Microbiology Education Series - Parasitology No. 2

Plasmodium falciparum

1	Background / History

• P.falciparum - Whilst there will be reference to other other human malarial species of Plasmodium, including Plasmodium ovale, Plasmodium malariae and Plasmodium vivax, P. falciparum will be specifically focused on throughout this text.   
• The name malaria derives from the Italian words meaning bad air, (mala aria). First described by Lancisi in 1717, malaria was given to mean, "the poisnous vapours of swamps".
• The causal link between malaria and mosquitoes may have been recognised as early as 2000 B.C. in India.
• In 1880 malarial parasites, (exflagellating microgametocytes), were first seen by Laveran, at a military hospital in Constantine, Algeria.
• In 1894 Mansen proposed that mosquitoes could transmit malaria, an assumption made centuries before in India, (see above).
• In 1898 the connection between malaria and mosquitoes was confirmed by Grassi and Ross.
• In 1900, Grassi proposed an erythrocytic stage in the malaria lifecycle, which was later confirmed by Short, Garnham, Covell and Shute, who identified P. vivax in the human liver.
• Nobel Prizes - four prizes have been awarded in the past for work involving malaria, Sir Ronald Ross. (1902), Charles Louis Alphonse Laveran, (1907), Julius Wagner-Jauregg, (1927) and Paul Herman Muller, (1948).
• P.falciparum - was cultured successfully for the very first time in 1976 paving the way for new drug and vaccine development.
• On a world-wide basis, malaria causes higher rates of mortality and morbidity than any other blood borne parasite. Globally, over one million people die every year from malaria, ( 2-3 deaths / minute ), of which around 30% maybe children in some developing countries. Every year around 350 to 500 million cases of malaria occur globally.
• Over 40% of the world's population live in geographic regions where malaria is prevalent, (e.g. parts of Africa, Asia, the Middle East, Central and South America, Hispaniola and Oceania). Roughly two billion persons may be susceptible to malaria according to the country they live in.
• P.falciparum is one species of Plasmodium that accounts for approximately 80% of all cases of malaria in humans; it is transmitted by the female Anopheles mosquito.
• P. falciparum is the most dangerous Anopheles-transmitted infection, with the highest rates of complication and mortality compared to other species of Plasmodium.
• The fight against malaria is hindered by both insecticide and drug resistance which is rapidly spreading.
• Evolution - Plasmodium reichenowi which is a recognised parasite of chimpanzees is the closest relative to P.falciparum and it is fascinating to note that these two species of Plasmodium may have evolved when chimpanzees and humans diverged. However, other data suggests, for example, low levels of polymorphism in the P. falciparum genome, may mean that this organism evolved much later than P. reichenowi.
• Cost to treat malaria - for approximately £0.07, an individual could be treated for malaria with either Chloroquine or Sulfadoxine-pyrimethamine. A course of potentially life saving quinine may cost as little as £1.35.

2	Classification

Table 1: Classification of Plasmodium falciparum.

Classification	P. falciparum
Kingdom	Protista
Phylum	Apicomplexa
Class	Aconoidasida
Order	Haemosporida
Family	Plasmodiidae
Genus	Plasmodium
Species	P. falciparum

 

• Gainham's classification of 1966 -  is based on morphological aspects of the life cycle of malaria, including the shapes of the trophozoite, gametocyte and oocyst, the number of nuclei in the exoerythrocytic and erythrocytic schizonts, pigment distribution and the nature of the damage caused by the parasite in the host cell. Biological criteria include: host and type of cell infected within the host, how long each stage of the life cycle lasts for, the presence or absence of relapse and the nature of vector and geographical distribution. This classification system, whilst limited in specificity, proves useful in differentiating and classifying species of Plasmodium.
• SSU rRNA gene sequences have been compared to reveal P. falciparum is more closely related to avian than mammalian plasmodia.
• Since 1978, the WHO proposed a useful classification scheme for malaria, (later modified by Cox, 1998).

• Isolate (or primary isolate) - parasites isolated from naturally infected host.
• Stock - parasite populations derived from serial passage in animals or culture from a primary isolate.
• Strain - parasite populations derived from a primary isolate having particular characteristics. A strain is well-defined Stock.
• Line - a parasite population originating from a normal strain but displaying differences from the parental strain, that can show changes in drug sensitivity and increased virulence.
• Stabilate - parasite populations frozen at one time.
• Clone - a parasite population originating from an individual, asexual parasite.

 

3	Morphology

Table 2. Life cycle stage morphology of P. falciparum.

Stages found in blood	Appearance of RBC	Appearance of parasite	View Images
Ring	Normal; multiple infections of RBC more common than in other species	Delicate cytoplasm; 1-2 small chromatin dots; occasional appliqué (accollé) forms
Trophozoite	Normal; rarely, Maurer's clefts (under certain staining conditions)	Seldom seen in peripheral blood; compact cytoplasm; dark pigment
Schizont	Normal; rarely, Maurer's clefts (under certain staining conditions)	Seldom seen in peripheral blood; mature = 8-24 small merozoites; dark pigment, clumped in one mass
Gametocyte	Distorted by parasite	Crescent or sausage shape; chromatin in a single mass (macrogametocyte) or diffuse (microgametocyte); dark pigment mass

•  Maurer's Cleft's - these structures are uniquely associated with p. falciparum and are thought to be pathogen induced, secretory organelles whose function is to concentrate virulence protein reporters ready for passing onto the host erythrocyte. Virulence of P. falciparum depends on the transfer of proteins from the parasite to the host red blood cell.
• Gametocyte - This is the sexual reproductive stage of the parasite, females being termed macrogametocytes and males called microgametocytes which circulate in an infected persons bloodstream. Once picked up by the female Anopholes mosquito, gamete formation and fertilization takes place in the midgut of the mosquito.
• Erythrocytic asexual-stage schizonts - This is a reproductive stage of the malarial parasite in the blood where merozoites are formed. Merozoites invade RBC's.
• Gametocytogenesis - The process where gametocytes are generated from asexual precursors.
• Merozoites - These parasitic forms are the daughter cells formed at two different stages in the life cycle of malaria parasites, (see below, Fig.4.), by asexual division at both the liver and the blood stage developing into schizonts which contain many merozoites. Mature schizonts and the host cells in which they reside rupture, releasing merozoites which go on to infect RBC's.
• Oocysts - These structures are located on the mosquitoes outer midgut wall and are formed after the fertilisation process. Mature oocysts rupture to liberate sporozoites.
• Schizogony - This is the scientific term for the asexual reproductive stage of malarial parasites. Many nuclear divisions give rise to the formation of a daughter cell or merozoite around each nucleus. Once again, Schizogony takes place within both infected liver cells and RBC's.
• Sporozoite - These structures represent the infective stage of the malarial parasite, residing in the Anopholes mosquitoes salivary glands until such a time that they are injected into their human host. Sporozoites are characteristically fragile, spindle-shaped parasitic stages which are systematically released into the mosquito haemocoel when the oocyst ruptures. The majority of sporozoites then instinctively travel to the mosquito salivary glands. Once injected into the human host, the sporozoites infect liver cells initially and then become untraceable in the bloodstream after only half an hour or so.
• Trophozoites - This is a malaria parasite developmental stage associated with RBC's. Once merozoites have entered RBC's they develop into trophozoites, early trophozoites being referred to as, "rings" or "ring stage parasites". Trophozoites then develop into schizonts.
• Applique forms - Applique is a term applied to the manner in which the ring stage of P. falciparum parasitises the marginal portion of erythrocytes.
• Rings - P.falciparum may show one or two chromatin dots in the ring form with occasional applique forms. The rings can show a well recognised, "headpones" appearance, which can be used to positively identify this species of Plasmodium. (see Fig.1 and Fig.2.).    

Fig.1. Giemsa stained RBC's showing the classic headphones appearance of P.falciparum.

Fig.2. Giemsa stained RBC's showing numerous P. falciparum ring structures within them.

Courtesy of the liverpool School of Tropical Medicine.

Genome Structure of Plasmodium

• Malarial genome - This genome is a complex structure and highly diverse even among isolates of the same species. It contains nuclear DNA plus two extrachromasomal forms of DNA, one of which may be related to the mitochondria, (6Kb) and one circular DNA form, (35Kb).
• Genome size - The total malarial genome size ranges from 20 to 40 Mb depending on the species.
• Base Composition - A+T rich. The percentage of each depends on the species.
• Malarial genes - In excess of 150 malarial genes have been uniquely identified, which have been sequenced and mapped onto their respective chromosmoes. Malarial parasites possess 14 chromosomes mapped by the malarial genome project.
• PFGE Analysis - This technique has shown that P.falciparum chromosomes vary in size from 0.6Mb to 3.0Mb. Chromosomes may alter in size during both the sexual stage of the life cycle as well as during mitosis.
• Southern Blot Fingerprinting - malarial parasite diversity has been highlighted by measuring restriction fragment length polymorphism, (RFLP's) with DNA probes. Nearly every isolate tested in a distinct geographical area produced a different Southern Blot Fingerprint.
• Genetic Polymorphism - This may be helpful for molecular epidemeology studies when trying to develop a suitable malarial vaccine or new drug development.
• Vaccine development - many malarial genes show a high frequency of tandem repeats and malarial antigens also show sequence homology. Repeat regions may be related to receptor binding or evasion from the host so can be targeted for vaccine development. However, the allelic polymorphism presents a major problem for vaccine development.
• Genetic diversity of malaria - This is achieved by the following:
  • cross fertilisation - during meiosis.
  • genomic reorganisation - during mitosis           

 

4	Replication / Life Cycle

Fig.3. Sexual life cycle of P. falciparum in the mosquito vector.

 

Fig.4. Asexual life cycle of P. falciparum in Humans.

 

5	Clinical Disease

A patient from an endemic region showing febrile illness may be considered to have malaria.
Exposure - after coming into contact with P. falciparum-infected persons, malaria would not normally manifest itself after a period of three months or so after the contact. This is not the case with other Plasmodium spp.
Incubation period - for P. faciparum malaria is typically 7-27 days, whilst the incubation period of P. malariae is longer, typically 23-69 days.
Life span of P. faciparum - is usually one year, but other species, for example, P. malariae may live for decades.
• Symptoms include fever, headache, malaise, vomiting and diarrhoea.
• Fever - quartian or tertian fever normally appears after a few days where body temperature may reach 41^oC accompanied by profuse sweating and rigors.
• A large proportion of the deaths caused by malaria are attributable to P.falciparum.
• Disease progression - deterioration from being a healthy individual to death via coma may only take a few hours in children if undiagnosed and untreated with antimalarial drugs.
• Parasitaemia - >1% of infected erythrocytes consistutes severe malarial disease.
• Cerebral malaria - this stage of malarial disease is characterised by convulsions and confusion along with reduced consciousness. Without treatment this condition usually results in death.
• Blackwater Fever - this condition is a result of extensive intravascular haemolysis affecting all RBC's culminating in dark urine.
• Severe falciparum malaria
  • Blood: severe anaemia, disseminated intravascular coagulation, (DIC)
  • Renal: haemoglobulinuria, (Blackwater Fever), oliguria.
  • CNS: cerebral malaria, (convulsions/coma).
  • GI: jaundice, vomiting, diarrhoea, splenic rupture.
  • Respiratory: acute respiratory distress syndrome, (ARDS).
  • Metabolic: metabolic acidosis/hypoglycaemia, (mainly children).
  • Shock: hyperpyrexia, hypotensive.
• In addition to transmission by Anopheles spp. malaria can also be transmitted by blood transfusion, by infected needes among drug users and by organ transplantation. Mosquitoes surviving an aeroplane journey from an endemic country may infect persons in a non-endemic area, so called 'airport' or 'baggage malaria'.

 

6	Epidemiology

• Stable malaria - malarial disease can be broadly defined into two categories, Stable malaria and Unstable malaria with many variations in between. Stable malaria's transmission occurs throughout the year and therefore is not seasonal with a good immunity in endemic populations. This type of malaria mainly affects young children and is difficult to control. It is prevalent in the coastal areas of Papua New Guinea as well as rural West and East African regions, etc.
• Unstable malaria - disease transmission is seasonal with variable intensity. Endemic population immunity is low and unstable malaria can affect all age groups, not only young children. It is easier to control than stable malaria and is prevalent in North West India, Plateau's of Madagascar and Ethiopia, etc.

Fig. 5. Anopholes mosquito drawing blood from a human host.

 

• Transmission - malaria can be transmitted by the following routes;
  • Female Anopholes mosquito bite.
  • Airport malaria - when mosquitoes are carried by aeroplane to non endemic areas. 
  • Contaminated blood transfusions.
  • Injecting drug users sharing needles, (very rarely).
  • Organ transplants.
  • Hospital-aquired infection, from contaminated medical equipment. 
• Transmission criteria - There are four important criteria relevant to the transmission of malaria, (see below).
  • The parasite - Species differ in; incubation period, lifespan, gametocyte appearance, relapsing illness.
  • The vector - Factors affecting the vector are; air temperature, relative humidity, breeding place, density of vectors versus humans, feeding frequency, lifespan, sporozoite rates, feeding frequency, exophagy, ( outdoor feeding ) or endophagy, ( indoor feeding ). 
  • Human host - Human behaviour, biological factors and interation with the vector affect disease outcome. Immunity against malaria can be identified in persons with B thalasaemia, Ovalocytosis and G6PD deficiency. Human sleep patterns, housing and occupation, health condition and local government economy and politics can all directly affect the epidemeological outcome of malaria.  
  • The environment - Factors that may affect the vector and the parasite are; rainfall, temperature, altitude and rate of flow in rivers and streams. Deforestation, dams, mining and irrigation as well as global warming can all contribute to increased incidence of malaria. War ravaged areas can also have a significant impact on the environment. 
• Malaria surveillance - Ongoing surveillance of malaria is important for the global control of the disease. However, diagnosis in the form of microscopy, antigen detection and molecular techniques, for example, PCR only measure the point prevalence of the disease at one moment in time. The problem is that Malaria is seasonal in some endemic areas.
• Antibody detection - Detection of antibody can be much more helpful by identifying geographic regions where malaria is transmitted, age and species related prevalence as well as the possible effects of control measures on an ongoing basis.
• The malarial parasite is temperature dependant and so endemic or epidemic areas are located in the tropics and sub tropics excluding areas with an altitude higher than 2000m.
• Malaria free zones - There are a number of global regions where malaria is not prevalent including, the vast majority of the mediterranean, Australia and the USA. However, it should be noted that even in malaria free zones, malaria can still be identified owing to increased immigration and global travel, etc.
• Pregnant women - have a much increased susceptiility to malaria, especially P.falciparum malaria. This parasite contributes to 8-14% of low birth weight children, consequently reducing survival rates.

  Fig.6. Global incidence of malaria: click here for map

7	Laboratory Diagnosis

• Tme of specimen collection - specimens should be collected before any drug treatment. If malaria is suspected there should be no delay in taking the sample.
• Type of sample recommended for microscopy - for the parasitic disease malaria anticoagulants can distort parasite morphology and staining properties making diagnosis difficult. Delay in taking the sample can also have a deleterious effect on the parasite. Capillary blood from a fingerstick, ear lobe, (large toe or heel in children), is therefore the sample of choice.   
• Diagnosis is routinely performed by preparing a thick and/or thin blood slide and staining with giemsa and examined microscopically.
• Examining thick smears
  • The smear is initially examined under low power, (10-20x), to detect large parasites, for example, microfilaria.
  • The smear is then observed using the 100x objective and oil immersoin. Ideal areas to examine are free of stain precipitate and contain 10-20 WBC's/field.
  • To determine 'No Parasites Found', (NPF): WHO recommends at least 100 fields, each containing at least 20 WBC's be screened. This gives a sensitivity of four parasites/ul blood.
  • In non-immune patients, symptomatic malaria can occur with lower parasite numbers, so screening of more fields is advisable according to clinical history.
• Examining thin smears
  • Thin smears are most useful for identifiying parasites already detected in thick smears.
  • Screen initially at low magnification, (10-20x), if not already performed on a thick smear.
  • Observe thin smear using 100x objective and oil immersion, examining at least 300 fields.
• Quantifiying malarial parasites
  • To quantify malarial parasites against RBC's, count parasite-infected RBC's in the thin smear and express the results as % parasitaemia. (%parasitaemia = (parasitised RBC's /total RBC's) x 100.
  • If parasitaemia is high (e.g., >10%) examine 500 RBC's. If the parasitaemia is low (e.g., <1%) examine at least 2000 RBC's.
  • Count asexual blood stage parasites and gametocytes separately.
• Quantitative Buffy Coat Analysis (QBC) - here blood is centrifuged and the resulting buffy coat is stained with fluorochrome, which highlights malarial parasites.
• Molecular techniques - gene sequencing and comparative gene analysis has allowed the laboratory diagnosis of many infectious diseases via the application of molecular biological techniques. In the case of Plasmodium, DNA is typically extracted from 200ul of whole blood.
• Nested PCR -  Detection and identification of Plasmodium is performed with a two-step, nested PCR using primers of Snounou et al. PCR products are visualised by agarose gel electrophoresis.
•  Real time PCR can be carried out in two hours compared to 7-8 hours for nested PCR and is far less labour intensive only having one step as apposed to two steps for nested PCR. Real time PCR is performed in a closed system where post PCR handling is not necessary. There have been a few real time PCR methods developed including one to simultaneously identify three major human malaria parasites; P.falciparum, P.ovale and P.vivax. Real time PCR may be used for non endemic malaria detection and drug efficacy studies. It is very important to quickly identify drug resistant strains of Plasmodium.
• Other PCR-based assays for P.falciparum detection - three PCR assays; stevor gene PCR, SSUrRNA gene PCR and msa-2 gene PCR  have been compared to reveal that the Stevor gene amplification is the most sensitive technique for P.falciparum detection and therefore should be used as a confirmatory test or reference standard. This assay can be used to detect very low parasitaemia.
• Fluorescent dyes - such as Acridine Orange and DAPI can be used to stain blood films for diagnosis of Plasmodium infection. Plasmodium staining with fluorochromes is rapid, (less than 1 min), and observation of slides can be performed at low magnification, (400X), allowing rapid screening of smears even with low parasitemia.
• It is important to note that all diagnostic techniques have their use, for example, PCR based assays cannot be used in malaria endemic, remote areas with no laboratories and poor facilities so microscopy has to be used. However, in non endemic areas where microscopy techniques may be poor and there are good facilities available then they are the assay of choice.

Fig.7. Acridine Orange, (left) and DAPI-stained blood film, (right) showing Plasmodium trophozoites.

Table 3. Rapid diagnostic tests for Plasmodium.

Kit Name	Type of Test	Product Details
Malaria-Ag (Cellabs)	EIA	Malaria Ag specifically detects HRP-2 secreted by P.falciparum at the merozoite, (RBC) stage of infection. Automated results are achieved in 2 hours, providing a reliable and highly sensitive alternative to microscopy and comes in a 192 test kit format with a long shelf life.
OptiMAL®  (Flow)	Rapid (LDH)	The OptiMAL® assay is a sensitive, simple to use dipstick assay that permits the detection of all major species of human malaria; and can distinguish between P. falciparum and P. vivax. In addition, the OptiMAL® assay can be used to monitor patient therapy.
MAKROmed (MAKROmed)	Rapid (HRP2)	In one specific study, the prevalence of placental parasitaemia was 22.6% by microscopy, 51.0% by PCR and 43.1% by MAKROmed RDT (sensitivity = 89%, specificity = 76%). Thus, the MAKROmed RDT is highly sensitive in the detection of placental malaria, but has lower than expected specificity.
Paracheck Pf (Orchid)	Rapid (HRP2)	Paracheck Pf is a immunochromatography test for P. falciparum. As the test sample flows through the membrane assembly of the dipstick after placing into the clearing buffer tube, the colored anti Pf HRP-2 antisera-colloidal gold conjugate (monoclonal) complexes the Pf HRP-2 in the lysed sample. This complex is immobilised by the anti Pf HRP-2 antisera coated on the membrane leading to formation of a pink band which confirms a positive test result.
Visitect Malaria Pf (Omega)	Rapid (HRP2)	Visitect Malaria COMBO Pan/Pf is a rapid immunochromatography test for the detection of P.falciparum, non P.falciparum malaria or mixed malaria infections. As the test sample flows through the membrane assembly of the device, after addition of the diluent buffer, the anti-pLDH and the anti-Pf HRP-2 coloured colloidal gold monoclonal antibody complexes with the pLDH and Pf HRP-2 if present in the lysed sample. This complex is immobilised by the anti-pLDH and anti-Pf HRP-2 antibodies coated on the membrane, leading to formation of pink coloured lines, a positive test result.

 

Table 4. Malarial diagnostic products available from Cosmos Biomedical Ltd.

Product	Product Code	CE Mark	Kit Details & IFUs
Malaria Pf Rapid Device (whole blood, 25 tests)	CB78/8/602		A rapid, qualitative, two site sandwich immunoassay for the determination of P. falciparum specific histidine rich protein–2 (Pf HRP-2) in whole blood. See IFU
Malaria Pv/Pf Rapid Device (whole blood, 25 tests)	CB78/8/604		A rapid, qualitative, two site sandwich immunoassay for the detection of P. falciparum specific histidine rich protein-2 (Pf HRP-2) and P. vivax specific pLDH. Also for use for specific detection and differentiation of P. falciparum and P. vivax malaria in areas with high rates of mixed infections. See IFU
Malaria Pan/Pf Rapid Device (whole blood, 25 tests)	CB78/8/606		A rapid, qualitative, two site sandwich immunoassay, for the detection of P. falciparum specific histidine rich protein-2 (Pf HRP-2) and pan specific pLDH. The test may also be used for differentiation of P. falciparum and other malarial species and for the follow up of anti-malarial therapy. See IFU
Malaria Pan/Pv/Pf Rapid Device (whole blood, 25 tests)	CB78/8/608		A rapid, qualitative, two site sandwich immunoassay for the detection of P. falciparum specific histidine rich protein-2 (Pf HRP-2), P. vivax specific pLDH and pan malaria specific pLDH. The test can be used for the specific detection of P. falciparum and P.vivax malaria, differentiation of other malarial species and for the follow up of anti malarial therapy. See IFU
Giemsa Stains	Various		See product details
Giemsa Powders	Various		See product details
Immersion Oil	Various		See product details
Microscopy Accessories	Various		See product details
Digital Microscope Eyepiece	CB/MA88		See product details

8	Treatment & Prevention / Control

• First malaria treatment - Huan del Vego first used a preparation of the South American cinchona tree bark for treating malaria as early as 1640.
• Crystalline Quinine - Pelletier and Caventou extracted pure quinine alkaloids from the cinchona tree bark in France in 1820 and named them quinine and cinchonine.
• Synthetic malarial drugs - In 1928 Atabrine was developed and used extensively to treat malaria but had the side effect of making the skin turn yellow. Chloroquine was developed by the Germans in the late 1930's and was extensively used in North Africa. 
• In the 1970's Artemisisin, derived from the Qinhao plant, (Artemisia annua. L ), was discovered, which was based on a chinese recipe from as early as the year 340 and has been successfully used as an antimalarial drug in the West since the 1980's.
• Chloroquine is the drug of choice for the different species of Plasmodium. However, some strains of P. vivax are resistant to this drug. For P. falciparum there is extensive global resistance.
• Developed countries - here P. falciparum is normally treated with quinine in the form of quinine sulphate. Severe cases would require intravenous infusion but those less severe require only oral administration of the drug.
• Side effects - nausea and tinnitus.
• Quinine-resistant strains - where resistance to this drug occurs, Fansidar may be given or tetracycline after the course of quinine is complete.
• Multidrug combinations - are available at a price, for example, Artemisinin combination therapy (ACT).
• Severe malaria - constitutes a parasite count of >1% in a patient who is non-immune. Intravenous quinine should be administered. Patients may need to me dialysed and ventillated and in severe cases receive blood transfusions. Hypoglycaemia may result from both quinine treatment and the malaria infection.

Table 5: Drugs used to treat severe P. falciparum malaria in adults.

	Hospital facilities	No hospital facilities
Chloroquine sensitive P. falciparum	Chloroquine: 10mg/kg, 8 hr infusion. 15mg/kg over 24 hr	Chloroquine: 2.5mg/kg every 4 hr. IM 25mg/kg or nasogastric tube
Chloroquine resistant P. falciparum	Quinine salt: 20mg/kg, 4 hr infusion. 10mg/kg over 4 hr every 8 hr or Artesunate 2.4mg/kg IV 1.2mg/kg	Quinine dihydrochloride IM (same as IV) or rectal suppositries containing Artemisinin or 100mg/day doxycycline or 250mg/week mefloquine

Prophylaxis for malaria

• No chloroquine resistance - 300mg/chloroquine/week or 200mg Proguanil/day
• Little chloroquine resistance - 300mg chloroquine/week and 200mg Proguanil/day
• Significant chloroquine resistance - 250mg mefloquine/week or 100mg doxycycline/day or 1 tablet malarone/day
• Prevention and control - many factors affect the control of malaria, including:

• Personal protection from vector bites using creams, nets, sprays, etc.
• Case treatment using antimalarial drugs.
• Vector eradication by drainage of marshes, use of insecticide, DDT, etc.

• WHO - this organisation began a worldwide campaign to eradicate malaria in the 1960's without success only to recommence in 1998.
• Recommendations - travellers going to areas where malaria is endemic should use insect nets sprayed with mosquito repellent. Antimalarial prophylaxis should be taken although individuals can still contract the disease.

Malarial vaccine

• Vaccine - to date, there is still no effective vaccine against malaria. Infected persons do not develop a complete immunity and therefore can become reinfected with malarial parasites.
• Evasion of the immune system - malarial parasites avoid being removed from the host by residing within liver cells and RBC's. The host immune system can be supressed by malarial parasites.  

 

 

9	References

• Snounou G et al. High sensitivity detection of human malaria parasites by the use of nested PCR. Mol Biochem Parasitol. 1993;61:315-320.
• Topley & Wilson's., Cox F.E.G, Kreier J.P, Wakelin D. (1998), MICROBIOLOGY AND MICROBIAL INFECTIONS. VOLUME 5. PARASITOLOGY. 20: p361-402.
• Microbiology An Introduction., Fith Edition. Totora, Funke, Case. 23: p316,506-507,577-579.
• Medical Microbiology., Fourth Edition. Murray P.R, Rosenthal K.S, Kobayashi G.S, Pfaller M.A. p683, 712-716.
• Clinical Bacteriology., Struthers J.K, Westran R.P. p166, p186. 
• Journal of Clinical Microbiology, March 2004,p.1214-1219,Vol.42,No.3.
• Trends in Parasitology, Volume 22, issue 9, September 2006p. 424-430. 
• Blood,15 February 2008, vol.111, No.4pp.2418-2426.

10	Acknowledgements

• The Carlo Denegri Foundation www.cdfound.to.it/hTML/pla1.htm
• Liverpool School of Tropical Medicine for images of P.falciparum, ring stage in RBC's.

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Web Links

1.  http://www.bmj.com/cgi/content/short/321/7259/484
2.  http://www.dpd.cdc.gov/dpdx/HTML/Frames/DiagnosticProocedures/body_dp_blood
3.  http://www.cdc.gov/malaria/diagnosis_treatment/diagnosis.htm
4.  http://www.sciencedirect.co/science?_ob=ArticleURL&_udi=B6W7G-4KF1HRW
5.  http://en.wikipedia.org/wiki/Plasmoium_falciparum
6.  http://cancerweb.ncl.ac.uk/cgi-bin/omd?applique+forms
7.  http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/4/2418
8.  http://www.malarialjournal.com/6/1/112
9.  http://www.cdc.gov/malaria/facts.htm
10.  http://www.who.int/tdr/publications/publications/malaria_diagnosis.htm

 

12	Disclaimer

The information contained in the Education Series text was obtained through collaboration with laboratories identifying and diagnosing Malaria as well as scientific publications and relevant text books. We believe the information specified in this text to be correct although it is the responsibility of the participant to confirm information validity. Cosmos Biomedical Ltd claim no responsibility for misinterpretation of information. Copyright ^© Cosmos Biomedical Ltd, 2006.

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Copyright

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