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How to Protect Yourself Against Malaria 1 4

How to Protect Yourself Against Malaria 1 4

From our Whitepaper Files: How to

> See companion document Protect Yourself Against World Malaria Risk Chart 2020 Edition

This content is no longer being reviewed or updated. Last update: December 11, 2020.

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THE ENEMY area. Of the 460 , 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 , searches for humans, monkeys, lizards, birds — carrying a host to supply her with blood. Blood is an different species of malaria parasites which absolute necessity for her because it provides the in turn infect only specific hosts. Of the protein needed for the development of her eggs approximately 50 different species of malaria which she later deposits in her breeding place. parasites sharing the genetic name , She has a tiny, elegant body, measuring only 5 infect humans: from 8 mm to 1 cm. She has dark spots on (the killer parasite); ; her wings, three pairs of long, slender legs and , and a prominent tubular proboscis with which . The latter, a malaria she draws blood. parasite of Old World monkeys, has been Fig. 1 Female Anopheles mosquito. TheAnopheles enters your room at night. identified to infecthumans ­ in Southeast Asia. Image source: World Health Organization You may recognize her by the way she rests In the past this parasite has been misdiagnosed on the wall — she stands on her head with the as Plasmodium­ malariae. tail-end of her body tilted upwards, protruding Malaria parasites are older than human- into the air like a rocket on a launching pad. kind. They have accompanied the of Malaria parasites are older She is unlike the common pests of our temperate primates throughout the geological ages from climates, the Culicinae (, Aedes, etc.), which their earliest ancestors up to the emergence of than humankind. They have assume a position parallel to the surface. humans. The parasites, too, underwent adaptive ­accompanied the evolution She is your enemy, because only she can changes and it is believed that the Plasmodium of primates throughout the harbour the human malaria parasite and carry falciparum, which causes the fatal form of geological ages from their it from an infected person to a new victim human malaria, is the latest evolved species of earliest ancestors up to the (male mosquitoes do not bite). In fact, in the parasite. The benignPlasmodium malariae, East Africa the same word, umbu, means both the oldest on the scale of evolution, may have emergence of humans. malaria and mosquito. Around the world, she been the first to invade humans. infects more than 200 million people with malaria and kills an estimated 430,000 people, THE BITE mostly children. The unprotected international traveller Now that she has entered your premises, the pays her a heavy toll — she is responsible for Anopheles waits patiently in a dark corner for the infecting thousands with malaria every year. right moment to strike. Attracted by the warmth Her bite is the direct cause of death for many of your body and the carbon dioxide you exhale, who contract the in their travels. she approaches silently. She does not hum or hover The more than 3,500 species of mosquitoes as other 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 4

i q r s h z l w v u t g m

p n b a c o

1 f e 3 2 d

Fig. 2 Life cycle of the malaria parasite.

blades bearing very fine teeth will lacerate the THE THREE LIVES OF skin like a microscopic saw, searching for a small THE MALARIA PARASITE vein. 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 be confused with a bacterium, which belongs to which is connected to the salivary glands. the plant kingdom. The parasite has a complex Through this duct she injects a few drops of her life cycle, reproducing first in the , then in saliva to act as a local anaesthetic so that you do the red blood cells and finally in the mosquito. not feel her bite. During these three cycles the parasite transforms Simultaneously with her saliva she will itself and emerges each time with new physical introduce into your bloodstream hundreds and biochemical characteristics. of motile sporozoites (Gr.: sporá=sowing, seed; zõon=animal). She acquired these organisms from The Liver: Hiding Place of the Parasite biting a person infected with malaria. They have The malaria organisms sporozoites( ) injected into been multiplying in her intestine for two weeks. 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; ontos=being), now con- same night. During her three-month life span she taining 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

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 on humans or on domestic red cell). Thehypnozoites enter into reproduc- new parasites, the sporozoites. As soon as these animals? Will she enter tive phases at different times(2e, 2f), even after ­sporozoites (4z) are released from the oocyst they human dwellings to bite or will months or years, depending upon the species, migrate to the salivary glands of the Anopheles, she feed outdoors? Does she and are therefore responsible for the well-known waiting to 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 trans- From the liver, the merozoites enter the blood- mission in a given area, one must take into stream and penetrate the red blood cells (3g), consideration the behaviour of the local species where they multiply in cycles. Each merozoite, of Anopheles. Understanding her habits will give feeding at the expense of the red cell, grows into you a better chance of protecting 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 of malaria in that they grow in the 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 help — the Anopheles mosquito. During evolu- of Anopheles: Rainfall and temperature. tion, an affinity developed between the malaria The rainy season, bringing an increase in the parasite and the Anopheles: the Anopheles requires anopheline population, will determine the blood for the protein she needs to lay her eggs ­annual high-risk period of malaria transmission. and the parasite requires a host in which it can Lower temperatures will decrease the Anopheles reproduce. populations and more importantly, will arrest

How to Protect Yourself Against Malaria 3 the development of parasites in the mosquito’s through several washes by binding themselves gut. Since temperature lowers with increased tightly to fabric. These products are available in altitude, transmission of the disease is not many travel health clinics and outdoor equip- possible over a certain height above sea level. ment stores. (Note: Permethrin solutions and See IAMAT’s World Malaria Risk Chart for sprays are not sold in Canada.) Follow the country details. ­manufacturer’s instructions.

The Super Anopheles 2. Use mosquito repellent With the knowledge of the habits of the Apply mosquito repellent – available in sprays, Anopheles, humans learned to fight her by lotions, and towelettes – to all exposed areas poisoning her resting places with DDT. of skin, as well as clothes, avoiding the eyes A single indoor spraying, leaving a layer of and mouth. Look for repellents containing microscopic crystals, made surfaces lethal to 20 – 30% DEET or 20% Picaridin. These mosquitoes for months. But, although this active ingredients keep mosquitoes away but residual reversed the odds in the do not kill them. Since repellent gradually struggle, within a few years the Anopheles had evaporates and some will be lost through developed a resistance to these chemicals. perspiration, swimming, and active exercise, Other pesticides followed, always with the re-apply every few hours according to the same inglorious result. Today, many species manufacturer’s directions for continuous of ­Anopheles have been reported resistant to protection. Caution: Repellent may damage traditional . The more recent plastic items such as eye-glass frames, watch insecticides, the carbamate compounds, are not crystals, and nail polish. suitable because of their high cost and short residual action period. Furthermore, some 3. Secure dwelling and sleeping area ­Anopheles are already showing resistance to Ensure that the window and door screens of these new compounds. Because of these ‘super your room fit tightly and are free of holes. At the ­Anopheles’, malaria is making a comeback in same time, check the screens to be sure the mesh areas where infection was reduced or eliminated. is small enough to prohibit the entrance of any This situation puts a renewed emphasis on mosquitoes. ­effective mosquito bite prevention methods and Use Pyrethrin insecticides (brand name: Raid their use. and others) indoors. Pyrethrin insecticide (active ingredient pyrethrin, extracted from the pyre- thrum flower, a member of the ­chrysanthemum METHODS OF PROTECTION family) kills mosquitoes instantly by acting on the central nervous system. Frequent spraying When in a malarious area, you need to use mul- is necessary since pyrethrin dissipates when tiple methods of protection to prevent mosquito exposed to air. Spray your bed net (if not bites and malaria infection. Remember: The already treated with permethrin) and under Anopheles can be difficult to detect and you may the bed, as well as walls, baseboards, corners, never know that you have been bitten until it’s ­furniture, behind picture frames and inside too late. For effective protection, use multiple ­closets in the bedroom, and under the sink Fig. 3 Example of a rectangular mosquito methods to prevent mosquito bites in combina- in the bathroom. Cover any food and cooking bed net with free-standing aluminum frame. tion with antimalarial drugs. utensils. Do not open windows while spraying, and allow vapour to settle before returning to MOSQUITO BITE PROTECTION: the room. Products with pyrethrin should be FOUR ESSENTIAL STEPS used with caution. Follow­ the manufacturer’s instructions. The following precautions require self-discipline and should be taken every day beginning at 4. Use a mosquito bed net sunset by anyone visiting malarious areas. A mosquito bed net is one of the most effec- tive forms of protection against malaria. This is 1. Wear protective clothing because it prevents mosquito bites while you are Beginning at sunset, wear long-sleeved shirts and asleep at night – the time when the Anopheles is long pants in light colours such as beige or yel- most active. In fact, studies have demonstrated low. Dark clothing attracts mosquitoes, as does that widespread use of bed nets is associated with the scent of perfume or after-shave lotion. 17% reduction in child mortality in countries Spray your clothes with products like where malaria is endemic. ­REPEL, Sawyer Permethrin Clothing Treatment In malarious areas, unscreened bedrooms or Coulston’s Duranon Tick Repellent. These require insecticide-treated mosquito bed nets repellents have been proven to be very effective (except in buildings with sealed windows and at repelling mosquitoes and remain effective central air conditioning). If possible, bed nets

IAMAT Whitepaper Files 4 All malaria 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 impor- tance for travellers and their physicians to consider fever and flu-like symptoms appearing 7 days, weeks or up 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.

should be rec­tangular in shape. Cone-shaped nets ANTIMALARIAL DRUGS are not ideal because your skin may touch the netting allowing the Anopheles to bite through. There are 2 types of antimalarial drugs used Ceiling hook bed nets may not be feasible due to to suppress the clinical symptoms of malaria, the height of the ceiling or problems installing but they will not prevent the establishment of a hook. a malaria infection. If antimalarial drugs were Netting should be made of cotton or synthetic true prophylactics (Gr.: prophylasso = to guard thread to allow the movement of air. The net must before) they would prevent malaria infection be white to allow mosquitoes to be seen against by killing the parasites (sporozoites) the moment the background and should have a wide, tightly they are introduced into your bloodstream woven border to be tucked under the mattress. by the bite of the Anopheles. A netting of 285 holes per square inch will Instead, antimalarial medications act prevent even the smallest Anopheles from penetrat- by eliminating the parasites during their ing. Not one single tear should be permitted multiplication phase in the liver stage since mosquitoes will spend hours searching for (antovaquone-, , and an opening. ) or their replication phase in the red blood cells, red cell cycle (chloroquine, How to use a bed net: During the day, the bed , and hydrochloride). net should be left hanging in a knot from the Suppressive medication will eliminate the Two factors influence the frame or the ceiling. Before retiring, lower the parasites caused by P. falciparum, P. malariae, and reproduction of Anopheles: net and search carefully for mosquitoes hidden P. knowlesi, but will not always prevent a delayed Rainfall and temperature. inside. Mend any holes or tears with adhesive first attack or relapses caused byP. vivax and The rainy season, bringing tape or thread. From inside, tuck the edge of P. ovale, which may appear months or years after an increase in the anopheline the bed net under the mattress, making sure discontinuing the suppressive drug. there are no openings. If you are camping, check population, determines the ­surrounding area for possible Anopheles • It is imperative that you take the medica- the annual high-risk period of ­breeding places. tion at regular intervals throughout your malaria transmission. Lower To provide additional protection, soak your stay in a malarious region, and you should temperatures will decrease the bed net in a permethrin solution like Sawyer continue to do so for 1-4 weeks (depend- Anopheles populations and will Permethrin Soak Treatment Kit. Permethrin ing on the regimen) after leaving the area. can repel and kill mosquitoes upon contact. • Taking the full course of suppressants is arrest the development of para- (Note: Permethrin solutions and sprays are not essential even for a short stay. Remember, sites in the mosquito’s gut. sold in Canada.) one single bite is sufficient to infect you. Bed nets are a highly effective form of protec- • If you are on a weekly regimen, always tion and should be used in conjunction with other take your suppressant the same day and mosquito bite prevention measures and preven- if you are on a daily regimen, take it at tive medication. Bed nets also provide protection the same hour every day. Establish this against other transmitted by mosquitoes, as a habit so you will not forget. Take such as filariasis, and prevent other insects, such as the suppressant with plenty of water to ticks, beetles, flies, and spiders, from entering your reduce stomach discomfort which may bed at night. occur occasionally.

How to Protect Yourself Against Malaria 5 Anopheles Culex

Fig. 4 Anopheles and Culex mosquitoes.

• Since an adequate concentration of 500 mg (300 mg base). START the drug in the blood is reached a few 1 WEEK BEFORE ENTERING hours after ingestion, you may start the MALARIOUS AREA, CONTINUE medication on the day of your departure. WEEKLY DURING YOUR STAY However, it is advisable to start your AND CONTINUE FOR regimen one to two weeks before leaving 4 WEEKS AFTER LEAVING. — while still at home you will acquire TAKE IT AFTER A MEAL TO confidence with the drug and you can AVOID STOMACH UPSETS. seek the advice of your family physician in case of any adverse reaction. b. Alternative: • It would be ideal to take a complete supply Hydrochloroquine sulfate of medication with you to avoid any (brand name: Plaquenil, Axemal problems getting the antimalarial drugs and others; generics available) that were prescribed for you in another TAKE IN WEEKLY DOSES OF country. Be aware of counterfeit malaria 400 mg (310 mg base). START medications at your destination. They’re 1 WEEK BEFORE ENTERING packaged very similarly to the real ones and MALARIOUS AREA, CONTINUE could put your life at risk. Always get your WEEKLY DURING YOUR STAY medication from a reputable pharmacist. AND CONTINUE FOR 4 WEEKS AFTER LEAVING.

CHEMOPROPHYLAXIS GUIDELINES c. Other options are - proguanil, doxycycline, mefloquine In offering guidance on the choice of antima- hydrochloride, or tafenoquine (see larial drugs, the main concern is to provide #2 for details). protection against Plasmodium falciparum, the most dangerous form of the illness. The dosages d. Travellers on short-term trips to below are for adults. For children see ‘Pediatric areas with mainly P. vivax malaria Malaria Chemoprophylaxis Dosages’ on page 12. can take primaquine phosphate ­Contraindications, precautions, and side effects (brand name: Primaquine, The recommendations for for the following medications are listed on Malarid): outlined here are intended as guidelines only page 10. TAKE 1 TABLET of 52.6 mg and may differ according to where you live, your health status, age, destination, trip itinerary, type (30 mg base) DAILY. START of travel, and length of stay. Seek further advice 1. Travellers to areas with P. falciparum 1-2 DAYS BEFORE ENTERING from your physician or travel health clinic for the malaria prophylactic regimen most appropriate to malaria sensitive to chloroquine should MALARIOUS AREA, CONTINUE your needs. take the following regimen: DAILY DURING YOUR STAY AND CONTINUE FOR 7 DAYS a. Chloroquine phosphate or sulfate AFTER LEAVING. (brand names: Aralen, Resochin and Note: Screening for G6PD levels others; generics available) must be done prior to taking TAKE IN WEEKLY DOSES OF this drug.

IAMAT Whitepaper Files 6 2. Travellers to areas with chloroquine e. Antimalarial regimen for travellers resistant and / or multidrug resistant who cannot follow one of the P. falciparum malaria should take above regimens: ONE of the following regimens: Take chloroquine or hydrochloro- quine (see #1 above). Note that a. Atovaquone-Proguanil these drugs are much less effective (brand names: Malarone, Malanil in this country than atovaquone- and others; generics available) proguanil, doxycycline or mefloquine TAKE 1 TABLET DAILY hydrochloride. Seek immediate (ATOVAQUONE 250 mg + medical attention if you have flu-like PROGUANIL 100 mg). START symptoms — fever, headache, nausea, 1-2 DAYS BEFORE ENTERING general malaise — appearing about THE MALARIOUS AREA, 7 days or later after entering the CONTINUE DAILY malarious area. DURING YOUR STAY AND Note: It is imperative to use a CONTINUE FOR 7 DAYS mosquito bed net to avoid the bite of AFTER LEAVING. the nocturnal Anopheles mosquito. Use repellents and insecticides as b. Doxycycline described in ‘Four Steps to Mosquito (brand name: Vibramycin and Protection’ on page 4. others; generics available) TAKE 1 TABLET OF 3. Travellers going to mefloquine DOXYCYCLINE (100 mg) hydrochloride and multidrug resistant DAILY. START 1 DAY BEFORE P. falciparum malaria areas should take ENTERING MALARIOUS an atovaquone-proguanil or doxycycline AREA, CONTINUE DAILY regimen as described above. Persons who DURING YOUR STAY AND cannot follow one of these regimens or CONTINUE FOR 4 WEEKS contemplate a long term visit to these AFTER LEAVING. areas should seek advice for a possible alternative drug regimen from a travel c. Mefloquine hydrochloride medicine specialist. Contact IAMAT (brand names: Lariam, Mephaquin, for referrals. Mefliam and others; generics Treatment of a breakthrough with available) multidrug resistant malaria should TAKE 1 TABLET OF 250 mg be given under medical supervision (228 mg base) ONCE A WEEK. and may include a variety of drugs in START 1-2 WEEKS BEFORE different combinations. Fast medical ENTERING THE MALARIOUS attention is imperative for successful AREA, CONTINUE WEEKLY treatment. Take a complete supply of DURING YOUR STAY AND CONTINUE FOR 4 WEEKS The following areas reportP. falciparum medication on your trip to AFTER LEAVING. malaria resistance to chloroquine, avoid any problems getting mefloquine hydrochloride and the antimalarial drugs that d. As an alternative to the above -: were prescribed for you. regimens, travellers on short Be aware of counterfeit trips can take Tafenoquine Cambodia: The provinces of Siem (brand name: Arakoda): Reap, Preah Vihear, Oddar Meancheay, malaria medications at your TAKE 1 TABLET OF 200 mg. Banteay Meanehey, Battambang, destination. They’re packaged START TAKING DAILY FOR Pailin, Pursat, Kampat, and Koh Kong. very similarly to the real ones 3 DAYS BEFORE ENTERING The southern and western provinces and could put your life at risk. MALARIOUS AREA AND also report resistance to , Always get your medication CONTINUE WEEKLY and . DURING YOUR STAY. Chloroquine resistance to P. vivax from a reputable pharmacist. AFTER LEAVING THE RISK malaria has also been reported in AREA, TAKE ONE TABLET this country. 1 WEEK AFTER THE Laos: The northwestern provinces LAST DOSE. of Bokeo and Louang Namtha Note: Tafenoquine is only available in bordering Myanmar|Burma and the USA and Australia. Screening for China; and the southern provinces G6PD levels must be done prior to of Salavan and Champasak bordering taking this drug. Thailand.

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.

Number Tablet base + Timing of dosage in a Antimalarial Drug1 Brand Name of Indications for Use salt content malarious area2 tablets

Atovaquone-Proguanil Malarone and 250 mg 1 Start: 1-2 days before All malarious areas. others; generics Atovaquone + During: Daily Breastfeeding mothers. 100 mg Proguanil After: 7 days after leaving Children > 5 kg / 11 lb. Chloroquine phosphate Aralen and others; 300 mg 1 or sulfate generics (500 mg salt) Start: 7 days before For chloroquine-sensitive areas. Dosages may differ slightly Alternative dose: 2 During: Once a week (all trimesters). among manufacturers 150 mg After: 4 weeks after leaving Breastfeeding mothers. (250 mg salt) Plaquenil and 310 mg 1 sulfate others; generics (400 mg salt) 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; 228 mg 1 Start: 1-2 weeks before All malarious areas. hydrochloride generics (250 mg salt) During: Once a week Pregnancy After: 4 weeks after leaving (all trimesters considered safe). Breastfeeding mothers. Tafenoquine Arakoda 200 mg 1 Start: 3 days before Persons 18 years of age and over. Only available in the During: Once a week All travellers, including mothers and USA and Australia. After: Once 7 days their breastfeeding babies must be after leaving screened for G6PD levels before taking this drug. Primaquine phosphate N/A 30 mg 1 Start: 1-2 days before For areas with primarily (52.6 mg salt) During: Daily P. vivax malaria. After: 7 days after leaving All 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 this page. 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.

Myanmar|Burma: The states of Vietnam: The provinces of Dak Lak, Bago, Kayah, Kachin, Kayin, Shan and Dak Nong, Gia Lai, Khan Hoa, Kon Tanintharyi (eastern half of the country Tum, Lam Dong, Ninh Thuan, Song Be including the areas bordering China, Laos and Tay Ninh. and Thailand). Resistance to is reported from southeastern parts of the country. Chloroquine resistance to DESCRIPTION OF ANTIMALARIAL P. vivax malaria has also been reported in DRUGS: CONTRAINDICATIONS, this country. PRECAUTIONS, AND SIDE EFFECTS Suriname: This country reports P. falciparum resistance to chloroquine, mefloquine hydrochloride, sulfadoxine- 1. Atovaquone-Proguanil pyrimethamine and some decline in This antimalarial is effective for the sensitivity. prevention of chloroquine-resistant and Thailand: The western border areas multidrug-resistant P. falciparum malaria. with Myanmar|Burma: forested hilly areas CAUTION: May cause mild side effects of Chang Rai, Chang Mai, Mae Hong when used for prophylaxis such as Son, Tak, Kanchanaburi, Ratchaburi and stomach upsets, vomiting, headaches, Petchaburi provinces (these areas also nausea. Take with food or milk. report P. falciparum ­resistance to quinine and artemisinin); the eastern border CONTRAINDICATIONS: ­areas with Cambodia: forested hilly areas Persons suffering from renal (kidney) of Ubon ­Ratchathani, Si Sa Ket, Surin, disorders or with known allergies to Buriram, Sa Kaeo, Chantaburi, and atovaquone or proguanil should not Trat provinces. use this drug. The safety of this drug

IAMAT Whitepaper Files 8 in pregnancy, nursing mothers and examination at least once a year to detect children weighing less than 5kg / 11 lb any changes in the retina. Travellers with has not been established. Atovaquone- a history of epilepsy should not take proguanil is available by prescription for chloroquine. prophylaxis and treatment. 3. Doxycycline 2. Chloroquine This drug belongs to the This antimalarial drug is commonly used group of and is effective in around the world for the suppression of preventing malaria in multidrug resistant P. falciparum malaria in areas where the areas. It is also used in combination with parasites are still sensitive to it. In case of quinine for the treatment of severe and infection, chloroquine will completely multidrug resistant malaria. malaria caused by sensitive strains of P. falciparum. For chloroquine-sensitive CAUTION: Doxycycline may cause malarious areas see IAMAT’s World photosensitive skin reactions. Avoid Malaria Risk Chart. exposure to direct sunlight and use sunscreen with high protection against Chloroquine is also the drug of choice UVA (long range ultraviolet radiation) to for the suppression of malaria caused by minimize risk of photosensitive reaction. P. vivax, P. ovale, P. malariae and It may also cause vaginal yeast infections P. knowlesi. Travellers should be aware in women, and produce - that chloroquine will not always prevent resistant pathogenic bacteria. Antibiotic- delayed first attacks or relapses of associated , a severe form of malaria months to years after departure diarrhea, can also follow with prolonged from malarious areas even when the use of this drug. chloroquine regimen has been followed meticulously. Depending on the CONTRAINDICATIONS: Doxycycline strain (subspecies) of the parasite, these should not be used by persons with delayed attacks develop in 30-70% known photosensitive skin reactions. of people. It is contraindicated­ for pregnant and breastfeeding women, and children INCONVENIENCES: The bitter taste younger than 8 years of age. makes the drug unpalatable. Minor permanently stain the teeth of unborn stomach upsets, itching skin, nausea and babies, infants and children up to eight diarrhea may occur; it may also cause years of age. blurred vision and a transitory headache. Hydroxychloroquine is an alternative 4. Mefloquine hydrochloride drug that may be better tolerated than This antimalarial is very effective for chloroquine. the prevention of chloroquine-resistant and multidrug-resistant P. falciparum CAUTION: Since chloroquine is malaria. However, it may not always deposited in high concentration in prevent a delayed first attack or relapses the liver and white blood cells, it caused by P. vivax. should be used with caution if you have a liver condition, alcoholism CAUTION: Side effects include nausea or a blood disorder. Patients on and headache, including neurological phenylbutazone should discontinue side effects such as dizziness, ringing of In offering guidance on the this drug while taking chloroquine the ears, and loss of balance. Psychiatric since it may enhance the chances of side effects include anxiety, depression, choice of antimalarial drugs, dermatitis. It may also aggravate the mistrustfulness, and hallucinations. the main concern is to provide condition of persons suffering from Neurological side effects can occur any protection against Plasmodium porphyria and . time during use and can last for long falciparum, the most dangerous periods of time or become permanent form of the illness. CONTRAINDICATIONS: Due to even after the drug is stopped. Seek the adverse effect of chloroquine medical advice if any neurological or on the optic nerve, persons with psychiatric side effects occur. diseases of the retina and optic nerve (e.g. diabetic retinopathy, optic neuritis) CONTRAINDICATIONS: Persons with should not use this drug. Persons a history of depression, anxiety, , contemplating a prolonged course schizophrenia or other psychiatric with chloroquine should have an eye disorders, as well as cardiac abnormalities,

How to Protect Yourself Against Malaria 9 liver diseases, or epilepsy should not use DRUGS USED FOR this drug. Mefloquine hydrochloride may MALARIA TREATMENT interact with agents such as beta blockers, digoxin, calcium channel blockers, and The following are some of the drugs used for metoclopramide. If mefloquine hydro- the treatment of malaria. chloride is taken for long term prophylaxis periodic liver function tests and ophthalmic -lumefantrine examinations should be performed. (brand name: Coartem) This drug is used for the treatment of severe 5. Tafenoquine malaria. It is a compound drug derived from This drug is used for prophylaxis for the Chinese medicinal plant Qinghao ( You will undoubtedly encounter persons typically on short-term travel. It annua) also known as sweet wormwood and is fellow travellers who are on a is also used for the treatment of P. vivax an Artemisinin (ACT). and P. ovale parasites in the liver stage to Do not use as malaria prophylaxis. different malaria suppressive prevent future malaria attacks. regimen. It is highly recom- Note: Tafenoquine is only available in the Atovaquone-Proguanil (brand name: mended that you continue with USA and Australia. Malarone; generics available) the medication prescribed for This drug is used for treatment of uncomplicated you by your doctor or travel CAUTION: Tafenoquine may cause malaria, but should not be used as treatment if nausea, dizziness, abdominal pain, taken for prophylaxis. health specialist and never vomiting, diarrhea, and back pain. switch to any medication Tafenoquine (brand name: Krintafel, offered as a “better choice” CONTRAINDICATIONS: This drug Kozenis) and Primaquine phosphate by other travellers. is contraindicated for persons with (brand name: Primaquine, Malarid) glucose-6-phosphate dehydrogenase These drugs are used for the eradication of deficiency (G6PD). All travellers must liver stage malaria parasites of P. vivax and be tested for G6PD levels before this P. ovale to prevent future malaria attacks. drug is prescribed or administered. It Tafenoquine and primaquine can also be used is contraindicated during pregnancy. as prophylaxis for persons on short term travel. Breastfeeding children must be tested for They are contraindicated for persons with G6PD deficiency before the mother can glucose-6-phosphate dehydrogenase (G6PD) take the medication. This drug is also deficiency. They are also contraindicated during contraindicated for persons under pregnancy. Patients (including breastfeeding 18 years of age and those with a history children) must be tested for G6PD before of psychiatric disorder or ongoing these drugs can be prescribed or administered. psychotic symptoms. Tafenoquine is also contraindicated for treatment (prevention of relapse) for persons 6. Primaquine under 16 years of age and should be used with This drug is used for prophylaxis for caution for persons with a history of psychiatric persons on short term travel to areas disorder or ongoing psychotic symptoms. with mostly P. vivax malaria or as an Tafenoquine should be co-administered with alternative drug regimen for travellers chloroquine or hydroxychloroquine for treatment who cannot take other antimalarial drugs. of P. vivax malaria, not plus It is also used for treatment to eradicate Piperaquine ­(DHA-PQP). P. vivax and P. ovale parasites in the liver Note: Tafenoquine is only available in the USA stage to prevent future malaria attacks. and Australia.

CAUTION: Primaquine may cause Quinine and nausea and abdominal pain. Take tablets Quinine sulfate (brand name: Qualaquin and with food. others), Quinine dihydrochloride (brand name: Quininject and others) and Quinidine CONTRAINDICATIONS: This drug gluconate (brand name: Quinaglute and others) is contraindicated for persons with are drugs derived from the bark and glucose-6-phosphate dehydrogenase used in combination with other antimalarial deficiency (G6PD). All travellers must drugs for the treatment of severe multidrug be tested for G6PD levels before this resistant P. falciparum malaria when drug is prescribed or administered. It is Artemisinin ­Combination Therapies (ACTs) also contraindicated during pregnancy. are not available. They must be administered Breastfeeding children must be tested for under close medical supervision due to G6PD deficiency before the mother can potential side effects.Do not use for take the medication. ­malaria prophylaxis.

IAMAT Whitepaper Files 10 MALARIA DRUGS AVAILABLE ABROAD -Pyrimethamine (brand name: Maloprim) Travellers to malarious areas will encounter This alternative to sulfadoxine-pyrimethamine fellow travellers who are on a different (Fansidar) should not be used for malaria malaria suppressive regimen. It is highly prophylaxis. recommended that you continue with the medication prescribed for you by your doctor (brand name: Halfan) or travel health specialist and never switch to Halofantrine is used for the treatment of any medication offered as a “better choice” by chloroquine-resistant and sulfadoxine- other travellers. pyrimethamine resistant P. falciparum malaria mostly in Africa. Not recommended for The following is a short discussion of some prophylaxis or treatment since this drug medications used abroad. causes severe adverse effects (including death) in persons with or without pre-existing cardiac If you have fever and flu-like Artemisinin Combination Therapies conditions. symptoms appearing 7 days, (ACT) weeks or up to several months Artemisinin (Qinghaosu) and its derivatives Proguanil (brand name: Paludrine) Artemether, Artesunate, Dihydroartemisinin Although proguanil hydrochloride is the oldest after your trip, don’t forget to are isolates of the Chinese medicinal plant and safest of malaria suppressants, P. falciparum tell your doctor that you were Qinghao () also known as parasites have become so highly resistant to it in a malarious area. Early sweet wormwood. These drugs are used in that its usefulness is seriously compromised in all diagnosis is essential combination with other antimalarial drugs malarious areas. Studies have shown that using for successful treatment. for the treatment of severe malaria. Do not use proguanil is less effective againstP. vivax, P. ovale, for malaria prophylaxis. P. malariae, P. knowlesi malaria than chloroquine. • Artemether-lumefantrine Proguanil should not be used on its own as (brand names: Coartem, Riamet) a malaria suppressant. • Artesunate + (brand name: Coarsucam) Sulfadoxine-pyrimethamine • Artesunate + Mefloquine (brand name: Fansidar) hydrochloride There is widespread resistance ofP. falciparum (brand name: Mefliam Plus malaria parasites against this drug. It should not and others) be used for prophylaxis as potential serious side • Artesunate + Sulfadoxine- effects may develop after multiple doses.­ pyrimethamine (brand names: Sulfadoxine-pyrimethamine is used in combination­ Artescope, Supysunate and others) with artesunate as an Artemisinin Combination • Dihydroartemisinin + Piperaquine Therapy (ACT) for treatment of severe malaria. (brand name: Artequick)

Amodiaquine Dihydrochloride EMERGENCY SELF TREATMENT (EST) (brand names: Camoquin, Flavoquine, ­others; generics) Travellers should take an Emergency Self Belonging to the same chemical family as Treatment regimen if: Fever, chills, and flu-like chloroquine (4-aminoquinoline), this symptoms occur in a remote area where qualified drug offers similar protection to chloroquine, medical attention cannot be reached within but experience has shown that it causes 24 hours; using a prophylactic regimen that is not serious side effects such as hepatitis and optimal due to resistance; or antimalarial prophy- ­agranulocytosis. Amodiaquine is used in lactics cannot be taken for medical reasons. ­combination with artesunate as an Artemisinin Combination Therapy (ACT) Discuss Emergency Self Treatment options with for the treatment of severe ­malaria. your physician before your trip and ensure that Do not use for malaria prophylaxis. you get specific written instructions, including indications, dosages, and information on side ef- Chloroquine-Proguanil fects. After taking Emergency Self Treatment, seek (brand name: Savarine) medical care for evaluation as soon as­ possible. This combination drug eliminates the difficulty of taking chloroquine on a Atovaquone-proguanil (Malarone) or artemether- weekly basis and proguanil on a daily lumefantrine (Coartem) are the drugs of choice basis. However, its usefulness is for EST for both adults and children, however, compromised by the high resistance of they both have contraindications. Also note that P. falciparum malaria to both chloroquine the Emergency Self Treament cannot be the and proguanil. same as your prophylactic regimen. See table

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.

Tablet base + Number of Antimalarial Drug1 Brand Name Weight Frequency salt content tablets2

Atovaquone- Malarone 62.5 mg Atovaquone < 5kg / 11lb ContraindicatedStart: 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 5 mg / kg Measure dose according to body Calculated up to Start: 1 week before phosphate or sulfate others; (8.3 mg / kg salt) weight a maximum of During: Once a week Dosages may differ generics 300 mg base / week After: 4 weeks after leaving slightly among manufacturers Hydroxychloro- Plaquenil and 5 mg / kg Measure dose according to body Calculated up to Start: 1 week before quine sulfate others; (6.5 mg / kg salt) weight a maximum of During: Once a week Dosages may differ generics 310 mg base / week After: 4 weeks after leaving slightly among manufacturers

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 Contraindicated Start: 1-2 days before Dosages may differ and others; During: Once a week > 8 years Calculated up to slightly among generics After: 4 weeks after leaving Measure dose according to body a maximum of manufacturers weight 100 mg / day Me oquine Lariam and 4.6 mg < 9 kg / 20 lb Calculated Start: 1-2 weeks hydrochloride others; (5 mg salt) Measure dose according to body according to 4.6 mg During: Once a week generics weight base / kg / week After: 4 weeks after leaving > 9-19 kg / 20-42 lb ¼ > 19-30 kg / 42-66 lb ½ > 30-45 kg / 66-99 lb ¾ > 45 kg / 99 lb 1 Primaquine N/A 0.5 mg Measure dose according to body Calculated up to Start: 1-2 days phosphate4 (0.8 mg salt) weight a maximum of During: Daily 30 mg base / da y 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 8. Talk to your healthcare provider to choose the best regimen for 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 ‘Emergency Self Treatment – Adult and Pediatric P. falciparum, P. malariae, P. knowlesi, Dosages’ on page 14. or a relapse of P. vivax or P. ovale malaria. For this reason, people who recently travelled to or lived in a ­malarious area cannot donate blood for ANTIMALARIAL REGIMENS 1 to 3 years, depending on the length of FOR CHILDREN their stay.

Parents should keep malaria medications out THE SEARCH FOR THE KILLER of reach of children since misuse can result in death. Breastfed infants are not protected by their mother’s prophylactic regimen, but must 1880 – Constantine, Algeria: The end of be given their own dosages according to their a superstition weight. Children should always sleep under a Thousands of years of superstition attributing bed net. Anti-mosquito repellents are safe but malaria (L.: mala aria = bad air) to some kind of should be applied sparingly to the exposed parts airborne poison is overthrown by French army of the body, avoiding the hands and face entirely. surgeon, Charles Louis Alphonse Laveran. He identified the malaria parasite for the first School age children are very vulnerable to time while microscopically examining the fresh malaria. Children on holidays to visit parents blood of a patient infected with P. falciparum working in the tropics should be watched to malaria. But it would take six years for the ensure that they continue taking the ­suppressive medical profession to recognize the importance regimen after their return to school. Their of Laveran’s discovery, as it was widely believed guardians must be warned that fever and flu-like that malaria was caused by bacteria instead symptoms appearing 7 days, weeks or up to of parasites. several months after their return may signify 1886 – Pavia, Italy Fig. 5 Patrick Manson, Scottish physician a malaria breakthrough and early diagnosis is who demonstrated how mosquitoes play imperative for successful treatment. See table, Camillo Golgi definitively identified two -hu a role in the spread of parasites. ‘Pediatric Malaria Chemoprophylaxis Dosages’ man malaria parasites: Plasmodium vivax and Image source: London School of Hygiene & on page 12. Plasmodium malariae. He described the asexual (painting by H.H. Salomon) multiplication of the parasite in the red corpuscle of the blood and demonstrated its relationship to ANTIMALARIAL REGIMENS DURING the periodic appearance of the fever characteristic PREGNANCY of malaria.

Since all drugs taken by a pregnant woman reach 1889 – Rome, Italy her unborn child, it is never advisable to take any Three years later, Ettore Marchiafava medications if not absolutely necessary. However, differentiated a third species of human malaria if travel to a malarious region cannot be avoided, parasites, Plasmodium falciparum, named for the risk of miscarriage or premature delivery as the crescent shape of the sexual form of the a result of contracting malaria far outweighs the parasite (L.: falx =sickle; parere =to bring forth). risk of possible side effects from antimalarial However, the mechanism of transmission of the drugs. Chloroquine is safe during pregnancy disease was still a mystery. in doses used for malaria prophylaxis. Mefloquine hydrochloride can be used during 1894 – London: the second and third trimesters, but studies Patrick Manson, The grey eminence suggest that it is also safe during the first behind malaria research trimester. Atovaquone-proguanil, doxycycline, Patrick Manson, an eminent Scottish physician, tafenoquine, and primaquine are contraindicated had discovered that mosquitoes could suck during pregnancy. up the microscopic threadlike worms from the blood of patients infected with a disease called filariasis. He believed that mosquitoes WHEN YOU RETURN… might also draw out the malaria parasites from human blood, and that transmission would Back home, you may experience flu-like ­occur by ingestion of water contaminated symptoms such as a general malaise, headache, by infected mosquitoes. and some fever. These can be signs of a malaria infection. Symptoms may appear 7 days, weeks, 1898 – Calcutta: or up to several months after your trip. Contact , “It is the bite” your doctor and tell them where you have been – Manson, realizing he could never experiment even if the fever develops months after you have enough in England to prove his theory, convinced returned. These signs could be a first attack of Ronald Ross, a British army surgeon who visited

How to Protect Yourself Against Malaria 13

EMERGENCY SELF 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 8. Talk to your healthcare provider to choose the best regimen for you or your child.

him in 1894, to carry on this research. 1898 – Baltimore Together they planned a series of experiments Later in the same year William George which Ross carried out upon his return to McCallum, a Canadian pathologist also India. Ross began by raising Culex and Aedes working with birds, was able to interpret and larvae, and let the adult mosquitoes feed describe the fertilization process of the parasite on patients with malaria. Then he let these taking place in the gut of the mosquito. mosquitoes bite volunteers, but with no result — since he wasn’t an entomologist he 1886-1899 – Rome: The magnificent four wasn’t aware that he was ­using the wrong Simultaneously, a group of Italians were working species of mosquito. After several unsuccessful to solve the puzzle of the transmission of malaria experiments, in April 1897, while working in in humans. From 1886 to 1896, Giuseppe Ootacamund (Ooty) near ­Madras, he saw for Bastianelli, Amico Bignami, Angelo Celli and the first time the dapple-wingedAnopheles , Giovanni Battista Grassi had been actively and started to experiment with this species. investigating the life cycle of the human malaria On August 20, 1897, looking through his parasites and making accurate descriptions of the microscope at the gut of mosquitoes which lesions produced by the parasites in the different had fed on a patient with malaria, he saw organs of the body. A breakthrough came with for the first time the human malaria parasite the observations by Grassi, a physician with a growing in the gut of Anopheles. keen interest in zoology, particularly mosquitoes. He noticed that when malaria was present there Unwillingly he had to interrupt his was always a large population of Anopheles, investigations, and when he moved to his while in areas of large Culex populations there new post in Calcutta he started working was no malaria. with the avian malaria parasites, which are transmitted by a Culex species. He proved From the Campagna Romana near Rome that the spindle-shaped malaria organisms he collected Anopheles mosquitoes which his (sporozoites), freed by the rupturing of colleague Bignami allowed to feed on a volunteer the fertilized eggs, migrate from the gut of patient from the Santo Spirito Hospital, the mosquito to its salivary glands, to be a few steps away from St. Peter’s Basilica. injected into the victim when the insect On November 1, 1898, the patient, Abele Sola, bites. As such, Ross is credited with the developed the classic symptoms of P. falciparum discovery that malaria is transmitted by the malaria. Together with Bastianelli and Celli, mosquito’s bite. they were able to reproduce malaria infections

IAMAT Whitepaper Files 14 in other volunteers and prove that only 1960s and 1970s, research focused on finding the Anopheles mosquito, and no other species, new antimalarial drugs partly spurred by US transmits malaria in humans. soldiers getting ill and dying from malaria in the Vietnam War. Much of the antimalarial drug 1936 – Rome: Giulio Raffaele research at that time was done by scientists at the discovers the liver cycle Walter Reed Army Institute of Research. While It was soon discovered that a link was miss- mefloquine hydrochloride and the tetracycline ing in the knowledge of the life cycle of the group of antibiotics were discovered to be malaria parasite. Still unexplained was the time ­effective antimalarials, they were not available elapsed between the introduction of the parasites to travellers. through the bite of the mosquito and the appearance of the symptoms of malaria. The 1980s saw the introduction of effective Giulio Raffaele discovered while working with antimalarial drugs in the marketplace such as birds that malaria parasites entering the host first sulfadoxine-pyrimethamine (Fansidar) and undergo a cycle of transformation within the halofantrine (Halfan). These drugs however, blood-forming cells of the liver. have serious side effects and are no longer recommended. The antimalarial medications 1948 – London: The final touch recommended for use today are relatively new. Now the road was open for British researchers­ In the US, mefloquine hydrochloride was Colonel H.E. Shortt and Percy Cyril Claude licensed in 1989, doxycycline was approved as an

Fig. 6 Percy Cyril Claude Garnham, Garnham to demonstrate the liver cycle of antimalarial in 1994, and atovaquone-proguanil who demonstrated the liver cycle of malaria the malaria parasite in humans. Following a in 2000. Also during this time, P. knowlesi was parasites in humans. period of extensive trials on monkeys, in 1948 a positively identified as the 5th malaria parasite Image source: Wellcome Collection human volunteer — a Mr. Howard — was bitten responsible for infecting humans in Southeast during three days by nearly eight hundred Anoph- Asia, being previously mistaken for P. malariae eles infected with Plasmodium falciparum. On the and P. falciparum. fifth day, a surgeon removed a small piece of tissue from his liver which, examined under the micro- Currently, there are several intensive efforts to scope, demonstrated the growth of the parasites in develop a vaccine against malaria. RTS,S / AS01 the liver cells. The last mystery of the life cycle of or Mosquirix is the first vaccine almost ready to the malaria parasite was finally unraveled. be marketed – it is undergoing pilot testing now. Clinical trials have shown that it provides partial protection against P. falciparum, the fatal form THE RACE AGAINST of malaria. Another vaccine, PfSPZ, has been AND shown to provide up to 100% protection against HOPE FOR A VACCINE P. falciparum in laboratory testing. It is now moving to testing to assess its effec- In the late 1950s there were reports of tiveness in the field. It is these types of initiatives P. falciparum resistance to choloroquine, the first that are key to successfully prevent, control, and line drug used to prevent malaria. During the eventually eradicate malaria.

Sources: CATMAT, CDC, DTG, WHO, 2019 World Malaria Report, , Hunter’s Tropical Medicine and Emerging Infectious Diseases, 9th ed., Tropical Infectious Diseases, 3rd ed., Prof. DDr. Martin Haditsch.

© Copyright 2020 IAMAT.

How to Protect Yourself Against Malaria 15

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