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Abstract

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. Most malaria infections in the United States and its territories occur among persons who have traveled to regions with ongoing malaria transmission. However, among persons who have not traveled out of the country, malaria is occasionally acquired through exposure to infected blood or tissues, congenital transmission, nosocomial exposure, or local mosquitoborne transmission. Malaria surveillance in the United States and its territories provides information on its occurrence (e.g., temporal, geographic, and demographic), guides prevention and treatment recommendations for travelers and patients, and facilitates rapid transmission control measures if locally acquired cases are identified.

Period Covered: This report summarizes confirmed malaria cases in persons with onset of illness in 2018 and trends in previous years.

Description of System: Malaria cases diagnosed by blood smear microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments through electronic laboratory reports or by health care providers or laboratory staff members directly reporting to CDC or health departments. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC clinical consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood specimens submitted by health care providers or local or state health departments. This report summarizes data from the integration of all cases from NMSS and NNDSS, CDC clinical consultations, and CDC reference laboratory reports.

Results: CDC received reports of 1,823 confirmed malaria cases with onset of symptoms in 2018, including one cryptic case and one case acquired through a bone marrow transplant. The number of cases reported in 2018 is 15.6% fewer than in 2017. The number of cases diagnosed in the United States and its territories has been increasing since the mid-1970s; the number of cases reported in 2017 was the highest since 1972. Of the cases in 2018, a total of 1,519 (85.0%) were imported cases that originated from Africa; 1,061 (69.9%) of the cases from Africa were from West Africa, a similar proportion to what was observed in 2017. Among all cases, P. falciparum accounted for most infections (1,273 [69.8%]), followed by P. vivax (173 [9.5%]), P. ovale (95 [5.2%]), and P. malariae (48 [2.6%]). For the first time since 2008, an imported case of P. knowlesi was identified in the United States and its territories. Infections by two or more species accounted for 17 cases (<1.0%). The infecting species was not reported or was undetermined in 216 cases (11.9%). Most patients (92.6%) had symptom onset <90 days after returning to the United States or its territories from a country with malaria transmission. Of the U.S. civilian patients who reported reason for travel, 77.0% were visiting friends and relatives. Chemoprophylaxis with antimalarial medications are recommended for U.S. residents to prevent malaria while traveling in countries where it is endemic. Fewer U.S. residents with imported malaria reported taking any malaria chemoprophylaxis in 2018 (24.5%) than in 2017 (28.4%), and adherence was poor among those who took chemoprophylaxis. Among the 864 U.S. residents with malaria for whom information on chemoprophylaxis use and travel region were known, 95.0% did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among 683 women with malaria, 19 reported being pregnant. Of these, 11 pregnant women were U.S. residents, and one of whom reported taking chemoprophylaxis to prevent malaria but her adherence to chemoprophylaxis was not reported. Thirty-eight (2.1%) malaria cases occurred among U.S. military personnel in 2018, more than in 2017 (26 [1.2%]). Among all reported malaria cases in 2018, a total of 251 (13.8%) were classified as severe malaria illness, and seven persons died from malaria. In 2018, CDC analyzed 106 P. falciparum-positive and four P. falciparum mixed species specimens for antimalarial resistance markers (although certain loci were untestable in some specimens); identification of genetic polymorphisms associated with resistance to pyrimethamine were found in 99 (98.0%), to sulfadoxine in 49 (49.6%), to chloroquine in 50 (45.5%), and to mefloquine in two (2.0%); no specimens tested contained a marker for atovaquone or artemisinin resistance.

Interpretation: The importation of malaria reflects the overall trends in global travel to and from areas where malaria is endemic, and 15.6% fewer cases were imported in 2018 compared with 2017. Of imported cases, 59.3% were among persons who had traveled from West Africa. Among U.S. civilians, visiting friends and relatives was the most common reason for travel (77.1%).

Public Health Actions: The best way for U.S. residents to prevent malaria is to take chemoprophylaxis medication before, during, and after travel to a country where malaria is endemic. Adherence to recommended malaria prevention strategies among U.S. travelers would reduce the number of imported cases. Reported reasons for nonadherence include prematurely stopping after leaving the area where malaria was endemic, forgetting to take the medication, and experiencing a side effect. Health care providers can make travelers aware of the risks posed by malaria and incorporate education to motivate them to be adherent to chemoprophylaxis. Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age, pregnancy status, medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Antimalarial use for chemoprophylaxis and treatment should be determined by the CDC guidelines, which are frequently updated. In April 2019, intravenous (IV) artesunate became the first-line medication for treatment of severe malaria in the United States and its territories. Artesunate was approved by the Food and Drug Administration (FDA) in 2020 and is commercially available (Artesunate for Injection) from major U.S. drug distributors (https://amivas.com). Stocking IV artesunate locally allows for immediate treatment of severe malaria once diagnosed and provides patients with the best chance of a complete recovery and no sequelae. With commercial IV artesunate now available, CDC will discontinue distribution of non–FDA-approved IV artesunate under an investigational new drug protocol on September 30, 2022. Detailed recommendations for preventing malaria are online at https://www.cdc.gov/malaria/travelers/drugs.html. Malaria diagnosis and treatment recommendations are also available online at https://www.cdc.gov/malaria/diagnosis_treatment. Health care providers who have sought urgent infectious disease consultation and require additional assistance on diagnosis and treatment of malaria can call the Malaria Hotline 9:00 a.m.–5:00 p.m. Eastern Time, Monday–Friday, at 770-488-7788 or 855-856-4713 or after hours for urgent inquiries at 770-488-7100. Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and public health efforts to prevent future infections and examine trends in malaria cases. Molecular surveillance of antimalarial drug resistance markers enables CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. A greater proportion of specimens from domestic malaria cases are needed to improve the completeness of antimalarial drug resistance analysis; therefore, CDC requests that blood specimens be submitted for any case of malaria diagnosed in the United States and its territories.

Introduction

Malaria, a febrile parasitic illness transmitted through the bite of an infective mosquito, was estimated to cause 241 million illnesses in 2020 and 627,000 deaths worldwide^[1]. In 2018, there were an estimated 228 million cases of malaria, globally, and 405,000 deaths^[2]. Malaria is transmitted in 85 countries, and approximately one half of the world population is at risk for infection^[1]. Since 2000, the global community has funded and implemented malaria control efforts and achieved an estimated 23 million fewer malaria cases in 2018 alone, compared with 2010, and cumulatively, these efforts have prevented millions of malaria deaths. However, during 2014–2018, the number of cases globally was stable^[2], and in 2020 the number of malaria cases increased compared with previous years, in part because of disruption of health services and interventions from the COVID-19 pandemic^[1]. In October 2021, the first malaria vaccine was recommended by the World Health Organization to protect infants and children aged 5–24 months living in moderate-to-high transmission areas^[3].

Plasmodium parasites that cause malaria are transmitted through the bite of an infective Anopheles mosquito, resulting in an intraerythrocytic illness, which can range from asymptomatic or mild to severe and fatal. Four species of Plasmodium cause illness in humans: P. falciparum, P. vivax, P. ovale species (caused by P. ovale curtisi and P. ovale wallikeri], and P. malariae. Simian malarias can also cause illness in humans, particularly P. knowlesi in Southeast Asia. P. falciparum causes the most infections worldwide; it is predominant in Africa where an estimated 95% of cases occur^[1,2], and partly because of a rapid replication rate, infections from this species can rapidly progress to severe illness, especially for infants and children aged <5 years and among persons who do not have acquired immunity^[4]. In 2018, P. vivax accounted for approximately 3% of cases worldwide. P. vivax is found in a broad geographical area and although it contributed <1% of cases in Africa, it made up 75% of cases in the Americas, 50% of cases in Asia, and approximately 30%–35% of cases in the Eastern Mediterranean and Western Pacific regions^[2]. Compared with P. vivax and P. falciparum, transmissions of P. ovale spp., P. malariae and P. knowlesi species are limited. Approximately 95% of P. ovale spp. cases were identified in Africa, with 5% in Asia^[5]. P. vivax and P. ovale parasites have a dormant stage (hypnozoite) in the liver, making relapse common during the period of 45 days to 3 years after an initial illness^[4]. P. vivax parasites transmitted in some areas of Asia can have a long incubation period, lasting 6 or more months from inoculation to symptom onset^[6–8]. P. malariae parasites are found throughout the tropics and subtropics and are often detected in mixed species infections. P. malariae parasites mature slowly in human and mosquito hosts and, although they do not typically cause severe symptoms in humans, can result in persistent low-density infections that can last for years, providing opportunities for ongoing transmission and health sequelae^[4,9]. P. knowlesi is predominantly a simian malaria found in Southeast Asia; however, it can be transmitted to persons, and in Malaysia, it has become the predominant species that causes malaria illness in humans^[10–12]. Exposure to forested areas with simian habitat is a risk factor for P. knowlesi, and these infections can be serious or fatal^[10,13].

Although malaria was eliminated from the United States* in the mid-1950s^[14], the Anopheles mosquito vector still exists throughout the United States^[15]. Since 1957, malaria surveillance has been supported to detect cases and prevent reintroduction, monitor antimalarial resistance, assess trends in case acquisition, and guide malaria prevention and treatment recommendations for U.S. residents. Most malaria cases diagnosed in the United States are imported from countries with ongoing mosquitoborne transmission. Occasionally, congenitally acquired cases, induced cases (resulting from exposure to blood or tissue products), and cryptic cases (for which exposure cannot be easily explained despite investigation by state and local health departments and CDC) occur. During 1957–2003, a total of 63 malaria outbreaks occurred in the United States. The last well-documented local mosquitoborne transmission occurred in 2003, when eight cases were diagnosed among nontravelers in Palm Beach, Florida^[16–18].

Clinical illness results from the presence of an asexual, intraerythrocytic stage of the parasite in red blood cells. Factors that contribute to variability in illness severity are complex and include the parasite species and density of infection, the patient’s age and immune response to the infection, the presence of acquired or protective immunity, the patient’s general health and nutritional constitution, chemoprophylaxis effects, and time to initiate appropriate treatment^[4]. Persons that live in areas with high malaria transmission who experience repeated malarial illnesses might develop partial protective immunity that can result in less severe illness or even asymptomatic parasitemia. However, without continual exposure, this semi-immunity will be lost within a few years^[19–21], and thus it is assumed that U.S. residents do not have any degree of protective immunity to malaria and are susceptible to severe illness and death. Although malaria symptoms vary by age and immunologic status, fever is the predominant symptom^[22]. Symptoms associated with uncomplicated malaria include chills, sweating, headache, fatigue, myalgia, cough, nausea, and mild anemia. If not treated promptly, malaria can rapidly progress and affect multiple organ systems and result in altered consciousness (cerebral malaria), seizures, severe anemia, acute kidney injury, liver failure, respiratory distress, coma, permanent disability, and death. Travel history should be routinely requested for patients with fever. All persons who have fever and who recently traveled to areas where malaria is endemic as well as persons who have unexplained fever, regardless of travel history, should be tested immediately for malaria.

To prevent malaria, CDC recommends that U.S. residents use chemoprophylaxis (i.e., antimalarial medication taken before, during, and after travel to a country with malaria transmission). Persons who intend to travel should ask their physician for a prescription for an antimalarial that is appropriate for the country or region of travel, the age of the patient, pregnancy status, and individual preferences (e.g., cost or regimen type [daily versus weekly]). CDC provides chemoprophylaxis guidelines to health care providers and the public (Table 1). Implementing mosquito avoidance measures provides additional protection and includes the use of repellents, use of permethrin-treated clothing, sleeping in screened sleep spaces, and using an insecticide-treated bed net^[23].

This report summarizes malaria cases reported to CDC with onset of symptoms in 2018, describes trends during previous years, and highlights information on risk factors and prevention. The intended audience includes public health authorities, health care providers, and persons traveling to areas with malaria transmission. Information on chemoprophylaxis, diagnosis, and treatment is provided for health care professionals and the public, and links to additional malaria information and resources are provided.