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Malaria Advice for southern Mozambique, Swaziland and South Africa www.malaria.org.

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PRODUCED BY THE MALARIA RESEARCH PROGRAMME OF THE MEDICAL RESEARCH COUNCIL !MEDICAL RESEARCH COUNCIL, 2001
FOR: THE REGIONAL MALARIA CONTROL COMMISSION 1. MINISTRY OF HEALTH SWAZILAND-SIMON KUNENE 2. MINISTRY OF HEALTH MOZAMBIQUE DR AVERTINO BARETTO 3. MINISTRY OF HEALTH SOUTH AFRICA-JOATHAM MTHEMBU 4. MEDICAL RESEARCH COUNCIL, SOUTH AFRICA-DR BRIAN SHARP

Acknowledgements: 1. The following sources are acknowledged for the figures used in this booklet:

Malaria - Topics in International Health CD-ROM published by the Wellcome Trust. The Mapping Malaria Risk in Africa (MARA) Collaboration. The Malaria Research Programme of the Medical Research Council

2. Document prepared by Marlies Craig, Brian Sharp and David le Sueur of the Medical Research Council, Malaria Research Programme, Durban, with contributions by Lee Baker and Karen Barnes. 3. Document production funded by the Business Trust

Table of Contents
General Information on Malaria...4 Distribution ...................................................................... 5 Life cycle ......................................................................... 8 1. The liver stage ......................................................... 9 2. The blood cycle ...................................................... 10 3. The cycle in the mosquito........................................ 11 Immunity ....................................................................... 11 Symptoms ..................................................................... 11 Diagnosis ...................................................................... 13 Prevention ..................................................................... 14 Personal protection .................................................... 14 Chemical prophylaxis ................................................. 15 Treatment...................................................................... 17 Common Myths.............................................................. 18 1. It is better not to take any prophylaxis, as it masks the symptoms and makes diagnosis difficult ...................... 18 2. There is this new deadly strain of malaria ................. 19 3. Malaria cannot be cured.......................................... 19 4. Prophylaxis need only be taken while in a malaria area?

................................................................................. 19 5. I wasnt bitten, can I stop taking my prophylaxis? ..... 20 Websites and phone numbers offering advice.....19

General Information on Malaria


Plasmodium is a group of one-celled, animal parasites that lives on the red cells in the blood of many birds, reptiles and mammals. There are four human malaria species - P. Falciparum, P. Ovale, P. Vivax and P. Malariae. P. Falciparum is by far the most dangerous. Unfortunately it is also the most common in Africa! Certain Anopheles mosquitoes transmit malaria. The parasite has to undergo a crucial development process in the mosquito, and this cannot happen in any other mosquito. Malaria kills roughly 850 000 people each year, most of whom are children under 5, and 90% of whom live in Africa, south of the Sahara. Each year there are probably more than 300 million cases of malaria. Malaria is responsible for one out of every 4 childhood deaths in Africa. Women are four times more likely to get sick, and twice as likely to die from malaria if they are pregnant. Malaria causes loss of productivity and therefore causes poverty and economic decline. The direct and indirect costs of malaria in Africa exceed $2 billion per year. The loss of productivity in African economies is much greater however: malaria slows economic growth in Africa by up to 1.3% each year. This slowdown in economic growth due to malaria is over and above the more readily observed short run costs of the disease. Since sub-Saharan Africa's GDP is around $300 billion, the short-term benefits of malaria control can reasonably be estimated at between $3 and $12 billion per year (Roll Back Malaria information booklet). The cheapest and safest malaria drug - chloroquine - is rapidly losing its effectiveness. In some parts of the world malaria is resistant to the four leading front-line drugs. Malaria quickly rebounded from the mass insecticide spraying campaigns in the

1950's and 60's. It then eluded mass treatment strategies based on a single drugs, such as chloroquine. Malaria can quickly adapt and rebound when efforts are fragmented and uncoordinated. Yet malaria deaths could be reduced with coordinated intervention. Distribution 1. Global Risk Plasmodium Falciparum: Africa (85-90% of cases), SE Asia, S America P. Vivax: S Asia, C America, C/E Africa P. Ovale: W/S Africa, W Pacific, P. Malariae: infrequent all over

Mixed infections are possible. P. Falciparum often overrides other species, which is why they are often overlooked, remain untreated and can flare up once P. Falciparum is removed.

2. Risk in Africa The figure below indicates the risk in Africa in terms of the number of months of transmission. Generally speaking, areas with 1-3 month risk are regarded as epidemic areas while those with 4-6 are areas where transmission is seasonal (normally

limited to the summer months). In areas of 7 months or more the risk is generally regarded as all year round as low levels of transmission may continue in so called non-suitable months

The figure below shows the approximate months in which malaria transmission starts and ends. Thus in the LSDI study area transmission starts in November/December and ends in May. Peak transmission is in February-March.

3. Malaria Risk for South Eastern Africa The figure below represents the current situation of malaria risk in south-eastern Africa. This figure was revised at the end of

2000 to take into account the recent increase in malaria transmission. The figure is based on current data and input from the Ministry of Health, Malaria Collaborative Forum and Medical Research Council.

BOTSWANA BOTSWANA
Alldays Alldays Swartwater Swartwater

ZIMBABWE
Messina Messina 1 1 Punda Maria Punda Maria Thohoyandou Thohoyandou Shingwedzi Shingwedzi 11 11 3 3

Louis Trichardt Louis Trichardt

Giyani Giyani Ellisras Ellisras Pietersburg Pietersburg 2 Tzaneen Tzaneen 2

NORTHERN PROVINCE
Thabazimbi Thabazimbi

12 12

NORTH-WEST

Letaba Letaba Phalaborwa Phalaborwa MOZAMBIQUE MOZAMBIQUE 5 5 4 4 Potgietersrus Potgietersrus Satara Satara 6 Hoedspruit Hoedspruit 6 7 7 8 8 Nwanedzi Nwanedzi Nylstroom Nylstroom 9 9 10 10 Pilgrims Pilgrims Rest Rest Skukuza Skukuza Sabie Sabie Lydenburg Lydenburg 11 11 Hazyview Hazyview White River River White Komatipoort Komatipoort Nelspruit Nelspruit GAUTENG Malelane Malelane Middelburg Middelburg Pretoria Pretoria Barberton Barberton

Take precautionary measures against mosquito bites throughout the year in ALL RISK areas High Risk Areas Antimalarial drugs* are recommended all year round Intermediate Risk Areas Travellers are advised to take antimalarial drugs from October through May, particularly for high risk people** Low Risk Areas No antimalarial drugs are recommended No Risk or no data
Mozambique Malaria all year round: antimalarial drugs* are recommended Swaziland Travellers are advised to take antimalarial drugs from October through May, particularly for high risk people**

MPUMALANGA
Ermelo Ermelo

Mbabane Mbabane Manzini Manzini

13 13 SWAZILANDNdumo 14 14 Ndumo

15 15

Manguzi Manguzi

Ingwavuma Ingwavuma
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Mbazwana Mbazwana Ubombo Ubombo


17 17 19 19 Hlabisa Hlabisa 21 21

18 18

Mahlabatini Mahlabatini

22 22

20 20

KWAZULU-NATAL KWAZULU-NATAL
Doringkop Doringkop

St St Lucia Lucia Mfolozi Mfolozi

Richards Bay Bay Richards Mtunzini Mtunzini Tugela Tugela

* Mefloquine OR Doxycycline (OR Chloroquine PLUS Proguanil) ** High risk people are children < 5 years, pregnant women & immunocompromised people (e.g. WHO stage 3 or 4 HIV, a person who has had a splenectomy, or who is on
immunosuppressant medication)

Durban Durban

Towns
Game Reserves:
13. Ndumu 14. Tembe 15. Kosi Bay 16. Itala 17. Mkuze 18. Sodwana 19. False Bay 20. Fanies Island 21. Hluhluwe 22. Umfolozi

1.Tshipese 2. Hans Merensky (Eiland) 3. Groot-Letaba 4. Klaserie 5. Sharalumi 6. Timbavati 7. Thornybush 8. Blyderivierpoort 9. Manyeleli 10. Sabie-Sand 11. Kruger National Park 12. Pilanesburg

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100

Kilometers

Life cycle In the human the parasite multiplies in two stages: first in the liver cells, then in the blood cells.

1. The liver stage Parasite forms (sporozoites), injected into a human from an infectious mosquito, first travel to the liver where they undergo a tremendous initial multiplication phase. One parasite cell in the liver stage produces 10 000 (in P. Vivax) to 30 000 (in P. Falciparum) merozoites (divided creatures). These then enter the blood system where they start multiplying further. The liver stage of the parasite can become dormant, and reemerge after 1-18 months (in P. Vivax / P. Ovale). Recurrence in P. Falciparum (<1 year in semi immunes) and P. Malariae (up to 50 years) is due to re-emergence of parasites living at very low levels in the blood.

2. The blood cycle In the blood stream the parasites invade red blood cells, feeding on them as they grow and divide, and finally break free, thereby destroying the cells. Each parasite produces 12 - 32 (in P. Falciparum, slightly less in other species) new parasites. Each new parasite then invades another red blood cell and starts dividing. This multiplication can quickly result in severe disease and death. Fever is caused by release of waste material when infected cells rupture in the blood. Cerebral malaria is caused by clotting of red blood cells in the brain blood capillaries as a result of the malaria infection. Severe anaemia is caused by destruction of both infected and uninfected cells by the parasite or by the body itself. The failure of other organs, like kidneys, liver and spleen, is caused by the flood of waste materials and the clotting of blood capillaries, to the point where the body can no longer cope. The blood cycle in P. Falciparum occurs in deep circulation, i.e. in the blood vessels of the inner organs. Only when the cells rupture do parasites appear in peripheral blood (where they can be picked up through a finger prick). That is why it is sometimes difficult to pick up parasites with the microscope, unless the blood was taken during a fever spell.

The maximum parasite density achieved by P. Falciparum is 2 000 000 parasites per micro litre (l), or 50 000 in P. Vivax, 30 000 in P. Ovale and 20 000 in P. Malariae. On average there are 5 000 000 red blood cells per l blood, so P. Falciparum can infect 40% of all red blood cells before death.

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3. The cycle in the mosquito Soon after infection of the human host, some parasites, instead of dividing, start forming sexual cells, called gametocytes (sex cell). A feeding mosquito then ingests these male and female cells. In the stomach of the mosquito the male cell forms several sperm, which fertilize the eggs. The fertilized ookinete (moving egg) then forces its way through the stomach wall into the body cavity of the mosquito, where it settles and starts dividing, forming 8-10 000 sporozoites (animal spores). The sporozoites then travel through the body fluids towards the mosquitoes salivary gland. From here they are injected into another human when the mosquito next feeds. After a mosquito bites and infected person, it takes about 10-20 days (depending on the temperature), before the mosquito can infect another person. Anopheles mosquitoes are not automatically carriers of malaria. Only after they have fed on a human with malaria and been infected themselves, and only after the parasite has completed its cycle inside the mosquito can the mosquito infect another human. Immunity Immunity is only acquired under conditions of frequent infection from a young age. The more frequently a person is infected, the greater the immunity becomes. Immunity does not prevent infection, but decreases disease and death, and increases rate of recovery. It can be lost when a person leaves the malaria area. Immunity is also specific to a particular species and stage of the parasite. It is transferred from the mother to the infant but remains active only for 3-6 months. Foetal haemoglobin also partially protects babies during the first few months. Symptoms From infection to first symptoms (incubation period) is usually 714 days.

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First symptoms

In Adults Feel weak, lethargic, uncomfortable, dizziness Chills, sweats, fever Muscular / abdominal pain Vomiting, watery diarrhoea

In Children Additional symptoms can occur: Cough, Rapid shallow breathing Feverish convulsions Rapid shallow breathing, cough, fever convulsions Cerebral: unrousable coma, convulsions, muscle spasm causing backward arching of body. Respiratory distress: deep breathing, flaring nostrils. Low blood glucose: restless/aggressive, coma, drowsy, convulsions, sweating

Uncomplicated Falciparum malaria Severe malaria (always Falciparum)

Fever, vomiting, diarrhoea, anaemia. In nonimmune people this rapidly becomes severe, life-threatening if it remains untreated. Cerebral: unrousable coma, convulsions, muscle spasm causing backward arching of body, facial grimace Kidney failure: low urine output (<400ml per day) Fluid on the lungs: laboured or rapid, shallow breathing, frothy sputum, lack of oxygen in tissues,

Other complications

In pregnancy

Anaemia, low blood sugar, failure of circulation (shock), repeated general convulsions, acid blood, spontaneous bleeding, red urine, o jaundice, fever 40 C. Maternal complications: increased risk of severe malaria, increased risk of death, especially in first pregnancy, sepsis or bleeding after delivery. More common and more often fatal than in nonpregnant women. Foetal complications: abortion, still birth, foetal anaemia, low birth weight, retarded growth of the foetus, premature delivery, baby born with malaria. Mainly due to cerebral malaria, kidney failure, fluid on the lung, or general organ failure Mainly due to cerebral malaria, respiratory distress, severe anaemia, low blood sugar

Cause of death

P. Vivax

P. Ovale

P. Malariae

Similar to uncomplicated P. Falciparum. Can have long latent periods and relapse after treatment. Death rarely due to ruptured spleen. Similar to uncomplicated P. Falciparum. More gradual onset than Vivax, can relapse, but less common. Death rare. Similar to uncomplicated P. Falciparum. More gradual onset, less severe symptoms, can recur after many years. Death rare.

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Malaria can easily be confused with many diseases including flu, blood poisoning, typhoid, dengue, viral haemorrhagic fevers, meningitis. Diagnosis By microscope: some blood is smeared on a glass slide and examined under the microscope, to find parasites in the red blood cells: The four species of malaria are distinguished by their different appearances of; trophozoites (Plate 1) schizonts (Plate 2) gametocytes (Plate 3), the staining, size and shape of infected red blood cells, and other characteristics.

For instance, Falciparum is identified by relative abundance of trophozoites, absence of schizonts and their distinctive bananashaped gametocytes. Schizonts in peripheral blood usually signals the presence of a species other than Falciparum. Malariae trophozoites often form a belt across the width of the red blood cell. Ovale is identified by its large, often convoluted trophozoites, and commonly deformed infected red blood cell (hence their name).

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Testing for malaria with a microscope takes time, electricity and a good microscopist. Over the last few years several malaria rapid tests have been developed, which make a rapid diagnosis possible. They require a drop of blood from a finger prick, and involve a paper test strip that is dipped into the blood and other solution(s). After a few minutes, during which the liquids are absorbed into the strip, a reading is obtained by the presence or absence of a coloured test line on a white background. There are several different products on the market now, and are roughly, equally effective. Most only detect P. Falciparum but a few can detect the presence of one of the other malaria species. Prevention Personal protection Malaria mosquitoes only bite after dark. The best prevention is personal protection against the malaria mosquito: Wear long sleeves and trousers in the late afternoon and night, stay indoors if possible. The latter advice is however often difficult to follow when on holiday in the tropics. Effective protection may be obtained by using a repellent on exposed skin. Additional protection may be obtained by applying repellent to clothes, as mosquitoes will often

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bite through clothes. Aerosol repellents can be used on clothes and often also give more effective coverage of exposed skin than a stick or roll on. Sticks and roll-ons are useful for application to areas such as the face, where an aerosol may affect sensitive areas (e.g.eyes). Sleep under an insecticideimpregnated bed net or in a netted tent or hut or in a house or caravan with screens. Close windows and doors at night. Spray insecticide aerosol and/or burn mosquito coil at night. Synthetic pyrethroids (e.g. Deltamethrin) are usually used to impregnate nets (and clothes) as these have very low toxicity to man. A dosage for a single net can usually be purchased as a tablet or small sachet. Re-treatment should be carried out at 6 monthly intervals or after washing. Chemical prophylaxis Drugs available for prophylaxis of malaria act on the parasites in the red blood cells and prevent disease from developing and typical symptoms from presenting. It is most important to take the recommended drugs exactly as prescribed and to complete the course. Failing to complete the course results in inadequate drug levels in the blood, allowing the parasites to multiply and malaria to develop. It is important to continue prophylaxis for 4 weeks after return from a malaria area. Even if the drug is only partially effective (e.g. in the case of partial drug resistance), parasite development is still inhibited, symptoms may take longer to appear, and may be less severe at first, than if no prophylaxis was taken. Malaria symptoms may only develop quite a while after leaving the malaria area. This may reduce suspicion of malaria to the detriment of the patient, especially as many people believe that prophylaxis is a guarantee against malaria. It is therefore very important that anyone experiencing any malaria or flu-like symptoms after having been in a malaria area seeks help immediately and informs their physician that they have been in a

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malaria area. Appropriate prophylaxis will considerably reduce the chances of being infected with malaria and therefore of unnecessary illness and death. However, no drug is guaranteed to protect everyone every time. Choices of prophylaxis: 1.Mefloquine Mefloquine (Lariam")( Meflium") is highly effective and has a simple weekly dosage. Start a week or two before, to check for possible side effects. Complete the course. Continue while in the area and for 4 weeks after leaving the area. Mefloquine has been taken up to 12 months without side effects. However, it has a number of contra-indications and requires a doctors prescription. It also has rare but severe neurological side effects. 2. Doxycycline This drug is highly effective in SE Asia, and resistance is rare. However, it is for short-term use only and can cause light sensitivity (Use a sunblock). Must be taken daily, starting 2 days before, during and for 4 weeks after leaving the area. It can cause failure of the birth control pill and an alternative form of contraception should be used. 3. Proguanil/Chloroquine combination Proguanil (Paludrine") every day; Chloroquine (Daramal" / Nivaquine"/ Promal") once a week. This combination can be taken safely up to 3 months, very cautiously for 6. Start a day before you leave. Not recommended for high-risk chloroquine resistance areas. Complete the course. Continue use for 4 weeks after leaving the area.

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Treatment Oral treatment is used for uncomplicated malaria, intravenous or intramuscular treatment for severe malaria. Symptomatic treatment is given for fever and other symptoms. Pyrimethamine-Sulphadoxine (Fansidar"): to treat chloroquine resistant uncomplicated malaria. Cheap. Convenient single-dose treatment. Sometimes causes vomiting and skin rashes. Resistance is developing in parts of Africa (Including KwaZuluNatal, South Africa), so medical advice should be sought if symptoms persist despite treatment. Quinine: to treat severe malaria and uncomplicated malaria resistant to chloroquine, Fansidar" and Mefloquine". Severe side effects, extremely bitter, therefore not often used as oral treatment. Intravenous treatment suitable for treating pregnant women and children. Chloroquine: cheapest, rapid action, symptomatic relief, but resistance to chloroquine is common, and it cannot clear the parasite. It is sometimes used in conjunction with Fansidar" because of rapid initial action. Not effective in non-immune patients in the southern, eastern and central African areas. Other treatments: fever-reducing drugs, antibiotics, physical cooling, rehydration Drug resistance should not be confused with: lack of compliance, inadequate dose, reinfection. Multi drug resistance is most common in SE Asia, especially borders of Thailand.

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Rapid malaria tests ICT (can detect all types of Plasmodium) Scientific Group Johannesburg toll free: 0800002639 Durban: 031 - 579 4701 Kat Quick Kat Medical Tel: 011 - 475 73 60/1 Fax: 011 - 475 73 62 Shawn Duke - 082 577 20 99 Cape Biotech MacMed consumables Franco Zorzi for direct purchase Tel: 011-6538556 Makro-Mal Makro Medical (Pty) ltd. Johannesburg Louis Roux / Colin Kramer 011 - 624 33 00 Durban: Debbie Craig 0832691507

Common Myths 1. It is better not to take any prophylaxis, as it masks the symptoms and makes diagnosis difficult This is incorrect. Not to take prophylaxis when visiting a malaria area puts travellers at risk of contracting a dangerous and life-threatening disease. Prophylactic drugs suppress parasite development, and therefore, even if not totally effective (due to partial drug resistance or non-compliance), symptoms tend to take longer to appear, may be less severe at first and development of complications is retarded. In the complete absence of drugs, parasites are able to multiply at phenomenal rates, and malaria can quickly get out of hand, and lead to severe complications and death, within 24 hours. Malaria is sometimes difficult to diagnose the standard way (by

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microscope) because malaria parasites are present in the peripheral blood only during a fever spell. If a finger prick is taken between fever spells, it is possible that the parasites are not picked up. As prophylaxis retards the parasite multiplication, it may indeed make diagnosis more difficult initially, but repeated blood smears or new and very sensitive rapid type tests will usually confirm malaria well before the patient is dangerously ill. Remember, even if malaria is diagnosed and treated in good time, it is still an extremely unpleasant and dangerous illness.

2. There is this new deadly strain of malaria Cerebral malaria is not a new strain; it is a complication of untreated Falciparum malaria. Early diagnosis and appropriate treatment should ensure that no one ever gets cerebral malaria. 3. Malaria cannot be cured Malaria can indeed be cured with the appropriate drugs. Due to drug resistance to certain drugs, it may take several attempts with different (combinations of) drugs to effect a complete cure. Also, because most common drugs only kill the blood and not the liver stages, the two malaria species that have dormant liver stages (Vivax and Ovale) often do not get removed initially. If the parasite species is not identified correctly, or if there were two species present in the blood, of which one was missed, malaria can flare up again, sometimes months and years later. However, once the species has been correctly identified, the liver stage can be successfully removed with Primaquine. 4. Prophylaxis need only be taken while in a malaria area The drugs that we have to prevent malaria are known as blood schizontocides, which means that they work on the parasite once it enters the red blood cells. This does not occur until 10-14 days

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after being bitten by an infected mosquito. If the drug is stopped before the parasites reach the blood cells, there will not be enough drug in the blood to kill the parasites and the prophylaxis will fail. It is therefore most important to continue taking prophylaxis for 4 weeks after leaving a malaria area. 5. I wasnt bitten; can I stop taking my prophylaxis? The female anopheles mosquito is not known as the silent killer for nothing. She does not buzz around your head at night, irritating you. You may not be aware of her presence at all. The reaction to her bite may also not be as pronounced as it is with other bloodsucking insects and you may be unaware of having been bitten. Phone numbers offering advice Dept. Health, Communicable diseases: (012) 3120000 Medicine Information Centre: TPS Drug Information Centre: Travel Clinic SAIMR: Glaxo Wellcome Malaria Hotline: (021) 448302 (011) 3394811 (011) 4899000 (011) 4033586

Travel Clinic Durban ICC: Tel: (031) 3601122, Fax: (031) 3601121, Email: travelc@icc.co.za British Airways Travel Clinic: (011) 8073132 / (021) 4193172 / (031) w-3032423 ah-3013737 www.malaria.co.za Malaria Research Programme, Medical Research Council www.malaria.org.za

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The Business Trust is an initiative of South African companies, working in partnership with government, to undertake targeted job creation and capacity building programmes. Its strategy focuses on Tourism for job creation, schooling for capacity building and is underpinned by support for a reduction in crime. The trust is committed to enhancing trust and building cooperative relations between business and government. Carefully selected strategic partners implement the Business Trust programmes, which aim to benefit the disadvantaged while the economy is put on a growth path that will provide sustained improvements in the lives of the majority of South Africans

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