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How to Protect Yourself Against Malaria 1 Fig

How to Protect Yourself Against Malaria 1 Fig

From our Whitepaper Files: How to

> See companion document Protect Yourself Against World Malaria Risk Chart 2015 Edition

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THE ENEMY area. Of the 460 species, approximately 100 can transmit malaria Sunset — the hunt for human blood begins. parasites. From dusk to dawn the female Anopheles, Mosquitoes prey on a variety of hosts — the malaria-carrying mosquito searches for a host humans, monkeys, lizards, birds — carrying to supply her with blood. Blood is an absolute different species of malaria parasites which in necessity for her because it provides the protein turn infect only specific hosts. Of the approxi- needed for the development of her eggs which mately 50 different species of malaria parasites she later deposits in her breeding place. sharing the genetic name , only She has a tiny, elegant body, measuring 5 infect humans: , from 8 mm to 1 cm. She has dark spots on the killer; ; , her wings, three pairs of long, slender legs and and . a prominent tubular proboscis with which The latter, a malaria parasite of Old World she draws blood. monkeys, has been identified to infect humans Fig. 1 Female Anopheles mosquito. TheAnopheles enters your room at night. in Southeast Asia. In the past this parasite has Image source: World Health Organization You may recognize her by the way she rests been misdiagnosed as Plasmodium malariae. on the wall — she stands on her head with the Malaria parasites are older than human- tail-end of her body tilted upwards, protruding kind. They have accompanied the of into the air like a rocket on a launching pad. primates throughout the geological ages from Malaria parasites are older She is unlike the common pests of our temperate their earliest ancestors up to the emergence of climates, the Culicinae (Culex, Aedes, etc.), which humans. The parasites, too, underwent adaptive than humankind. They have assume a position parallel to the surface. changes and it is believed that the Plasmodium ­accompanied the evolution She is your enemy, because only she can falciparum, which causes the fatal form of of primates throughout the harbour the human malaria parasite and carry human malaria, is the latest evolved species of geological ages from their it from an infected person to a new victim. the parasite. The benignPlasmodium malariae, earliest ancestors up to the In fact, in East Africa the same word, umbu, the oldest on the scale of evolution, may have means both malaria and mosquito. Around been the first to invade humans. emergence of humans. the world, she infects more than 200 million people with malaria and kills an estimated THE BITE 627,000 people, mostly children. The unprotected international traveller Now that the burglar has entered your premises pays her a heavy toll — she is responsible for she is waiting in a dark corner for the right infecting thousands with malaria every year. moment to rob you of your blood. The insidious Her bite is the direct cause of death for many Anopheles, attracted by the warmth of your body who contract the in their travels. (Male and the carbon dioxide you exhale, approaches mosquitoes do not bite.) silently. She does not hum or hover as other The more than 3,500 species of mosquitoes mosquitoes do. are grouped into the family of Culicidae, of In a moment she will land on an exposed part which the genera Aedes, Anopheles and Culex are of your body and pull out from her proboscis the most widespread. Throughout the world, her armament, consisting of six stylets. First, two each species of Anopheles is peculiar to a localized needle-pointed stylets will stab your skin, then two

How to Protect Yourself Against Malaria 1 Fig. 2 Life cycle of the malaria parasite.

blades bearing very fine teeth will lacerate the skin THE THREE LIVES OF like a microscopic saw, searching for a small vein. THE MALARIA PARASITE Soon she pierces the vessel with a flexible tube, the “food canal” through which blood is The malaria organism is aprotozoan conveyed into her mouth. During the feeding, (Gr.: proto=primitive; zõon=animal), that is to she will introduce into the wound her sixth say a microscopic, single-celled animal, not to weapon, a hollow stylet containing a duct which be confused with a bacterium, which belongs to is connected to the salivary glands. Through this the plant kingdom. The parasite has a complex duct she injects a few drops of her saliva to act as a life cycle, reproducing first in the , then in local anaesthetic so that you do not feel her bite. the red blood cells and finally in the mosquito. Simultaneously with her saliva she will During these three cycles the parasite transforms introduce into your bloodstream hundreds itself and emerges each time with new physical of motile sporozoites (Gr.: sporá=sowing, seed; and biochemical characteristics. zõon=animal). These malaria organisms have been multiplying in her intestine for two weeks, The Liver: Hiding Place of the Parasite the result of having bitten a person infected The malaria organisms sporozoites( ) injected into with malaria. the body by the bite of the infected mosquito Soon she will fly away, loaded to twice her remain in the bloodstream for only a short period unfed weight with blood, to conceal herself in — see the illustration of the Life Cycle of the The most dangerous species a dark corner of your room. During the forty- Malaria Parasite (Fig. 2) — usually less than one eight hours it takes to digest the blood she has hour. They disappear from the circulation and of Anopheles attack humans taken, her ovaries will completely develop and she establish themselves in the cells of the liver (2a), between dusk and dawn; will be ready to lay her eggs. where they commence cycles of reproduction, a midnight to 4 am is the peak At sundown she will leave your room for her process lasting from six to twelve days, depending time. This means you are breeding place nearby. She can breed almost on the species. This stage corresponds to the in- a prime target when you are anywhere water collects — a footprint, a puddle, cubation period of the disease. During this time, a tire track, even a coconut shell or a man-made each sporozoite grows through repeated divisions most vulnerable — asleep. container. After laying her eggs, her ovarian cycle of the nucleus into one large cell named schizont starts again, and she may return to see you the (Gr.: schizein=to divide; on ontos=being), now same night. During her three-month life span she containing thousands of tiny new parasites (2b). may lay up to three thousand eggs. The increased pressure causes theschizont This shuttling between blood source and to burst and release these newly formed parasites, breeding place makes malaria a ‘focus’ disease; called merozoites (Gr.: meros=part, zõon=animal) that is to say, its area of infective activity is (2c), which leave the liver and enter the localized and dependent upon the radius of red blood cells where they initiate cycles of the flight range of theAnopheles , usually from reproduction. a few hundred yards to a mile. On entering the liver, all sporozoites of Plas- The most dangerous species ofAnopheles attack modium falciparum, Plasmodium malariae, and humans between dusk and dawn; midnight to Plasmodium knowlesi immediately enter into a 4 am is the peak time. This means you are a prime reproductive phase which exhausts itself after one target when you are most vulnerable — asleep. generation. If you are harbouring an infection

IAMAT Whitepaper Files 2 caused by these parasites, suppressive When the Anopheles bites an infected person, will eliminate the parasites from the red blood the merozoites drawn from the bloodstream are cells, and because no new invasions from the digested in the stomach of the mosquito, liver can occur, you will be completely cured of while the gametocytes (4q) develop in the the infection (2a, 2b, 2c). intestine into mature cells called gametes, the However, Plasmodium vivax and Plasmodium female ovule and the male spermatozoon (4r). Like humans, anopheline ovale enter the liver cell as two different forms The fertilized eggs,ookinete (Gr.: õon=egg; mosquitoes are concerned of sporozoites: one strain immediately enters kinesis=motion) (4t), moves to the outside wall with food, shelter and into a phase of reproduction (2a, 2b, 2c); and of the mosquito gut where, by secreting a cyst the other, called hypnozoite (Gr.: hypno=sleep, wall around itself, it develops into an oocyst reproduction. Will she feed zõon=animal), lies dormant in the liver cell (2d (4u, v), which will give rise to a myriad of new on humans or on domestic red cell). Thehypnozoites enter into reproduc- parasites, the sporozoites. As soon as these sporozo- animals? Will she enter tive phases at different times(2e, 2f), even after ites (4z) are released from the oocyst they migrate human dwellings to bite or will months or years, depending upon the species, to the salivary glands of the Anopheles, waiting to she feed outdoors? Does she and are therefore responsible for the well-known be injected into the next victim. relapses of Plasmodium vivax and Plasmodium The endless cycle starts all over again. prefer to bite soon after dusk, ovale. These relapses may persist for months or late at night or at dawn? years, even though an antimalarial regimen has HOW TO AVOID ANOPHELES’ BITE been meticulously followed.

The Red Cell: Life at The World of Anopheles the Expense of the Red Corpuscle To visualize the mechanism of malaria transmis- From the liver, the merozoites enter the blood- sion in a given area, one must take into con- stream and penetrate the red blood cells (3g), sideration the behaviour of the local species of where they multiply in cycles. Each merozoite, Anopheles. The knowledge of her habits will give feeding at the expense of the red cell, grows into you a better chance to protect yourself against a ring-shaped parasite called trophozoite (Gr.: her bite. trophé=nourishment; zõon=animal) (3h). Upon Like humans, anopheline mosquitoes are reaching its full size (about .016 mm), each concerned with food, shelter and reproduc- trophozoite, through repeated divisions of the tion. Will she feed on humans or on domestic nucleus, forms a schizont, a cluster containing animals? Will she enter human dwellings to bite sixteen to twenty-four new oval-shaped parasites, or will she feed outdoors? Does she prefer to again called merozoites (3l). When the infected bite soon after dusk, late at night or at dawn? red blood cells burst, the merozoites flood the cir- Will she use houses as a daytime resting place culation and invade fresh red blood cells to start or will she seek shelter in dense vegetation? new cycles of reproduction (3m, n, o, p). These Will she breed in peridomestic waters such as cycles repeat themselves every two to three days small ponds, footprints or artificial containers, depending on the species. The rhythmic release or far away in large bodies of water? Differ- of so many parasites into the circulation — ent preferences characterize each species. Take estimated at a quarter of a billion — coincides for instance Anopheles gambiae, the mosquito with the characteristic clinical picture of malaria: responsible for so many deaths in Africa south periodic high fever, preceded by shivering and of the Sahara. She chooses her breeding place a followed by profuse sweating. few yards from your habitation. She may even be travelling with you by car, plane or boat. In fact The Mosquito: she once crossed the Atlantic by boat spreading The Sexual Life of the Parasite malaria along the northeastern coast of Brazil. Some merozoites are distinguished from others On the other hand, the main vector of malaria in that they grow in the red blood cell without in the Philippines, the Anopheles flavirostris, has dividing. They transform themselves into sexual different habits. She prefers to breed along the cells, the male and female gametocytes (Gr.: margins of foothill streams and lakes, and her gameté=wife, gamétes=husband; kútos=cell) which presence is confined to rural areas. That is why, are necessary for the perpetuation of the parasite although there is no malaria in large cities like (3q). However, they can mature only outside Manila, there is malaria transmission in African the human body, and because they cannot leave cities south of the Sahara. the bloodstream on their own, they need outside Two factors influence the reproduction of help — the Anopheles mosquito. During evolu- Anopheles: Rainfall and temperature. The rainy tion, an affinity developed between the malaria season, bringing an increase in the anopheline parasite and the Anopheles: the Anopheles requires population, will determine the annual high-risk blood for the protein she needs to lay her eggs period of malaria transmission. Lower tempera- and the parasite requires a host in which it can tures will decrease the Anopheles populations and reproduce. more importantly, will arrest the development of

How to Protect Yourself Against Malaria 3 parasites in the mosquito’s gut. Since tempera- holes along the diagonal.) Not one single tear ture lowers with increased altitude, transmission should be permitted since mosquitoes will spend of the disease is not possible over a certain height hours searching for an opening. above sea level. See IAMAT’s World Malaria Soaking your bed net in a permethrin Risk Chart for country details. solution like Sawyer Permethrin Soak Treatment Kit will impregnate it and provide additional The Super Anopheles protection since it kills the mosquitoes on With the knowledge of the habits of the contact. Similarly, spraying your clothes with Anopheles, humans learned to fight her by products like REPEL, Sawyer Permethrin Cloth- poisoning her resting places with DDT. ing Treatment or Coulston’s Duranon Tick A single indoor spraying, leaving a layer of Repellent have proven to be very effective microscopic crystals, made surfaces lethal to binding themselves tightly to the fabric and mosquitoes for months. But, although this remaining effective through several washings. residual reversed the odds in the Follow the manufacturer’s instructions. These struggle, within a few years the Anopheles had products are available in many travel health developed a resistance to these chemicals. Other clinics and outdoor equipment stores. (Note that pesticides followed, always with the same inglori- permethrin products are not sold in Canada.) ous result. Today, many species of Anopheles have There are several good reasons for using bed been reported resistant to traditional . nets in addition to preventive medication: The more recent insecticides, the carbamate compounds, are not suitable because of their • It provides protection when the Anopheles To accommodate a real need for a practical high cost and short residual action period. mosquito is most active, chances of bed net, IAMAT has designed La Mosquette,TM Furthermore, some Anopheles are already show- infection are reduced. a light-weight, portable free-standing ing resistance to these new compounds. Because Some malariologists estimate that with aluminum frame and a rectangular bed net of these ‘super Anopheles’, malaria is making a proper use of bed nets malaria cases could treated with permethrin. It is available at cost comeback in areas where infection was reduced be reduced by two-thirds. for U.S./CAN $140. Shipping is included. or eliminated. This situation puts a renewed • It offers protection from other emphasis on the mechanical forms of protection. transmitted by mosquitoes, such as filariasis, known for massive MECHANICAL PROTECTION swelling of the limbs. • It also protects against ticks, beetles, flies, Mechanical forms of protection are still spiders and other insects which may enter the most effective means of preventing the spread your bed. of malaria. FOUR STEPS TO Window and Door Screens MOSQUITO PROTECTION Ensure that the window and door screens of your room fit tightly and are free of holes. The following precautions require self-discipline At the same time check the screens to be sure and should be taken every day beginning at the mesh is small enough to prohibit the sunset by anyone visiting malarious areas. entrance of any mosquitoes. Step 1: Protective clothing The Mosquito Bed Net Beginning at sunset, wear long-sleeved shirts In malarious areas, unscreened bedrooms and long pants in light colours such as beige or require insecticide-treated mosquito bed nets yellow. Dark clothing attracts mosquitoes, as except in buildings with sealed windows and does the scent of perfume or after-shave lotion. central air conditioning. If possible, bed nets should be rectangular rather than cone-shaped Step 2: Mosquito repellent to prevent skin contact with the netting Apply mosquito repellent – available in sprays, allowing the Anopheles to bite through. lotions and towelettes – to all exposed areas of Fig. 3 Mosquito bed net, portable, Netting should be made of cotton or skin, as well as clothes, avoiding eyes and light-weight La Mosquette™ with free- standing aluminum frame. ­synthetic thread to allow the movement of air. mouth. Look for repellents containing 20 - 30% The net must be white to allow mosquitoes to be DEET or 20% Icardin. These active ingredients seen against the background and should have a keep mosquitoes away but do not kill them. wide, tightly woven border to be tucked under Since repellent gradually evaporates and some the mattress. will be lost through perspiration, swimming A netting with twenty-six holes per square and active exercise, re-apply every few hours inch will prevent even the smallest Anopheles according to the manufacturer’s directions for from penetrating. (This figure is obtained by continuous protection. Caution: Repellent may adding the number of holes along the bottom damage plastic items such as eye-glass frames, line of a square inch of net and the number of watch crystals, and nail polish.

IAMAT Whitepaper Files 4 All malaria infections are serious illnesses and must be treated as a medical emergency. Travellers should be aware that infection with Plasmodium falciparum  Important... malaria is the most dangerous and often fatal form of the disease.

About Malaria The appearance of resistant and / or multidrug resistant Infections and P. falciparum in many malarious areas makes the choice of suppressive drugs Early Diagnosis problematic as none of the currently used are 100% effective. Regardless of which is being used, it is of utmost im- portance for travellers and their physicians to consider fever and flu-like symp- toms appearing 7 days to several months after leaving a malarious area as a malaria breakthrough. Early diagnosis is essential for successful treatment.

Reliable information on malarious areas, sound knowledge of your destination’s geography, including understanding the feeding and breeding habits of the local Anopheles mosquitoes, will help you to take the appropriate protective measures. See IAMAT’s World Malaria Risk Chart for country details.

Step 3: Pyrethrin insecticides Instead, antimalarial medications act (brand name: Raid and others) by eliminating the parasites during their Pyrethrin insecticides (active ingredient multiplication phase in the liver stage pyrethrin, extracted from the pyrethrum flower, (- and ) or a member of the chrysanthemum family) kills their replication phase in the red blood cells, mosquitoes instantly by acting on the central red cell cycle (chloroquine, , nervous system. Frequent spraying is necessary and hydrochloride). Suppressive since pyrethrin dissipates when exposed to air. medication will eliminate the parasites caused Spray bed net (if not treated with permethrin) by P. falciparum, P. malariae, and P. knowlesi, and under the bed, as well as walls, baseboards, but will not always prevent a delayed first attack corners, furniture, behind picture frames and or relapses caused by P. vivax and P. ovale, inside closets in the bedroom, and under which may appear months or years after the sink in the bathroom. Cover any food and discontinuing the suppressive drug. cooking utensils. Do not open windows while spraying, and allow vapour to settle before • It is imperative that you take the returning to the room. Products with pyrethrin medication at regular intervals should be used with caution. Follow the throughout your stay in a malarious manufacturer’s instructions. region, and you should continue to do so for 1-4 weeks (depending on the Two factors influence the Step 4: Preparing your bed for the night regimen), after leaving the area. reproduction of Anopheles: During the day, the bed net should be left hanging • Taking the full course of suppressants is Rainfall and temperature. in a knot from the frame or the ceiling. Before essential even for a short stay. Remember, The rainy season, bringing retiring lower the net and search carefully for one single bite is sufficient to infect you. an increase in the anopheline mosquitoes hidden inside. Mend any holes or tears • If you are on a weekly regimen, always with adhesive tape or thread. Tuck the edge of the take your suppressant the same day and population, determines bed net under the mattress, making sure there are if you are on a daily regimen, take it at the annual high-risk period of no openings. If you are camping check surround- the same hour every day. Establish this malaria transmission. Lower ing area for possible Anopheles breeding places. as a habit so you will not forget. Take temperatures will decrease the the suppressant with plenty of water to Anopheles populations and will reduce stomach discomfort which may ANTIMALARIAL DRUGS occur occasionally. arrest the development of para- • Since an adequate concentration of sites in the mosquito’s gut. There are 2 types of antimalarial drugs used the drug in the blood is reached a few to suppress the clinical symptoms of malaria, hours after ingestion, you may start the but they will not prevent the establishment of medication on the day of your departure. a malaria infection. If antimalarial drugs were However, it is advisable to start your true prophylactics (Gr.: prophylasso = to guard regimen one to two weeks before leaving before) they would prevent malaria infection — while still at home you will acquire by killing the parasites (sporozoites) the moment confidence with the drug and you can they are introduced into your bloodstream seek the advice of your family physician by the bite of the Anopheles. in case of any adverse reaction.

How to Protect Yourself Against Malaria 5 Anopheles Culex

Fig. 4 Anopheles and Culex mosquitoes.

• It would be ideal to take a complete supply TAKE IN WEEKLY DOSES OF of medication with you to avoid any 400 mg (310 mg base). START problems getting the antimalarial drugs 1 WEEK BEFORE ENTERING that were prescribed for you in another MALARIOUS AREA, CONTINUE country. Be aware of counterfeit malaria WEEKLY DURING YOUR STAY medications at your destination. They’re AND CONTINUE FOR 4 WEEKS packaged very similarly to the real ones and AFTER LEAVING. could put your life at risk. Always get your medication from a reputable pharmacist. c. Other options are atovaquone- proguanil, doxycycline, or mefloquine hydrochloride CHEMOPROPHYLAXIS GUIDELINES (see #2 for details).

In offering guidance on the choice of antimalarial 2. Travellers to areas with chloroquine drugs, the main concern is to provide protec- resistant and / or multidrug resistant tion against Plasmodium falciparum, the most P. falciparum malaria should take dangerous form of the illness. The dosages below ONE of the following regimens: are for adults. For children see ‘Pediatric Malaria Chemoprophylaxis Dosages’ on page 12. a. Atovaquone-proguanil (brand names: Malarone, Malanil 1. Travellers to areas with P. falciparum and others; generics available) malaria sensitive to chloroquine should TAKE 1 TABLET DAILY take the following regimen: (ATOVAQUONE 250 mg + PROGUANIL 100 mg). START a. Chloroquine phosphate or sulfate 1-2 DAYS BEFORE ENTERING (brand names: Aralen, Resochin and THE MALARIOUS AREA, others; generics available) CONTINUE DAILY DURING TAKE IN WEEKLY DOSES OF YOUR STAY AND CONTINUE 500 mg (300 mg base). START FOR 7 DAYS AFTER LEAVING. 1 WEEK BEFORE ENTERING MALARIOUS AREA, CONTINUE b. Doxycycline WEEKLY DURING YOUR STAY (brand name: Vibramycin and AND CONTINUE FOR others; generics available) 4 WEEKS AFTER LEAVING. TAKE 1 TABLET OF TAKE IT AFTER A MEAL TO DOXYCYCLINE (100 mg) AVOID STOMACH UPSETS. DAILY. START 1 DAY BEFORE ENTERING MALARIOUS AREA, b. Alternative: CONTINUE DAILY DURING Hydrochloroquine sulfate YOUR STAY AND CONTINUE (brand name: Plaquenil, Axemal FOR 4 WEEKS AFTER LEAVING. and others; generics available)

IAMAT Whitepaper Files 6 c. Mefloquine hydrochloride Treatment of a breakthrough with (brand names: Lariam, Mephaquin, multidrug resistant malaria should be Mefliam and others; generics given under medical supervision and may available) include a variety of drugs in different TAKE 1 TABLET OF 250 mg (228 combinations. Fast medical attention is mg base) ONCE A WEEK. START imperative for successful treatment. 1-2 WEEKS BEFORE ENTERING THE MALARIOUS AREA, The following areas have reported CONTINUE WEEKLY DURING multidrug resistant P. falciparum: YOUR STAY AND CONTINUE FOR 4 WEEKS AFTER LEAVING. Cambodia: The provinces of Siem Reap, Preah Vihear, Oddar Meancheay, Banteay d. An alternative to above regimens: Meanehey, Battambang, Pailin, Pursat, Travellers on short term trips to Kampat, and Koh Kong. The southern areas with mainly P. vivax malaria and western provinces also report can take primaquine phosphate resistance to , and (brand name: Primaquine): pyperaquine. TAKE 1 TABLET OF 52.6 mg Laos: The northwestern provinces (30 mg base) DAILY. START 1-2 of Bokeo and Louang Namtha bordering DAYS BEFORE ENTERING Myanmar | Burma and China; and MALARIOUS AREA, CONTINUE the southern provinces of Salavan DAILY DURING YOUR STAY (Saravane) and Champasak bordering AND CONTINUE FOR 7 DAYS Thailand. AFTER LEAVING. Myanmar | Burma: The states of Note: Primaquine is contraindicated Bago, Kayah, Kachin, Kayin, Shan and for persons with G6PD (glucose Tanintharyi (eastern half of the country 6-phosphate dehydrogenase) deficiency. including the areas bordering China, Laos Screening for G6PD levels must be done and Thailand). Resistance to prior to prescribing or using this drug. is reported. Suriname: This country reports e. Antimalarial regimen P. falciparum resistance to chloroquine, for travellers who cannot follow one mefloquine hydrochloride, - of the above regimens: and some decline in Take chloroquine or hydrochloro- sensitivity. quine (see #1 above). Note that Thailand: The western border areas these drugs are much less effective with Myanmar | Burma – forested in this country than atovaquone- hilly areas of Chang Rai, Chang Mai, proguanil, doxycycline or mefloquine Mae Hong Son, Tak, Kanchanaburi, hydrochloride. Seek immediate Ratchaburi and Petchaburi provinces Take a complete supply of medical attention if you have flu-like (these areas also report P. falciparum symptoms — fever, headache, nausea, resistance to quinine and artemisinin); medication on your trip to general malaise — appearing about the eastern border areas with avoid any problems getting 7 days or later after entering the Cambodia: forested hilly areas of the antimalarial drugs that malarious area. Ubon Ratchathani, Si Sa Ket, Surin, were prescribed for you. Note: It is imperative to use a mosquito Buriram, Sa Kaeo, Chantaburi, and Be aware of counterfeit bed net to avoid the bite of the nocturnal Trat provinces. Anopheles mosquito. Use repellents and Vietnam: The provinces of Binh malaria medications at your insecticides as described in ‘Four Steps to Phoc, Dak Lak, Dak Nong, Gia Lai, destination. They’re packaged Mosquito Protection’ on page 4. Khan Hoa, Kon Tum, Lam Dong, Ninh very similarly to the real ones Thuan, Song Be, Tay Ninh. and could put your life at risk. 3. Travellers going to mefloquine Always get your medication hydrochloride and multidrug resistant P. falciparum malaria areas should take DESCRIPTION OF ANTIMALARIAL from a reputable pharmacist. an atovaquone-proguanil or doxycycline DRUGS: CONTRAINDICATIONS, regimen as described above. Persons who PRECAUTIONS, AND SIDE EFFECTS cannot follow one of these regimens or contemplate a long term visit to these areas should seek advice for a possible 1. Atovaquone-proguanil alternative drug regimen from a travel This antimalarial is effective for the medicine specialist. Contact IAMAT prevention of chloroquine-resistant and for referrals. multidrug-resistant P. falciparum malaria.

How to Protect Yourself Against Malaria 7 ADULT MALARIA CHEMOPROPHYLAXIS DOSAGES For recommended antimalarial drugs at your destination, consult IAMAT’s World Malaria Risk Chart for country details.

Tablet salt Number 1 Timing of dosage in a Antimalarial Drug Brand Name content + of 2 Indications for Use malarious area (base content) tablets

Atovaquone-proguanil Malarone and 250 mg 1 Start: 1-2 days before All malarious areas. others; Generics Atovaquone + During: Daily Mothers breastfeeding children 100 mg Proguanil After: 7 days after leaving > 5 kg / 11 lb. Chloroquine phosphate Aralen and others; 500 mg (300 mg) 1 or sulfate Generics Start: 7 days before For chloroquine-sensitive areas. Dosages may differ slightly Alternative dose: 2 During: Once a week (all trimesters). among manufacturers 250 mg (150 mg) After: 4 weeks after leaving Breastfeeding mothers.

Hydroxychloroquine Plaquenil and 400 mg (310 mg) 1 sulfate others; Generics Same as above. Same as above. Dosages may differ slightly among manufacturers Doxycycline Vibramycin and 100 mg 1 Start: 1-2 days before others; Generics During: Daily All malarious areas. After: 4 weeks after leaving Me oquine Lariam and others; 250 mg (228 mg) 1 Start: 1-2 weeks before All malarious areas. hydrochloride Generics During: Once a week Pregnancy After: 4 weeks after leaving (all trimesters considered safe). Breastfeeding mothers. Primaquine phosphate Primaquine 52.6 mg (30 mg) 1 Start: 1-2 days before For areas with primarily During: Daily P. vivax malaria. After: 7 days after leaving Travellers, including mothers and their breastfeeding babies must be screened for G6PD levels before taking this drug.

1 All antimalarial drugs have precautions and contraindications. See ‘Description of Antimalarial Drugs: Contraindications, Precautions, and Side Effects’ on page 7. Talk to your healthcare provider to choose the best regimen for you. 2 Depending on the regimen, take your antimalarial daily at the same time every day or weekly during the same day of the week. This will help you remember to take the medication.

CAUTION: May cause mild side- P. knowlesi. Travellers should be aware effects when used for prophylaxis such that chloroquine will not always prevent as stomach upsets, vomiting, headaches, delayed first attacks or relapses of nausea. Take with food or milk. malaria months to years after departure from malarious areas even when the CONTRAINDICATIONS: chloroquine regimen has been followed Persons suffering from renal (kidney) meticulously. Depending on the strain disorders or with known allergies to (subspecies) of the parasite, these delayed atovaquone or proguanil should not attacks develop in 30-70% of people. use this drug. The safety of this drug in pregnancy, nursing mothers and INCONVENIENCES: The bitter taste children weighing less than 5kg / 11 lb makes the drug unpalatable. Minor has not been established. Atovaquone- stomach upsets, itching skin, nausea and proguanil is available by prescription for diarrhea may occur; it may also cause prophylaxis and treatment. blurred vision and a transitory headache. is an alternative 2. Chloroquine drug that may be better tolerated than This antimalarial drug is commonly used chloroquine. around the world for the suppression of P. falciparum malaria in areas where the CAUTION: Since chloroquine is parasites are still sensitive to it. In case of deposited in high concentration in the infection, chloroquine will completely liver and white blood cells, it should malaria caused by sensitive strains of be used with caution if you have a P. falciparum. For chloroquine-sensitive liver condition, alcoholism or a blood malarious areas see IAMAT’s World disorder. Patients on phenylbutazone Malaria Risk Chart. should discontinue this drug while taking chloroquine since it may enhance Chloroquine is also the drug of choice the chances of dermatitis. It may also for the suppression of malaria caused by aggravate the condition of persons P. vivax, P. ovale, P. malariae and suffering from porphyria and .

IAMAT Whitepaper Files 8 CONTRAINDICATIONS: Due to neurological or psychiatric side the adverse effect of chloroquine on effects occur. the optic nerve, persons with diseases of the retina and optic nerve (e.g. diabetic CONTRAINDICATIONS: Persons with retinopathy, optic neuritis) should not a history of depression, anxiety, , use this drug. Persons contemplating schizophrenia or other psychiatric disorders, a prolonged course with chloroquine as well as cardiac abnormalities, liver should have an eye examination at least diseases, or epilepsy should not use this once a year to detect any changes in drug. Mefloquine hydrochloride may the retina. Travellers with a history of interact with agents such as beta blockers, epilepsy should not take chloroquine. digoxin, calcium channel blockers, and metoclopramide. If mefloquine hydro- 3. Doxycycline chloride is taken for long term prophylaxis This drug belongs to the periodic liver function tests and ophthalmic group of and is effective in examinations should be performed. preventing malaria in multidrug resistant areas. It is also used in combination with 5. Primaquine quinine for the treatment of severe and This drug is used for prophylaxis for multidrug resistant malaria. persons on short term travel to areas with mostly P. vivax malaria or as an CAUTION: Doxycycline may cause alternative drug regimen for travellers photosensitive skin reactions. Avoid who cannot take other antimalarial drugs. exposure to direct sunlight and use It is also used for treatment to eradicate sunscreen with high protection against P. vivax and P. ovale parasites in the liver UVA (long range ultraviolet radiation) to stage to prevent future malaria attacks. minimize risk of photosensitive reaction. It may also cause vaginal yeast infections CAUTION: Primaquine may cause in women, and produce - nausea and abdominal pain. Take tablets resistant pathogenic bacteria. Antibiotic- with food. associated , a severe form of diarrhea, can also follow with prolonged CONTRAINDICATIONS: This drug is use of this drug. contraindicated for persons with glucose- 6-phosphate dehydrogenase deficiency CONTRAINDICATIONS: Doxycycline (G6PD). All travellers must be tested for should not be used by persons with known G6PD levels before this drug is prescribed photosensitive skin reactions. It is contra­ or administered. It is also contraindicated indicated for pregnant and breastfeeding during pregnancy. Breastfeeding children women, and children younger than 8 years must be tested for G6PD deficiency before of age. permanently stain the mother can take the medication. the teeth of unborn babies, infants and children up to eight years of age. DRUGS USED FOR 4. Mefloquine hydrochloride TREATMENT OF MALARIA This antimalarial is very effective for the prevention of chloroquine-resistant The following are some of the drugs used for and multidrug-resistant P. falciparum the treatment of malaria. malaria. However, it may not always In offering guidance on the prevent a delayed first attack or relapses -lumefantrine caused by P. vivax. (brand name: Coartem) choice of antimalarial drugs, This drug is used for the treatment of severe the main concern is to provide CAUTION: Side effects include malaria. It is a compound drug derived from protection against Plasmodium nausea and headache, including the Chinese medicinal plant Qinghao ( falciparum, the most dangerous neurological side effects such as dizziness, annua) also known as sweet wormwood and is form of the illness. ringing of the ears, and loss of balance. an Artemisinin (ACT). Psychiatric side effects include anxiety, Do not use as . depression, mistrustfulness, and hallucinations. Neurological side Atovaquone-proguanil (brand name: effects can occur any time during use Malarone; generics available) and can last for long periods of time This drug is used for treatment of uncomplicated or become permanent even after the drug malaria, but should not be used as treatment if is stopped. Seek medical advice if any taken for prophylaxis.

How to Protect Yourself Against Malaria 9 Primaquine phosphate • Artesunate + Sulfadoxine- (brand name: Primaquine) pyrimethamine (brand names: This drug is used for the eradication of liver stage Artescope, Supysunate and others) malaria parasites of P. vivax and P. ovale to prevent • + future malaria attacks. Primaquine is also used for (brand name: Artequick) prophylaxis for persons on short term travel to areas with mostly P. vivax or chloroquine- Dihydrochloride resistant P. falciparum malaria. It is contra- (brand names: Camoquin, Flavoquine, indicated for persons suffering from glucose-6- ­others; generics) phosphate dehydrogenase (G6PD) deficiency. Belonging to the same chemical family as It is also contraindicated during pregnancy and chloroquine (4-Aminoquinoline), this drug You will undoubtedly encounter breastfeeding children must be tested for G6PD offers similar protection to chloroquine, but fellow travellers who are on a deficiency before the mother can take the medica- experience has shown that it causes serious side tion. Patients must be tested for G6PD deficiency effects such as hepatitis and agranulocytosis. different malaria suppressive before this drug is prescribed or administered. Amodiaquine is used in combination with regimen. It is highly recom- artesunate as an Artemisinin Combination mended that you continue with Quinine and Therapy (ACT) for the treatment of severe the medication prescribed for Quinine sulfate (brand name: Qualaquin and ­malaria. Do not use for malaria prophylaxis. you by your doctor or travel others), Quinine dihydrochloride (brand name: Quininject and others) and Quinidine gluconate Chloroquine-Proguanil health specialist and never (brand name: Quinaglute and others) are drugs (brand name: Savarine) switch to any medication of- derived from the bark and used in This combination drug eliminates the fered as a “better choice” by combination with other antimalarial drugs for difficulty of taking chloroquine on a weekly other travellers. the treatment of severe multidrug resistant basis and proguanil on a daily basis. However, P. falciparum malaria when Artemisinin Com- its usefulness is compromised by the high bination Therapies (ACTs) are not available. resistance of P. falciparum malaria to both They must be administered under close medical chloroquine and proguanil. supervision due to potential side effects.Do not use for malaria prophylaxis. -Pyrimethamine (brand name: Maloprim) This alternative to sulfadoxine-pyrimethamine MALARIA DRUGS AVAILABLE ABROAD (Fansidar) should not be used for malaria prophylaxis. Travellers to malarious areas will encounter fel- low travellers who are on a different malaria sup- (brand name: Halfan) pressive regimen. It is highly recommended that Halofantrine is used for the treatment of chloro- you continue with the medication prescribed for quine-resistant and sulfadoxine-pyrimethamine you by your doctor or travel health specialist and resistant P. falciparum malaria mostly in Africa. never switch to any medication offered as a “bet- Not recommended for prophylaxis or treat- ter choice” by other travellers. ment since this drug causes severe adverse effects (including death) in persons with or without The following is a short discussion of some pre-existing cardiac conditions. medications used abroad. Proguanil (brand name: Paludrine) Artemisinin Combination Therapies (ACT) Although proguanil hydrochloride is the oldest Artemisinin (Qinghaosu) and its derivatives and safest of malaria suppressants, P. falciparum Artemether, Artesunate, Dihydroartemisinin parasites have become so highly resistant to it are isolates of the Chinese medicinal plant that its usefulness is seriously compromised in all Qinghao () also known as malarious areas. Studies have shown that using sweet wormwood. These drugs are used in proguanil is less effective againstP. vivax, P. ovale, combination with other antimalarial drugs P. malariae, P. knowlesi malaria than chloroquine. for the treatment of severe malaria. Do not use Proguanil should not be used on its own as for malaria prophylaxis. a malaria suppressant. • Artemether-lumefantrine (brand names: Coartem, Riamet) Sulfadoxine-pyrimethamine • Artesunate + Amodiaquine (brand name: Fansidar) (brand name: Coarsucam) There is widespread resistance ofP. falciparum • Artesunate + Mefloquine malaria parasites against this drug. It should not hydrochloride be used for prophylaxis as potential serious side (brand name: Mefliam Plus effects may develop after multiple doses. Sulfa- and others) doxine-pyrimethamine is used in combination

IAMAT Whitepaper Files 10 with artesunate as an Artemisinin Combination drugs. Chloroquine is safe during pregnancy Therapy (ACT) for treatment of severe malaria. in doses used for malaria prophylaxis. Mefloquine hydrochloride can be used during the second and third trimesters, but studies STAND-BY EMERGENCY TREATMENT suggest that it is also safe during the first (SBET) trimester. Atovaquone-proguanil, doxycycline and primaquine are contra- Travellers in remote areas where medical atten- indicated during pregnancy. tion cannot be sought within 24 hours or on a prophylactic regimen which is not optimal due to resistance, should discuss with their physician WHEN YOU RETURN… the options for a self-treatment regimen in case of fever, chills and flu-like symptoms. Back home from the tropics you may feel a general malaise, headache and some fever, all If you have a fever or flu-like Atovaquone-proguanil (Malarone) or symptoms usually associated with the flu. symptoms appearing 7 days or artemether-lumefantrine (Coartem) are recom- Remember to tell your doctor where you have several months after your trip, mended for both adults and children, however, been even if the fever develops months after they both have contraindications. Also note that your return since such an episode could be a don’t forget to tell your doctor the stand-by treatment cannot be the same as the first attack ofP. falciparum, P. malariae, that you were in a malarious prophylactic regimen. Talk to your doctor before P. knowlesi, or a relapse of P. vivax or P. ovale area. Early diagnosis is essen- taking these drugs for emergency treatment. malaria. For this reason blood is not accepted tial for successful treatment. See table, ‘Stand-By Emergency Treatment – from donors who have been in a malarious area Adult and Pediatric Dosages’ on page 14. for 1 year and for 3 years if you have lived in a malaria endemic zone.

ANTIMALARIAL REGIMENS THE SEARCH FOR THE KILLER FOR CHILDREN

Parents should keep malaria medications out November 6, 1880 – Constantine, Algeria: of reach of children since misuse can result in The end of a superstition death. Breastfed infants are not protected by Thousands of years of superstition attributing their mother’s prophylactic regimen, but must malaria (L.: mala aria = bad air) to some kind of be given their own dosages according to their airborne poison is overthrown by French army weight. Children should always sleep under a surgeon, Charles Louis Alphonse Laveran. bed net. Anti-mosquito repellents are safe but He identified the malaria parasite for the first time should be applied sparingly to the exposed parts while examining with the aid of a microscope the of the body, avoid hands and face. fresh blood of a patient infected with P. falciparum malaria. But Laveran’s times were under the spell School age children are very vulnerable to of the genius Louis Pasteur, and the bold idea that ­malaria. Children on holidays to visit parents malaria was caused by the presence of millions of working in the tropics should be watched to minute animal parasites in the blood, and not by ensure that they continue taking the suppres- bacteria, was difficult to accept. It took six years for sive regimen after their return to school. Their the skeptical medical profession to recognize the guardians must be warned that fever and flu-like importance of his discovery. symptoms appearing 7 days to several months after their return may signify a malaria break- 1886 – Pavia, Italy through and early diagnosis is imperative for Camillo Golgi definitively identified two human successful treatment. See table, ‘Pediatric Malaria malaria parasites: Plasmodium vivax and Plasmo- Chemoprophylaxis Dosages’ on page 12. dium malariae. He described the asexual multiplica- tion of the parasite in the red corpuscle of the blood and demonstrated its relationship to the periodic ANTIMALARIAL REGIMENS DURING appearance of the fever characteristic of malaria. PREGNANCY 1889 – Rome, Italy Since all drugs taken by a pregnant woman reach Three years later, Ettore Marchiafava her unborn child, it is never advisable to take any differentiated a third species of human malaria medications if not absolutely necessary. However, parasites, Plasmodium falciparum, named for if travel to a malarious region cannot be avoided, the crescent shape of the sexual form of the the risk of miscarriage or premature delivery as parasite (L.: falx =sickle; parere =to bring forth). a result of contracting malaria far outweighs the However, the mechanism of transmission of the risk of possible side effects from antimalarial disease was still a mystery.

How to Protect Yourself Against Malaria 11 PEDIATRIC MALARIA CHEMOPROPHYLAXIS DOSAGES For recommended antimalarial drugs at your destination, consult IAMAT’s World Malaria Risk Chart for country details.

1 Tablet salt content Number of Antimalarial Drug Brand Name Weight 2 Frequency (base content) tablets

Atovaquone- Malarone 62.5 mg Atovaquone < 5kg / 11lb Contraindicated Start: 1-2 days before Proguanil Pediatric + 5-8kg / 11-18 lb ½ During: Daily 25 mg Proguanil After: 1 week after leaving > 8-10 kg / 18-24 lb ¾ > 11-20 kg / 24-44 lb 1 > 20-30 kg / 44-66 lb 2 > 30-40 kg / 66-88 lb 3 > 40 kg / 88 lb 1 adult tablet Chloroquine Aralen and 8.3 mg / kg Corresponds approximately to: Start: 1 week before phosphate or sulfate others; (5 mg / kg) 15-20 kg / 33-44 lb ½ During: Once a week Dosages may differ Generics Calculated up to a 20-25 kg / 44-55 lb ¾ After: 4 weeks after leaving slightly among maximum of 300 mg 25-35 kg / 55-77 lb 1 manufacturers base per week 35-50 kg / 77-110 lb 1½

> 50 kg / 110 lb 2 Hydroxychloro- Plaquenil and 6.5 mg / kg Start: 1 week before quine sulfate others; (5 mg / kg) Same as above Same as above During: Once a week Dosages may differ Generics Calculated up to a After: 4 weeks after leaving slightly among maximum of 310 mg manufacturers base per week

Chloroquine sulfate Nivaquine 1 tsp. = 5 ml (25 mg) of Corresponds approximately to: ½ tsp. Start: 1 week before syrup3 Syrup chloroquine base 5-9 kg / 11 lb = 2.5 mL During: Once a week 10-19 kg / 24-43 lb = 5 mL 1 tsp. After: 4 weeks after leaving

20-29 kg / 44-65 lb = 10 mL 2 tsp.

30-39 kg / 66-87 lb = 15 mL 3 tsp. 40-49 kg / 88-109 lb = 20 mL 4 tsp. > 50 kg / 110 lb = 25 mL 5 tsp. Doxycycline Vibramycin 2.2 mg / kg < 8 years or < 25 kg / 55 lb Contraindicated Start: 1-2 days before Dosages may differ and others; Calculated up to a During: Once a week 25-35 kg / slightly among Generics maximum of 100 mg / After: 4 weeks after leaving manufacturers day > 35 kg / 110 lb > 50 kg / 110 lb Me oquine Lariam and 5 mg (4.6 mg) / kg < 9 kg Measure dose Start: 1-2 weeks hydrochloride others; according to body During: Once a week Generics weight After: 4 weeks after leaving Corresponds approximately to: 1/8 > 5-10 kg / 11-24 lb > 10-20 kg / 24-44 lb ¼ > 20-30 kg / 44-66 lb ½ > 30-45 kg / 66-99 lb ¾ > 45 kg / 99 lb 1 Primaquine Primaquine 0.8mg (0.5 mg) / kg Measure dose according to body Calculated up to a Start: 1-2 days phosphate4 weight maximum of 30 During: Daily mg base per day After: 1 week after leaving

1 All antimalarial drugs have precautions and contraindications. See ‘Description of Antimalarial Drugs: Contraindications, Precautions, and Side Effects’ on page 7. Talk to your healthcare provider to choose the best regimen for you or your child. 2 Your pharmacist will be able to crush tablets and prepare pediatric dosages in gelatin capsules if needed. 3 Nivaquine Syrup is not available in the United States or Canada, but can be purchased in Europe and malarious areas. 4 Children must be screened for G6PD levels before using this drug.

IAMAT Whitepaper Files 12 1894 – London: 1886-1899 – Rome: The magnificent four Patrick Manson, The grey eminence Simultaneously, a group of Italians were working behind malaria research to solve the puzzle of the transmission of malaria Patrick Manson, an eminent Scottish physician, in humans. From 1886 to 1896, Giuseppe had discovered that mosquitoes could suck Bastianelli, Amico Bignami, Angelo Celli and up the microscopic threadlike worms from Giovanni Battista Grassi had been actively the blood of patients infected with a disease investigating the life cycle of the human malaria called filariasis. He believed that mosquitoes parasites and making accurate descriptions of the might also draw out the malaria parasites from lesions produced by the parasites in the different human blood, and that transmission would oc- organs of the body. A breakthrough came with cur by ingestion of water contaminated the observations by Grassi, a physician with a by infected mosquitoes. keen interest in zoology, particularly mosquitoes. He noticed that when malaria was present there July 4, 1898, Calcutta: was always a large population of Anopheles, Ronald Ross, “It is the bite” while in areas of large Culex populations there Manson, realizing he could never experiment was no malaria. enough in England to prove his theory, con- vinced Ronald Ross, a British army surgeon who From the Campagna Romana near Rome visited him in 1894, to carry on this research. he collected Anopheles mosquitoes which his Together they planned a series of experiments colleague Bignami allowed to feed on a volunteer which Ross carried out upon his return to India. patient from the Santo Spirito Hospital, Ross began by raising Culex and Aedes larvae, a few steps away from St. Peter’s Basilica. and let the adult mosquitoes feed on patients On November 1, 1898, the patient, Abele Sola, with malaria. Then he let these mosquitoes bite developed the classic symptoms of P. falciparum volunteers, but with no result — since he wasn’t malaria. Together with Bastianelli and Celli,

Fig. 5 Patrick Manson, Scottish physician an entomologist he wasn’t aware that he was us- they were able to reproduce malaria infections who demonstrated how mosquitoes play ing the wrong species of mosquito. After several in other volunteers and prove that only a role in the spread of parasites. unsuccessful experiments, in April 1897, while the Anopheles mosquito, and no other species, Image source: London School of Hygiene & working in Ootacamund (Ooty) near Madras, transmits malaria in humans. (painting by H.H. Salomon) he saw for the first time the dapple-winged Anopheles, and started to experiment with this 1936 – Rome: Giulio Raffaele species. On August 20, 1897, looking through discovers the liver cycle his microscope at the gut of mosquitoes which It was soon discovered that a link was miss- had fed on a patient with malaria, he saw for the ing in the knowledge of the life cycle of the first time the human malaria parasite growing in malaria parasite. Still unexplained was the time the gut of Anopheles. elapsed between the introduction of the parasites through the bite of the mosquito and the Unwillingly he had to interrupt his appearance of the symptoms of malaria. investigations, and when he moved to his Giulio Raffaele discovered while working with new post in Calcutta he started working birds that malaria parasites entering the host first with the avian malaria parasites, which are undergo a cycle of transformation within the transmitted by a Culex species. He proved blood-forming cells of the liver. that the spindle-shaped malaria organisms (sporozoites), freed by the rupturing of 1948, London: The final touch the fertilized eggs, migrate from the gut of Now the road was open for British researchers the mosquito to its salivary glands, to be injected Colonel H.E. Shortt and Percy Cyril Claude into the victim when the insect bites. To Ross Garnham to demonstrate the liver cycle of goes the credit for the discovery that malaria is the malaria parasite in humans. Following a transmitted by mosquito bite. period of extensive trials on monkeys, in 1948 a human volunteer — a Mr. Howard — was 1898 – Baltimore bitten during three days by nearly eight hundred Later in the same year William George Anopheles infected with Plasmodium falciparum. McCallum, a Canadian pathologist also On the fifth day, a surgeon removed a small working with birds, was able to interpret and piece of tissue from his liver which, examined describe the fertilization process of the parasite under the microscope, demonstrated the growth taking place in the gut of the mosquito. of the parasites in the liver cells. The last mystery of the life cycle of the malaria parasite was finally unraveled.

How to Protect Yourself Against Malaria 13

STAND-BY EMERGENCY TREATMENT – ADULT AND PEDIATRIC DOSAGES

Antimalarial Drug1 Brand Name Adults Children

Atovaquone-proguanil Malarone and Dose: 250 mg atovaquone + 100 mg proguanil Dose: 62.5 mg atovaquone + 25 mg proguanil Do not use if you’re taking others; Generics Take 4 tablets (as a single dose) once a day for Take indicated dose once a day for 3 consecutive this drug for prophylaxis, 3 consecutive days, for a total of 12 tablets. days. Seek medical care as soon as possible. are pregnant or Seek medical care as soon as possible. < 5kg / 11lb Contraindicated breastfeeding children 5-8 kg / 11-18 lb 2 pediatric tablets < 5 kg / 11 lb. Discuss alternatives with your > 8-10 kg / 18-24 lb 3 pediatric tablets healthcare provider. > 11-20 kg / 24-44 lb 1 adult tablet > 20-30 kg / 44-66 lb 2 adult tablets > 30-40 kg / 66-88 lb 3 adult tablets > 40 kg / 88 lb 4 adult tablets Artemether- Coartem, Riamet Dose: 20 mg artemether + 120 mg lumefantrine Dose: 20 mg artemether + 120 mg lumefantrine Lumefantrine The number of tablets to take is based on your weight. Take indicated dose twice a day for 3 consecutive Do not use if you have For adults > 35 kg / 77 lb take 4 tablets per dose twice days. On day 1, take the 2nd dose 8 hours after the 1st taken meoquine a day for 3 consecutive days, for a total of 24 tablets. dose. On days 2 and 3, take your dose twice a day. hydrochloride for On day 1, take the 2nd dose 8 hours after the 1st dose. < 5kg / 11lb Contraindicated prophylaxis, are pregnant On days 2 and 3, take your dose twice a day. 5-15 kg / 11-33 lb 1 tablet or breastfeeding children 15-25 kg / 33-55 lb 2 tablets < 5 kg / 11 lb. Discuss alternatives with your 25-35 kg / 55-77 lb 3 tablets healthcare provider. > 35 kg / > 77 lb 4 tablets

1 All antimalarial drugs have precautions and contraindications. See ‘Description of Antimalarial Drugs: Contraindications, Precautions, and Side Effects’ on page 7. Talk to your healthcare provider to choose the best regimen for you or your child.

THE RACE AGAINST In the US, mefloquine hydrochloride was AND licensed in 1989, doxycycline was approved as an HOPE FOR A VACCINE antimalarial in 1994, and atovaquone-proguanil in 2000. Also during this time, P. knowlesi was In the late 1950s there were reports of positively identified as the 5th malaria parasite P. falciparum resistance to choloroquine, the first responsible for infecting humans in Southeast line drug used to prevent malaria. During the Asia, being previously mistaken for P. malariae 1960s and 1970s, research focused on finding and P. falciparum. new antimalarial drugs partly spurred by US soldiers getting ill and dying from malaria in the Currently, there are several intensive efforts to Vietnam War. Much of the antimalarial drug develop a vaccine against malaria. RTS,S / AS01 research at that time was done by scientists at the or Mosquirix is the first one that is almost ready Walter Reed Army Institute of Research. While to be marketed. It’s being developed by Glaxo- mefloquine hydrochloride and the tetracycline SmithKline and the non-profit organization group of antibiotics were discovered to be effective PATH Initiative which receives

Fig. 6 Percy Cyril Claude Garnham, antimalarials, they were not available to travellers. funding from the Bill and Melinda Gates Foun- who demonstrated the liver cycle of malaria dation for the project. Clinical trials have shown parasites in humans. The 1980s saw the introduction of effective that it provides partial protection Image source: Wellcome Collection antimalarial drugs in the marketplace such as against P. falciparum, the fatal form of malaria. sulfadoxine-pyrimethamine (Fansidar) and It’s these types of partnerships that are key to halofantrine (Halfan). These drugs however, have successfully prevent, control, and the eventual serious side effects and are no longer recom- eradication of malaria. mended. The antimalarial medications recom- mended for use today are relatively new.

IAMAT Whitepaper Files 14

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