Malaria

POSTGRADUATE CLASS
Prof. Walter Jaoko
Department of Medical Microbiology
University of Nairobi
 Objectives

At the end of this lecture you should be able to:

• Describe the epidemiology of malaria
• Outline the species of Plasmodium parasite
• Describe the life cycle of malaria
• Describe the clinical presentation of malaria,
including its complications
• Describe the laboratory diagnosis of malaria
• Outline the treatment of malaria
• Discuss malaria prevention and control
 Outline of presentation

• Introduction
• Life cycle
• Clinical presentation (+ Complications)
• Laboratory diagnosis
• Treatment
• Prevention
 Introduction
• Malaria – None motile protozoal dx
• Transmitted by Anopheles mosquitoes
• Mal-aria – italian for ‘bad air’
• Endemic in most tropical regions of the world
• 5 plasmodium sp causing human infection
• P.falciparum, P.vivax, P.malariae , P.ovale, P.
knowlesi
• P.falciparum most important, rapid, most death
• Accounts for >85% of malaria in East Africa
• 500 M exposed to endemic malaria
• 2-3 M deaths/yr (1-1.5 M children, mostly in
Africa)
Malaria endemic regions
 Introduction-2
• Endemic malaria - areas of high transmission
• Epidemic malaria - ‘highland’ & arid/semi-arid
• Imported malaria – travel & migration, any country
• Airport malaria - USA, Belgium, Switzerland, UK
• No history of recent travel to endemic areas
• Easily missed (dangerous)
• ?infected mosquitoes entering non-endemic areas,
biting people living around airports
• Not common, spraying of aeroplanes before taking off
 Life cycle
• Mosquito deposites sporozoites during blood meal,
sporozoites > 30 min in circulation >liver schizonts
(with merozoites) [exo-erythrocytic schizogony] >
blood > RBCs trophozoites > schizonts (merozoites)
[erythrocytic schizogony]> gametocytes > picked
by mosquitoes > gametes (male & female) > sexual
reproduction > zygote > ookinete > penetrate wall
of stomach > oocysts > rupture > sporozoites >
salivary glands [sporogony]
• Hypnozoite stage (sleeping/resting stage)
• P. ovale & P. vivax
• Responsible for relapsing malaria
Anopheles mosquito
 Clinical presentation-1
(Simple uncomplicated malaria)
• Irregular fever (tertian [48 hrs]– P. falciparum,
P. vivax, P. ovale; quartan [72 hrs] - malariae)
with chills (rigors)
• Headache, nausea, loss of appetite, dizziness,
vomiting, muscle aches, joint pains, general
malaise, diarrhoea
• High temperature, jaundice, pallor, abdominal
tenderness, splenomegaly, hepatomegaly
 Clinical presentation-2
(Severe & complicated malaria)
• Cerebral malaria, convulsions, hypoglycaemia,
hyperpyrexia, severe anaemia, renal failure,
acidosis, hyperbilirubinaemia, pulmonary
oedema/acute respiratory distress syndrome),
haemoglobinuria (black water fever), algid
malaria (circulatory shock due to
bacteremia/septicaemia), disseminated
intravascular coagulopathy (DIC), abortion,
premature birth, low birth weight , intrauterine
death,
• Hyper-reactive malaria splenomegaly (HMS),
previously tropical splenomegaly syndrome (TSS)
Cerebral malaria

Pl. falciparum. In cerebral malaria, numerous petechiae appear in

the brain. Copyright ITM
Severe anaemia
Anaemia
Pulmonary oedema
Hyper-reactive malaria splenomegaly
Nephrotic syndrome (P. malariae)
 Laboratory diagnosis

• Gold standard = thick + thin blood films

• Stain (Giemsa, Fields etc)
• Examine thick film 1st under microscope - put
a drop of blood at centre of slide, spread to
size of a shilling coin, let dry, stain, examine
DON’T FIX
• If parasites seen, thin film to confirm species
• Thin film - blood at edge of slide, spread with
2nd slide, allow film to dry, fix, stain, examine
under microscope
Laboratory diagnosis (cont’d)
 Laboratory diagnosis (cont’d)

• Giemsa stain - best if few thick films, slow

• Field’s stain – best if many thick films, very
quick
• Other diagnostic methods
• Ag detection - parasite-specific lactate dehydrogenase
(pLDH) in P.falciparum infection, fast, high sensitivity
& specificity, but unable to quantify parasite load,
distinguish parasite species, & Ag may be detected 2
wks post-treatment hence not always active infection
• QBC – centrifuge blood in capillary tubes precoated
with acridine orange (OA), stains parasite DNA, view
UV light microscope, high sensitivity, cant distinguish
young P. falciparum & P. vivax trophozoites
• PCR – Experimental, detects <10 parasites/10uL
blood, may prove valuable for diagnosis & sp
identification of malaria, special equipment required
P. Falciparum - RBCs not enlarged, rings appear fine & delicate, may
have several in one cell, may have two chromatin dots, presence of
marginal forms, Maurer's dots may be present.
Thick film – positive malaria slide
 Treatment of uncomplicated P.
falciparum malaria
• Drug resistance – chloroquine; amodiaquine;
sulfur/pyrimethamine; mefloquine etc.
• Currently Artemesinin combination treatment
(ACT)
• Artemesinine + proguanil (AP)
• Artemesinine + sulphur/pyrimethamine (ASP)
• Artemesinine + mefloquine (AM)
• Amodiaquine-artesunate (ASAQ)
• Dihydroartemisinin-Piperaquine (DHA-PIP)
• Pyronaridine-Artesunate (PYR-ART)
• Kenya, artemesinin+lumefantrine (AL)
 Treatment of severe/complicated P.
falciparum malaria
• Quinine - IV in a 5% dextrose drip
• + doxycycline (if not contraindicated)
• Artemesinin IM
• cure rates similar to quinine
• easier to administer
• safe in pulmonary oedema
• Treat other exisiting conditions
• hypoglycaemia (glucose IV)
• anaemia (transfusion)
• convulsions (diazepam or paraldehyde )
• renal failure (dialysis)
• hyperpyrexia (antipyretic)
• pulmonary oedema (diuretics etc)
 Treatment of P. ovale and P. vivax
malaria
• Chloroquine
• Quinine
• ACTs

Add: Primaquine – kills hypnozoites

 Prevention
• Residual insecticide spray
• Insecticide treated bed nets
• Mosquito repellent
• Mosquito larvicides
• Mosquito window screens
• Environmental management
• Clearing bushes
• Filling trenches
• Removal of old tyres, empty tins etc
• Protective clothing
• Air-conditioners/fan
• Prophylaxis
 Prevention
• Prophylaxis
– Who should be given prophylaxis in malaria zones?
o Tourists, expatriates, missionaries
o Sickle-cell disease patients
o Splenectomized individuals
o pregnant mothers
o ?Children under 5 yrs
– What should be used?
o mefloquine weekly
o doxycycline daily
o malarone (atovaquone+pyrimethamine)
 Malaria Prevention in Pregnancy
• IPTp – Intermittent preventive treatment in pregnancy
• Sulphadoxine-pyrimethamine (SP)
– Although not used in malaria treatment due to resistance
– Concentrates in the placenta killing malaria parasites there
– Reduces malaria attacks in mother
– Associated with better pregnancy outcomes e.g fever premature
births, fewer low birth weight babies, fewer babies who are small
for gestational age, fewer neonatal deaths etc.
– Resistance emerging
– Alternatives being considered
– Trials on-going on Dihydroartemisinin + piperaquine