What is the most effective and safe malaria prophylaxis during pregnancy?

Evidence summary

Malaria is a parasitic infection that causes significant morbidity and mortality worldwide, with more than 500 million people becoming severely ill every year.² For pregnant women, malarial infection can be severe, with high fevers, chills, and anemia leading to increased risk of poor maternal and fetal outcomes—including death. Pregnant women are also more likely to become infected and to develop more severe disease—they attract twice as many mosquitoes as nonpregnant women and have a relative immuno-suppression.³

TABLE
Antimalarials for prophylaxis: Chloroquine, mefloquine are best choices during pregnancy

Chemoprophylaxis lowers rates of maternal infection

Although prophylaxis for pregnant patients traveling to malarial regions is a public concern, data for decision-making must be extrapolated from the available evidence, which is based primarily on women living in endemic areas. In a Cochrane systematic review, antimalarials were found to decrease the incidence of maternal infections (relative risk [RR]=0.27; 95% confidence interval [CI], 0.17–0.44) and reduce maternal anemia (RR=0.62; 95% CI, 0.50–0.78) in low-parity women—ie, during a first or second pregnancy.³

In low-parity women, these drugs were also found to decrease perinatal death (RR=0.73; 95% CI, 0.53–0.99) and low birth weight (RR=0.57; 95% CI, 0.46–0.72) associated with malarial infection. When used in all parity groups, antimalarials were somewhat less effective, yet still reduced maternal infections (RR=0.53; 95% CI, 0.33–0.86); the effects were similar with all antimalarials tested.^3,4

Chloroquine, mefloquine are safe in pregnancy, doxycycline is not

While chemoprophylaxis in pregnancy appears efficacious, a major question remains—which agents are safest for both the woman and fetus? Some drugs routinely used in nonpregnant individuals should not be offered to pregnant women because of known direct effects on the fetus. Doxycycline is teratogenic, and primaquine poses a significant risk of fetal intravascular hemolysis in G6PD-deficient fetuses.⁵ Other drugs, such as atovaquone/proguanil and artesunate, are not well studied in pregnancy, and therefore are not recommended for use unless other options are not available.^2,6

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 gastrointestinal upset as the most common adverse effects.
• Mefloquine is usually well tolerated, but can cause dose-related neuropsychiatric effects; it is contraindicated in those with a history of epilepsy or psychiatric disease.
• Sulfadoxine and pyrimethamine are not normally used as prophylaxis for any patient, due to the risk of toxic epidermal necrolysis and Stevens-Johnson syndrome, and the possible risk of jaundice and kernicterus if used in the third trimester of pregnancy.
• Quinine, which can be used for treatment or prophylaxis, may cause hypoglycemia, an effect that is more pronounced during pregnancy and requires close monitoring of blood glucose levels.^5,7

Given these reaction profiles, chloroquine or mefloquine are usually the best choice with their superior safety and efficacy.

Figure
Best protection: Avoidance

Recommendations from others

The World Health Organization (WHO) recommends pregnant women avoid travel to malarial regions. If travel is required, WHO recommends chloroquine as first-line prophylaxis in pregnancy (plus proguanil if the region exhibits emerging chloroquine resistance). In areas with proven chloroquine resistance, mefloquine is the drug of choice. Other antimalarials—such as quinine, pyrimethamine, sulfadoxine, and artesunate—should not be withheld if the preferred drugs are not available, or if the infection is life-threatening.²

The Centers for Disease Control and Prevention (CDC) also recommends avoiding travel to malaria-endemic regions during pregnancy, but if travel is necessary, the CDC advises use of chloroquine (or mefloquine in regions with chloroquine resistance). The CDC discourages the use of atovaquone/proguanil, doxycycline, and primaquine, due to known adverse fetal effects or inadequate experience in pregnancy.⁶

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Malaria is a parasitic infection that causes significant morbidity and mortality worldwide, with more than 500 million people becoming severely ill every year.² For pregnant women, malarial infection can be severe, with high fevers, chills, and anemia leading to increased risk of poor maternal and fetal outcomes—including death. Pregnant women are also more likely to become infected and to develop more severe disease—they attract twice as many mosquitoes as nonpregnant women and have a relative immuno-suppression.³

TABLE
Antimalarials for prophylaxis: Chloroquine, mefloquine are best choices during pregnancy

Chemoprophylaxis lowers rates of maternal infection

Although prophylaxis for pregnant patients traveling to malarial regions is a public concern, data for decision-making must be extrapolated from the available evidence, which is based primarily on women living in endemic areas. In a Cochrane systematic review, antimalarials were found to decrease the incidence of maternal infections (relative risk [RR]=0.27; 95% confidence interval [CI], 0.17–0.44) and reduce maternal anemia (RR=0.62; 95% CI, 0.50–0.78) in low-parity women—ie, during a first or second pregnancy.³

In low-parity women, these drugs were also found to decrease perinatal death (RR=0.73; 95% CI, 0.53–0.99) and low birth weight (RR=0.57; 95% CI, 0.46–0.72) associated with malarial infection. When used in all parity groups, antimalarials were somewhat less effective, yet still reduced maternal infections (RR=0.53; 95% CI, 0.33–0.86); the effects were similar with all antimalarials tested.^3,4

Chloroquine, mefloquine are safe in pregnancy, doxycycline is not

While chemoprophylaxis in pregnancy appears efficacious, a major question remains—which agents are safest for both the woman and fetus? Some drugs routinely used in nonpregnant individuals should not be offered to pregnant women because of known direct effects on the fetus. Doxycycline is teratogenic, and primaquine poses a significant risk of fetal intravascular hemolysis in G6PD-deficient fetuses.⁵ Other drugs, such as atovaquone/proguanil and artesunate, are not well studied in pregnancy, and therefore are not recommended for use unless other options are not available.^2,6

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 gastrointestinal upset as the most common adverse effects.
• Mefloquine is usually well tolerated, but can cause dose-related neuropsychiatric effects; it is contraindicated in those with a history of epilepsy or psychiatric disease.
• Sulfadoxine and pyrimethamine are not normally used as prophylaxis for any patient, due to the risk of toxic epidermal necrolysis and Stevens-Johnson syndrome, and the possible risk of jaundice and kernicterus if used in the third trimester of pregnancy.
• Quinine, which can be used for treatment or prophylaxis, may cause hypoglycemia, an effect that is more pronounced during pregnancy and requires close monitoring of blood glucose levels.^5,7

Given these reaction profiles, chloroquine or mefloquine are usually the best choice with their superior safety and efficacy.

Figure
Best protection: Avoidance

Recommendations from others

The World Health Organization (WHO) recommends pregnant women avoid travel to malarial regions. If travel is required, WHO recommends chloroquine as first-line prophylaxis in pregnancy (plus proguanil if the region exhibits emerging chloroquine resistance). In areas with proven chloroquine resistance, mefloquine is the drug of choice. Other antimalarials—such as quinine, pyrimethamine, sulfadoxine, and artesunate—should not be withheld if the preferred drugs are not available, or if the infection is life-threatening.²

The Centers for Disease Control and Prevention (CDC) also recommends avoiding travel to malaria-endemic regions during pregnancy, but if travel is necessary, the CDC advises use of chloroquine (or mefloquine in regions with chloroquine resistance). The CDC discourages the use of atovaquone/proguanil, doxycycline, and primaquine, due to known adverse fetal effects or inadequate experience in pregnancy.⁶

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Malaria is a parasitic infection that causes significant morbidity and mortality worldwide, with more than 500 million people becoming severely ill every year.² For pregnant women, malarial infection can be severe, with high fevers, chills, and anemia leading to increased risk of poor maternal and fetal outcomes—including death. Pregnant women are also more likely to become infected and to develop more severe disease—they attract twice as many mosquitoes as nonpregnant women and have a relative immuno-suppression.³

TABLE
Antimalarials for prophylaxis: Chloroquine, mefloquine are best choices during pregnancy

Chemoprophylaxis lowers rates of maternal infection

Although prophylaxis for pregnant patients traveling to malarial regions is a public concern, data for decision-making must be extrapolated from the available evidence, which is based primarily on women living in endemic areas. In a Cochrane systematic review, antimalarials were found to decrease the incidence of maternal infections (relative risk [RR]=0.27; 95% confidence interval [CI], 0.17–0.44) and reduce maternal anemia (RR=0.62; 95% CI, 0.50–0.78) in low-parity women—ie, during a first or second pregnancy.³

In low-parity women, these drugs were also found to decrease perinatal death (RR=0.73; 95% CI, 0.53–0.99) and low birth weight (RR=0.57; 95% CI, 0.46–0.72) associated with malarial infection. When used in all parity groups, antimalarials were somewhat less effective, yet still reduced maternal infections (RR=0.53; 95% CI, 0.33–0.86); the effects were similar with all antimalarials tested.^3,4

Chloroquine, mefloquine are safe in pregnancy, doxycycline is not

While chemoprophylaxis in pregnancy appears efficacious, a major question remains—which agents are safest for both the woman and fetus? Some drugs routinely used in nonpregnant individuals should not be offered to pregnant women because of known direct effects on the fetus. Doxycycline is teratogenic, and primaquine poses a significant risk of fetal intravascular hemolysis in G6PD-deficient fetuses.⁵ Other drugs, such as atovaquone/proguanil and artesunate, are not well studied in pregnancy, and therefore are not recommended for use unless other options are not available.^2,6

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 gastrointestinal upset as the most common adverse effects.
• Mefloquine is usually well tolerated, but can cause dose-related neuropsychiatric effects; it is contraindicated in those with a history of epilepsy or psychiatric disease.
• Sulfadoxine and pyrimethamine are not normally used as prophylaxis for any patient, due to the risk of toxic epidermal necrolysis and Stevens-Johnson syndrome, and the possible risk of jaundice and kernicterus if used in the third trimester of pregnancy.
• Quinine, which can be used for treatment or prophylaxis, may cause hypoglycemia, an effect that is more pronounced during pregnancy and requires close monitoring of blood glucose levels.^5,7

Given these reaction profiles, chloroquine or mefloquine are usually the best choice with their superior safety and efficacy.

Figure
Best protection: Avoidance

Recommendations from others

The World Health Organization (WHO) recommends pregnant women avoid travel to malarial regions. If travel is required, WHO recommends chloroquine as first-line prophylaxis in pregnancy (plus proguanil if the region exhibits emerging chloroquine resistance). In areas with proven chloroquine resistance, mefloquine is the drug of choice. Other antimalarials—such as quinine, pyrimethamine, sulfadoxine, and artesunate—should not be withheld if the preferred drugs are not available, or if the infection is life-threatening.²

The Centers for Disease Control and Prevention (CDC) also recommends avoiding travel to malaria-endemic regions during pregnancy, but if travel is necessary, the CDC advises use of chloroquine (or mefloquine in regions with chloroquine resistance). The CDC discourages the use of atovaquone/proguanil, doxycycline, and primaquine, due to known adverse fetal effects or inadequate experience in pregnancy.⁶

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.