Introduction 1

1. Introduction 1 Malaria Welcome to the malaria module! 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. Children under 5 are the major at risk group in malarious regions. Inset: An Anopheles mosquito taking a blood meal Sources:http://www.ifnc.org/pictures.html http://phil.cdc.gov/phil/quicksearch.asp For more information about the authors and reviewers of this module, click here

2. How to use this module • This self-directed learning (SDL) module has been designed for medical and other health care students • We suggest that start with the learning objectives and try to keep these in mind as you go through the module slide by slide, in order and at your own pace. • Print-out the malaria SDL answer sheet. Write your answers to the questions on the mark sheet as best you can before looking at the answers. • Repeat the module until you have achieved a mark of > 22/27 (>80%). • You should research any issues that you are unsure about. Look in your textbooks, access the on-line resources indicated at the end of the module and discuss with your peers and teachers. • Finally, enjoy your learning! We hope that this module will be enjoyable to study and complement your learning about malaria from other sources.

3. Introduction 2 Learning Outcomes By the end of the module, you would be expected to be able to describe: • How P. falciparum malaria is a major killer of people in warm climates and that children <5 years, pregnant women and non-immune visitors/immigrants are at greatest risk • The 4 main species of malaria, their geographical distribution and the major stages of the life cycle • How malaria is transmitted by the female anopheles mosquito and how levels of endemicity vary according to climate and mosquito ecology • How parasite and host factors determine disease severity • The clinical features of simple, uncomplicated disease and 8 important severe manifestations of malaria • How malaria is diagnosed by blood film examination, antigen detection and molecular methods • The role of chloroquine, quinine, artemesinin and other drugs in treatment • How malaria can be prevented by reducing man-mosquito contact, chemoprophylaxis, intermittent presumptive treatment and what approaches are being taken in vaccine development

4. What is malaria ? Malaria is a disease caused by single-celled protozoan parasites of the genus Plasmodium. The 4 species that commonly infect man are:

5. This can be divided into: The “direct” health burden: morbidity and mortality The “indirect” burden: impaired human and economic development Click on the boxes to find out more The burden of malaria Direct burden Indirect burden

6. Geographical Distribution of Malaria Although previously widespread, today malaria is confined mainly to Africa, Asia and Latin America. About 40% of the world’s population is at risk of malaria.It is endemic in 91 countries, with small pockets of transmission occurring in a further 8 countries. Malaria is transmitted by the female anopheles mosquito. Factors which affect mosquito ecology, such as temperature and humidity, are key determinants of malaria transmission. Mosquitoes breed in hot, humid areas and below altitudes of 2000 meters. Development of the malaria parasite occurs optimally between 25-30oC and stops below 16oC. Indigenous malaria has been recorded as far as 64oN and 32oS. Malaria has actually increased in sub-Saharan Africa in recent years. The major factor has been the spread of drug-resistant parasites. Other important factors include the persistence of poverty, HIV/AIDS, mosquito resistance to insecticides, weak health services, conflict and population migration.

7. Malaria epidemics occur when transmission increases amongst susceptible populations. Epidemics do not occur in holoendemic areas because of the high level of immunity. Holoendemic or highly endemic Intense transmission occurs throughout the year. Severe malaria and deaths occur mainly in children under 5 years. Pregnant women are also highly susceptible, especially in the fist pregnancy, because immune defence mechanisms are impaired during pregnancy. Hyperendemic Intense but seasonal transmission; malaria occurs in all age groups and is an important cause of deaths. Mesoendemic Moderatetransmission; malaria becomes a more important disease. Endemicity and immunity to malaria “Endemicity” refers to the level of transmission of malaria. Malaria is endemic in an area or community when there is a constant incidence of cases over successive years. People gradually develop immunity to malaria if continuously exposed. Malaria endemicity can be classified as: Hypoendemic Little transmission; malaria has little effect on the population.

8. End of Section 1 Well done! You have come to the end of the first section. , We suggest that you answer Question 1 to assess your learning so far. Please remember to write your answers on the mark sheet before looking at the correct answers! Click to Reveal Answers

9. Question 1Write “T” or “F” on the answer sheet. When you have completed all 5 questions, click on the box and mark your answers. Click for the correct answer • P. ovale occurs mainly in West Africa • P. falciparum is the most important species of malaria • The largest burden of malaria occurs in South East Asia • Malaria epidemics are likely to occur in a holoendemic area e) Environmental factors which affect mosquito breeding are closely related to the intensity of malaria transmission a b c d e

10. 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 be able to produce eggs. Male mosquitoes do not transmit malaria as they feed on nectar and plant juices and not blood. There are about 380 species of anopheles mosquito but only about 60 are able to transmit malaria. Like all mosquitoes, anopheles breed in water - hence accumulation of water favours the spread of the disease. The flight range of Anopheles is only about 2-3 km but they may travel further if blown by the wind or carried in ships or aeroplanes. How is malaria transmitted? Female Anopheles mosquito taking a blood meal Source:http://phil.cdc.gov/phil/quicksearch.asp

11. Plasmodium infects the human and insect host alternatively and several phases of the parasite occur. The duration of each phase varies according to the species and is as follows for P. falciparum: How does infection develop ? Mosquito phase: During feeding, the mosquito injects anticoagulant saliva into the blood stream. If the mosquito is infected, the saliva contains primitive stages of malaria called sporozoites. Hepatic, tissue or pre-erythrocytic phase: Sporozoites immediately invade liver cells and begin to develop. The infected hepatocyte ruptures to release merozoites after about 5-7 days. Erythrocytic phase: Merozoites then invade red blood cells. The red cells lyse and this causes bouts of fever and other symptoms. This cycle repeats about every 36 hours as merozoites invade other red cells. Then the cycle repeats Sexual phase: Sexual forms develop and are ingested when another female anopheles mosquito feeds. These develop into sporozoites in the gut of the insect host and migrate to its salivary glands. The life cycle of the malaria parasite is shown on the next slide

12. The Malaria Parasite Life Cycle Click on the diagram to explore different areas of the life cycle Show Me

13. Severity of disease and host factors In addition to parasite factors, several host factors determine the outcome of exposure to malaria: • Naturally-acquired immunity. People who are constantly exposed to malaria gradually acquire immunity, firstly againstclinical disease and later against parasite infection.Clinical manifestations of malaria are most severe in the non-immune. In holoendemic areas, these are children aged <5 years and pregnant women (especially primagravidae). People of any age from areas that are free from malaria, or have limited malaria transmission, are at risk when they are exposed to malaria. • Red cell and haemoglobin variants. Well known examples of inherited factors that protect against malaria are Haemoglobin S carrier state, the thalassaemias and Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Malaria provides the best known example whereby an environmental factor (malaria) has selected human genes because of their survival advantage. • Foetal haemoglobin (HbF): High levels of HbF occur in neonates, and in some people with inherited haemoglobin variants, protect against severe forms of P. falciparum malaria. • Duffy blood group: P. vivax requires the Duffy blood receptor to enter red blood cells. Therefore, people who do not carry the Duffy blood group are resistant to this malaria species. This explains the rarity of P. vivax in Africa, as most Africans are Duffy blood group negative.

14. End of Section 2 Well done! This is the end of the second section. We suggest that you proceed to answer questions 2 and 3 to assess your learning further. Do remember to write your answers on the mark sheet before looking at the right answer!

15. Question 2: Parasite factors and disease severity. Study the table below. Write down on your answer sheet 2 features of the biology of P. falciparum which contribute to it being responsible for nearly all severe malaria. Then click on the box and mark your answers. Click here for the answers * Incubation period is the number of days from exposure (injection of sporozoites) to the onset of clinical symptoms.

16. Question 3: The following people are at risk of severe malaria:Write “T” or “F” on the answer sheet. When you have completed all 7 questions, click on the box and mark your answers. Click for the correct answer a • Pregnant women • Neonates • Immigrants from Europe • A 20 year old man who has lived all of his life in Nigeria • A 3 year old girl resident in an area holoendemic for malaria • A 10 year old child with sickle cell disease • A 3 year old boy with Duffy negative blood group b c d e f g

17. The clinical course of P. falciparum Following a bite by an infected mosquito, many people do not develop any signs of infection. If infection does progress, the outcome is one of three depending on the host and parasite factors enumerated in the previous slides:

18. A. Asymptomatic parasitaemia This is usually seen in older children and adults who have acquired “clinical immunity” to disease as a consequence of living in areas with high malaria endemicity. There are malaria parasites in the peripheral blood but no symptoms. These individuals may be important reservoirs for disease transmission. Some individuals may even develop “anti-parasite immunity” so that they do not develop parasitaemia following infection.

19. B. Simple, uncomplicated malaria This can occur at any age but it is more likely to be seen in individuals with some degree of immunity to malaria. The affected person, though ill, does not manifest life-threatening disease. Fever is the most constant symptom of malaria. It may occur in paroxysms when lysis of red cells releases merozoites resulting in fever, chills and rigors (uncontrollable shivering). Children with malaria waiting to be seen at a malaria clinic in the south western part of Nigeria. Identifying children with severe malaria, and giving them prompt treatment, is a major challenge when large numbers attend clinics.

20. 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). Typical paroxysms thus occur every 2nd day or more frequently in P. falciparum (“sub-tertian” malaria) 3rd day in P. vivax and P. ovale (“tertian” malaria) 4th day in P. malariae infections, (“quartan” malaria) The periodicity of malaria fever 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.

21. Other features of simple, uncomplicated malaria include: • Vomiting • Diarrhoea – more commonly seen in young children and, when vomiting also occurs, may be misdiagnosed as viral gastroenteritis • Convulsions – commonly seen in young children. Malaria is the leading cause of convulsions with fever in African children. • Pallor – resulting mainly from the lysis of red blood cells. Malaria also reduces the synthesis of red blood cells in the bone marrow. • Jaundice – mainly due to haemolysis. Malaria is a multisystem disease. Other common clinical features are: • Anorexia • Cough • Headache • Malaise • Muscle aches • Splenomegaly • Tender hepatomegaly These clinical features occur in “mild” malaria. However, the infection requires urgent diagnosis and management to prevent progression to severe disease.

22. Cerebral malaria Severe malaria anaemia Hypoglycaemia Metabolic acidosis Acute renal failure Pulmonary oedema Circulatory collapse, shock or “algid malaria” Blackwater fever C. Severe and complicated malaria 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!

23. Summary of differences in the clinical features of severe malaria in adults and children Frequency of occurrence

24. End of Section 3 You have made tremendous progress! This is the end of the third section. You should now be able to answer Question 4 to assess what you have learnt. You are to remember to write your answers on the mark sheet before looking at the right answer!

25. Question 4: Clinical malariaWrite “T” or “F” on the answer sheet. When you have completed all 7 questions, click on the box and mark your answers. Click for the correct answer • Asymptomatic parasitaemia signifies acquired immunity to malaria • Symptoms typically occur during the hepatic phase of infection • Young children with mild malaria require urgent assessment and treatment • A single convulsion signifies severe disease • The clinical signs of acidosis are rapid respirations with deep breathing • Acute renal failure occurs in older children and adults • A patient with malaria and dark urine is unlikely to be anaemic a b c d e f g

26. Malaria is a multisystem disease. It presents with a wide variety of non-specific clinical features: there are no pathognomonic symptoms or signs. Many patients have fever, general aches and pains and malaise and are initially misdiagnosed as having “flu”. P. falciparum malaria can be rapidly progressive and fatal. Prompt diagnosis saves lives and relies on astute clinical assessment: A good history Residence or a recent visit (in the preceding 3 months) to a malaria endemic area History of fever (may be paroxysmal in nature) Recognise significance of non-specific clinical features such as vomiting, diarrhoea, headache, malaise Physical examination Identify signs consistent with malaria:fever, pallor, jaundice, splenomegaly Exclude other possible causes of fever (e.g. signs of viral and bacterial infections) The diagnosis of malaria should be considered in any unwell person who has been in a malarious area recently Diagnosis

27. 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 Source- SOM 208 Microbiology Syllabus Show Me

28. Appearance of P. falciparum in thin blood films 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

29. Other methods of diagnosis of malaria These are not routinely used in clinical practice. They include : • 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. • 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. • Fluorescent techniques. Relatively low specificity and sensitivity. Cannot identify the parasite species. Expensive and requires skilled personnel. • Serologic tests. Based on immunofluorescence detection of antibodies against Plasmodium species. Useful for epidemiologic and not diagnostic purposes.

30. patient factors age, pregnancy, prior treatment or chemoprophylaxis, likelihood of drug compliance severity of the infection simple, uncomplicated or severe, complicated malaria parasitefactors species, drug sensitivity Treatment The treatment of malaria depends on a number of factors which include : In the absence of reliable diagnosis, clinical assessment alone can not differentiate malaria from other common febrile illnesses. In this situation, anti-malarial treatment should be given routinely for people with fever.

31. Treatment of uncomplicated malaria – single agents National treatment guidelines for first-line treatment are available in most malarious countries. Commonly used drugs include: • 4-aminoquinolines - chloroquine • cheap and widely available and previously the most widely used antimalarial drug. Use is now severely limited because of widespread resistance of P. falciparum in South East Asia, East and West Africa. • blood schizonticide - kills the erythrocyte stages but has no effect on the exo-erythrocytic (liver) stages or gametocytes. • P. vivax is usually sensitive to chloroquine, although resistance is emerging. • Amodiaquine is an alternative for chloroquine-resistant falciparum malaria. • Sulphadoxine-pyrimethamine – “Fansidar”; first line treatment for P. falciparum malaria in many countries, although resistance to this drug has also developed rapidly. • 8- aminoquinolines: Primaquine is active against the exo-erythrocytic forms of P. vivax and P. ovale and isadded to treatment to prevent relapses. • Less commonly used drugs for first-line treatment are quinine, mefloquine (schizonticide; neuropsychiatric adverse effects), halofantrine (schizonticide; may cause cardiac arrhythmias and sudden death) and atovaquone-proguanil.

32. Treatment of uncomplicated malaria – drug combinations • The rapid emergence of resistance to drugs when used as single agents has led to the development of drug combinations for first-line treatment. • Combinations combine two or more schizonticidal drugs which act independantly of each other. This reduces the development of parasite resistance to the drugs used in the combination. • Artemisinin and its derivatives (artemether, artesunate, artheether; based on the Chinese herb quinhaosu) are rapidly active against erythrocytic stages and also gametocytes (therefore, may reduce transmission). Current levels of resistance are low. • Several combinations include an artemisinin derivative; e.g. dihydroartemisinin + piperaquine; artesunate + chlorproguanil/dapsone • Examples of other drug combinations are chlorproguanil + dapsone (Lapdap), atovaquone + proguanil (Malarone). • The choice of which combination to use depends on many factors, including the existing pattern of resistance and cost. • As well as drug treatment, supportive treatment for associated problems such as high fever, dehydration and anaemia are important!

33. Drugs Quinine is the most widely used drug. It is administered by rate-controlled intravenous infusion. Where this is not possible, it can be administered by deep intramuscular injection. This is less desirable because of slow and uncertain absorption and risks such as injection abscess and muscle necrosis. Artemisinin derivatives are also used to treat severe malaria. At rural clinics where it is not possible to give injections, artemesinin suppositories can be used whilst the patient is being transferred. Supportive therapy A vital adjunct to clinical management. It includes the general care of the unconscious patient, careful fluid balance, control of seizures, nasogastric tube feeding, correction of metabolic derrangements (e.g. hypoglycaemia, metabolic acidosis) and blood transfusion for severe anaemia. Bacterial infection can also co-exist with severe malaria and require antibiotic treatment. Treatment of severe, complicated malaria

34. Malaria prevention and control Reducing man-mosquito contact Insecticide-treated nets (ITNs) are relatively cheap and, if used correctly, an effective means of preventing malaria. The development of longlasting nets may help to overcome the requirement to re-treat nets with insecticide regularly. The major difficulty remains achieving high coverage rates of ITNs in the most at-risk populations. Historically, indoor house-spraying with residual insecticides (e.g. DDT) achieved many successes but was not sustainable. However, some countries still use this approach as part of their public health measures against malaria. Other means to reduce contact for individuals are wearing of protective clothing and insect repellents at dawn and dusk. Families are advised to prioritise the use of bed nets for children under 5 years and pregnant women – the family members at most risk of developing severe malaria.

35. Malaria prevention and control Chemoprophylaxis Chemoprophylaxis is the administration of drugs to individuals likely to be exposed to malaria. • Indicated in travellers and also pregnant women and people with sickle cell disease living in malaria endemic areas • Effective malaria prophylaxis is challenging because of cost, drug resistance and adverse effects. • The recommendations vary according to likely parasite resistance and patient characteristics (e.g. age, breastfeeding, pregnancy). • Commonly-used drugs include chloroquine and proguanil, mefloquine and malarone.

36. Malaria prevention and control Vaccines against P. falciparum -1 Why is a malaria vaccine needed? Despite well-tested and proven public health interventions to prevent malaria, the disease burden due to malaria has increased in recent years. This has occurred for several reasons: • Population growth • The parasite constantly develops resistance to the commonly-used and affordable drugs • Anopheles mosquitoes develop resistance to insecticide • Malaria control programmes are often not well implemented or are interrupted by conflict • Increased tourism and migration of non-immune people into malarious areas A malaria vaccine offers the prospect of an affordable intervention that could be administered as part of existing immunisation programmes.

37. Is a malaria vaccine possible? There are several factors which suggest that immunisation against malaria is possible: Natural immunity against malaria develops after repeated exposure Passive immunity occurs in young infants (probably as a result of maternal antibody) and also in individuals who were given purified immunoglobulins from people with natural immunity Administration of UV attenuated sporozoites confers protection Experimental malaria vaccines have shown some modest efficacy in clinical trials So why is developing a vaccine difficult? There are several obstacles: P. falciparum is a highly complex parasite with different antigens at different stages of the life cycle Many of these antigens show marked polymorphism Single parasite clones show antigenic variability; the parasite constantly changes its antigens The basis of naturally-acquired immunity is not well understood There is no animal model to help with the development and testing of vaccine candidates Malaria prevention and control Progress towards a vaccine

38. Malaria prevention and control What vaccines are under development? There are around 75 candidate vaccines under development. Vaccines can be grouped according to the stage of the parasite life cycle: Pre-erythrocytic: aim to prevent clinical disease by targetting sporozoites and intra-hepatocytes stages Transmission-blocking: aim to prevent human-to-human transmission by targeting the sexual stages in the mosquito Erythrocytic or blood stage: aim to reduce disease severity by preventing invasion or increasing the clearance of red cells.

39. Malaria prevention and control What are the leading vaccine candidates? There are hundreds of parasite proteins which could form targets for vaccines. Various strategies of stimulating the host’s immune response are being evaluated including prime-boost, virosomes and synthetic parasite peptides. Most of the vaccines currently under development are targeted against: • the circumsporozoite protein (CSP) • the merozoite surface protein (MSP) • the apical membrane antigen (AMA-1) The most advanced vaccine to date, RTS,S/AS02A, has been developed jointly by GlaxoSmithKline and the Malaria Vaccine Initiative. It is a pre-erythrocytic, sub-unit vaccine which combines CSP with the hepatitis-B surface antigen. Clinical trials have shown that this vaccine reduced malaria episodes by 30% and severe malaria by 58% in children in Mozambique.

40. Malaria in pregnancy More than 45 million women (30 million in Africa) become pregnant in malaria endemic areas each year. The adverse effects of malaria affect primigravidae more than multigravidae and HIV infection increases malaria in pregnancy. The following adverse events are well-recognised: Mother: • Anaemia • Cerebral malaria • Hypoglycaemia • Puerperal sepsis • Pulmonary oedema and heamorrhage Fetus: • Abortion and stillbirth • Preterm delivery • Intra-uterine growth retardation (IUGR) and anaemia Infant: • Low birth weight (<2500 gms; both prematurity and IUGR may contribute) • Reduced levels of maternal antibody (e.g. against tetanus)

41. Malaria in pregnancyPrevention and control As usual, this requires using more than one approach that are appropriate to the local situation. The following are key components of malaria control programmes for pregnant women recommended by WHO: • Prompt and effective case management according to national treatment guidelines. Commonly used drugs include chloroquine, sulfadoxine-pyrimethamine and quinine. • Insecticide-treated mosquito nets (ITNs) • Intermittent preventive treatment (IPT): the administration of an anti-malarial drug (e.g. sulphadoxine-pyrimethamine) in areas of stable malaria transmission whether or not women show symptoms or have parasites in the blood. 3 full doses are given at least 1 month apart during the second and third trimesters. IPT has now replaced chemoprophylaxis (e.g. with chloroquine) in many countries. Source: http://phil.cdc.gov/phil/quicksearch.asp

42. International initiatives • Many international organisations are involved in the fight against malaria. • The WHO in partnership with UNICEF, UNDP and the World Bank initiated Roll Back Malaria (RBM) in 1998 to promote an effective control strategy to combat the disease. The goal of RBM is to halve the world’s burden of malaria by 2010. RBM was later joined by a broader group of partners including governments of countries affected by the disease, multi and bilateral agencies, NGOs, international private sector representative and research groups. • RBM focuses on – • Rapid clinical case detection and provision of prompt access to effective malaria treatment, especially in the home. • Preventing and controlling malaria during pregnancy. • Promoting the use of insecticide treated bed nets (ITN) as a means of prevention, especially in young children and pregnant women. • Dealing effectively with malaria in emergency and epidemic situations. Prompt effective malaria treatment saves lives

43. End of Section 4 You have come a long way! This is the last of the sections. For the section just ended, you should be able to answer Question 5 to assess what you have learnt. It is still required that you put down your answers on the mark sheet before looking at the right answer!

44. Question 5: Malaria diagnosis, prevention and treatmentWrite “T” or “F” on the answer sheet. When you have completed all 6 questions, click on the box and mark your answers. 7. Quiz 1 Click for the correct answer • A well-prepared and stained thick blood film is usually the most practical way to diagnose malaria • Chloroquine prophylaxis is recommended during pregnancy in East Africa • More than one anti-malarial drug should be used for first-line treatment • Quinine is the drug of choice for severe malaria • Poor compliance with antimalarial therapy favours the development of resistance • Insecticide-impregnated bednets are used to prevent malaria mainly in travellers a b c d e f

45. Sources of information • Malaria. Greenwood BM, Bojang K, Whitty CJ, Targett GA. Review; Lancet 2005; 365:1487-98. • http://mosquito.who.int/cmc_upload/0/000/015/372/RBMInfosheet_1.htm These WHO fact sheets developed by the Roll Back Malaria Partnership cover many different aspects of malaria – including prevention with insecticide-treated bed nets and treatment with atemesinin-based combination therapies • http://www.cdc.gov/malaria/ The US Centre for Disease Control and Prevention site for malaria • http://www.malaria.org/ Follow the “Learn about malaria” link on the Malaria Foundation’s website. This contains numerous useful and accessible resources. • http://www.rph.wa.gov.au/labs/haem/malaria/ An interactive resource from the Royal Perth Hospital, Western Australia. Contains useful self-assessment exercises in malaria diagnosis by microscopy that are set in the context of clinical cases. • Towards an effective malaria vaccine. Aide P, Bassat Q, Alonso P. Arch Dis Child 2007;92:476-9. • Malaria. A handbook for Health Professionals. Malaria Consortium. Macmillan Publishers Limited; 2007.

46. End of Module Well done! Now that you have completed the malaria module and attempted sectional questions, you may wish to take on the full quiz to assess your learning for the whole module. Please print out the questions The questions may differ slightly from those you have come across in the sectional assessment but are based on the material covered in this module. END OF MODULE QUIZ You will also find a link to the answers at the end of the quiz to measure your performance Please attempt this as many times as you wish.

47. The “direct” burden • Every year, there are about 500 million clinical attacks of malaria. Of these, 2-3 million are severe and about 1 million people die (about 3000 deaths every day). • Malaria in pregnancy accounts for about 25% of cases of severe maternal anaemia and 10-20% of low birthweight. Low birthweight due to malaria accounts for about 5-10% of neonatal and infants deaths. • 80% of all malaria cases occur in tropical Africa where the disease • accounts for 10-30% of all hospital admissions • is responsible for 15-25% of deaths in children aged <5 years - about 800,000 child deaths every year. • kills an African child every 30 seconds Back

48. The “indirect” burden of malaria • Human development:Impaired intellectual development, developmental abnormalities (especially following cerebral malaria), lost school attendance and productivity at work • Economics: Malaria retards economic development in the developing world. The cost of a single bout of malaria is equivalent to over 10 working days in Africa. The cost of treatment is between $US0.08 and $US5.30, depending on the type of drugs prescribed as required by the local pattern of drug resistance. • Total cost of malaria in Africa in terms of healthcare, treatment and lost productivity, is currently estimated to be >$US12 billion every year. Back