Treatment of malaria in the United States: a systematic review.

CONTEXT: Many US clinicians and laboratory personnel are unfamiliar with the diagnosis and treatment of malaria. OBJECTIVES: To examine the evidence base for management of uncomplicated and severe malaria and to provide clinicians with practical recommendations for the diagnosis and treatment of malaria in the United States. EVIDENCE ACQUISITION: Systematic MEDLINE search from 1966 to 2006 using the search term malaria (with the subheadings congenital, diagnosis, drug therapy, epidemiology, and therapy). Additional references were obtained from searching the bibliographies of pertinent articles and by reviewing articles suggested by experts in the treatment of malaria in North America. EVIDENCE SYNTHESIS: Important measures to reduce morbidity and mortality from malaria in the United States include the following: obtaining a travel history, considering malaria in the differential diagnosis of fever based on the travel history, and prompt and accurate diagnosis and treatment. Chloroquine remains the treatment of choice for Plasmodium falciparum acquired in areas without chloroquine-resistant strains. In areas with chloroquine resistance, a combination of atovaquone and proguanil or quinine plus tetracycline or doxycycline or clindamycin are the best treatment options. Chloroquine remains the treatment of choice for all other malaria species, with the exception of P vivax acquired in Indonesia or Papua New Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine plus tetracycline or doxycycline as alternatives. Quinidine is currently the recommended treatment for severe malaria in the United States because the artemisinins are not yet available. Severe malaria occurs when a patient with asexual malaria parasitemia, and no other confirmed cause of symptoms, has 1 or more designated clinical or laboratory findings. The only adjunctive measure recommended in severe malaria is exchange transfusion. CONCLUSIONS: Malaria remains a diagnostic and treatment challenge for US clinicians as increasing numbers of persons travel to and emigrate from malarious areas. A strong evidence base exists to help clinicians rapidly initiate appropriate therapy and minimize the major mortality and morbidity burdens caused by this disease.

Malaria surveillance--United States, 2010.

PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquito-borne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in persons with onset of illness in 2010 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consults. Data from these reporting systems serve as the basis for this report. RESULTS: CDC received 1,691 reported cases of malaria, including 1,688 cases classified as imported, one transfusion-related case, and two cryptic cases, with an onset of symptoms in 2010 among persons in the United States. The total number of cases represents an increase of 14% from the 1,484 cases reported for 2009. Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 58%, 19%, 2%, and 2% of cases, respectively. Thirteen patients were infected by two or more species. The infecting species was unreported or undetermined in 18% of cases. Among the 898 cases in U.S. civilians for whom information on chemoprophylaxis use and travel area was known, 45 (5%) reported that they had followed and adhered to a chemoprophylactic drug regimen recommended by CDC for the areas to which they had traveled. Forty-one cases were reported in pregnant women, among whom only two (5%) adhered to chemoprophylaxis. Among all reported cases, 176 (10%) were classified as severe infections, of which nine were fatal. INTERPRETATION: The number of cases reported in 2010 marked the largest number of cases reported since 1980. Despite the apparent progress in reducing the global burden of malaria, many areas remain malaria endemic and the use of appropriate prevention measures by travelers is still inadequate. PUBLIC HEALTH ACTIONS: Travelers visiting friends and relatives (VFR) continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFR travelers need to be developed and implemented to have a substantial impact on the numbers of imported malaria cases in the United States. A large number of pregnant travelers diagnosed with malaria did not take any chemoprophylaxis. Pregnant women traveling to areas in which malaria is endemic are at higher risk for severe malaria and must use appropriate malaria prevention strategies including chemoprophylaxis. Malaria prevention recommendations are available online (http://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Clinicians should consult the CDC Guidelines for Treatment of Malaria and contact the CDC's Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online (http://www.cdc.gov/malaria/diagnosis_treatment) or by calling the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713).

Malaria surveillance--United States, 2009.

PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in persons with onset of illness in 2009 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases diagnosed by blood film, polymerase chain reaction or rapid diagnostic tests are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consults. Data from these reporting systems serve as the basis for this report. RESULTS: CDC received reports of 1,484 cases of malaria, including two transfusion-related cases, three possible congenital cases, one transplant case and four fatal cases, with an onset of symptoms in 2009 among persons in the United States. This number represents an increase of 14% from the 1,298 cases reported for 2008. Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 46%, 11%, 2%, and 2% of cases, respectively. Thirteen patients were infected by two or more species. The infecting species was unreported or undetermined in 38% of cases. Among the 1,484 cases 1,478 were classified as imported. Among the 103 U.S. civilians for whom information on chemoprophylaxis use and travel area was known, only 34 (33%) reported that they had followed and adhered to a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Nineteen cases were reported in pregnant women, among whom none adhered to chemoprophylaxis. Almost 22% of the cases among pregnant women were treated with an inappropriate treatment drug regimen, of which 39% were among cases with either a P. vivax or P. ovale infection where primaquine was not taken. Among all the reasons for travel, travelers visiting friends and relatives (VFR) and missionaries were the groups with the lowest proportion of chemoprophylexis use. INTERPRETATION: A notable increase in the number of malaria cases was reported from 2008 to 2009; however, the number of cases in 2009 is consistent with the average number of cases reported during the preceding 4 years. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. Furthermore, treatment of malaria, while appropriate for the majority of cases, was insufficient for a large number of P. vivax and P. ovale infections, putting patients at risk for relapsing malaria. PUBLIC HEALTH ACTIONS: Decreasing the number of malaria cases in subsequent years will require conveying the importance of adhering to appropriate preventive measures for malaria specifically targeting travelers visiting friends and relatives, missionary, and pregnant populations. Clinicians require education on the need to encourage use of malaria prophylaxis and need further information on the appropriate diagnostic and treatment guidelines for malaria. Malaria prevention recommendations are available online (http://www.cdc.gov/malaria/travelers/ or http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/malaria.aspx#990). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the individual patient's age and medical history, the likely site of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Clinicians should consult the CDC Guidelines for Treatment and contact the CDC's Malaria Hotline for case management advisement when needed. Malaria treatment recommendations can be obtained online (http://www.cdc.gov/malaria/diagnosis_treatment) or by calling the Malaria Hotline (770-488-7788).

Malaria surveillance - United States, 2008.

PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in patients with onset of illness in 2008 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are mandated to be reported to local and state health departments by health-care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), and direct CDC consultations. Data from these reporting systems are the basis for this report. RESULTS: CDC received reports of 1,298 cases of malaria with an onset of symptoms in 2008 among patients in the United States, a decrease of 13.8% from the 1,505 cases reported for 2007 (p<0.001). These cases included one cryptic [corrected] case, one congenital case, and two fatal cases. Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 40.6%, 14.6%, 1.5%, and 1.4% of cases, respectively. The first documented case of simian malaria, P. knowlesi, was reported in a U.S. traveler. Eight (0.6%) of the 1,298 patients were infected by two or more species. The infecting species was unreported or undetermined in 41.2% of cases. Based on estimated volume of travel from the World Tourism Organization, the highest estimated relative case rates of malaria among travelers occurred among those returning from countries in West Africa. A total of 508 U.S. civilians acquired malaria abroad; among the 480 civilians for whom chemoprophylaxis information was known, 344 (71.7%) reported that they had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Fourteen cases were reported in pregnant women, among whom none adhered to a complete prevention drug regimen. INTERPRETATION: A significant decrease in the number of malaria cases occurred from 2007 to 2008. No change occurred in the proportions of cases caused by the various Plasmodium species. U.S. civilians traveling to countries in West Africa had the highest estimated relative case rates. In the majority of reported cases, U.S. civilians who acquired malaria abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired the infection. PUBLIC HEALTH ACTIONS: Persons traveling to an area in which malaria is endemic should take steps to prevent malaria, which might include taking one of the recommended chemoprophylaxis regimens appropriate for the region of travel and using personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should always include blood-film tests for malaria with results available immediately. Malaria infections can be fatal if not diagnosed and treated promptly. Malaria prevention recommendations are available from CDC online (http://wwwn.cdc.gov/travel/contentDiseases.aspx#malaria) or by calling the Malaria Hotline (telephone 770-488-7788). Malaria treatment recommendations can be obtained from CDC online (http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm) or by calling the Malaria Hotline.

Malaria surveillance--United States, 2006.

PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, and P. malariae). These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in persons with onset of illness in 2006 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film or polymerase chain reaction (PCR) are mandated to be reported to local and state health departments by health-care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), and direct CDC consultations. Data from these reporting systems serve as the basis for this report. RESULTS: CDC received reports of 1,564 cases of malaria among persons in the United States with onset of symptoms in 2006, six of which were fatal. This is an increase of 2.4% from the 1,528 cases reported for 2005. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 39.2%, 17.6%, 2.9%, and 3.0% of cases, respectively. Ten patients (0.6%) were infected by two or more species. The infecting species was unreported or undetermined in 36.6% of cases. Compared with 2005, the largest increases in cases were from Asia (16.0%). Based on estimated volume of travel, the highest estimated relative case rates of malaria among travelers occurred among those returning from West Africa. Of 602 U.S. civilians who acquired malaria abroad and for whom chemoprophylaxis information was known, 405 (67.3%) reported that they had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Seventeen cases were reported in pregnant women, among whom only one reported taking chemoprophylaxis precautions. Six deaths were reported; five of the persons were infected with P. falciparum and one with P. malariae. INTERPRETATION: Despite the 2.4% increase in cases from 2005 to 2006, the numbers of malaria cases remained relatively stable during 2001--2006. No change was detected in the proportion of cases by species responsible for infection. U.S. civilians traveling to West Africa had the highest estimated relative case rates. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. PUBLIC HEALTH ACTIONS: Additional investigations were conducted of the six fatal cases that occurred in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should always include blood-film tests for malaria, with results made available immediately. Malaria infections can be fatal if not diagnosed and treated promptly. CDC recommendations concerning malaria prevention are available at http://wwwn. cdc.gov/travel/contentdiseases.aspx#malaria or by calling the CDC Malaria Branch on weekdays (telephone: 770-488-7788; Monday--Friday, 8:00 A.M.--4:30 P.M. EST); during evenings, weekends, and holidays, call the CDC Director's Emergency Operations Center (telephone: 770-488-7100), and ask to page the person on call for the Malaria Branch. Recommendations concerning malaria treatment are available at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the CDC Malaria Hotline.

Malaria surveillance - United States, 2005.

PROBLEM/CONDITION: Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to or from areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in persons with onset of illness in 2005 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film or polymerase chain reaction (PCR) are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,528 cases of malaria, including seven fatal cases, with an onset of symptoms in 2005 among persons in the United States or one of its territories. This number represents an increase of 15.4% from the 1,324 cases reported for 2004. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 48.6%, 22.1%, 3.5%, and 2.5% of cases, respectively. Twelve patients (0.8% of total) were infected by two or more species. The infecting species was unreported or undetermined in 22.6% of cases. Compared with 2004, the largest increases in cases came from the Americas (23.1%; n = 213) and Asia and the Middle East (18.6%; n = 204). On the basis of estimated volume of travel, the highest estimated case rates of malaria among travelers occurred among those returning from West Africa. Of 870 U.S. civilians who acquired malaria abroad, only 160 (18.4%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Two patients became infected in the United States, both attributed to congenital transmission; both were infected with P. vivax. Seven deaths were attributed to malaria, all caused by infection with P. falciparum. INTERPRETATION: The 15.4% increase in malaria cases in 2005, compared with 2004, resulted primarily from increases in the number of cases reported from Asia and the Middle East and from the Americas. This increase might in part reflect more complete reporting and in part increased travel to malarious areas. No change was noted in proportions of cases from other areas of the world, or in species responsible for the infection. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. U.S. civilians who traveled to West Africa had the highest estimated relative case rate. PUBLIC HEALTH ACTIONS: Additional investigations were conducted for the seven fatal cases and two infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include at least one blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC at http://www.cdc.gov/travel or by calling the Malaria Hotline (telephone 770-488-7788). Recommendations for malaria treatment can be obtained at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.

Malaria surveillance--United States, 2004.

PROBLEM/CONDITION: Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in persons with onset of illness in 2004 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,324 cases of malaria, including four fatal cases, with an onset of symptoms in 2004 among persons in the United States or one of its territories. This number represents an increase of 3.6% from the 1,278 cases reported for 2003. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 49.6%, 23.8%, 3.6%, and 2.0% of cases, respectively. Seventeen patients (1.3% of total) were infected by two or more species. The infecting species was unreported or undetermined in 262 (19.8%) cases. Compared with 2003, the number of reported malaria cases acquired in the Americas (n = 173) increased 17.7%, whereas the number of cases acquired in Asia (n = 172) and Africa (n = 809) decreased 2.8% and 3.7%, respectively. Of 775 U.S. civilians who acquired malaria abroad, only 160 (20.6%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Four patients became infected in the United States; three cases were attributed to congenital transmission and one to laboratory-related mosquitoborne transmission. Four deaths were attributed to malaria, including two caused by P. falciparum, one by P. vivax, and one by a mixed infection with P. falciparum and P. malariae. INTERPRETATION: The 3.6% increase in malaria cases in 2004, compared with 2003, resulted primarily from an increase in the number of cases acquired in the Americas but was offset by a decrease in the number of cases acquired in Africa and Asia. This limited increase might reflect local changes in disease transmission, increased travel to regions in which malaria is endemic, or fluctuations in reporting to state and local health departments. These changes likely reflect expected variation in annual reporting and should not be interpreted as indicating a longer-term trend. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. PUBLIC HEALTH ACTIONS: Additional investigations were conducted for the four fatal cases and four infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC at http://www.cdc.gov/travel or by calling the Malaria Hotline at telephone 770-488-7788. Recommendations concerning malaria treatment can be obtained at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.

Malaria surveillance--United States, 2003.

PROBLEM/CONDITION: Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. In the United States, cases can also occur through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report covers cases with onset of illness in 2003, and summarizes trends over previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,278 cases of malaria with an onset of symptoms in 2003, including seven fatal cases, among persons in the United States or one of its territories. This number represents a decrease of 4.4% from the 1,337 cases reported for 2002. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 53.3%, 22.9%, 3.6%, and 2.6% of cases, respectively. Twelve patients (0.9% of total) were infected by two or more species. The infecting species was unreported or undetermined in 212 (16.6%) cases. Compared with 2002, the number of reported malaria cases acquired in Asia (n = 177) and the Americas (n = 147) increased by 3.5% and 4.3% respectively, whereas the number of cases acquired in Africa (n = 840) decreased by 7.0%. Of 762 U.S. civilians who acquired malaria abroad, 132 (17.3%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Ten patients became infected in the United States, including one probable transfusion-related, one in which epidemiologic investigations failed to identify any apparent mode of acquisition, and eight which were introduced cases as a result of local mosquitoborne transmission. Of the seven deaths attributed to malaria, five were caused by P. falciparum, and a species was not identified in the other two. INTERPRETATION: The 4.4% decrease in malaria cases in 2003, compared with 2002, resulted primarily from a decrease in cases acquired in Africa, but this decrease was offset by an increase in the number of cases acquired in the Americas and Asia. This small decrease probably represents year-to-year variation in malaria cases, but also could have resulted from local changes in disease transmission, decreased travel to malaria-endemic regions, or fluctuation in reporting to state and local health departments. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country in which they acquired malaria. PUBLIC HEALTH ACTION: Additional information was obtained concerning the seven fatal cases and the 10 infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently experiences a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC by calling the Malaria Hotline at 770-488-7788 or by accessing CDC's Internet site at http://www.cdc.gov/travel. Recommendations concerning diagnosis of malaria and its treatment can be obtained by calling the Malaria Hotline or accessing CDC's Internet site at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm.