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Travelers should start on chloroquine 1 to 2 weeks before entering an area without chloroquine resistance (strength of recommendation [SOR]: C, based on expert opinion). In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel (SOR: B, based on prospective patient-oriented outcomes and expert opinion).
Before prescribing medications, determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/yellowBookCh5MalariaYellowFeverTable.aspx (SOR: C, based on patient-oriented expert opinion).
5 tips to help travelers avoid malaria
Brian V. Reamy, MD
Uniformed Services University, Bethesda, Md
Despite our best efforts, more than 10,000 American and European travelers contract malaria each year. Five clinical pointers are helpful in prescribing malaria prophylaxis and preventing malaria in travelers.
1. Advise patients that they’ll need to get their antimalarials before they leave for their trip. The CDC recommends against the purchase of antimalarials while overseas because of concerns about product quality.
2. Encourage patients to plan ahead. Most local community pharmacies do not routinely stock antimalarials and must special order them. If a patient mentions an upcoming trip, advise them that they’ll need to allow an extra 2 weeks to obtain their medications.
3. Consult 1 of 2 continuously updated Web sites prior to selecting a medication for malaria prophylaxis: wwwn.cdc.gov/travel/destinationList.aspx or www.who.int/ith/en.
Start times vary from 1 day to several weeks prior to travel based on the medication selected.
4. Encourage patients to spray clothing with permethrin prior to travel. Permethrin remains effective as a repellent even after months of clothing use and multiple washes.
5. Encourage travelers to finish their medication after they return and to report unexplained fevers for up to 1 year after travel.
Evidence summary
Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.
Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.1
Timing and dosage of prophylactic drugs
Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations2,3 with consideration for side-effect profiles are given in the TABLE.
In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood levels.4 The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel.
The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”4 One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).5
One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly.4 A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.4
While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,6 clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.4,7
TABLE
Evidence-based recommendations for prevention of malaria2-3,8
| DRUG | USAGE | ADULT DOSE | TREATMENT SCHEDULE |
|---|---|---|---|
| Atovaquone/proguanil Contraindicated in pregnancy | Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P falciparum | 1 tablet orally each day 250 mg atovaquone and 100 mg proguanil hydrochloride) | Daily from 1 day prior to entry until 7 days after leaving |
| Chloroquine | Prophylaxis only in areas with chloroquine-sensitive P falciparum | 300 mg base (500 mg salt) orally, once/week | Weekly from 2 weeks prior to entry until 4 weeks after leaving (take on the same day of the week) |
| Doxycycline Contraindicated in children <8 years of age and pregnant women | Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P falciparum | 100 mg orally, daily | Daily from 1 day prior to entry until 4 weeks after leaving |
| Mefloquine | Prophylaxis in areas with chloroquine-resistant P falciparum | 228 mg base (250 mg salt) orally, once/week | Weekly from 2–7 weeks before entry until 4 weeks after leaving (take on the same day of the week) |
| Primaquine | An option for prophylaxis in special circumstances | 30 mg base (52.6 mg salt) orally, daily | Daily from 1 day prior to entry until 7 days after leaving |
Recommendations from others
The World Health Organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to allow side effects to be detected before travel so that possible alternatives can be considered.”8
Centers for Disease Control and Prevention recommendations integrate recommendations from WHO and Cochrane.
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.
1. Chen LH, Keystone JS. New strategies for the prevention of malaria in travelers. Infect Dis Clin North Am 2005;19:185-210.
2. Physicians’ Desk Reference. 61st ed. Montvale, NJ: Thomson; 2007:2786.
3. Parise M, Barber A, Mali S. Prevention of specific infectious diseases—malaria. In Arguin PM, Kozarsky PE, Navin AW (eds), Health Information for International Travel 2005-2006. Atlanta, Ga: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention; 2007. Available at: wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx. Accessed on October 11, 2007.
4. Boudreau E, Schuster B, Sanchez J, et al. Tolerability of prophylactic Lariam regimens. Trop Med Parasitol 1993;44:257-265.
5. Slutsker LM, Khoromana CO, Payne D, et al. Mefloquine therapy for Plasmodium falciparum. malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. Bull World Health Organ 1990;68:53-59.
6. Lobel HO, Miani M, Eng T, et al. Long-term malaria prophylaxis with weekly mefloquine. Lancet 1993;341:848-51.
7. Schlagenhauf P. Mefloquine for malaria chemoprophylaxis 1992-1998: a review. J Travel Med 1999;6:122-133.
8. International Travel and Health 2005. Chapter 7: Malaria. Geneva: World Health Organization; 2005. Available at: whqlibdoc.who.int/publications/2005/9241580364_chap7.pdf. Accessed on October 11, 2007.
Travelers should start on chloroquine 1 to 2 weeks before entering an area without chloroquine resistance (strength of recommendation [SOR]: C, based on expert opinion). In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel (SOR: B, based on prospective patient-oriented outcomes and expert opinion).
Before prescribing medications, determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/yellowBookCh5MalariaYellowFeverTable.aspx (SOR: C, based on patient-oriented expert opinion).
5 tips to help travelers avoid malaria
Brian V. Reamy, MD
Uniformed Services University, Bethesda, Md
Despite our best efforts, more than 10,000 American and European travelers contract malaria each year. Five clinical pointers are helpful in prescribing malaria prophylaxis and preventing malaria in travelers.
1. Advise patients that they’ll need to get their antimalarials before they leave for their trip. The CDC recommends against the purchase of antimalarials while overseas because of concerns about product quality.
2. Encourage patients to plan ahead. Most local community pharmacies do not routinely stock antimalarials and must special order them. If a patient mentions an upcoming trip, advise them that they’ll need to allow an extra 2 weeks to obtain their medications.
3. Consult 1 of 2 continuously updated Web sites prior to selecting a medication for malaria prophylaxis: wwwn.cdc.gov/travel/destinationList.aspx or www.who.int/ith/en.
Start times vary from 1 day to several weeks prior to travel based on the medication selected.
4. Encourage patients to spray clothing with permethrin prior to travel. Permethrin remains effective as a repellent even after months of clothing use and multiple washes.
5. Encourage travelers to finish their medication after they return and to report unexplained fevers for up to 1 year after travel.
Evidence summary
Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.
Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.1
Timing and dosage of prophylactic drugs
Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations2,3 with consideration for side-effect profiles are given in the TABLE.
In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood levels.4 The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel.
The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”4 One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).5
One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly.4 A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.4
While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,6 clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.4,7
TABLE
Evidence-based recommendations for prevention of malaria2-3,8
| DRUG | USAGE | ADULT DOSE | TREATMENT SCHEDULE |
|---|---|---|---|
| Atovaquone/proguanil Contraindicated in pregnancy | Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P falciparum | 1 tablet orally each day 250 mg atovaquone and 100 mg proguanil hydrochloride) | Daily from 1 day prior to entry until 7 days after leaving |
| Chloroquine | Prophylaxis only in areas with chloroquine-sensitive P falciparum | 300 mg base (500 mg salt) orally, once/week | Weekly from 2 weeks prior to entry until 4 weeks after leaving (take on the same day of the week) |
| Doxycycline Contraindicated in children <8 years of age and pregnant women | Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P falciparum | 100 mg orally, daily | Daily from 1 day prior to entry until 4 weeks after leaving |
| Mefloquine | Prophylaxis in areas with chloroquine-resistant P falciparum | 228 mg base (250 mg salt) orally, once/week | Weekly from 2–7 weeks before entry until 4 weeks after leaving (take on the same day of the week) |
| Primaquine | An option for prophylaxis in special circumstances | 30 mg base (52.6 mg salt) orally, daily | Daily from 1 day prior to entry until 7 days after leaving |
Recommendations from others
The World Health Organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to allow side effects to be detected before travel so that possible alternatives can be considered.”8
Centers for Disease Control and Prevention recommendations integrate recommendations from WHO and Cochrane.
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.
Travelers should start on chloroquine 1 to 2 weeks before entering an area without chloroquine resistance (strength of recommendation [SOR]: C, based on expert opinion). In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel (SOR: B, based on prospective patient-oriented outcomes and expert opinion).
Before prescribing medications, determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/yellowBookCh5MalariaYellowFeverTable.aspx (SOR: C, based on patient-oriented expert opinion).
5 tips to help travelers avoid malaria
Brian V. Reamy, MD
Uniformed Services University, Bethesda, Md
Despite our best efforts, more than 10,000 American and European travelers contract malaria each year. Five clinical pointers are helpful in prescribing malaria prophylaxis and preventing malaria in travelers.
1. Advise patients that they’ll need to get their antimalarials before they leave for their trip. The CDC recommends against the purchase of antimalarials while overseas because of concerns about product quality.
2. Encourage patients to plan ahead. Most local community pharmacies do not routinely stock antimalarials and must special order them. If a patient mentions an upcoming trip, advise them that they’ll need to allow an extra 2 weeks to obtain their medications.
3. Consult 1 of 2 continuously updated Web sites prior to selecting a medication for malaria prophylaxis: wwwn.cdc.gov/travel/destinationList.aspx or www.who.int/ith/en.
Start times vary from 1 day to several weeks prior to travel based on the medication selected.
4. Encourage patients to spray clothing with permethrin prior to travel. Permethrin remains effective as a repellent even after months of clothing use and multiple washes.
5. Encourage travelers to finish their medication after they return and to report unexplained fevers for up to 1 year after travel.
Evidence summary
Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.
Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.1
Timing and dosage of prophylactic drugs
Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations2,3 with consideration for side-effect profiles are given in the TABLE.
In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood levels.4 The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel.
The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”4 One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).5
One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly.4 A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.4
While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,6 clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.4,7
TABLE
Evidence-based recommendations for prevention of malaria2-3,8
| DRUG | USAGE | ADULT DOSE | TREATMENT SCHEDULE |
|---|---|---|---|
| Atovaquone/proguanil Contraindicated in pregnancy | Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P falciparum | 1 tablet orally each day 250 mg atovaquone and 100 mg proguanil hydrochloride) | Daily from 1 day prior to entry until 7 days after leaving |
| Chloroquine | Prophylaxis only in areas with chloroquine-sensitive P falciparum | 300 mg base (500 mg salt) orally, once/week | Weekly from 2 weeks prior to entry until 4 weeks after leaving (take on the same day of the week) |
| Doxycycline Contraindicated in children <8 years of age and pregnant women | Prophylaxis in areas with chloroquine-resistant or mefloquine-resistant P falciparum | 100 mg orally, daily | Daily from 1 day prior to entry until 4 weeks after leaving |
| Mefloquine | Prophylaxis in areas with chloroquine-resistant P falciparum | 228 mg base (250 mg salt) orally, once/week | Weekly from 2–7 weeks before entry until 4 weeks after leaving (take on the same day of the week) |
| Primaquine | An option for prophylaxis in special circumstances | 30 mg base (52.6 mg salt) orally, daily | Daily from 1 day prior to entry until 7 days after leaving |
Recommendations from others
The World Health Organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to allow side effects to be detected before travel so that possible alternatives can be considered.”8
Centers for Disease Control and Prevention recommendations integrate recommendations from WHO and Cochrane.
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.
1. Chen LH, Keystone JS. New strategies for the prevention of malaria in travelers. Infect Dis Clin North Am 2005;19:185-210.
2. Physicians’ Desk Reference. 61st ed. Montvale, NJ: Thomson; 2007:2786.
3. Parise M, Barber A, Mali S. Prevention of specific infectious diseases—malaria. In Arguin PM, Kozarsky PE, Navin AW (eds), Health Information for International Travel 2005-2006. Atlanta, Ga: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention; 2007. Available at: wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx. Accessed on October 11, 2007.
4. Boudreau E, Schuster B, Sanchez J, et al. Tolerability of prophylactic Lariam regimens. Trop Med Parasitol 1993;44:257-265.
5. Slutsker LM, Khoromana CO, Payne D, et al. Mefloquine therapy for Plasmodium falciparum. malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. Bull World Health Organ 1990;68:53-59.
6. Lobel HO, Miani M, Eng T, et al. Long-term malaria prophylaxis with weekly mefloquine. Lancet 1993;341:848-51.
7. Schlagenhauf P. Mefloquine for malaria chemoprophylaxis 1992-1998: a review. J Travel Med 1999;6:122-133.
8. International Travel and Health 2005. Chapter 7: Malaria. Geneva: World Health Organization; 2005. Available at: whqlibdoc.who.int/publications/2005/9241580364_chap7.pdf. Accessed on October 11, 2007.
1. Chen LH, Keystone JS. New strategies for the prevention of malaria in travelers. Infect Dis Clin North Am 2005;19:185-210.
2. Physicians’ Desk Reference. 61st ed. Montvale, NJ: Thomson; 2007:2786.
3. Parise M, Barber A, Mali S. Prevention of specific infectious diseases—malaria. In Arguin PM, Kozarsky PE, Navin AW (eds), Health Information for International Travel 2005-2006. Atlanta, Ga: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention; 2007. Available at: wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx. Accessed on October 11, 2007.
4. Boudreau E, Schuster B, Sanchez J, et al. Tolerability of prophylactic Lariam regimens. Trop Med Parasitol 1993;44:257-265.
5. Slutsker LM, Khoromana CO, Payne D, et al. Mefloquine therapy for Plasmodium falciparum. malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. Bull World Health Organ 1990;68:53-59.
6. Lobel HO, Miani M, Eng T, et al. Long-term malaria prophylaxis with weekly mefloquine. Lancet 1993;341:848-51.
7. Schlagenhauf P. Mefloquine for malaria chemoprophylaxis 1992-1998: a review. J Travel Med 1999;6:122-133.
8. International Travel and Health 2005. Chapter 7: Malaria. Geneva: World Health Organization; 2005. Available at: whqlibdoc.who.int/publications/2005/9241580364_chap7.pdf. Accessed on October 11, 2007.
Evidence-based answers from the Family Physicians Inquiries Network