Summary of Practical Advice
Malaria can be a very dangerous disease. It can progress very rapidly, so it is important to treat as early as possible.
The general advice to take prophylaxis usually comes from travel clinics advising people who will be in malarial areas for a week or a month. For people living in these areas, years of prophylaxis in not a good idea. No prophylaxis works 100% and may be as low as 60% because of compliance.
You should always carry an active treatment, even if using prophylaxis. Most long-term travellers and people living in malarial areas take no prophylaxis and treat ASAP whenever they MIGHT have malaria symptoms. They never leave the house without Coartem. Many have had malaria 15-20 times.
Routine: normal mosquito prevention: long pants, socks and tops, and repellent in evening and night, mosquito net.
Prophylaxis: No prophylaxis works 100%, irrelevant of the drug used. Some only use anti malarias in small kids because you can’t tell you how they feel.
Usually expensive in Western countries, South Africa and Botswana (they are very low risk areas). From Victoria Falls north and high-risk malaria areas all prophylaxis and treatment drugs are available at any pharmacy over the counter or on the side of the road.
1. Doxycycline. Advantage is that it can be started only a few days before needed. Taken daily. Needs to be taken for 4 weeks after you have left an at-risk area. It is the typical go to drug for backpackers as it is the cheapest. Contraindicated in children under 8 and in pregnancy.
Side effects. Nausea, sun sensitivity.
2. Mefloquine (Lariam/Vibramycin). Start two weeks before entering an area with malaria and for 4 weeks after leaving. Take once a week with a full glass of water and food. May be better for long trips as taken once per week. Possibly the least effective.
Side effects. With a reputation for causing vivid dreams, the mere mention of the drug often gets a negative reaction from fellow travellers. Dizziness, headache, vivid dreams, nightmares, visual and auditory hallucinations, anxiety, depression, unusual behavior, insomnia, and suicidal ideations may occur in as many as 25% but only about 11-17% are incapacitated to some degree. Safe in pregnancy.
3. Malarone or Malanil (Atovaquone/Proguanil). Start 1-2 days before arrival. Take daily and for 7 days after risk.
Side effects. Well tolerated with uncommon side effects. Suitable for children. It can’t be taken for more than 90 days.
Cost. Very expensive in Westen countries. It is easy to find over the counter in less developed countries more cheaply. The malarone generic, Mozitech, is relatively cheap and available without prescription at pharmacies in South Africa.
Treatment: Even if using prophylaxis, you should always carry an active treatment. Most long-term travelers take no prophylaxis and treat ASAP whenever they MIGHT have malaria symptoms. If you wake up with a bad hang over and it doesn’t go away, take the treatment as it is most likely malaria. The longer you don’t treat, the worse it will get and often rapidly. If you catch it early, it’s not much worse than a cold. If in doubt take Coartem anyway. No harm done. No side effects. Just wasted $10, worst case scenario. Don’t drink alcohol for at least 2 weeks or it may come back.
1. Artemether/Lumefantrine (sold under the trade name Coartem) is a combination of the two drugs taken orally. It is an effective and well-tolerated malaria treatment, providing high cure rates even in areas of multi-drug resistance. It is not used to prevent malaria. It is not available as a generic medication. Cost north of Botswana $4-10 (all same drug in same packages). It is very difficult to get it in South Africa without a prescription and only given there after you are proven to be malaria positive.
Side effects: muscle and joint pains, fever, loss of appetite, and headache. It is safe for use in pregnancy.
Dosage. The tablets are Artemether 80mg and Lumefantrene 480mg – each equal to 4 tablets of the older formulation. Adults and children 2 months of age and older weighing 35 kilograms or more at first symptoms: 1 tablet, then 1 in 8 hours and then 1 twice a day for two days – ie. 6 tablets for the total course. Cost at a pharmacy in N’djamena 450 CFA for each course. Food, in particular fat, enhances the absorption of both artemether and lumefantrine, take with food as food is tolerated.
2. Malarone. 4 tablets once/day X 3 days.
PROPHYLAXIS
Different preventative drugs can and are recommended in various parts of the world due to prevalence and resistance, but there are essentially five core malaria prophylaxis drugs. Typically you will be recommended Malarone unless travelling over 90 days. All have pros and cons, but with some treatments pros come at high costs or other side effects.
It needs to be emphasized that any medication listed here is vastly superior to not taking anything, and hoping for the best. Some Malaria strains are deadly and kill fast (90% of malaria deaths are children under the age of five, mainly in sub-Saharan Africa) – especially when you haven’t been exposed to malaria since birth.
The main five anti-malarials are all easily absorbed provided you don’t have any stomach problem like diarrhoea/vomiting. Lastly, taking the medications faithfully and not stopping until 4 weeks (1 in the case of Malarone) after exiting the malarial zone is incredibly important and cannot be over emphasised.
Again: it is quite possible to visit a country with a malarial risk and never get anywhere near that risk area (Cambodia, Bolivia, Thailand, South Africa, Iran, Namibia, China, Burma, Nepal – there are loads of them!).
1. Chloroquine [which is often combined with Proguanil].
Cheaper and more available as a generic. Started only a few days before needed and needs to be taken for 4 weeks after you have left an at risk area (so to cover yourself for 1 day would need a 4 week + 1 day course). Taken daily.
2. Doxycycline.
Started only a few days before needed and needs to be taken for 4 weeks after you have left an at risk area (so to cover yourself for 1 day would need a 4 week + 1 day course). Taken daily. It is the typical go to drug for backpackers as it is the cheapest and available at low cost in larger Asia and African cities (obviously buy from a reputable looking pharmacy and get advice on usage / side effects. Doxycycline is irritating so after taking it, one should maintain an upright position (don’t go to sleep) for an hour to decrease the chance that it will reflux back up. Doxycycline is can also be used to treat traveller’s diarrhoea (and acne), so using it daily to protect against malaria will also help to prevent traveller’s diarrhoea… or so the theory goes. This is because it is an antibiotic – this also means that if you are on the contraceptive pill then you will have to take extra precautions during sex. It also increases photosensitivity so use sun block.
3. Mefloquine (Lariam/Vibramycin).
Mefloquine is useful as a first or second line drug for the prevention of malaria in all areas except for those where parasites may have resistance to multiple drugs. It is typically taken for one to two weeks before entering an area with malaria (Doxycycline and atovaquone/proguanil provide protection within one to two days and may be better tolerated). Since compliance is always an issue, Mefloquine is easier because it is only taken once a week and has a long half life. It should be taken with a full glass of water and with food.
Mefloquine is used as a treatment for chloroquine-sensitive or resistant Plasmodium falciparum malaria, and is deemed a reasonable alternative for uncomplicated chloroquine-resistant Plasmodium vivax malaria. It is not recommended for severe malaria infections, particularly infections from P. falciparum, which should be treated with intravenous antimalarials. Mefloquine does not eliminate parasites in the liver phase of the disease, and people with P. vivax malaria should be treated with a second drug that is effective for the liver phase, such as primaquine.
Adverse effects. With a reputation for causing vivid dreams, the mere mention of the drug seems to inevitably get a negative reaction from fellow travellers. But not everyone reacts badly. Dizziness, headache, vivid dreams, nightmares, visual and auditory hallucinations, anxiety, depression, unusual behavior, insomnia, and suicidal ideations may occur in as many as 25% of people taking it but when some measure of subjective severity is applied to the rating of adverse events, about 11-17% of travellers are incapacitated to some degree.
Mefloquine is contraindicated in those with a previous history of seizures or a recent history of psychiatric disorders. Severe side effects requiring hospitalization are rare, about 1 in 10,000.
In pregnant travelers, it appears to pose minimal risk to the fetus. It is widely used for the treatment of malaria in pregnancy.
4. Primaquine.
Taken daily and needs only be taken for 7 days after risk. Like Doxycycline is easy to find over the counter abroad cheaply in less developed countries, but like Doxycycline has a reputation of causing upset stomachs.
5. Malarone or Malanil (Atovaquone/Proguanil)
It is taken daily and needs only be taken for 7 days after risk. Malarone is suitable for children and well tolerated with side effects uncommon. It can’t be taken for more than 90 days, which is just as well as it is pretty [read: very] expensive. Because of the cost, buy only for where you really need and consider alternatives if on a budget.
The best drug to carry with you for emergency treatment – with first symptoms empirically start Malarone 4 tablets once/day X 3 days.
AREAS AT RISK FOR MALARIA
The blanket answer is that a ‘risk’ exists in almost all countries in Asia (below Mongolia/Kazakhstan), Africa and Latin America with the notable exceptions of Libya, Chile, Tunisia and Uruguay. If you want to see ‘the map’ take a look at the somewhat paranoid CDC Malaria page. However, this ‘risk’ really does vary and to colour an entire country red due to a sometimes localised and seasonal risk is kind of missing the mark. Whereas a serious risk may exist in a pocket of a country (say Thailand), there are many, many other regions where very little or no risk exists. So research carefully.
Take for example Nepal; Katmandu and a normal trekking circuit poses no risk from malaria, but due to a risk in the lower lying parts of the country the whole country often gets a warning. The same can be said for Latin America outside of the Amazon basin, which is often bypassed by travellers or visited for only a few days.
Travel to rural areas always involves more potential exposure to malaria than in the larger cities. For example, the capital cities of Manila, Bangkok and Colombo are essentially malaria-free. However, as noted, malaria is present in many other places (especially rural areas) of these countries. By contrast in West Africa, Ghana and Nigeria have malaria throughout the entire country. However, the risk will always be lower in the larger cities where independent travellers tend to focus their travels since these act as the main transport hubs. It is really worth mentioning that there is a ton of misinformation floating around on the net and among backpackers on the road.
Of the 3500 types of mosquito (20 more are discovered every year) only a few carry killer diseases such as Malaria. The female (it would have to be!) Anopheles malarial mosquito bites mainly between 2300 and 0400 at night and this is when it is particularly important not to get bitten. Also worth mentioning is the Aedes mosquito (spreading dengue and yellow fever) bites during the day. Both feed at ground level so cover up your ankles with a little repellent. No Malaria medication protects you 100%, and the best thing you can and should always do is not get bitten, which is a different topic.
On an African trip (where most of this information applies mainly to – don’t take it as seriously if visiting South America (outside the Amazon interior), South Africa or Asia) – you might meet several travellers who have contracted malaria even when taking prophylaxis, which goes a long way to illustrate the importance of covering up and not getting bitten. Individuals normally recovered with no problems (after some time out) and in a few cases, were not even aware that they were infected until taking a malaria test (prick on the finger blood test available cheaply in sub-Saharan Africa). Even taking malaria tablets meticulously and doing everything possible to avoid being bitten, it is possible to get a strain resistant to prophylactic drugs. Untreated malaria is very dangerous, but responds well to prompt treatment.
Once infected, malaria can ‘live in your system for a while until it decides to attack’. It is not preferable to attempt self-diagnosis (as tests are easily and cheaply available in East/West Africa and if you have a fever get tested soon).
While travelling long-term in Africa perhaps the most sensible precaution you can take on top of avoiding bites is to purchase on your arrival ‘Arinate’ (Artesunate 100mg) or similar. This comes in a kit of six pills available from any pharmacy, priced at about US$5. At any sign of a fever (symptoms can take a week or more to show – unfortunately your weekly Lariam can knock them continually on the head) and if medical advice is unavailable, you can start self treatment. Still aim to get tested as soon as possible: you may have typhoid. Having such treatment available not only allows for peace of mind, but is useful should you enter a risk area when it is not practical to take prophylactics, i.e. you are only there for a few days (Etosha NP, Kruger NP, jungle areas of South America being good examples).
Remember, it’s always a little dangerous to assume that your choice of malaria prophylaxis is available in the country you’ll be visiting, but most third-world countries stock at least chloroquine and normally doxycycline (certainly the major cities of Africa and Asia do), but Malarone will be harder to find. Quinine is normally available too, but is not recommended. For the record a spot check in Kampala, Dar es Salaam and Bangkok in 2015 found with ease (over the counter) Mefloquine (x 4, priced around US$10-15) and Doxycycline (x 10, priced US$1-3).
As a footnote, many feel the focus on Malaria is misdirected, Dengue fever is common in regions such as SE Asia (its geographic spread is similar to that of malaria). The carrying mosquitoes of Dengue live indoors and bite during the day, when most are least vigilant. Dengue can be every bit as dangerous as malaria.
However there’s no need for paranoia – a quick squirt of repellent on the ankles or covering up is a simple, easy and effective measure. In contrast to malaria, which is more common in rural areas, it is larger cities that present the greater risk from Dengue fever.
WHY BOTHER GOING to ALL THIS HASSEL/COST?
Once in a while, you will meet travellers who refuse to take prophylaxis, either because they want to acquire resistance to malaria or else because they believe there is a homeopathic cure for this killer disease. Unfortunately (especially in Africa), they think they are being very clever. But travellers can’t acquire effective resistance to malaria and if anyone knows of a homeopathic cure, please let us [and the medical profession] know. It is personal choice what you do but, especially in East/West Africa not using a prophylactic drug when in a high risk areas for long periods is risking your life in a manner both unnecessarily (the drugs are cheap in Africa/Asia) and foolishly. Pills aside the most important thing is to always sleep under a treated net when in high risk regions.
PROTECTION AGAINST MOSQUITOES, TICKS & OTHER ARTHROPODS
Vaccines or chemoprophylactic drugs are available to protect against some vectorborne diseases such as yellow fever, Japanese encephalitis, and malaria; however, travel health practitioners should advise travellers to use repellents and other general protective measures against biting arthropods. The effectiveness of malaria chemoprophylaxis is variable, depending on patterns of drug resistance, bioavailability, and compliance with medication, and no similar preventive measures exist for other mosquito borne diseases such as dengue, chikungunya, Zika, and West Nile encephalitis or tick borne diseases such as Lyme borreliosis, tick borne encephalitis, and relapsing fever.
GENERAL PROTECTIVE MEASURES
Avoid outbreaks. To the extent possible, travellers should avoid known foci of epidemic disease transmission. The CDC Travellers’ Health website provides updates on regional disease transmission patterns and outbreaks (www.cdc.gov/travel).
Be aware of peak exposure times and places. Exposure to arthropod bites may be reduced if travellers modify their patterns or locations of activity. Although mosquitoes may bite at any time of day, peak biting activity for vectors of some diseases (such as dengue and chikungunya) is during daylight hours. Vectors of other diseases (such as malaria) are most active in twilight periods (dawn and dusk) or in the evening after dark. Avoiding the outdoors or taking preventive actions (such as using repellent) during peak biting hours may reduce risk. Place also matters: ticks and chiggers are often found in grasses, woodlands, or other vegetated areas. Local health officials or guides may be able to point out areas with increased arthropod activity.
Wear appropriate clothing. Travellers can minimize areas of exposed skin by wearing long-sleeved shirts, long pants, boots, and hats. Tucking in shirts, tucking pants into socks, and wearing closed shoes instead of sandals may reduce risk. Repellents or insecticides, such as permethrin, can be applied to clothing and gear for added protection.
Check for ticks. Travellers should inspect themselves and their clothing for ticks during outdoor activity and at the end of the day. Prompt removal of attached ticks can prevent some infections. Showering within 2 hours of being in a tick-infested area reduces the risk of some tick borne diseases.
Bed nets. When accommodations are not adequately screened or air-conditioned, bed nets are essential in providing protection and reducing discomfort caused by biting insects. If bed nets do not reach the floor, they should be tucked under mattresses. Bed nets are most effective when they are treated with a pyrethroid insecticide. Pretreated, long-lasting bed nets can be purchased before traveling, or nets can be treated after purchase. Effective, treated nets may also be available in destination countries. Nets treated with a pyrethroid insecticide will be effective for several months if they are not washed. Long-lasting pretreated nets may be effective for much longer.
Insecticides and spatial repellents. More spatial repellent products are becoming commercially available. These products, containing active ingredients such as metofluthrin and allethrin, augment aerosol insecticide sprays, vaporizing mats, and mosquito coils that have been available for some time. Such products can help to clear rooms or areas of mosquitoes (spray aerosols) or repel mosquitoes from a circumscribed area (coils, spatial repellents). Although many of these products appear to have repellent or insecticidal activity under particular conditions, they have not yet been adequately evaluated in peer-reviewed studies for their efficacy in preventing vector borne disease. Travellers should supplement the use of these products with repellent on skin or clothing and using bed nets in areas where vector borne diseases are a risk or biting arthropods are noted. Since some products available internationally may contain pesticides that are not registered in the United States, it may be preferable for travellers to bring their own. Insecticides and repellent products should always be used with caution, avoiding direct inhalation of spray or smoke.
Optimum protection can be provided by applying the repellents described in the following sections to clothing and to exposed skin.
REPELLENTS FOR USE ON SKIN AND CLOTHING
Products containing the following active ingredients typically provide reasonably long-lasting protection:
• DEET (chemical name: N,N-diethyl-m-tolua-mide or N,N-diethyl-3-methyl-benzamide). Products containing DEET include, but are not limited to, Off!, Cutter, Sawyer, and Ultrathon.
• Skin So Soft. This Avon product generally available only online or from a personal sales rep is used by the British Army and is highly recommended. It is clear and goes on easily with a nice scent.
• Picaridin (KBR 3023 [Bayrepel] and icaridin outside the United States; chemical name: 2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester). Products containing picaridin include, but are not limited to, Cutter Advanced, Skin So Soft Bug Guard Plus, and Autan (outside the United States).
• Oil of lemon eucalyptus (OLE) or PMD (chemical name: para-menthane-3,8-diol), the synthesized version of OLE. Products containing OLE and PMD include, but are not limited to, Repel and Off! Botanicals. “Pure” oil of lemon eucalyptus (essential oil not formulated as a repellent) is not recommended; it has not undergone similar, validated testing for safety and efficacy, is not registered with EPA as an insect repellent, and is not covered by this recommendation.
• IR3535 (chemical name: 3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester). Products containing IR3535 include, but are not limited to, Skin So Soft Bug Guard Plus Expedition and SkinSmart.
EPA characterizes the active ingredients DEET and picaridin as “conventional repellents” and OLE, PMD, and IR3535 as “biopesticide repellents,” which are either derived from or are synthetic versions of natural materials.
Repellent Efficacyy
Published data indicate that repellent efficacy and duration of protection vary considerably among products and among mosquito and tick species. Product efficacy and duration of protection are also markedly affected by ambient temperature, level of activity, amount of perspiration, exposure to water, abrasive removal, and other factors. In general, higher concentrations of active ingredient provide longer duration of protection, regardless of the active ingredient. Products with <10% active ingredient may offer only limited protection, often 1–2 hours. Products that offer sustained-release or controlled-release (microencapsulated) formulations, even with lower active ingredient concentrations, may provide longer protection times. Studies suggest that concentrations of DEET above approximately 50% do not offer a marked increase in protection time against mosquitoes; DEET efficacy tends to plateau at a concentration of approximately 50%. CDC recommends using products with ≥20% DEET on exposed skin to reduce biting by ticks that may spread disease.
Recommendations are based on peer-reviewed journal articles and scientific studies and data submitted to regulatory agencies. People may experience some variation in protection from different products. Regardless of what product is used, if travellers start to get insect bites they should reapply the repellent according to the label instructions, try a different product, or, if possible, leave the area with biting insects.
Ideally, repellents should be purchased before traveling and can be found online or in hardware stores, drug stores, and supermarkets. A wide variety of repellents can be found in camping, sporting goods, and military surplus stores. When purchasing repellents overseas, look for the active ingredients specified above on the product labels; some names of products available internationally have been specified in the list above.
Repellents and Sunscreen
Repellents that are applied according to label instructions may be used with sunscreen with no reduction in repellent activity; however, limited data show a one-third decrease in the sun protection factor (SPF) of sunscreens when DEET-containing insect repellents are used after a sunscreen is applied. Products that combine sunscreen and repellent are not recommended, because sunscreen may need to be reapplied more often and in larger amounts than needed for the repellent component to provide protection from biting insects. In general, the recommendation is to use separate products, applying sunscreen first and then apply the repellent. Due to the decrease in SPF when using a DEET-containing insect repellent after applying sunscreen, travellers may need to reapply the sunscreen more frequently.
Repellents and Insecticides for Use on Clothing
Clothing, hats, shoes, bed nets, jackets, and camping gear can be treated with permethrin for added protection. Products such as Permanone and Sawyer, Permethrin, Repel, and Ultrathon Permethrin Clothing Treatment are registered with EPA specifically for use by consumers to treat clothing and gear. Alternatively, clothing pretreated with permethrin is commercially available, marketed to consumers in the United States as Insect Shield, BugsAway, or Insect Blocker.
Permethrin is a highly effective insecticide-acaricide and repellent. Permethrin-treated clothing repels and kills ticks, chiggers, mosquitoes, and other biting and nuisance arthropods. Clothing and other items must be treated 24–48 hours in advance of travel to allow them to dry. As with all pesticides, follow the label instructions when using permethrin clothing treatments.
Permethrin-treated materials retain repellency or insecticidal activity after repeated laundering but should be retreated, as described on the product label, to provide continued protection. Clothing that is treated before purchase is labeled for efficacy through 70 launderings. Clothing treated with the other repellent products described above (such as DEET) provides protection from biting arthropods but will not last through washing and will require more frequent reapplications.
Precautions when Using Insect Repellents
Travellers should take the following precautions:
• Apply repellents only to exposed skin or clothing, as directed on the product label. Do not apply repellents under clothing.
• Never use repellents over cuts, wounds, or irritated skin.
• When using sprays, do not spray directly on face—spray on hands first and then apply to face. Do not apply repellents to eyes or mouth, and apply sparingly around ears.
• Wash hands after application to avoid accidental exposure to eyes or ingestion.
• Children should not handle repellents. Instead, adults should apply repellents to their own hands first, and then gently spread on the child’s exposed skin. Avoid applying directly to children’s hands. After returning indoors, wash your child’s treated skin and clothing with soap and water or give the child a bath.
• Use just enough repellent to cover exposed skin or clothing. Heavy application and saturation are generally unnecessary for effectiveness. If biting insects do not respond to a thin film of repellent, apply a bit more.
• After returning indoors, wash repellent-treated skin with soap and water or bathe. Wash treated clothing before wearing it again. This precaution may vary with different repellents—check the product label.
If a traveler experiences a rash or other reaction, such as itching or swelling, from an insect repellent, the repellent should be washed off with mild soap and water and its use discontinued. If a severe reaction has occurred, a local poison-control center should be called for further guidance, if feasible. Travellers seeking health care because of the repellent should take the repellent to the doctor’s office and show the doctor. Permethrin should never be applied to skin but only to clothing, bed nets, or other fabrics as directed on the product label.
Children and Pregnant Women
Most repellents can be used on children aged >2 months. Protect infants aged <2 months from mosquitoes by using an infant carrier draped with mosquito netting with an elastic edge for a tight fit. Products containing OLE specify that they should not be used on children aged <3 years. Other than the safety tips listed above, EPA does not recommend any additional precautions for using registered repellents on children or on pregnant or lactating women.
MALARIA in the UNITED STATES
Malaria was eliminated from the United States in the early 1950’s. Approximately 1,500–2,000 cases of malaria are reported every year in the United States, almost all in recent travellers. Reported malaria cases reached a 40-year high of 1,925 in 2011. First- and second-generation immigrants from malaria-endemic countries returning to their “home” countries to visit friends and relatives tend not to use appropriate malaria prevention measures and thus are more likely to become infected with malaria.
Between 1957 and 2014, in the United States, 63 outbreaks of locally transmitted mosquito-borne malaria have occurred; in such outbreaks, local mosquitoes become infected by biting persons carrying malaria parasites (acquired in endemic areas) and then transmit malaria to local residents.
Of the species of Anopheles mosquitoes found in the United States, the three species that were responsible for malaria transmission prior to elimination (Anopheles quadrimaculatus in the east, An. freeborni in the west, and An. pseudopunctipennis along the U.S./Mexico border) are still prevalent; thus there is a constant risk that malaria could be reintroduced in the United States.
During 1963-2012, 97 cases of transfusion-transmitted malaria were reported in the United States; approximately two thirds of these cases could have been prevented if the implicated donors had been deferred according to established guidelines.
MALARIA WORLDWIDE
3.4 billion people live in areas at risk of malaria transmission in 106 countries and territories. The World Health Organization estimates that in 2013 malaria caused 198 million clinical episodes, and 500,000 deaths.
Among the malaria species that infect humans, P. vivax and P. ovale can develop dormant liver stages that can reactivate after symptomless intervals of up to 2 (P. vivax) to 4 years (P. ovale).
Pregnant women have increased susceptibility to P. falciparum malaria; in malaria-endemic countries, P. falciparum contributes to 8-14% of low birth weight, which in turn decreases the chance of a baby’s survival.
An experienced laboratory technician or pathologist can distinguish between P. falciparum, P. vivax, P. malariae, and P. ovale based on the appearance of the parasites and infected blood cells. Under the microscope, P. knowlesi can resemble either P. falciparum or P. malariae. Increasingly reference diagnostic tools like PCR are employed to confirm malaria infection and to determine definitively which species are involved.
OTHER FACTS
Four times, the Nobel Prize in Physiology or Medicine has been awarded for work associated with malaria: to Sir Ronald Ross (1902), Charles Louis Alphonse Laveran (1907), Julius Wagner-Jauregg (1927), and Paul Hermann Müller (1948).
Two important currently used antimalarial drugs are derived from plants whose medicinal values had been noted for centuries: artemisinin from the Qinghaosu plant (Artemisia annua, China, 4th century) and quinine from the cinchona tree (Cinchona spp., South America, 17th century).
The natural ecology of malaria involves malaria parasites infecting successively two types of hosts: humans and female Anopheles mosquitoes. In humans, the parasites grow and multiply first in the liver cells and then in the red cells of the blood. In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites (“merozoites”) that continue the cycle by invading other red cells.
The blood stage parasites are those that cause the symptoms of malaria. When certain forms of blood stage parasites (“gametocytes”) are picked up by a female Anopheles mosquito during a blood meal, they start another, different cycle of growth and multiplication in the mosquito.
After 10-18 days, the parasites are found (as “sporozoites”) in the mosquito’s salivary glands. When the Anopheles mosquito takes a blood meal on another human, the sporozoites are injected with the mosquito’s saliva and start another human infection when they parasitize the liver cells.
Thus the mosquito carries the disease from one human to another (acting as a “vector”). Differently from the human host, the mosquito vector does not suffer from the presence of the parasites.
Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony). Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites. Some parasites differentiate into sexual erythrocytic stages (gametocytes). Blood stage parasites are responsible for the clinical manifestations of the disease.
The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal. The parasites’ multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito’s stomach, the microgametes penetrate the macrogametes generating zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts. The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito’s salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.
Human Factors And Malaria
Biologic characteristics and behavioral traits can influence an individual’s risk of developing malaria and, on a larger scale, the intensity of transmission in a population.
DISEASE.
Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and death. Malaria disease can be categorized as uncomplicated or severe (complicated). In general, malaria is a curable disease if diagnosed and treated promptly and correctly.
All the clinical symptoms associated with malaria are caused by the asexual erythrocytic or blood stage parasites. When the parasite develops in the erythrocyte, numerous known and unknown waste substances such as hemozoin pigment and other toxic factors accumulate in the infected red blood cell. These are dumped into the bloodstream when the infected cells lyse and release invasive merozoites. The hemozoin and other toxic factors such as glucose phosphate isomerase (GPI) stimulate macrophages and other cells to produce cytokines and other soluble factors which act to produce fever and rigors and probably influence other severe pathophysiology associated with malaria.
Plasmodium falciparum-infected erythrocytes, particularly those with mature trophozoites, adhere to the vascular endothelium of venular blood vessel walls and do not freely circulate in the blood. When this sequestration of infected erythrocytes occurs in the vessels of the brain it is believed to be a factor in causing the severe disease syndrome known as cerebral malaria, which is associated with high mortality.
Incubation Period. Following the infective bite by the Anopheles mosquito, a period of time (the “incubation period”) goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.
Antimalarial drugs taken for prophylaxis by travellers can delay the appearance of malaria symptoms by weeks or months, long after the traveller has left the malaria-endemic area. (This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the infective mosquito bite.)
Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in areas where malaria occurs during the past 12 months.
Uncomplicated Malaria
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of: a cold stage (sensation of cold, shivering), a hot stage (fever, headaches, vomiting; seizures in young children) and finally a sweating stage (sweats, return to normal temperature, tiredness). Classically (but infrequently observed) the attacks occur every second day with the “tertian” parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the “quartan” parasite (P. malariae).
More commonly, the patient presents with a combination of the following symptoms: fever, chills, sweats, headaches, nausea and vomiting, body aches and general malaise.
In countries where cases of malaria are infrequent, these symptoms may be attributed to influenza, a cold, or other common infections, especially if malaria is not suspected. Conversely, in countries where malaria is frequent, residents often recognize the symptoms as malaria and treat themselves without seeking diagnostic confirmation (“presumptive treatment”).
Physical findings may include: elevated temperatures, perspiration, weakness, enlarged spleen, mild jaundice, enlargement of the liver, and increased respiratory rate
Diagnosis of malaria depends on the demonstration of parasites in the blood, usually by microscopy. Additional laboratory findings may include mild anemia, mild decrease in blood platelets (thrombocytopenia), elevation of bilirubin, and elevation of aminotransferases.
Severe Malaria
Severe malaria occurs when infections are complicated by serious organ failures or abnormalities in the patient’s blood or metabolism. The manifestations of severe malaria include:
Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities
Severe anemia due to hemolysis (destruction of the red blood cells)
Hemoglobinuria (hemoglobin in the urine) due to hemolysis
Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment
Abnormalities in blood coagulation
Low blood pressure caused by cardiovascular collapse
Acute kidney failure.
Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycaemia
Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.
Severe malaria is a medical emergency and should be treated urgently and aggressively.
Malaria Relapses
In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks (“relapses”) after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites (“hypnozoites”) that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.
Other Manifestations of Malaria
Neurologic defects may occasionally persist following cerebral malaria, especially in children. Such defects include trouble with movements (ataxia), palsies, speech difficulties, deafness, and blindness.
Recurrent infections with P. falciparum may result in severe anemia. This occurs especially in young children in tropical Africa with frequent infections that are inadequately treated.
Malaria during pregnancy (especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.
On rare occasions, P. vivax malaria can cause rupture of the spleen.
Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with P. malariae.
Hyperreactive malarial splenomegaly (also called “tropical splenomegaly syndrome”) occurs infrequently and is attributed to an abnormal immune response to repeated malarial infections. The disease is marked by a very enlarged spleen and liver, abnormal immunologic findings, anemia, and a susceptibility to other infections (such as skin or respiratory infections).
Where Malaria Occurs
Where malaria is found depends mainly on climatic factors such as temperature, humidity, and rainfall. Malaria is transmitted in tropical and subtropical areas, where Anopheles mosquitoes can survive and multiply and Malaria parasites can complete their growth cycle in the mosquitoes (“extrinsic incubation period”).
Temperature is particularly critical. For example, at temperatures below 20°C (68°F), Plasmodium falciparum (which causes severe malaria) cannot complete its growth cycle in the Anopheles mosquito, and thus cannot be transmitted.
In many malaria-endemic countries, malaria transmission does not occur in all parts of the country. Even within tropical and subtropical areas, transmission will not occur: at very high altitudes, during colder seasons in some areas, in deserts (excluding the oases), in some countries where transmission has been interrupted through successful control/elimination programs.
Generally, in warmer regions closer to the equator, transmission will be more intense and malaria is transmitted year-round. The highest transmission is found in Africa South of the Sahara and in parts of Oceania such as Papua New Guinea.
In cooler regions, transmission will be less intense and more seasonal. There, P. vivax might be more prevalent because it is more tolerant of lower ambient temperatures.
In many temperate areas, such as Western Europe and the United States, economic development and public health measures have succeeded in eliminating malaria. However, most of these areas have Anopheles mosquitoes that can transmit malaria, and reintroduction of the disease is a constant risk.
DETERMINE RISK
Determine if malaria transmission occurs at the destinations
Obtain a detailed itinerary including all possible destinations that may be encountered during the trip and check to see if malaria transmission occurs in these locations. The Malaria Information by Country Table provides detailed information about the specific parts of countries where malaria transmission does or does not occur. It also provides additional information including the species of malaria that occur there, the presence of drug resistance, and the specific medicines that CDC recommends for use for malaria prevention in each country where malaria transmission occurs.
Another way of finding this information is through the CDC Malaria Map Application. This web-based tool is particularly useful for obtaining information about malaria transmission in specific parts of countries.
Conduct an individualized risk assessment. Prevention of malaria involves a balance between ensuring that all people who will be at risk of infection use the appropriate prevention measures, while preventing adverse effects of those interventions among people using them unnecessarily. An individual risk assessment should be conducted for every traveler, taking into account not only the destination country, but also the detailed itinerary, including specific cities, types of accommodation, season, and style of travel. In addition, conditions such as pregnancy or the presence of antimalarial drug resistance at the destination may modify the risk assessment.
Choose the most appropriate malaria prevention measures.. Based on the risk assessment, specific malaria prevention interventions should be used by the traveler. Often this includes avoiding mosquito bites through the use of repellents or insecticide treated bed nets, and specific medicines to prevent malaria.
If malaria prevention medicines will be needed for the traveler, the Malaria Information by Country Table lists the CDC-recommended options. For many destinations, there are multiple options available. Factors to consider are the patient’s other medical conditions, medications being taken (to assess potential drug-drug interactions), the cost of the medicines, and the potential side effects.
TIPS ON CHOOSING the RIGHT DRUG for an INDIVIDUAL TRAVELLER
The Drugs for Malaria Prevention table provides prescription dosing information for both adults and children.
In some countries (including those with malaria risk), drugs may be sold that are counterfeit (“fake”) or substandard (not made according to United States standards). Such drugs may not be effective. Antimalarial drugs should always be purchased before traveling overseas!
Some things that travellers can use to protect themselves against malaria: malaria pills; insect repellent; long-sleeved clothing; bed net; and flying insect spray. Also air conditioned or screened quarters.)
Know the symptoms of malaria
The interventions used to prevent malaria can be very effective when used properly, but none of them are 100% effective.
If symptoms of malaria occur, the traveler should seek immediate medical attention.
Malaria is always a serious disease and may be a deadly illness. Travellers who become ill with a fever or flu-like illness either while traveling in a malaria-risk area or after returning home (for up to 1 year) should seek immediate medical attention and should tell the physician their travel history.
Treatment. Travellers who are assessed at being at high risk of developing malaria while traveling should consider carrying a full treatment course of malaria medicines with them. Providing this reliable supply of medicine (formerly referred to as standby or emergency self-treatment) will ensure that travellers have immediate access to an appropriate and high quality medicine if they are diagnosed with malaria while abroad. Depending on the medicine they are using for prevention, this could either be atovaquone/proguanil Malarone – the best drug to carry with you for emergency treatment – with first symptoms empirically start Malarone 4 tablets once/day X 3 days.
Artemether/lumefantrine.
Be aware of blood donation eligibility. Travellers are often surprised to learn that even if they adhered to all of the prevention advice and did not become sick with malaria, recent travel to a place where malaria transmission occurs is an exclusion criterion for blood donation.
