Malaria Surveillance — United States, 2018

Results

General Surveillance

CDC received 1,823 reports of confirmed malaria cases among persons tested in the United States with onset of symptoms in 2018 (Table 2). These cases represented a 15.6% relative decrease from 2017 (n = 2,161), which had the most reported confirmed cases since 1971 when there were 3,180 cases (51) (Figure 1). Of the 1,823 cases reported in 2018, a total of 1,788 (98.1%) were imported from countries where malaria was endemic, one case was induced from a bone marrow transplant, and one was investigated and classified as cryptic. Of the 33 (1.8%) cases that were unable to be classified, 15 of these reports contained only laboratory or demographic information, and 18 patients were lost to follow-up for the case investigation. In 2018, of the 1,823 confirmed cases, 58.5% occurred among U.S. civilians, 2.1% among U.S. military personnel, 20.6% among non-U.S. residents, and 18.9% among persons for whom residence status was not reported (Table 2 and Table 3). In 2018, seven persons in the United States died from malaria.

Since 1972, the numbers of malaria cases have been increasing, with an average gain of 29.2 cases per year (R² = 0.753) (Table 2 and Figure 1). The number of malaria cases among the U.S. civilian population has increased over time, with approximately 22 cases added each year during 1972–2018 (R² = 0.888). In contrast, the trajectory of the accumulation of military and non-U.S. resident cases was flat during this period (R² = 0.021 and R² = 0.016, respectively) (Figure 1).

Among all cases identified in the United States, a total of 61.8% of patients were male, 76.6% were adults aged 18–64 years, and 67.1% were Black or African American (76.1% among patients with known race), and 2.0% were Hispanic or Latino (Table 3). A total of 294 (16.1%) infants, children, and adolescents aged <18 years received a diagnosis of malaria in the United States in 2018, and 66 (22.5%) of these were aged <5 years. In 2018, a total of 132 persons with malaria were aged ≥65 years.

The primary reason for travel was reported for 1,330 (74.4%) of 1,788 imported cases (Table 3). Of these, more than one half of all cases (833 [62.6%]) and more than three fourths of U.S. civilian cases (673 [77.0%]) reported traveling to visit friends and relatives (VFR). In 2018, the number and proportion of cases in non-U.S. residents that traveled to the United Sates to visit family or friends decreased (82 cases [26.0%] in 2018 compared with 144 cases [35.2%] in 2017). Traveling to the United States as an immigrant or refugee was reported for 183 patients (13.8%). Others reported traveling for tourism (86 cases [6.5%]), business (81 cases [6.1%]), missionary (55 cases [4.1%]), or for education as a student or teacher (42 cases [3.1%]). Traveling as part of an air or ship crew, Peace Corps, foreign military, or for other reasons was reported by <1.0% of patients. In 2018, a total of 183 (58.1%) non-U.S. residents with malaria reported having traveled to the United States as a refugee or immigrant. This is a proportional increase compared with the 186 cases (45.5%) in non-U.S. residents who had traveled to the United States as a refugee or immigrant in 2017.

Among the 1,788 cases of malaria imported into the United States in 2018, a total of 1,768 cases (98.9%) had information reported for the month of illness onset (Figure 2). Overall, the mean number of imported cases per month was 147.3. More cases than average were reported for May–September; the highest number of cases (231) was reported in August followed by July (210) and September (198). The lowest number of cases occurred in February (60 cases) and March (75 cases). P. falciparum cases accounted for approximately 70.3% of cases reported with seasonal information, and approximately 103.6 P. falciparum cases were reported per month. P. vivax and P. ovale cases, including 13 mixed infections containing P. vivax or P. ovale, together accounted for approximately 15.2% of all cases with seasonal information, with an average of 22.4 cases per month. In 2018, the number of imported malaria cases was 324 less than the imported malaria cases in 2017 (2,112 imported malaria cases in 2017, of which 2,009 [95.1%] had information on the month of illness onset). The seasonal trends were similar between the years.

Plasmodium Species

In 2018, a total of 1,607 (88.2%) cases reported the Plasmodium species, a similar proportion to 2017 (1,935 cases [89.5%]) (Table 4). Specimens from 209 (11.5%) malaria patients were sent to CDC for confirmatory diagnostic testing and CDC was able to determine the species for 195 (93.3%) of them.

Among the 1,607 cases with Plasmodium species determined, most cases speciated were P. falciparum (1,273 cases) (Table 4). Although this is the highest proportion (79.2%) of P. falciparum cases reported during 2014–2018, it is fewer than the numbers of cases identified in 2016 and 2017 (1,419 [76.6%] in 2016 and 1,523 [78.7%] in 2017). During 2014–2018, there was an average increase of 76.2 P. falciparum cases per year. In 2018, a total of 173 (10.8%) P. vivax cases were confirmed, a similar proportion to what was observed in 2017 (216 cases [11.2%]). During 2014–2018, there has been a decreasing trend in the number of P. vivax cases, with an average of 7.8 fewer cases per year. Approximately 6% of cases in 2018 (95 [5.9%] and 2017 (119 [6.2%]) were P. ovale; approximately 3% of cases were P. malariae (48 [3.0%] in 2018 and 55 [2.8%] in 2017). For the first time since 2008, there was one imported P. knowlesi case (52,53). The adult patient had traveled to Southeast Asia and reported mosquito exposures while in forests. It is unknown if the patient took chemoprophylaxis to prevent malaria. The patient experienced uncomplicated malaria, was treated with atovaquone-proguanil, and recovered.

In 2018, a total of 17 (1.1%) malaria cases with mixed species were reported, a similar proportion to that in 2017 (22 cases [1.1%]). Of the mixed species malaria cases, 14 were from Africa, two from South America, and one from an unknown region. Nine malaria cases with mixed infections were P. falciparum and P. ovale (seven were PCR confirmed; eight cases came from Africa and one from an unknown country); four cases were P. falciparum and P. malariae (all PCR confirmed; all came from Africa); two cases were P. falciparum and P. vivax (both PCR confirmed; both came from South America); one case was P. malariae and P. ovale (not PCR confirmed; came from Africa); and one was P. vivax and P. ovale (PCR confirmed; came from Africa).

Of the 1,788 imported malaria cases in 2018, a total of 692 (38.7%) were PCR confirmed (Table 5). Among all 1,823 cases, 705 (38.7%) were PCR confirmed in 2018, more than the proportion of PCR confirmed in 2017 (764 cases [35.4%]). This includes the P. knowlesi case, and 82.4% of the reported cases with mixed infections (14 of 17 cases). Approximately one half of all P. ovale and P. malariae cases were PCR confirmed (51 of 95 [53.7%] of P. ovale, and 24 of 48 [50.0%] of P. malariae). A total of 542 (42.6%) of P. falciparum and 62 (35.8%) of P. vivax cases were PCR confirmed. Eleven cases (5.0%) with unknown species reported were PCR confirmed to the Plasmodium genus level.

Among the 1,584 imported malaria cases with the Plasmodium species determined, 1,238 (78.2%) had complete information on the travel return and illness onset dates allowing for calculation of the interval between these dates (Table 6). Among these patients, regardless of infecting species, 173 (14.0%) had illness onset before the return to the United States and 1,063 (85.9%) had illness onset before or within 29 days of arrival to the United States. Among patients with P. falciparum, 99% had illness onset before return to, or less than 90 days from the date of arrival to the United States (994 of 1,004 cases). In contrast, approximately 40% of P. vivax and P. ovale patients had illness onset 90 or more days after their return to the United States (51 [40.8%] of P. vivax cases, and 26 [40.6%] of P. ovale cases), consistent with the potential for these species to relapse because of the persistence of liver hypnozoites, or to have an extended incubation period before symptom onset (4,6–8). Of infections with any species reported, 98.9% (1,224 cases) had illness onset within 1 year of returning from a country where malaria is endemic. Twelve of 14 infections that occurred more than 1 year after return to the United States were P. vivax (eight cases) and P. ovale (four cases). Of the two P. falciparum cases with illness reported more than 1 year after return, one was a PCR-confirmed infection in an asymptomatic bone marrow transplant donor (see induced case summary for more information), and the other case was blood smear confirmed infection in a U.S. resident who had traveled to West Africa,^§ with no reason for travel or travel duration reported.

Among all 1,823 malaria cases, information on history of malaria for the infected patient in the previous year was available for 1,285 (70.5%) cases; of these, 244 (19.0%) patients had malaria previously, and all cases were imported. Of the 14 mixed species infections with information, eight (57.1%) patients reported a previous history of malaria, as did 48.0% (61 of 127 cases) of patients with P. vivax, 27.8% (20 of 72 cases) with P. ovale, 22.2% (eight of 36 cases) with P. malariae, and 13.8% (128 of 927 cases) with P. falciparum infections. Among cases where the species of the current illness was known, the species of the previous infection was identified for 43 patients with a history of malaria (22 were P. falciparum, 19 were P. vivax, and one each was P. ovale and P. malariae). Concordance between the species of the acute illness and the reported prior illness was observed for 37 (86.1%) of 43 reports containing information on the species of the prior infection (19 were P. vivax infections, 17 were P. falciparum, and one was P. ovale). The 20 cases in patients currently and previously infected with P. vivax or P. ovale were considered possible relapses because these species can retain dormant hypnozoites, and the previously reported infection was with the same species; other relapse cases might have occurred, although they could not be classified as such because of missing information reported. Fourteen (70.0%) possible relapse cases had information on the time between the previous and current illnesses; the mean number of days between previous and relapsing illness was 187.6 days (range: 52–377 days). Of the 19 likely P. vivax relapse cases, eight originated from Africa, six cases from Asia, three cases were from South America, and one each from Oceania and Central America. One likely P. ovale relapse case was from Africa. Date information for the previous illness was reported for six of 17 P. falciparum infections with a history of malaria and concordant prior species reported, and three (50.0%) of these indicated that the prior illness occurred within 35 days from the current illness, suggesting that treatment failure might have contributed to the current illness diagnosed in the United States.

Region of Acquisition and Diagnosis

The region of travel was reported for 1,722 (96.3%) of the 1,788 imported cases (Table 3). Of these, 1,519 (88.2%) cases were acquired in Africa, 141 (8.2%) in Asia, 35 (2.0%) in South America, 21 (1.2%) in Central America and the Caribbean, and six (<1.0%) in Oceania. Of the 1,519 cases acquired in Africa, 1,061 cases (69.8%) were from West Africa. No differences in the proportions of cases by region in 2018 were observed compared with 2017; however, in 2018, there was an increase in cases with an unknown region of acquisition (66 cases [3.7%] in 2018 versus 39 cases [1.9%] in 2017). The proportion of cases from Africa was comparable in 2018 (88.2%) and 2017 (87.8%), and in both years, approximately two thirds of cases acquired in Africa originated from West Africa (1,061 of 1,519 cases [69.8%] in 2018; 1,216 of 1,819 cases [66.9%] in 2017). Four of the five countries where the highest number of cases were acquired in 2018 were within West Africa (Nigeria, 402 cases; Sierra Leone, 152 cases; Ghana, 132 cases; Liberia, 122 cases); 103 cases were acquired from Cameroon, in Central Africa, which is the fifth highest country of acquisition. The top five countries of acquisition were the same in 2017. Ninety-two percent of U.S. civilians acquired malaria in Africa, (970 [92.3%]), and among these, 713 (73.5%) were from West Africa; this is a higher proportion than in 2017 (1,162 [90.1%] cases from Africa, and of these, 796 [68.5%] cases from West Africa). In 2018, a greater proportion of U.S. civilians (970 cases [92.3%]) had acquired malaria from Africa than non-U.S. resident (304 cases [81.7%]). Likewise, a greater proportion of U.S. residents acquired malaria from West Africa (713 [67.8%]) compared with non-U.S. residents (170 [45.7%]).

A similar proportion of imported malaria cases was acquired from Asia in 2018 (7.9%) as in 2017 (8.6%), although there were 40 fewer cases from this region in 2018 (181 cases in 2017 versus 141 cases in 2018). Most of the cases (122 cases [86.5%]) acquired from Asia in 2018 originated from India (53 cases), Afghanistan (53 cases), and Pakistan (16 cases). A decrease in cases from India accounts for the fewer cases originating from Asia (105 cases from India in 2017 versus 53 cases from India in 2018); whereas the numbers of cases from Afghanistan and Pakistan were steady in these years (48 and 53 cases from Afghanistan, and 18 and 16 cases from Pakistan, in 2017 and 2018, respectively). Less than 4% of U.S. residents acquired malaria from Asia (40 cases [3.9%]), compared with 14.5% of non-U.S. residents (54 cases).

Less than 2% of malaria cases were acquired from South America (35 cases [2.0%]) and from Central America or the Caribbean (21 cases [1.2%]), comparable to cases from these regions in 2017. As in 2017, in 2018, six (<1.0%) persons acquired malaria from Papua New Guinea in the Oceania region.

The primary reason for travel and the region of acquisition were known for 1,321 (73.9%) of 1,788 imported cases (Table 7). Of 828 patients who were VFR travelers, 776 (93.7%) traveled in Africa, and VFR traveling accounted for 66.7% of cases acquired in Africa. A total of 143 refugee or immigrant patients (79.0%) traveled from Africa, 37 (20.4%) from Asia, and one from Central America and the Caribbean (<1%).

Confirmed malaria cases were classified according to location of diagnosis or residence of the infected person. All U.S. states and reporting jurisdictions (e.g., New York City and Washington, DC) reported at least two malaria cases in 2018; in addition, the Commonwealth of the Northern Mariana Islands reported one malaria case. States and territories reporting one or more cases were categorized into quartiles (Figure 3). The 14 states in the upper quartile account for 74.5% of cases (1,359 cases) and include New York City (234 cases), Maryland (193 cases), Texas (143 cases), California (100 cases), New Jersey (94 cases), Pennsylvania (93 cases), Florida (70 cases), Virginia (66 cases), Georgia (66 cases), New York State (63 cases [not including New York City]), Illinois (63 cases), Massachusetts (60 cases), Ohio (57 cases), and Minnesota (57 cases). Thirteen of 14 states in the upper quartile were the same in 2017 and 2018; in 2018, Illinois gained 10 cases compared with 2017 (53 cases) and was included in the upper quartile for this year.

Chemoprophylaxis Use Among U.S. Residents

Among 1,788 imported malaria cases in 2018, a total of 1,102 were U.S residents (civilian and military personnel), and information about chemoprophylaxis use was reported for 974 (88.4%). Approximately 735 (75%) of these patients reported not taking any malaria chemoprophylaxis medication, a larger proportion than what was observed in 2017 (829 [71.7%] of 1,157 U.S. residents with data on prophylaxis use). Altogether, among the 864 U.S. resident imported cases with complete information on chemoprophylaxis, 43 (5.0%) were adherent to an appropriate regimen, 745 (86.2%) did not take chemoprophylaxis or took a regimen that was not consistent with CDC treatment guidelines, and 76 (8.8%) took an appropriate prevention medication but missed doses. The proportion of U.S. resident cases who were adherent to a correct chemoprophylaxis regimen in 2018 was similar to that observed in 2017 (67 patients [6.7%]).

Although approximately equal numbers of the 239 U.S. resident patients who took any chemoprophylaxis were VFR travelers (120 patients [50.2%]) or persons who traveled for other reasons (119 patients [49.8%]), a lower proportion of VFR travelers (17.7% of 677 patients) reported taking any prophylaxis compared with non-VFR travelers (28.0% of 425 patients). Of the 239 patients who reported taking any chemoprophylaxis for preventing malaria during travel, 146 reports provided the name of the antimalarial taken; 48 (32.9%) took doxycycline, 42 (28.8%) took atovaquone-proguanil, 32 (21.9%) took mefloquine, seven (4.8%) took chloroquine, three (2.1%) took primaquine, and 14 (9.6%) took two or more antimalarials for prophylaxis. Among all patients who reported taking any prophylaxis, 200 (83.7%) provided information on adherence; 133 (66.5%) patients did not take all doses, and of these, 89 (66.9%) provided at least one reason why chemoprophylaxis doses were missed. Multiple reasons for missing chemoprophylaxis medications could be provided for each patient, and these reasons included forgetting to take the medication (30 patients [33.7%]); prematurely stopping prophylaxis after returning home from travel (24 patients [27.0%]); running out of the medication during travel (16 patients [18.0%]); incorrectly taking the medication (nine patients [10.1%]); reporting that the prophylaxis was not needed (seven patients [7.9%]); having lost, stolen or destroyed medication (four patients [4.5%]); being advised by others to stop (two patients [2.2%]); and other reasons (four patients [4.5%]). Chemoprophylaxis regimens differ in the requirement to adhere to them after travel is concluded; doxycycline and mefloquine should be taken for 28 days after return, and atovaquone-proguanil should be taken for 7 days after return (34). Of the 24 persons who reported missing doses of chemoprophylaxis because they stopped it prematurely after travel, the name of the chemoprophylaxis medication was reported for 19 (79.2%) persons. Regimens that had longer posttravel requirements were more commonly stopped prematurely; 10 (52.6%) patients took doxycycline alone, four (21.1%) patients took mefloquine alone, two (10.5%) patients took doxycycline or mefloquine along with primaquine, and three (15.8%) patients took atovaquone-proguanil.

Of 146 patients who reported the name of the chemoprophylaxis antimalarial taken to prevent malaria, 144 (98.6%) also had the country of acquisition reported so that the appropriateness of the regimen could be ascertained. Of these, 134 (93.1%) reported taking an antimalarial that was correct for the region of travel and 10 (6.9%) did not take a recommended medication. Of 134 patients who took a correct prophylaxis regimen for the region of travel, adherence information was reported for 119 (88.8%) patients and 76 (63.9%) reported missing doses.

Of the 43 persons who reported taking all doses of an appropriate chemoprophylaxis regimen, 23 (53.5%) had P. falciparum infections, 11 (25.6%) P. vivax, five (11.6%) P. ovale, two (4.7%) P. malariae, and two (4.7%) an undetermined species. Primary prophylaxis can prevent acute illness of P. vivax and P. ovale infections, although patients might experience a relapsing infection unless primaquine was taken to eliminate dormant hypnozoites (radical cure). For the 16 patients who reported adherence to chemoprophylaxis and were infected with P. vivax or P. ovale parasites, seven patients had traveled in Asia; six in Africa; and one each in Central America and the Caribbean, South America, and Oceania. Of these 16 patients, five took mefloquine for prophylaxis, four took atovaquone-proguanil, two took doxycycline, and five patients took two or more antimalarials for chemoprophylaxis. The time between return to the United States and onset was available for 14 of 16 patients with P. vivax or P. ovale infections; of these, 11 (78.6%) had onset dates more than 45 days from return, suggesting that the infection could be consistent with a relapsing illness.

Of the 25 patients who reported complete adherence to an appropriate chemoprophylaxis regimen and were infected with P. falciparum (n = 23) and P. malariae (n = 2), all had traveled to Africa. Twenty-one had information on the interval between the return date and onset of illness; of these, 20 (95.2%) had illness onset within 30 days of return to the United States, nine took atovaquone-proguanil, seven took doxycycline or mefloquine, and two took two or more antimalarials for prevention.

In 2018, specimens were not tested for molecular markers of resistance for any of the patients who reported adherence to chemoprophylaxis. Possible explanations for nonrelapsing Plasmodium infections (e.g., P. falciparum or P. malariae) in patients who adhered to chemoprophylaxis include inadequate dosing or malabsorption of the medication, inaccurate reporting of adherence, emerging parasite resistance, or chemoprophylaxis failure.

Uncomplicated Malaria

Among the 1,823 confirmed malaria cases in 2018, a total of 1,572 (86.2%) were uncomplicated, a similar proportion to 2017 (85.6%). Treatment information was reported for 1,296 (82.4%) of cases with uncomplicated malaria, and the most common antimalarial treatment administered was atovaquone-proguanil, given to 789 (60.9%) of 1,296 patients with medications recorded, followed by artemether-lumefantrine for 213 (16.4%) patients. A quinine regimen was recorded for 159 (12.3%) patients, chloroquine for 91 (7.0%) patients, and mefloquine for 40 (3.1%) patients.

Among 1,572 patients with uncomplicated malaria, 988 (62.8%) were hospitalized for their illness. Of the 1,059 patients with uncomplicated P. falciparum infections, 700 (66.1%) were hospitalized; of the 165 patients with uncomplicated P. vivax infections, 115 (69.7%) were hospitalized; of the 88 patients with uncomplicated P. ovale infections, 61 (69.3%) were hospitalized; of the 45 patients with uncomplicated P. malariae infections, 23 (51.1%) were hospitalized; of the 15 patients with uncomplicated mixed species infections, five (33.3%) were hospitalized; and of the 199 patients with unknown species of malaria, 84 (42.2%) were hospitalized. One patient with an uncomplicated P. knowlesi infection was not hospitalized.

The CDC Guidelines for Treatment of Malaria in the United States, herein referred to as the CDC guidelines, provide guidance for the treatment of malaria according to species, disease severity, pregnancy status, and region of acquisition (32). Of the 1,572 patients with uncomplicated malaria, 1,282 (81.6%) patients had records containing treatment and travel information; appropriate treatment was given to 1,176 (91.7%) patients. Of 1,032 patients with uncomplicated P. falciparum illness, information was available to determine appropriateness of treatment for 911 (88.3%), and treatment was given according to guidelines for 861 (94.5%) patients. In 2018, there were 45 patients with uncomplicated P. malariae and one with P. knowlesi infections; among these 46 patients, sufficient information was recorded for 37 (80.4%), and appropriate treatment was given to 35 (94.6%).

Among 281 patients with confirmed P. vivax or P. ovale infections (including 13 mixed infections with P. vivax or P. ovale), 265 (94.3%) of these were uncomplicated; one patient with a P. vivax infection was pregnant. In addition to an antimalarial for the acute infection, an 8-aminoquinoline (in 2018 primaquine was the only option) is recommended to prevent P. vivax or P. ovale relapse among persons who are not pregnant and who are glucose-6-phosphate dehydrogenase (G6PD) competent. Of the 265 patients with uncomplicated P. vivax or P. ovale species infections, treatment and travel data were available for 225 (84.9%). Appropriate treatment for the acute illness was given to 194 (86.2%) patients with uncomplicated infections with P. vivax or P. ovale. Primaquine to prevent relapsing illness because of dormant hypnozoites was reported as treatment for 102 (52.6%) of these patients. A total of 137 patients with uncomplicated malaria were given primaquine; 18 persons with P. falciparum or P. malariae infections had documented primaquine treatment, which is not recommended. Seventeen patients with unknown species determination were given primaquine.

Of 1,572 patients with uncomplicated malaria, 223 (14.2%) reported a history of malaria in the previous 12 months, a similar proportion to what was observed in 2017 (280 [15.1%] of 1,849 patients with uncomplicated malaria). The species for the current, acute illness was reported for 206 (92.4%) of these patients, and 117 (56.8%) were P. falciparum, 59 (28.6%) were P. vivax, 16 (7.8%) were P. ovale, and seven (3.4%) each were P. malariae and mixed species infections.

Severe Malaria

In 2018, there were 251 (13.8%) patients with severe malaria; this is similar to 2017, when 312 (14.4%) patients had severe malaria. Seven patients with severe illness died from malaria (2.8%) and all were infected with P. falciparum. The patient with an induced malaria infection (acquired from a bone marrow transplant) and the patient with a cryptic infection (where the origin was not determined) had severe malaria. A total of 177 (70.5%) patients with severe malaria were adults aged 18–64 years; 48 (19.1%) were infants, children, and adolescents aged <18 years, and 26 (10.4%) were adults aged ≥65 years. Of the 48 pediatric patients with severe malaria, 12 (25.0%) were aged <5 years. Of all 1,397 adults aged 18–64 years with malaria, 12.7% had severe malaria; this is a lower proportion than the 132 adults aged ≥65 years, of which 19.7% had severe malaria. Of the 294 infants, children, and adolescents aged <18 years with malaria, 16.3% had severe malaria; of the 66 infants and children aged <5 years with malaria, 18.2% had severe malaria. These proportions were similar to adults aged 18–64 years. Four patients with severe malaria were pregnant.

Among the 251 patients with severe malaria, the species was determined for 234 (93.2%). A total of 214 persons (91.5%) had P. falciparum infections, eight (3.4%) had P. vivax, seven (3.0%) had P. ovale, and approximately 1% had P. malariae (3 [1.3%]) or mixed species (2 [0.9%]) infections. The residence status was recorded for 218 (86.9%) of 251 severe cases, and 174 (79.8%) patients were civilian U.S. residents, four (1.8%) were U.S. military patients, and 40 (18.3%) were non-U.S. residents. Among the 1,066 U.S. civilians with malaria, a higher proportion had severe cases (174 [16.3%]) compared with non-U.S. residents (40 of 375 [10.7%]). The residence status was recorded for six of the seven patients with fatal cases, and all were among U.S. civilians.

Of the 176 U.S. residents with imported severe malaria (civilian and military), chemoprophylaxis use was reported for 165 (93.8%), and 138 (83.6%) reported taking no chemoprophylaxis medication for malaria prevention before, during, or after travel. Of the 27 who reported taking any chemoprophylaxis, 10 did not provide information on the regimen or adherence, 14 took a regimen that was not consistent with CDC guidelines or missed doses of a correct regimen, and three reported taking all doses of a correct regimen. Of the three patients with severe malaria who adhered to a recommended chemoprophylaxis regimen, two took atovaquone-proguanil, and one took doxycycline. Potential reasons for chemoprophylaxis failure in these patients with severe malaria include inadequate dosing or malabsorption of the chemoprophylaxis medication, inaccurate reporting of adherence, or emerging parasite resistance.

Patients with severe malaria can have multiple clinical complications. Among patients with severe malaria in 2018, acute kidney injury was the most common complication and was experienced by 38 (15.1%) patients, cerebral malaria by 34 (13.5%) patients, acute respiratory distress syndrome by 22 (8.8%) patients, and severe anemia by 22 (8.8%) patients. Parasitemia was reported for 196 (78.1%) of 251 patients with severe malaria, and 134 (68.4%) of these had ≥5.0% parasitized red blood cells. CDC guidelines in 2018 stated that patients with severe malaria should be treated aggressively in an inpatient setting with IV quinidine gluconate or artesunate. Hospitalization status was reported for 250 (99.6%) severe cases, and 235 (94.0%) of these patients were hospitalized. Of the 251 patients with severe malaria, treatment information was available for 242 (96.4%), and parenteral treatment was administered to 151 (62.4%). Of the 151 patients who received parenteral treatment, 118 (78.1%) received quinidine gluconate, 21 patients received artesunate (13.9%), and 12 patients received both quinidine gluconate and artesunate (7.9%). Sufficient treatment and travel information was available for 238 (94.8%) of 251 patients with severe malaria to assess appropriateness of treatment, and 124 (52.1%) of patients with severe malaria did not receive treatment according to CDC guidelines; this is similar to what was observed in 2017 (45.2% of patients with severe malaria received inappropriate treatment). Patients with severe malaria were more likely to have inappropriate treatment (124 of 238 [52.1%]) compared with those with uncomplicated malaria (106 [8.3%] of 1,277).

Of 251 patients with severe malaria, 21 (8.4%) reported a history of malaria during the previous 12 months. This is a similar proportion to what was observed in 2017 (35 [11.2%] of 312 patients with severe malaria had a history of malaria). The species for the current, acute illness was reported for 19 of 21 patients with a history of malaria, and 11 of these were P. falciparum (57.9%), four (21.1%) were P. ovale, two (10.5%) were P. vivax and one each (5.3%) were P. malariae and mixed species infection. Among the 234 patients with severe malaria and the current infecting species determined, a higher proportion of patients with non-falciparum infections (eight of 20 [40.0%]) had recent illness compared with 11 (5.1%) of 214 patients with a current P. falciparum infection.

Special Populations

Military personnel. Among the 38 cases of malaria confirmed in U.S. military personnel, 25 cases were acquired from Asia (19 cases from Afghanistan and six cases from South Korea), 12 were from Africa (three cases from Africa, unspecified; five from West Africa; three from Eastern Africa; and one from Central Africa); and the country of acquisition was not reported for one case. Four military patients acquired malaria after traveling to Africa to visit friends and relatives, and travel was not deployment related. Twenty-five (65.8%) U.S. military personnel reported taking any prophylaxis; of these, seven (28.0%) took all doses of a correct regimen. Eleven P. falciparum and one P. ovale infections were acquired by U.S. military members who had traveled to Africa. Of the 25 military patients who had traveled to Asia, 24 infections were confirmed as P. vivax, and one patient did not have the species confirmed. The one military patient for whom the country of origin was unknown was infected with P. falciparum. Of the 25 military personnel who acquired malaria in Asia, complete information on the date of return to the United States after travel and the onset date was available for 22, and the mean time from the travel return date to symptom onset was 186.6 days. Four U.S. military patients had severe illness, two with P. falciparum acquired in Africa or an unknown country, and two with P. vivax acquired in Afghanistan. All four military patients with severe illness were treated with IV medication for severe malaria (three with quinidine and one with artesunate). All U.S. military patients recovered from their illness.

Pregnant women. Of 683 women, 19 (2.8%) were pregnant, 15 had uncomplicated illness, and four pregnant women had severe malaria. All pregnant women acquired malaria in Africa; 15 were P. falciparum, one was P. vivax, and three had infections where the species was not determined. The residence status for all pregnant women was reported, and 11 were U.S. residents (nonmilitary). Of the 11 pregnant women who were U.S. residents, nine traveled to visit friends and relatives, one for tourism, and one for an unknown reason. Of the eight non-U.S. residents who traveled to the United States, four were refugees or immigrants, two visited friends or family, and one each traveled to the United States for a medical reason or for an unknown reason. Five pregnant women reported having a history of malaria in the 12 months before the current illness, and four of them were non-U.S. residents.

Antimalarial drug choices to prevent or treat malaria during pregnancy are limited because of the safety profile of medications approved for pregnancy and drug resistance patterns. In most areas where malaria is endemic, only mefloquine is approved for chemoprophylaxis; until 2018, only mefloquine or quinine with clindamycin was recommended as treatment for uncomplicated malaria during pregnancy (32). Chloroquine for chemoprophylaxis or treatment of uncomplicated malaria is recommended only for pregnant women to use when their travel is within limited geographical areas where chloroquine-sensitive malaria is transmitted. Primaquine can cause hemolytic anemia among persons with G6PD deficiency and should not be administered during pregnancy. Of 11 pregnant women who were U.S. residents, 10 provided information on chemoprophylaxis use, nine did not take chemoprophylaxis to prevent malaria during travel, and one reported adhering to an unnamed medication for the prevention of malaria.

Of the 15 pregnant women with uncomplicated malaria, two were missing treatment information. Among the 13 pregnant women with uncomplicated malaria and sufficient information to assess the appropriateness of treatment, six were treated according to CDC guidelines (four with quinine and clindamycin and two with mefloquine). In April 2018, the treatment guidelines changed to recommend artemether-lumefantrine for pregnant women in the second or third trimester or in the first trimester if other options are not available and the benefits outweigh the risks (54). Five pregnant women with uncomplicated malaria were treated with artemether-lumefantrine in 2018; three had onset dates after the guidelines changed, and two were treated with artemether-lumefantrine before April 2018. The gestational age of the pregnancy was not documented on the malaria case report for any of the women receiving artemether-lumefantrine, making it difficult to assess the appropriateness of treatment for those treated after the update in recommendations. Two women with P. falciparum infections were administered inappropriate treatment; one was treated with atovaquone-proguanil and one with chloroquine and clindamycin. None of the pregnant women with uncomplicated malaria were administered primaquine.

Severe malaria in pregnant women should be treated aggressively with IV regimens; in the United States during 2018, the treatment options for severe malaria were quinidine-gluconate or artesunate. Three of the four patients with severe malaria were not treated according to guidelines. Two pregnant women with severe malaria were treated with oral medications only, and two women were treated with a parenteral antimalarial (quinidine-gluconate). Although pregnancy outcomes are not known, all pregnant women with severe malaria recovered, and no case of congenital malaria was reported in 2018.

Drug Resistance Markers

CDC received 154 (8.4%) whole blood specimens for molecular surveillance from patients who received a malaria diagnosis in 2018. A total of 43 of these specimens were PCR confirmed as P. vivax (n = 16), P. ovale (n = 17), P. malariae (n = 7), or as Plasmodium genus (n = 3); no molecular resistance testing was performed. For one specimen that was PCR confirmed as a mixed infection with P. falciparum and P. ovale, no amplification of resistance markers was achieved because of a low level of parasitemia. A total of 110 specimens, including 106 P. falciparum and four mixed species infections (three P. falciparum and P. malariae and one P. falciparum and P. ovale) underwent amplification and analysis of resistance mutations for at least one antimalarial drug (Table 8). The region of acquisition was known for 108 (98.2%) of 110 specimens tested for antimalarial resistance; of these, 107 (99.1%) were acquired from Africa and one (<1%) from Asia.

Of the 101 (98.2%) specimens that amplified for five pyrimethamine loci, two specimens (acquired from Africa) had no resistance markers, six (5.9%) had two resistance markers, and 93 (92.1%) had three or more resistance markers. A total of 103 specimens (96.6%) had five sulfadoxine resistance loci analyzed; 54 (52.4%) of these had no markers of resistance, 27 (26.2%) had one resistance marker, 15 (14.6%) had two resistance markers, and seven (6.8%) had three or more resistance marker mutations. All 110 specimens were examined for chloroquine resistance at five loci. No chloroquine resistant markers were identified for 60 (54.5%) specimens, one (<1%) specimen (from Asia) had two resistant markers, and 49 (44.5%) had three chloroquine resistance markers. Copy number variation of the mefloquine locus (pfmdr1) is associated with mefloquine resistance, and 99 (90.0%) specimens were examined; two (2.0%) specimens from Africa had more than one copy of pfmdr1. The genes associated with atovaquone and artemisinin (pfk13) resistance were evaluated in 96 (87.3%) and 110 (100%) specimens, respectively, and no markers of resistance were identified for either antimalarial.

Because of widespread resistance to pyrimethamine and sulfadoxine, CDC does not recommend using drugs containing these components to treat patients with malaria in the United States (32). All patients with chloroquine resistance markers had exposure to malaria in Africa or Asia, which are considered regions with chloroquine resistance, so this antimalarial is not recommended as treatment for these patients. The two patients with multiple copies of the mefloquine (pfmdr1) gene had traveled to Ivory Coast and Liberia to visit friends and relatives, both had uncomplicated malaria, and both were treated appropriately with atovaquone-proguanil and recovered; no prophylaxis use was reported for either patient.

Selected Malaria Case Reports

Cryptic Case

Patient. In early October, an otherwise healthy man aged 43 years developed onset of fever, weakness, arthralgias, and dark urine. Four days later, he was admitted to the hospital and received a diagnosis of severe P. falciparum malaria with 10.7% parasitemia and acute kidney injury. Quinidine was not available at the hospital or in the surrounding area, and he was started on an oral antimalarial regimen while artesunate was requested from CDC. The morning of his second day of admission, artesunate treatment was initiated and followed by oral atovaquone-proguanil, and the patient recovered.

Investigation. Patient blood specimens were sent to CDC, and PCR confirmed P. falciparum infection. The patient was interviewed twice, once by the health care provider and a second time by the state health department. The man was born in Ghana but had not lived there since 1995; he moved to the United States from Germany in 2008. His most recent international travel to a country where malaria is endemic was approximately 10 years earlier, and he denied having a recent history of malaria. The patient did not agree to a passport review, and no official travel documents could be verified. The patient did not report exposure to blood products, IV drug use, or another unusual exposure. No family or friends had been ill with a febrile illness, and the patient did not have an immunosuppressive condition. To rule out the possibility of local transmission, the state health department identified two additional patients who had received diagnoses of P. falciparum malaria with geographical and temporal proximity to the patient with cryptic malaria. One patient who lived approximately 20 miles away was diagnosed with P. falciparum that was acquired from travel to Togo 7 weeks before the patient with cryptic malaria had symptom onset. The other patient with P. falciparum had symptom onset approximately 4 weeks before the symptom onset of the patient with cryptic malaria and lived 6 miles from the patient with the cryptic case; this infection was acquired in Tanzania. Specimens from all three cases were submitted to CDC for PCR species confirmation and genetic characterization to determine parasite relatedness; drug resistance markers were evaluated, and neutral microsatellite analysis was conducted. Mutations observed in the pfcrt, pfdhps, pfdhfr, and pfmdr1 genes from all specimens were indicative of parasites acquired in Africa. Seven neutral microsatellites were examined, and the three specimens had different microsatellite profiles indicating that the parasites were unrelated. County mosquito surveillance data were reviewed to assess the possibility of local mosquitoborne transmission, but there were no Anopheles mosquitos trapped during the 2018 summer season in the county where the patient resides. It is unlikely that this case-patient with cryptic malaria acquired P. falciparum infection through local mosquitoborne transmission. Possible explanations for this cryptic case include nondisclosed travel or, less likely after 10 years, recurrence of malaria from late emergence of asymptomatic parasitemia.

Induced Case

Recipient. A woman aged 24 years with sickle cell disease received a familial bone marrow transplant (BMT). Fifteen days after the transplant, she experienced fever, and the following day Plasmodium parasites with 10% parasitemia were identified on a routine blood smear. The patient had no clinical complications documented, was treated with parenteral quinidine-gluconate, doxycycline, and atovaquone-proguanil, and recovered. CDC confirmed P. falciparum infection by microscopy and PCR.

Investigation. The recipient had never traveled to an area where malaria is endemic nor had she experienced a previous malaria illness. The BMT donor had traveled to Ghana 1.5 years before donation. Upon returning from travel, the donor reported malaria-like symptoms that eventually resolved. Blood smears at the time were negative, and the donor was not treated for malaria.

Donor specimens collected after the BMT were tested by CDC. No Plasmodium parasites were detected in the donor blood smear. A donor whole blood specimen was positive for P. falciparum by real-time PET-PCR with a cycle threshold value of 38, which is close to the threshold for positivity (40), indicating a low level of parasitemia. The donor was also positive for Plasmodium genus and P. falciparum antibodies, but negative for parasite antigens. Microsatellite genotype testing was performed on both recipient and donor specimens; however, this was successful only for the recipient specimen so the genetic signatures could not be compared. The investigation concluded that the recipient acquired a P. falciparum infection after a BMT from a donor with asymptomatic parasitemia.

Seven Fatal Cases

Six men and one woman died from severe malaria in the United States in 2018. Their mean age was 59.1 years; the youngest was aged 41 years and the oldest was aged 72 years. Three were Black or African American, three were White (one of whom was of Hispanic or Latino), and one had an unreported race. The residence status was reported for six of seven fatal cases, and all were among U.S. residents. All had traveled to countries in Africa and were infected with P. falciparum. The reason for travel was reported for six patients; three had traveled for business, one for tourism, one for education purposes, and one to visit friends or relatives. All patients sought care for their symptoms (range: within 2–14 days after symptoms onset), and six were hospitalized; the mean time from symptom onset to hospital admission was 7.2 days (range: 2–14 days). Two patients sought care 2–3 days after symptom onset, but received diagnoses of influenza, were discharged, and did not receive a prompt workup for malaria. One of these patients was found deceased at home 6 days after the first medical evaluation and received a diagnosis of malaria upon autopsy. Parasitemia was reported for five of seven patients, with a mean of 17.5% (range: 4%–30%). Clinical complications were reported for six cases and included renal failure (five patients), cerebral malaria (four patients), and acute respiratory distress syndrome (one patient). Antimalarial medication was administered to six patients: one was treated with oral medication alone, two were treated with quinidine-gluconate, one was treated with artesunate, and two were treated with both quinidine-gluconate and artesunate. Each fatal case had delayed diagnosis, delayed treatment, or inappropriate treatment for severe malaria. Four patients received appropriate parenteral treatment for severe malaria, but initial care seeking was delayed by 5–14 days. One patient sought care within 2 days of symptom onset, but the diagnosis of malaria was missed, and the patient died without further care. One patient sought care from a primary care provider within 3 days of symptom onset, but the diagnosis of malaria was missed, and the patient did not receive a diagnosis until 3 days later when brought to the emergency department in poor condition 6 days after symptom onset; appropriate treatment was given, but the patient died. One patient sought care within 2 days of symptom onset and received inappropriate (oral antimalarial) treatment for severe malaria.