PregnancyOne of the advantages of mefloquine is that it is the onlydrug that can be taken during pregnancywhen traveling tochloroquine-resistant areas. It is officially recommendedfor the second and third trimesters of pregnancy. Limiteddata also suggest that its use during the first trimester issafe. Therefore, mefloquine should be recommended to apregnant woman who cannot avoid traveling to endemicareas during her first trimester [7].ContraindicationsDue to the possible drug-associated neuropsychiatric effects,mefloquine is contraindicated in travelers who haveseizure disorders. In addition, it should not be given totravelers with active psychiatric disorders, such as depression,anxiety, psychosis, or any other major psychiatricdisorders. It is advisable not to prescribe this drug to patientswith a history of such psychiatric disorders, even ifthey are currently stable [15].HypersensitivityBecause the drug is related to quinine, it should notbe given to persons with known hypersensitivity tomefloquine 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 ofallergy to any of the tetracycline classes.

Atovaquone–proguanil is indicated for P. falciparum prophylaxis.It should be taken daily, beginning 1 day beforeentering the endemic area, throughout the staythere, and for 7 days after leaving the area. (Its rolein the treatment of falciparum malaria is discussed inChapter 21.)In the USA, it is indicated without a time limitation,meaning that long–term travelers, expatriates, and militarypersonnel on long-termmissions can use it. In severalEuropean countries, its use is limited to short-termtravelers(30–90 days) because data on its safety with prolongeduse are lacking.It is indicated for children above 5 kg, but dose shouldbe modified according to weight (see Appendix A).

Atovaquone–proguanil is contraindicated in patientswithsevere renal failure (creatinine clearance <30 mL/min)and in those with known allergies to one of the drugcomponents. The drug is contraindicated in pregnancy,because there is not sufficient information about its safetyin pregnancy.

Risk factors for acquiring severe malaria in endemiccountries are youth and pregnancy, especially first pregnancy.Young children are victims of severe malaria due to theirlack of immunity to malaria, which is only acquired afterseveral attacks. At infancy they are still protected bytheir mothers’ antibodies, transmitted transplacentally,and usually those over the age of 5 years have acquiredimmunity from repeated attacks.Pregnancy can be considered a temporarily acquiredimmune deficiency state in pregnantwomen. It is not clearwhy mainly primigravidae are affected. The susceptibility

of pregnant women to malaria is usually seen during thesecond and third trimesters and continues through theearly postpartum period [19].There is no clear evidence of whether the immune deficiencystate of HIV patients in Africa increases their riskof acquiring severe malaria.Risk factors among travelersIn contrast to the situation in endemic countries, amongtravelers, older age appears to be a risk factor. In a nationwideIsraeli study of 135 patients, all nonimmune travelerswith falciparum malaria, 84 (62%) were <40 yearsold, and only 5% of the patients in this age group developedsevere malaria, compared to 18% of the subjectswho were >40 years old (odds ratio 4.29). Moreover, alldeaths occurred in the latter group. Male subjects, whoare overrepresented among malaria cases, did not differ