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Current malaria prophylaxis

Malaria is one of the most dangerous infectious diseases in the tropics. It is transmitted through the bite of plasmodia-infected Anopheles mosquitoes. Life-threatening organ damage can occur, particularly with malaria tropica. Therefore, when traveling to malaria endemic areas, the available, effective prophylactic measures should be used. The two most important prevention strategies are avoiding mosquito bites (exposure prophylaxis) and killing plasmodia that have already penetrated (chemoprophylaxis). A vaccination is currently not available.


All travelers should be informed about malaria prophylaxis by a doctor. With this, malaria can be prevented with a high degree of probability. Only the Caribbean Islands (except Dominican Republic and Haiti), Tunisia, Seychelles, Réunion, Israel, Lebanon, Kuwait, Abu Dhabi, Dubai, Maldives, Brunei, Hong Kong, Korea, Singapore, Taiwan, Australia, New Zealand are malaria-free in the tropics and subtropics , Cook Islands, Fiji, French Polynesia, New Caledonia. The points listed in the text box must be taken into account when giving advice (1, 8).


Exposure prophylaxis
The consistent application of the measures to avoid insect bites can significantly reduce the risk of malaria:
! Rubbing uncovered areas of skin with mosquito repellants (repellents),
! Wearing clothing that covers the skin,
! Stay in mosquito-proof rooms (air conditioning, fly screens),
! Use of mosquito nets,
! the additional use of insecticides in aerosols, vaporizers, incense coils ("mosquito coils") and the like and for the impregnation of mosquito nets can offer additional protection.


Drug malaria prophylaxis
Chemoprophylaxis is generally recommended when traveling to malaria areas and can still significantly reduce the risk even in areas with the spread of resistant malaria tropica pathogens. The drug prevention (chemoprophylaxis) of malaria is made more difficult by the spread of resistances, which - depending on region and extent - are already possible against any of the available antimalarials. Resistance to quinine, mefloquine, halofantrine and artemisinin are still rare. Some antimalarials are unsuitable for prophylaxis or carry the risk of significant side effects. The decision on the type of malaria prophylaxis must be made by the doctor individually based on the specific travel destination as well as the travel time, the travel duration and the travel style. The personal circumstances of the traveler (such as previous illnesses, intolerance, medication intake) must also be taken into account.


Chloroquine
Chloroquine can be used for prophylaxis in areas without chloroquine resistance. Occasional side effects include short-term stomach upset, fibrillation of the eyes and dizziness. Permanent damage to the retina is only to be expected in rare cases if it is taken continuously for years. After five years of regular chloroquine intake, ophthalmologic examinations should therefore be carried out every six months. In areas without chloroquine resistance, chloroquine can also be used for emergency self-treatment if malaria is suspected. According to the current state of knowledge, chloroquine can also be used by pregnant women and small children. Chloroquine is contraindicated in psoriasis and porphyria. If epileptics are receiving adequate therapy, chloroquine may be given in consideration of the risk of malaria.


Proguanil
In areas with chloroquine resistance, Proguanil can be taken in addition to chloroquine prophylaxis. This enables an additional protective effect to be achieved. After taking Proguanil, temporary hair loss or stomach problems may occur, and very rarely mouth ulcerations. According to the current state of knowledge, proguanil can also be used in pregnant women and small children. In the event of kidney failure, the dose must be reduced (creatinine clearance 20 to 60 ml / min / 1.73 m2: 100 mg daily; 10 to 20 ml / min / 1.73 m2: 50 mg daily; < 10="" ml/min/1,73="" m2:="" 50="" mg="" jeden="" zweiten="" tag).="" proguanil="" eignet="" sich="" nicht="" zur="">


Mefloquine
In areas with a very high risk of malaria and frequent chloroquine resistance, prophylaxis with mefloquine currently offers the best protection. Mefloquine can also be used for emergency self-treatment if malaria is suspected. Because of occasionally severe neuropsychiatric side effects (6), neither people with a history of mental illness or seizures nor people with responsible work and special spatial orientation requirements (such as pilots, scuba divers, mountaineers) should use mefloquine as a prophylaxis. In addition, mefloquine should not be given to patients with cardiac conduction disorders or at the same time as quinidine-type drugs. According to the current state of knowledge, an interaction with beta blockers, calcium channel blockers or other antiarrhythmics cannot be completely ruled out. Nausea, dizziness, sleep disorders and allergic skin reactions have also been observed as side effects. Side effects are much rarer with prophylactic use than with therapeutic use. Pregnant women in the first trimester and small children up to 15 kg body weight should not take mefloquine. Pregnancy should be prevented for three months while taking mefloquine and after the last dose. Mefloquine is mainly metabolised and excreted via the liver; a dose reduction is not necessary, even in dialysis patients.


Other anti-malarial drugs
Some drugs will only be used in individual cases, for example in the case of contraindications to the above-mentioned anti-malarial drugs or in particular situations of resistance.
Halofantrine can only be used for therapy, but not for prophylaxis, of malaria. Halofantrine can lead to life-threatening arrhythmias. Therefore, halofantrine is generally no longer recommended as a drug for emergency self-treatment, despite its good effectiveness and subjectively low side effects. It is contraindicated in known heart diseases and in combination with drugs that can prolong the QT time. Any pre-existing QT prolongation must be ruled out by an EKG. Due to a lack of experience, halofantrine must not be taken during pregnancy or by small children weighing less than ten kilograms.
Quinine is primarily used in the therapy of the complicated malaria tropica. In exceptional cases it can also be used for emergency self-treatment.
Doxycycline alone is not suitable for therapy. It is important for prophylaxis in areas with chloroquine and mefloquine resistance such as in the border areas of Thailand to Cambodia and Myanmar (Burma). It should be taken with plenty of fluids to prevent damage to the mucous membrane in the esophagus. Phototoxic reactions of exposed skin areas can occur. Pregnant women and children under eight years of age should not be given doxycycline. Sulfadoxine pyrimethamine is no longer used for prophylaxis; it is still often used for therapy, especially in Africa. Sulfadoxine pyrimethamine is no longer on the market in Germany. It is only recommended for emergency self-treatment in exceptional cases. Artemisinin derivatives (for example artesunate, artemether) are increasingly used in malaria therapy, especially in Southeast Asia; they are not yet approved in Germany. They are currently not recommended for emergency self-treatment.


Emergency self-treatment
If chemoprophylaxis is inadequate in areas of resistance, a therapeutic dose of a reserve drug should be carried with you, which is taken in the event of symptoms suspecting malaria and unavailable medical help (emergency self-treatment or "standby" treatment). However, this should only be an emergency measure until medical help is obtained (5). Taking a malaria medication with you for any emergency self-treatment without taking prophylactic medication is an option in the case of short-term exposure to malaria (only a few days) or when traveling to areas with a very low incidence of malaria or in the case of known intolerance to malaria prophylaxis.
Malaria symptoms are fever, feeling very sick, headache and body aches, chills and more. Due to the symptoms of the disease, the diagnosis of "malaria" can neither be guaranteed nor ruled out. This is only possible by detecting parasites in the blood. The incubation period is at least seven days (2, 7).
In general, mefloquine should be carried with you for emergency self-treatment, when traveling to areas without chloroquine resistance possibly also chloroquine, only in exceptional cases sulfadoxine / pyrimethamine, halofantrine or quinine (see Tables 1 and 2).


Special groups of people


Toddlers and infants
Malaria prevention in infants and small children consists primarily in consistent exposure prophylaxis (mosquito nets over beds and play areas). Mosquito repellants should not be used on children for a long time because of possible side effects. Acute repellents can cause irritation of the mucous membranes, especially in babies. Chloroquine and paludrine are suitable for chemoprophylaxis in infants from the sixth week. Mefloquine may only be used from a body weight of 15 kilograms. Because of possible side effects on tooth maturation and bone formation, doxycycline may only be prescribed from the age of eight. Malaria prophylaxis is also required for fully breastfed infants, as the breast milk of the chemoprophylaxis-consuming mother does not provide adequate protection for the infant.


Pregnant and breastfeeding women
A malaria infection during pregnancy means a considerable risk for the mother and the fetus. For this reason, pregnant women should be advised against staying in malaria endemic areas, especially in areas with chloroquine resistance. If a stay is unavoidable, consistent preventive measures must be taken. According to current knowledge, chloroquine and proguanil can be used prophylactically during pregnancy and breastfeeding (3). According to the current state of knowledge, mefloquine must not be taken in the first trimester. Doxycycline is contraindicated in pregnancy. Mefloquine, halofantrine, or doxycycline should not be used during breast-feeding.


People with long or frequent stays in the tropics
Experience in the tropics and observance of health protection measures, in particular mosquito repellent and malaria prevention with medication, are very different for these groups of people. These travelers need individual medical advice before their assignments, in which the expected risk is assessed according to activity, region, season, resistance of the pathogens and tolerability of the medication and a corresponding recommendation is made. This advice requires the doctor to have knowledge of tropical medicine.
Even in the case of long-term stays and multiple stays in malaria areas, prevention should always be carried out with medication. If there is a high risk of malaria, chemoprophylaxis is particularly important during the rainy season or when traveling with limited mosquito protection. With this recommendation, the expected protective effect against the possible undesirable side effects of the drug must be weighed even more precisely than with short tourist trips. Therefore, only preparations come into consideration, the application of which over a longer period of time or several times a year do not cause any significant side effects and at the same time allow an adequate protective effect to be expected. Chloroquine and proguanil are suitable for long-term prevention. Currently, mefloquine is only recommended for stays of up to around three months. On the basis of more recent studies, however, it is becoming possible to use mefloquine over a longer period of time without a significant increase in side effects (4).


Prophylaxis recommendations for different travel areas
According to the World Health Organization (WHO), the malaria areas are divided into zones A, B and C depending on the resistance situation (graphic). Zone A includes areas without chloroquine resistance or without Plasmodium falciparum, Zone B are areas with chloroquine resistance and Zone C are areas with high-grade chloroquine resistance or with multi-resistance. Within these individual zones, however, the malaria risk can be very different even within a country (9). The recommendations for the most important travel areas are therefore given below as an orientation aid for advisory practice. In individual cases, other recommendations may be necessary for the traveler according to individual considerations (e.g. stay only in large cities, stay only for a few days, intolerance). In the case of previous illnesses such as renal insufficiency, doctors experienced in tropical medicine, tropical medicine facilities or appropriate vaccination centers should be consulted.


Africa
! Tunisia: no risk of malaria.
! Morocco, Algeria, Libya: very low risk of malaria, malaria prophylaxis is usually not required.
! Egypt: low risk of malaria in the summer months (June to October) in El Fayoum, malaria prophylaxis usually not required.
! Tropical Africa (including Madagascar): high risk of malaria: continuous medication prophylaxis with mefloquine is recommended for a travel time of up to three months, as this provides the highest protection; A combination of chloroquine and proguanil with emergency medication can also be considered.
! Namibia, Botswana: Malaria prophylaxis only for the north of the countries with mefloquine or with chloroquine and proguanil with emergency medication.
! Republic of South Africa: Malaria prophylaxis only for the border area to Zimbabwe and Mozambique with mefloquine or with chloroquine and proguanil with emergency medication. For short stays in the Kruger Park, it is sufficient to take a malaria drug with you as emergency therapy.
! Mauritius: very low risk of malaria in the north, malaria prophylaxis is generally not required.
! Seychelles, Réunion: no risk of malaria.


Asia and Oceania
In general, the capitals of Asia are malaria-free (exceptions: New Delhi, Rangoon). The overall risk of malaria is lower than in Africa, but chloroquine resistance can be found in many areas.
! Israel, Kuwait, Lebanon, Abu Dhabi, Dubai: no risk of malaria.
! Turkey: low risk in Southeast Anatolia and on the Turkish Riviera; Malaria prophylaxis is usually not required.
! Iraq, Iran, Jordan, Syria: low risk; Malaria prophylaxis is usually not required.
! Yemen, Oman: prophylaxis with chloroquine and proguanil with an emergency medication is recommended for these areas.
! Saudi Arabia: urban areas of the western province largely free of malaria; for other parts of the country prophylaxis with chloroquine and proguanil with an emergency medication is recommended.
! Maldives: no risk of malaria.
! Bangladesh, Bhutan, India, Nepal, Pakistan, Sri Lanka: prophylaxis with chloroquine and proguanil with emergency medication recommended for these areas (areas in the Himalayas above 2500 meters are free of malaria).
! Brunei, Japan, Hong Kong, Korea, Singapore, Taiwan: no risk of malaria.
! China (PR): low risk of malaria in north and north-east China; usually no prophylaxis required; higher risk in south and south-east China (especially in Yünnan and on the island of Hainan), prophylaxis with chloroquine and proguanil with emergency medication or with mefloquine recommended for stays in rural areas.
! Indonesia (except Irian Jaya), Philippines, West Malaysia: prophylaxis with chloroquine with emergency medication is recommended for these areas; under certain circumstances (for example in Bali and Java in Indonesia) it is only possible to take a malaria drug as emergency therapy The Philippine islands of Cebu, Leyte, Bohol and Catanduanes are malaria-free.
! Thailand: Bangkok and Pattaya with the immediate vicinity, Chiang-Mai and the immediate vicinity, larger cities in southern Thailand and the islands there (Phuket, Ko Samui and others): for these areas, prophylactic medication is usually unnecessary; Other parts of the country: in addition to consistent mosquito protection, continuous prophylaxis with mefloquine is recommended for these areas.
! Burma (Myanmar), Indonesia (Irian Jaya), East Malaysia, Laos, Cambodia, Vietnam: in addition to consistent mosquito protection, continuous drug prophylaxis with mefloquine is recommended for these areas. Note on Cambodia and the border areas of Thailand with Cambodia, Laos and Burma: Due to the frequent mefloquine resistance, malaria prophylaxis with doxycycline can also be considered as an alternative.
! Papua New Guinea, Vanuatu: high risk of malaria; Continuous drug prophylaxis with mefloquine is recommended for these areas.


Central America
Generally speaking, there is a low risk of malaria in Central America. Tertiana malaria occurs predominantly. Malaria occurs in areas below 1000 m altitude, the capital cities are usually free of malaria. In the Caribbean, malaria tropica occurs in Haiti and in the Dominican Republic; the other islands are malaria free. Malaria prophylaxis with chloroquine is recommended for the following areas:
! Mexico: Caribbean coast, border areas with Guatemala, Pacific coast (except the Baja California peninsula); In Yucatan, usually a doctor should be consulted if there is a fever or emergency self-therapy with chloroquine is sufficient;
! Guatemala: deep regions, stretches of coast, border area with Belize;
! Belize: whole country;
! Honduras: stretches of coast;
! El Salvador: stretches of coast;
! Nicaragua: whole country;
! Costa Rica: stretches of coast, deep regions;
! Panama: west of the Panama Canal, low risk; east of the Panama Canal in the jungle areas and in the border area with Colombia high risk: Mefloquine or chloroquine and proguanil with emergency medication;
! Haiti: whole country;
! Dominican Republic: only in the border areas with Haiti low risk of malaria; Malaria prophylaxis is generally not required for pure bathing trips and day trips to the surrounding area.


South America
In the Amazon basin and the tributaries there is a risk of malaria with multiple resistant pathogens. Here, malaria prophylaxis with mefloquine or chloroquine and proguanil with an emergency medication is recommended. The coastal area on the Pacific has a low risk of malaria. Either malaria prophylaxis with chloroquine and emergency medication is recommended, or only emergency medication is recommended.
! Venezuela: Caracas, Isla Marguerita and the coastal region are malaria-free; Prophylaxis recommended for trips inland to the Orinoco River, the regions south of the Orinoco and the border areas with Brazil, Colombia and Guyana.
! Guiana, Suriname: Risk of Malaria Across the Country.
! Colombia: Central area including Bogotá malaria-free; Prophylaxis for border areas with Panama, the Pacific coast and the Amazon region (lowlands).
! Ecuador: no risk of malaria in the central highlands; low risk of malaria on the Pacific coast; It is recommended to take emergency medication or prophylaxis with you; in the Amazon: prophylaxis recommended.
! Peru: low risk of malaria in the central highlands; higher risk of malaria on the Pacific coast: it is recommended to take emergency medication or prophylaxis with you; Prophylaxis recommended in the Amazon region.
! Brazil: Malaria prophylaxis recommended for rural areas; the entire east coast and the coastal provinces south of Fortaleza are malaria-free.
! Bolivia: Malaria prophylaxis only in the Amazon region.
! Argentina, Paraguay: very low risk of malaria, no prophylaxis recommended.
! Chile, Uruguay: no risk of malaria.


Information opportunities
The brochure "International Travel and Health. Vaccination Requirements and Health Advice" published annually by the WHO is recommended for quick information. If you have specific questions about the prevention, detection and treatment of malaria, it is advisable to seek advice from a local tropical medicine practitioner, a tropical medicine facility or an appropriate vaccination center.


How this article is cited:
Dt Ärztebl 1996; 93: A-1955-1960
[Issue 30]


literature
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5. Nothdurft H D, Jelinek T, Pechel S M, Hess F, Maiwald H, Marschang A, von Sonnenburg F, Weinke Th, Löscher T: Stand-by treatment of suspected malaria in travelers. Trop Med Parasitol 1995; 46: 161-163
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8 WHO: International Travel and Health. Vaccination Requirements and Health Advice. Situation as on January 1, 1996. WHO, Geneva 1996
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Address for the authors:
PD Dr. med. Gerd-Dieter Burchard
Bernhard Nocht Institute for Tropical Medicine
Bernhard-Nocht-Strasse 74
20359 Hamburg