurring during infection with P. falciparum which, if not effectively treated, threatens the life of the patient with in 1 to 3 days

• In children & non immune adults, can cause coma & death – Cerebral malaria.

• Occurs as a result of capillary blockage.

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Anaemia

• Can be severe & occur rapidly, particularly in young children

• Occurs due to destruction of parasitised RBCs – phagocytosis & destruction in the spleen

• Decreased production of RBCs in the bone marrow.

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Black Water Fever

• Occurs in previously infected subjects• Can also occur in non immune adults

with severe falciparum malaria, and also as a complication of quinine therapy.

• A rare but acute condition characterised by sudden & massive hemolysis of parasitised & non parasitised RBCs followed by fever and haemoglobinuria.

• Often fatal due to renal failure

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Black Water Fever

• Difficult to find the parasites in the blood following a hemolytic attack.• Urine appears dark red to brown black due to the presence of free Hb.• Clinical features – fever, rigor, aching

pains in the loin, icterus, bilious vomiting, circulatory collapse, haemoglobinuria & acute renal failure.

• Treatment – Chloroquine, blood transfusion, peritoneal dialysis in ARF.

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Recurrence of Malaria• Two types of recurrences known in

malaria:1. Recrudescence –

– seen in P. falciparum & P. malariae– due to persistence of blood infection (some

erythrocytic forms evade host immunity) even after clinical illness has subsided.

– The numbers may increase later, leading to reappearance of clinical symptoms

– Occur mostly up to one year or so but in P. malariae, it can occur even after decades

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Recurrence of Malaria

2. Relapse– Occurs due to a special form of

parasites – hypnozoites.

– Hypnozoites are the sporozoites that remain dormant after infecting liver

– Activated from time to time to initiate pre erythrocytic schizogony - Exoerythrocytic schizogony

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Laboratory Diagnosis

• Microscopy – detecting & identifying malarial parasites in peripheral blood films.

• Concentrating parasites in venous blood by centrifugation when they can not be found in blood films

• Using a rapid malaria Ag or enzyme detection test

• Other tests – Hb, PCV, Blood glucose, total WBC & platelet count.

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Examination of Blood film

• Collection of blood - best prepared directly from

capillary blood in EDTA bulb (used within 30 mins)

• Time of collection - as soon as possible if

malaria is suspected before administering antimalarials during pyrexial phase

Investigations

Blood Film Examination

Thick and thin blood films (or “smears”) have remained the gold standard for the diagnosis of malaria. The films are stained and examined by microscopy.

Thick blood film - Used for detecting malaria: a larger volume of blood is examined allowing detection of even low levels of parasitaemia. Also used for determining parasite density and monitoring the response to treatment.

Thin blood film – Gives more information about the parasite morphology and, therefore, is used to identify the particular infecting species of Plasmodium.

Show Me

Show Me

Ring forms or trophozoites; many red cells infected – some with more than one parasite

Gametocytes (sexual stages); After a blood meal, these forms will develop in the mosquito gut

http://phil.cdc.gov/phil/quicksearch.asp

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Buffy Coat preparation

• To concentrate malarial parasite• Centrifuge EDTA anticoagulated

venous blood in a thin bore capillary tube

• Buffy coat layer is formed between the RBCs & the plasma.

• Break the tube & transfer buffy coat & RBCs to a slide - make a thin smear – air dry – fix with ethanol – stain with Giemsa.

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Quantitative Buffy Coat

• Capillary tube is coated with an anticoagulant & Acridine orange fluorescent dye

• After centrifugation, the tube can be used for two purpose:

1. Complete blood count2. Identification of malarial parasite

using a fluorescence microscope.

Other methods of diagnosis of malaria

These are not routinely used in clinical practice. They include : a) Antigen capture kits. Uses a dipstick and a finger prick blood

sample. Rapid test - results are available in 10-15 minutes. Expensive and sensitivity drops with decreasing parasitaemia.

b) PCR based techniques. Detects DNA or mRNA sequences specific to Plasmodium. Sensitivity and specificity high but test is expensive, takes several hours and requires technical expertise.

c) Fluorescent techniques. Relatively low specificity and sensitivity. Cannot identify the parasite species. Expensive and requires skilled personnel.

d) Serologic tests. Based on immunofluorescence detection of antibodies against Plasmodium species. Useful for epidemiologic and not diagnostic purposes.

Parasitized RBC

• All: Plasmodium falciparum.• Young (reticulocytes, larger rbc):

Plasmodium ovale and Plasmodium vivax.• Old (smaller rbc): Plasmodium malariae.

Malaria in pregnancy

More than 45 million women (30 million inAfrica) become pregnant in malaria endemic areas each year.

Common adverse effects of malaria in pregnancy include:• Maternal anaemia• Stillbirths• Premature delivery and intrauterine growth retardation result in the delivery of low

birth weight infants

The WHO now recommends intermittent preventive treatment (IPT): the administration of anti-malarial drugs (e.g. sulphadoxine-pyrimethamine) during antenatal care whether or not women show symptoms. IPT has been shown to substantially reduce the risk of maternal anaemia in the mother and low birth weight in the newborn.

Previously, chemoprophylaxis (e.g. with chloroquine) was recommended for all women living in malaria endemic areas.

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ChloroquineFansidar

(Sulfadoxine/pyrimethamine)Quinine

ArtesunateHalofantrinDoxycycline

Malarone (Atovaquone/proguanil)

Primaquine

Treatment Prophylaxis

ChloroquineDaraprimproguanil

Chloroquine/proguanilSulfadoxine/

pyrimethamineSulfa/dapsone

MefloquineAtovaquone/proguanil

DoxycyclinePrimaquine

Antimalarial drugs

Treatment of Chloroquine resistant malaria

Quinine + tetracyclineor clindamycin

or Fansidar (sulfadoxine and pyrimethamine)Malarone (paludrine/atovaquone)Mefloquine (a quinoline methanol)

Qinghaosu (artemesinin)

Malaria Prevention

Mosquito avoidance - evening and night behavior

- mosquito nets- air conditioning

- screens- mosquito repellants

- pyrethrin coilsMosquito killing - destroying breeding sites

- fog spraying- residual spraying

Plasmodium killing - chemoprophylaxis

Despite all these advances, malaria will likely be with us as long as there are humans on this earth.