Malaria is a major public healthproblem in warm climates especiallyin developing countries.It is a leading cause of disease anddeath among children under fiveyears, 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 risk 90% 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. vivaxP. falciparumP. malariaeP. ovale• Plasmodium parasites are highly specific with female Anophelesmosquitoes
Landmarks in the evolution of Malaria• 1880 – Laveran identified the malarial parasite inan 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 stainingmethod• 1897 – Ronald Ross while in Calcutta, India,demonstrated Anopheles sp. of mosquitoes asvectors of malaria.Got Nobel prize for his work in 1902
26/04/07Transmission & Life CycleDefinitive host Female Anopheles mosquitoIntermediate host ManInfective form SporozoitesPortal of entry SkinMode of transmission Bite of an infected mosquitoSite of localization First in liver cells & then inRBCs
Malaria parasites are transmitted from oneperson to another by the bite of a femaleanopheles mosquito. The female mosquito bites during dusk and dawnand needs a blood meal to feed her eggs. Male mosquitoes do not transmit malaria as theyfeed on plant juices and not blood. There are about 60 species of anopheles are ableto transmit malaria. Like all mosquitoes, anopheles breed in water -hence accumulation of water favours the spreadof the disease.
26/04/07Incubation period• P. vivax• P. ovale 10 to 14 days• P. falciparum• P. malariae 18 days to 6weeks
Infection SporozoitesLiverAsexualcycleG ametocytesMerozoitesTransmissionto mosquitoClick on thediagram to exploredifferent areas ofthe life cycle
26/04/07Clinical Features• Series of febrile paroxysms – fever is causedby the release of merozoites & toxins fromruptured erythrocytic schizont which in turncauses the release of cytokines.Quartan malaria – every 72 hrsTertian malaria - every 48 hrs* each paroxysm has 3 stages - cold stage(rigors), hot stage (high temp., body & jointpains, vomiting & diarrhoea) andperspiration stage (fall in temp.)
Erythrocytic schizogony is thetime taken for trophozoites tomature into merozoites beforerelease when the cell ruptures.It is shortest in P. falciparum (36hours), intermediate in P. vivaxand P. ovale (48 hours) andlongest in P. malariae (76hours).Note how the frequency of spikes of fever differ accordingto the Plasmodium species. In practice, spikes of fever inP. falciparum, occur irregularly - probably because of thepresence of parasites at various stages of development.
o Vomitingo Diarrhoea – more commonly seen in young children and, when vomiting also occurs, may be misdiagnosed asviral gastroenteritiso Convulsions – commonly seen in young children. Malaria is the leading cause of convulsions with fever in Africanchildren.o Pallor – resulting mainly from the lysis of red blood cells. Malaria also reduces the synthesis of red blood cells inthe 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 hepatomegalyThese clinical features occur in “mild” malaria. However, the infection requires urgent diagnosis andmanagement to prevent progression to severe disease.
26/04/07Falciparum Malaria• Most widespread• Accounts for 80% of malaria cases worldwide• Most pathogenic of human malaria species• Untreated infections - severe disease & evendeath, particularly in young children, pregnantwoman & non immune adults.
1. Cerebral malaria2. Severe malaria anaemia3. Hypoglycaemia4. Metabolic acidosis5. Acute renal failure6. Pulmonary oedema7. Circulatory collapse, shock or“algid malaria”8. Blackwater feverNearly all severe disease and the estimated >1 million deaths from malariaare due to P. falciparum. Although severe malaria is both preventable andtreatable, it is frequently a fatal disease.The following are 8 important severe manifestations of malaria:Click on each severe manifestation for detailsNote: It is common for an individual patient to have more thanone severe manifestation of malaria!
26/04/07Pernicious Malaria• Def: refers to a series of phenomenon occurringduring infection with P. falciparum which, if noteffectively treated, threatens the life of the patientwith in 1 to 3 days• In children & non immune adults, can cause coma &death – Cerebral malaria.• Occurs as a result of capillary blockage.
26/04/07Anaemia• Can be severe & occur rapidly, particularly inyoung children• Occurs due to destruction of parasitised RBCs– phagocytosis & destruction in the spleen• Decreased production of RBCs in the bonemarrow.
26/04/07Black Water Fever• Occurs in previously infected subjects• Can also occur in non immune adults with severefalciparum malaria, and also as a complication ofquinine therapy.• A rare but acute condition characterised by sudden& massive hemolysis of parasitised & nonparasitised RBCs followed by fever andhaemoglobinuria.• Often fatal due to renal failure
26/04/07Black Water Fever• Difficult to find the parasitesin the blood following ahemolytic attack.• Urine appears dark red tobrown black due to thepresence 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, peritonealdialysis in ARF.
26/04/07Recurrence of Malaria• Two types of recurrences known in malaria:1. Recrudescence –– seen in P. falciparum & P. malariae– due to persistence of blood infection (some erythrocyticforms evade host immunity) even after clinical illness hassubsided.– The numbers may increase later, leading to reappearanceof clinical symptoms– Occur mostly up to one year or so but in P. malariae, itcan occur even after decades
26/04/07Recurrence of Malaria2. Relapse– Occurs due to a special form of parasites –hypnozoites.– Hypnozoites are the sporozoites that remaindormant after infecting liver– Activated from time to time to initiate preerythrocytic schizogony - Exoerythrocyticschizogony
26/04/07Laboratory Diagnosis• Microscopy – detecting & identifying malarialparasites in peripheral blood films.• Concentrating parasites in venous blood bycentrifugation when they can not be found in bloodfilms• Using a rapid malaria Ag or enzyme detection test• Other tests – Hb, PCV, Blood glucose, total WBC &platelet count.
26/04/07Examination of Blood film• Collection of blood- best prepared directly from capillaryblood in EDTA bulb (used within 30mins)• Time of collection- as soon as possible if malaria issuspected before administeringantimalarials during pyrexial phase
InvestigationsBlood Film ExaminationThick and thin blood films (or “smears”) have remainedthe gold standard for the diagnosis of malaria. Thefilms are stained and examined by microscopy.Thick blood film - Used for detecting malaria: a largervolume of blood is examined allowing detection ofeven low levels of parasitaemia. Also used fordetermining parasite density and monitoring theresponse to treatment.Thin blood film – Gives more information about theparasite morphology and, therefore, is used toidentify the particular infecting species ofPlasmodium.Show MeShow Me
Ring forms or trophozoites; manyred cells infected – some with morethan one parasiteGametocytes (sexual stages); After a bloodmeal, these forms will develop in themosquito guthttp://phil.cdc.gov/phil/quicksearch.asp
26/04/07Buffy Coat preparation• To concentrate malarial parasite• Centrifuge EDTA anticoagulated venous bloodin a thin bore capillary tube• Buffy coat layer is formed between the RBCs &the plasma.• Break the tube & transfer buffy coat & RBCs toa slide - make a thin smear – air dry – fix withethanol – stain with Giemsa.
26/04/07Quantitative Buffy Coat• Capillary tube is coated with an anticoagulant& Acridine orange fluorescent dye• After centrifugation, the tube can be used fortwo purpose:1. Complete blood count2. Identification of malarial parasite using afluorescence microscope.
Other methods of diagnosis of malariaThese are not routinely used in clinical practice. They include :a) Antigen capture kits. Uses a dipstick and a finger prick bloodsample. Rapid test - results are available in 10-15 minutes.Expensive and sensitivity drops with decreasing parasitaemia.b) PCR based techniques. Detects DNA or mRNA sequencesspecific to Plasmodium. Sensitivity and specificity high but test isexpensive, takes several hours and requires technical expertise.c) Fluorescent techniques. Relatively low specificity andsensitivity. Cannot identify the parasite species. Expensive andrequires skilled personnel.d) Serologic tests. Based on immunofluorescence detection ofantibodies against Plasmodium species. Useful for epidemiologicand not diagnostic purposes.
Parasitized RBC• All: Plasmodium falciparum.• Young (reticulocytes, larger rbc):Plasmodium ovale and Plasmodium vivax.• Old (smaller rbc): Plasmodium malariae.
Malaria in pregnancyMore 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 lowbirth weight infantsThe WHO now recommends intermittent preventive treatment (IPT): the administrationof anti-malarial drugs (e.g. sulphadoxine-pyrimethamine) during antenatal carewhether or not women show symptoms. IPT has been shown to substantiallyreduce the risk of maternal anaemia in the mother and low birth weight in thenewborn.Previously, chemoprophylaxis (e.g. with chloroquine) was recommended for all womenliving in malaria endemic areas.