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What Is the Most Effective and Safe Malaria Prophylaxis During Pregnancy?

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What Is the Most Effective and Safe Malaria Prophylaxis During Pregnancy? From the CLINICAL INQUIRIES Family Physicians Inquiries Network Scott A. Wiltz, MD, MPH What is the most effective and Paul Crawford, MD Eglin Air Force Base Family Medicine Residency, and safe malaria prophylaxis Eglin Air Force Base, Fla William Nichols, Librarian during pregnancy? Eglin Air Force Base, Fla Evidence-based answer Chloroquine and mefloquine have superior [SOR]: A, based on systematic review of safety profiles in pregnancy, though all consistent, good-quality patient-oriented antimalarials are effective for prophylaxis. evidence). Antimalarials will decrease the severity of You can determine malaria risk and maternal malaria infection and malaria- sensitivity of Plasmodium species by country associated anemia, while decreasing the at wwwn.cdc.gov/travel/destinationList. incidence of low birth weight and perinatal aspx.1 Urge women to delay travel until after death in women having their first or pregnancy if possible2 (SOR: C, based on second baby (strength of recommendation patient-oriented expert opinion). Clinical commentary Don’t forget to discuss mosquito netting provide verbal and written counsel regarding FAST TRACK and insect repellant malaria personal protection measures. Urge women to Adverse outcomes associated with malaria Because mosquitoes usually feed at night, during pregnancy include restricted fetal travelers should remain within screened delay travel to growth, low birth weight, preterm delivery, areas after dusk, use permethrin-treated malaria-endemic congenital infection, spontaneous abortion, bed nets, wear protective clothing, and areas until after and perinatal death. You should counsel apply insect repellant. Advise patients who pregnancy travelers to avoid travel to areas where travel to malaria-endemic areas to quickly malaria is endemic during pregnancy. report febrile illnesses and to disclose their For those who are unable to avoid travel histories to healthcare providers. travel, or who reside in malaria-endemic Meg Hayes, MD areas during pregnancy, physicians should Department of Family Medicine, focus not only on chemoprophylaxis, but Oregon Health and Science University, Portland z Evidence summary ing to increased risk of poor maternal Malaria is a parasitic infection that and fetal outcomes—including death. causes significant morbidity and mor- Pregnant women are also more likely to tality worldwide, with more than 500 become infected and to develop more million people becoming severely ill severe disease—they attract twice as every year.2 For pregnant women, many mosquitoes as nonpregnant malarial infection can be severe, with women and have a relative immuno- high fevers, chills, and anemia lead- suppression.3 C ON TI NUE D www.jfponline.com VOL 57, NO 1 / JANUARY 2008 51 ES I R I TABLE INQU Antimalarials for prophylaxis: AL C Chloroquine, mefloquine are best choices during pregnancy PREGNANCY CLINI DRUG EFFIcacY SAFetY CLass* AVAILABILITY Chloroquine Good Excellent C Worldwide Chloroquine/proguanil Good Excellent C Worldwide Mefloquine Excellent Good C Worldwide Quinine Excellent Good C† Worldwide Atovaquone/proguanil Excellent Good C (poorly Worldwide studied) Artesunate Excellent Good N/A Asia, Africa, limited in UK, not in US Primaquine Good Fair C‡ Worldwide Doxycycline Excellent Fair D Worldwide (teratogenic) Sulfadoxine/pyrimethamine Fair Poor C Worldwide, but restricted in US Note: Prescribers and patients are urged to refer to the CDC reference about pregnancy in malaria (wwwn.cdc. gov/travel/contentMalariaPregnantPublic.aspx) and to specific country information regarding sensitivities of malaria (wwwn.cdc.gov/travel/destinationList.aspx). * Pregnancy class C: animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women, despite potential risks. * Pregnancy class D: There is positive evidence of human fetal risk based on adverse reaction data from investiga- tional or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women, despite potential risks. † Monitor patients for maternal hypoglycemia. ‡ There is no evidence of teratogenicity, but primaquine is associated with fetal intravascular hemolysis. FAST TRACK Give pregnant Chemoprophylaxis lowers rates larial infection. When used in all parity women verbal and of maternal infection groups, antimalarials were somewhat written counsel on Although prophylaxis for pregnant pa- less effective, yet still reduced maternal avoiding exposure tients traveling to malarial regions is a infections (RR=0.53; 95% CI, 0.33– by using public concern, data for decision-mak- 0.86); the effects were similar with all ing must be extrapolated from the avail- antimalarials tested.3,4 permethrin-treated able evidence, which is based primarily netting and insect on women living in endemic areas. In Chloroquine, mefloquine are safe repellant a Cochrane systematic review, antima- in pregnancy, doxycycline is not larials were found to decrease the inci- While chemoprophylaxis in pregnancy dence of maternal infections (relative appears efficacious, a major question risk [RR]=0.27; 95% confidence interval remains—which agents are safest for [CI], 0.17–0.44) and reduce maternal both the woman and fetus? Some drugs anemia (RR=0.62; 95% CI, 0.50–0.78) routinely used in nonpregnant individu- in low-parity women—ie, during a first als should not be offered to pregnant or second pregnancy.3 women because of known direct effects In low-parity women, these drugs on the fetus. Doxycycline is teratogenic, were also found to decrease perinatal and primaquine poses a significant risk of death (RR=0.73; 95% CI, 0.53–0.99) fetal intravascular hemolysis in G6PD- and low birth weight (RR=0.57; 95% deficient fetuses.5 Other drugs, such as CI, 0.46–0.72) associated with ma- atovaquone/proguanil and artesunate, are 52 VOL 57, NO 1 / JANUARY 2008 THE JOURNAL OF FaMILY PRactIce Malaria prophylaxis in pregnancy not well studied in pregnancy, and there- FIGURE fore are not recommended for use unless Best protection: other options are not available.2,6 Avoidance Among drugs that are well studied and without known direct fetal-damaging effects, adverse drug reaction profiles can guide use based on disease prevalence and drug-resistance patterns. • Chloroquine is widely used because it is inexpensive and well tolerated, with only pruritus, mouth ulcers, and gastro- intestinal upset as the most common ad- Chloroquine and mefloquine are the safest antimalarials verse effects. for use in pregnant women, but personal protection • Mefloquine is usually well tolerated, measures are also critical. Above, an Anopheles stephensi mosquito expelling a droplet of blood from but can cause dose-related neuropsychi- its abdomen after having engorged itself on its human atric effects; it is contraindicated in those host’s blood. (Source: CDC.) with a history of epilepsy or psychiatric disease. and Prevention (CDC) also recommends • Sulfadoxine and pyrimethamine are avoiding travel to malaria-endemic re- not normally used as prophylaxis for any gions during pregnancy, but if travel is patient, due to the risk of toxic epider- necessary, the CDC advises use of chlo- mal necrolysis and Stevens-Johnson syn- roquine (or mefloquine in regions with drome, and the possible risk of jaundice chloroquine resistance). The CDC dis- and kernicterus if used in the third trimes- courages the use of atovaquone/progua- ter of pregnancy. nil, doxycycline, and primaquine, due to • Quinine, which can be used for treat- known adverse fetal effects or inadequate ment or prophylaxis, may cause hypogly- experience in pregnancy.6 n cemia, an effect that is more pronounced during pregnancy and requires close Acknowledgments FAST TRACK monitoring of blood glucose levels.5,7 The opinions and assertions contained herein are the private views of the authors and not to be construed The World Health Given these reaction profiles, chlo- as official, or as reflecting the views of the US Air Force roquine or mefloquine are usually the Medical service or the us air Force at large. Organization best choice with their superior safety recommends and efficacy. References chloroquine 1. Centers for Disease Control and Prevention Web site. Destinations: CDC Traveler’s Health. Available as first-line Recommendations from others at: wwwn.cdc.gov/travel/destinationList.aspx. Ac- The World Health Organization (WHO) cessed on December 7, 2007. prophylaxis 2. Malaria. In: International Travel and Health. Ge- recommends pregnant women avoid neva, Switzerland: World Health Organization; in pregnancy travel to malarial regions. If travel is re- 2007. Available at: whqlibdoc.who.int/publica- tions/2005/9241580364_chap7.pdf. Accessed on quired, WHO recommends chloroquine December 7, 2007. as first-line prophylaxis in pregnancy 3. Orton L, Garner P. Drugs for treating uncomplicated (plus proguanil if the region exhibits malaria in pregnant women. Cochrane Database Syst Rev 2005; (3):CD004912. emerging chloroquine resistance). In 4. Garner P, Gülmezoglu AM. Drugs for preventing areas with proven chloroquine resis- malaria in pregnant women. Cochrane Database tance, mefloquine is the drug of choice. Syst Rev 2006; (4):CD000169. 5. Phillips-Howard PA, Wood D. The safety of antimalar- Other antimalarials—such as quinine, ial drugs in pregnancy. Drug Saf 1996; 14:131–145. pyrimethamine, sulfadoxine, and artesu- 6. Centers for Disease Control and Prevention Web site. Diseases: Malaria: Prevention, Pregnant Wom- nate—should not be withheld if the pre- en, Public Info. Available at: wwwn.cdc.gov/travel/ ferred drugs are not available, or if the contentMalariaPregnantPublic.aspx. Accessed on December 7, 2007. infection is life-threatening.2 7. Taylor WR, White NJ. Antimalarial drug toxicity: a The Centers for Disease Control review. Drug Saf 2004; 27:25–61. www.jfponline.com VOL 57, NO 1 / JANUARY 2008 53.
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