Pregnancy One of the advantages of mefloquine is that it is the only drug that can be taken during pregnancywhen traveling

to chloroquine-resistant areas. It is officially recommended for the second and third trimesters of pregnancy. Limited data also suggest that its use during the first trimester is safe. Therefore, mefloquine should be recommended to a pregnant woman who cannot avoid traveling to endemic areas during her first trimester [7]. Contraindications Due to the possible drug-associated neuropsychiatric effects, mefloquine is contraindicated in travelers who have seizure disorders. In addition, it should not be given to travelers with active psychiatric disorders, such as depression, anxiety, psychosis, or any other major psychiatric disorders. It is advisable not to prescribe this drug to patients with a history of such psychiatric disorders, even if they are currently stable [15]. Hypersensitivity Because the drug is related to quinine, it should not be given to persons with known hypersensitivity to mefloquine or to quinine compounds. It is also not recommended for travelers with cardiac conduction abnormalities.

Contraindications are for pregnant women, breastfeedingmothers, children under 8, and those with a history of allergy to any of the tetracycline classes.

Atovaquoneproguanil is indicated for P. falciparum prophylaxis. It should be taken daily, beginning 1 day before entering the endemic area, throughout the stay there, and for 7 days after leaving the area. (Its role in the treatment of falciparum malaria is discussed in Chapter 21.) In the USA, it is indicated without a time limitation, meaning that longterm travelers, expatriates, and military personnel on long-termmissions can use it. In several European countries, its use is limited to short-termtravelers (3090 days) because data on its safety with prolonged use are lacking. It is indicated for children above 5 kg, but dose should be modified according to weight (see Appendix A). Atovaquoneproguanil is contraindicated in patientswith severe renal failure (creatinine clearance <30 mL/min) and in those with known allergies to one of the drug components. The drug is contraindicated in pregnancy, because there is not sufficient information about its safety in pregnancy. Risk factors for acquiring severe malaria in endemic countries are youth and pregnancy, especially first pregnancy. Young children are victims of severe malaria due to their lack of immunity to malaria, which is only acquired after several attacks. At infancy they are still protected by their mothers antibodies, transmitted transplacentally, and usually those over the age of 5 years have acquired immunity from repeated attacks. Pregnancy can be considered a temporarily acquired immune deficiency state in pregnantwomen. It is not clear why mainly primigravidae are affected. The susceptibility of pregnant women to malaria is usually seen during the second and third trimesters and continues through the

early postpartum period [19]. There is no clear evidence of whether the immune deficiency state of HIV patients in Africa increases their risk of acquiring severe malaria. Risk factors among travelers In contrast to the situation in endemic countries, among travelers, older age appears to be a risk factor. In a nationwide Israeli study of 135 patients, all nonimmune travelers with falciparum malaria, 84 (62%) were <40 years old, and only 5% of the patients in this age group developed severe malaria, compared to 18% of the subjects who were >40 years old (odds ratio 4.29). Moreover, all deaths occurred in the latter group. Male subjects, who are overrepresented among malaria cases, did not differ