Malaria Surveillance --- United States, 2000

Louise M. Causer, M.B.B.S.^1,2
Robert D. Newman, M.D.^1,2
Ann M. Barber²
Jacquelin M. Roberts, M.S.²
Gail Stennies, M.D.²
Peter B. Bloland, D.V.M.²
Monica E. Parise, M.D.²
Richard W. Steketee, M.D.^2
1Epidemic Intelligence Service
Epidemiology Program Office
²Division of Parasitic Diseases
National Center for Infectious Diseases

Abstract

Problem/Condition: Malaria is caused by four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). Malaria is 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 occur through exposure to infected blood products, by congenital transmission, or locally through mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.

Period Covered: Cases with onset of illness during 2000.

Description of System: Malaria cases confirmed by blood smear are 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 1,402 cases of malaria with an onset of symptoms during 2000 among persons in the United States or one of its territories. This number represents a decrease of 9.0% from the 1,540 cases reported for 1999. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 43.6%, 37.2%, 4.8%, and 2.3% of cases, respectively. Nine patients (0.6% of total) were infected by >2 species. The infecting species was unreported or undetermined in 161 (11.5%) cases. Compared with 1999, the number of reported malaria cases acquired in Africa decreased by 13.1% (n = 783), and a decrease of 3.3% (n = 238) occurred in cases acquired in Asia. Cases from the Americas decreased by 1.1% (n = 271) from 1999. Of 825 U.S. civilians who acquired malaria abroad, 190 (23.0%) 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, two through congenital transmission and two through probable induced transmission. Six deaths were attributed to malaria, four caused by P. falciparum, one caused by P. malariae, and one by P. ovale.

Interpretation: The 9.0% decrease in malaria cases in 2000, compared with 1999, resulted primarily from decreases in cases acquired in Africa and Asia. This decrease could have resulted from local changes in disease transmission, decreased travel to these regions, fluctuation in reporting to state and local health departments, or an increased use of effective antimalarial chemoprophylaxis. 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 Actions: Additional information was obtained concerning the six fatal cases and the 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 travelers should use 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 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.

Introduction

Malaria is caused by infection with one or more of four species of Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, and P. malariae) that can infect humans. The infection is transmitted by the bite of an infective female Anopheles sp. mosquito. Malaria infection remains a devastating global problem, with an estimated 300--500 million cases occurring annually (1). Forty-one percent of the world's population lives in areas where malaria is transmitted (e.g., parts of Africa, Asia, the Middle East, Central and South America, Hispaniola, and Oceania) (1), and 700,000--2.7 million persons die of malaria each year, 75% of them African children (2). In previous years, malaria was endemic throughout much of the continental United States; an estimated 600,000 cases occurred during 1914 (3). During the late 1940s, a combination of improved socioeconomic conditions, water management, vector-control efforts, and case management was successful at interrupting malaria transmission in the United States. Since then, malaria case surveillance has been maintained to detect locally acquired cases that could indicate the reintroduction of transmission and to monitor patterns of antimalarial drug resistance that guide prevention recommendations for U.S. travelers. Anopheline mosquitos remain seasonally present in all states except Hawaii.

Through 2000, the majority of cases of malaria diagnosed in the United States have been imported from regions of the world where malaria transmission is known to occur, although congenital infections and infections resulting from exposure to blood or blood products are reported in the United States also. In addition, a limited number of cases are reported that might have been acquired through local mosquitoborne transmission (4).

State and local health departments and CDC investigate malaria cases acquired in the United States, and CDC analyzes data from imported cases to detect acquisition trends. This information is used to guide malaria prevention recommendations for travelers abroad. For example, an increase in P. falciparum malaria among U.S. travelers to Africa, an area with increasing chloroquine resistance, prompted CDC to change the recommended chemoprophylaxis regimen from chloroquine to mefloquine in 1990 (5).

The signs and symptoms of malaria illness are varied, but the majority of patients experience fever. Other common symptoms include headache, back pain, chills, increased sweating, myalgia, nausea, vomiting, diarrhea, and cough. The diagnosis of malaria should be considered for persons who experience these symptoms and who have traveled to an area with known malaria transmission. Malaria should also be considered in the differential diagnoses of persons who experience fevers of unknown origin, regardless of their travel history. Untreated P. falciparum infections can rapidly progress to coma, renal failure, pulmonary edema, and death. Asymptomatic parasitemia can occur among persons who have been long-term residents of malarious areas. This report summarizes malaria cases reported to CDC with onset of symptoms in 2000.

Methods

Data Sources

Malaria case data are reported to the National Malaria Surveillance System (NMSS) and the National Notifiable Diseases Surveillance System (NNDSS) (6). Although both systems rely on passive reporting, the numbers of reported cases might differ between the two systems because of differences in collection and transmission of data. A major difference in the data collected in these two systems is that NMSS receives more detailed clinical and epidemiologic data regarding each case (e.g., information concerning the area to which the infected person has traveled). This report presents only data regarding cases reported to NMSS.

Cases of blood-film--confirmed malaria among civilians and military personnel are identified by health-care providers or laboratories. Each slide-confirmed case is reported to local or state health departments and to CDC on a uniform case report form that contains clinical, laboratory, and epidemiologic information. CDC staff review all report forms when received and request additional information, if necessary (e.g., when no recent travel to a malarious country is reported). Reports of other cases are telephoned directly by health-care providers to CDC, usually when assistance with diagnosis or treatment is requested. All cases that have been acquired in the United States are investigated, including all induced and congenital cases and possible introduced or cryptic cases. Information derived from uniform case report forms is entered into a database and analyzed annually.

Definitions

The following definitions are used in this report: 

• Laboratory criteria for diagnosis: Demonstration of malaria parasites in blood films.
• Confirmed case: Symptomatic or asymptomatic infection that occurs in a person in the United States who has microscopically confirmed malaria parasitemia, regardless of whether the person had previous episodes of malaria while in other countries. A subsequent episode of malaria is counted as an additional case if the identified Plasmodium sp. differs from the initially identified species. A subsequent episode of malaria occurring in a person while in the United States could indicate a relapsing infection or treatment failure resulting from drug resistance if the identified Plasmodium sp. is the same species identified previously.

This report also uses terminology derived from the recommendations of the World Health Organization; (7). Definitions of the following terms are included for reference:

• Autochthonous malaria:
  Indigenous. Mosquitoborne transmission of malaria in a geographic area where malaria occurs regularly.
  Introduced. Mosquitoborne transmission of malaria from an imported case in an area where malaria does not occur regularly.
• Imported malaria: Malaria acquired outside a specific area. In this report, imported cases are those acquired outside the United States and its territories (Puerto Rico, Guam, and the U.S. Virgin Islands).
• Induced malaria: Malaria acquired through artificial means (e.g., blood transfusion or using shared common syringes).
• Relapsing malaria: Renewed manifestations (i.e., clinical symptoms or parasitemia) of malarial infection that is separated from previous manifestations of the same infection by an interval greater than the usual periodicity of the paroxysms.
• Cryptic malaria: An isolated malaria case that cannot be linked epidemiologically to secondary cases.

Microscopic Diagnosis of Malaria

The early diagnosis of malaria requires that physicians consider malaria in the differential diagnosis of every patient who is experiencing fever; the evaluation of such a patient should include taking a comprehensive travel history. If malaria is suspected, a Giemsa-stained smear of the patient's peripheral blood should be examined for parasites. Thick and thin blood films must be prepared correctly because diagnostic accuracy depends on blood-film quality and examination by experienced laboratory personnel* (see Appendix for procedures for accurately diagnosing malaria).

Results

General Surveillance

During 2000, CDC received 1,402 malaria case reports occurring among persons in the United States and its territories, representing a 9.0% decrease from the 1,540 cases reported for 1999 (8). This incidence is the third highest number of reported cases since 1980 and represents the second highest number of U.S. civilian cases reported in the past 30 years (Table 1). In 2000, a total of 827 cases occurred among U.S. civilians, compared with 833 cases reported for 1999, and the number of cases among foreign civilians also decreased from 381 cases to 354 (Figure 1). Cases among U.S. military personnel decreased from 55 to 46 in 2000. In 175 cases, information was insufficient to determine civilian or military status.

Plasmodium Species

The infecting species of Plasmodium was identified in 1,241 (88.5%) of the cases reported in 2000. P. falciparum and P. vivax were identified in blood smears from 43.6% and 37.2% of infected persons, respectively (Table 2). The 611 P. falciparum cases reported for 2000 represented a 13.7% decrease from the 708 cases in 1999, whereas the number of P. vivax infections increased by 10.6% (from 472 in 1999 to 522 in 2000). Among 1,181 cases in which both the region of acquisition and the infecting species were known, 75.6% of infections acquired in Africa were attributed to P. falciparum; 13.2% were attributed to P. vivax. The converse was true of infections acquired in the Americas and Asia: 86.5% and 85.9% were attributed to P. vivax, and only 7.3% and 8.3% were attributed to P. falciparum, respectively.

Region of Acquisition and Diagnosis

Approximately 99% (n = 1,398) of reported cases were imported. Of 1,330 imported cases in which the region of acquisition was known, the majority (58.9%; n = 783) were acquired in Africa; 20.1% (n = 271) and 17.9% (n = 238) were acquired in the Americas and Asia, respectively (Table 3). The highest concentration of cases acquired in Africa came from countries in West Africa (66.7%; n = 522), whereas the majority of cases acquired in Asia came from the Indian subcontinent (67.2%; n = 160). The other regions where imported cases of malaria were acquired were Central America and the Caribbean (15.0%; n = 200), South America (4.3%; n = 57), and Oceania (1.7%; n = 22). Information regarding region of acquisition was missing for 68 (4.9%) of the imported cases. The number of reported malaria cases acquired in Africa decreased by 13.1% (n = 783), compared with 1999. The same number of cases acquired in the Americas (n = 271) were reported for 2000 as compared with 1999. Cases from Asia decreased by 3.3% (n = 238), compared with 1999.

In the United States, the five health departments reporting the highest number of malaria cases were New York City (n = 220), California (n = 194), New York State (n = 77), Texas (n = 70), and Illinois (n = 67) (Figure 2). All of these health departments reported a decrease in cases compared with 1999. This overall decrease in reported number of cases might reflect a decreased rate of international travel, a reduced risk for malaria among travelers, poorer access to health care, or fluctuation in surveillance by state and local health departments.

Interval Between Arrival and Illness

The interval between date of arrival in the United States and onset of illness and the infecting Plasmodium species were known for 623 (44.6%) of the imported cases of malaria (Table 4). Symptoms began before arrival in the United States for 63 (10.1%) persons, whereas symptoms began after arrival in the United States for 560 (89.9%) of these patients. Clinical malaria developed within 1 month after arrival in 313 (80.9%) of the 387 P. falciparum cases and in 75 (38.9%) of the 193 P. vivax cases (Table 4). Only 5 (0.8%) of the 560 persons became ill >1 year after returning to the United States.

Imported Malaria Cases

Imported Malaria Among U.S. Military Personnel

In 2000, a total of 46 cases of imported malaria were reported among U.S. military personnel. Of the 45 cases for whom information regarding chemoprophylaxis use was available, seven patients were not using any prophylaxis.

Imported Malaria Among Civilians

A total of 1,179 imported malaria cases were reported among civilians. Of these, 825 (70.0%) cases occurred among U.S. residents, and 354 (30.0%) cases occurred among residents of other countries (Table 5). Of the 825 imported malaria cases among U.S. civilians, 555 (67.3%) had been acquired in Africa, an increase of 1.1% from cases reported in 1999. Asia accounted for 106 (12.8%) cases of imported malaria among U.S. civilians, whereas travel to the Central American and Caribbean regions accounted for an additional 90 (10.9%) cases. Of the 354 imported cases among foreign civilians, the majority of cases were acquired in either Africa (n = 150; 42.4%) or Asia (n = 90; 25.4%).

Antimalarial Chemoprophylaxis Use

Chemoprophylaxis Use Among U.S. Civilians

Information concerning chemoprophylaxis use and travel area was known for 758 (91.9%) of the 825 U.S. civilians who had imported malaria. Of these 758 persons, 452 (59.6%) had not taken any chemoprophylaxis, and 94 (12.4%) had not taken a CDC-recommended drug for the area visited (9). Only 190 (25.1%) U.S. civilians had taken a CDC-recommended medication (9). Data for the specific drug taken were missing for the remaining 22 (2.9%) travelers. A total of 128 (67.4%) patients on CDC-recommended prophylaxis had taken mefloquine weekly; 22 (11.6%) had taken doxycycline daily; and 21 (11.1%) who had traveled only in areas where chloroquine-resistant malaria has not been documented, had taken chloroquine weekly. Nineteen patients (10.0%) had taken combinations of drugs that included >1 CDC-recommended drugs for the travel region. Of the 94 patients taking a nonrecommended drug, 54 (57.4%) reported taking chloroquine either alone or in combination with another ineffective drug during travel to an area where chloroquine resistance has been documented.

Malaria Infection After Recommended Prophylaxis Use

A total of 236 patients (i.e., 190 U.S. civilians, 32 persons in the U.S. military, 6 foreign civilians, and 8 persons whose information regarding their status was missing) experienced malaria after taking a recommended antimalarial drug for chemoprophylaxis. Information regarding infecting species was available for 209 (88.6%) patients taking a recommended antimalarial drug; the infecting species was undetermined for the remaining 27.

Cases of P. vivax or P. ovale After Recommended Prophylaxis Use. Of the 236 patients who experienced malaria after recommended chemoprophylaxis use, 121 cases (51.3%) were caused by P. vivax and 10 (4.2%) by P. ovale. Notes on the malaria case surveillance reports indicated that 25 (19.1%) of these 131 patients were noncompliant with antimalarial prophylaxis.

A total of 39 (29.8%) cases of P. vivax or P. ovale occurred >45 days after arrival in the United States. These cases were consistent with relapsing infections and, thus, do not indicate prophylaxis failures. Information was insufficient, because of missing data regarding symptom onset or return date, to assess whether 77 cases were relapsing infections. Fifteen cases, all caused by P. vivax, occurred <45 days after the patient returned (n = 12) or before return (n = 3) to the United States. Of these 15 patients, five were known to be noncompliant with their antimalarial chemoprophylaxis. Region of acquisition varied for the 10 remaining case patients who were not known to be noncompliant (one from West Africa, one from East Africa, one from Central Africa,^† five from Central America, and two from Papua New Guinea). Blood samples were not available; therefore, serum drug levels were not measured for any of these patients. The probable explanations for these cases are either inappropriate dosing or noncompliance that was not reported. Evidence is lacking that would indicate any new area of chloroquine-resistant P. vivax.

Cases of P. falciparum and P. malariae After Recommended Prophylaxis Use. The remaining 105 cases of malaria reported among persons who had taken a recommended antimalarial drug for chemoprophylaxis include 61 cases of P. falciparum, 16 cases of P. malariae, one case of mixed infection, and 27 cases in which the infecting species was unidentified.

A total of 59 of the 61 P. falciparum cases among those who reported taking a recommended antimalarial drug were acquired in Africa, one in the Caribbean, and one in South America. In 24 (39.3%) of these 61 cases, noncompliance with antimalarials was reported. Of the remaining 37 cases of P. falciparum for which patient compliance was unknown, the majority were acquired in Africa (n = 35): 24 in West Africa, seven in East Africa, one in Central Africa, one in Southern Africa,^§ and two in an unspecified African region. Two cases were acquired outside Africa: one in the Caribbean (Haiti) and one in South America (Brazil). Serum drug levels were not available for any of these 37 patients.

Eight of the 16 P. malariae cases among those who reported taking a recommended antimalarial drug were acquired in Africa. In three (18.8%) of these 16 cases, noncompliance with antimalarials was reported. In the 13 remaining cases, whether the patient complied with prophylaxis was unknown; four had traveled in the Americas, five in Africa, three in Asia, and one in Oceania.

Purpose of Travel

Purpose of travel to malaria-endemic areas was reported for 635 (77.0%) of the 825 U.S. civilians with imported malaria (Table 6). Of the U.S. civilians with malaria, the largest percentage (35.9%) were persons who had visited friends or relatives in malarious areas; the second and third largest percentages, 10.3% and 10.2%, had traveled for tourism and to do missionary work, respectively.

Malaria During Pregnancy

A total of 35 cases of malaria were reported among pregnant women in 2000, representing 7.8% of cases among women. Fifteen (42.9%) were among U.S. civilians. Eleven of these 15 women (73.3%) had traveled to visit friends and relatives, of whom 72.7% traveled in Africa. Only 1 pregnant woman (6.9%) reported taking prophylaxis, compared with 31.1% of nonpregnant women. Twelve women (86.7%) were hospitalized, compared with 56.3% of nonpregnant women.

Malaria Acquired in the United States
Congenital Malaria

Two cases of congenital malaria were reported in 2000 and are described in the following case reports: 

• Case 1. On September 7, 2000, a previously healthy 10-week-old female infant residing in North Carolina experienced fever and dark urine (10). Examination revealed a temperature of 103.7ºF but no other abnormal findings. Laboratory studies included an elevated white blood cell count (24,600/µL) and low hemoglobin (8.7 g/dL). She was admitted to a local hospital to rule out sepsis, and intravenous therapy with ampicillin and cefotaxime was begun. On September 8, blood films for malaria were obtained and were reported the next day to contain P. malariae. Treatment with chloroquine was initiated. Bacterial cultures of urine, blood, and cerebrospinal fluid obtained at admission indicated no growth. The child's clinical status improved, and she was discharged on September 13, having completed chloroquine treatment in the hospital.

The mother reported that her pregnancy had been uncomplicated, and the neonate had been born by cesarean delivery because of failure to progress during labor. The infant had not traveled outside her home city or received any blood products. Both parents had emigrated from the Democratic Republic of the Congo (formerly Zaire), the father 5 years previously and the mother 4 years previously. The mother reported being treated for malaria with a full course of chloroquine before leaving the Congo in 1996. Both parents reported no episodes of malaria, febrile illness, foreign travel, or blood transfusion after arriving in the United States.

Pretreatment malaria testing of the mother with thick and thin blood films prepared at four different times did not indicate malaria parasites (drawn September 10, 12, 13, and 21). Subsequent serologic testing revealed positive immunoglobulin G (IgG) titers against P. falciparum and P. malariae (both 1:16,384), and against P. vivax and P. ovale (both 1:1,024), indicating previous infection with malaria. Polymerase chain reaction (PCR) analysis on blood collected on September 22 was negative for Plasmodium species. However, she was presumptively treated with chloroquine.

• Case 2. In November 2000, a male infant, aged 1 month, was admitted to a Georgia hospital because of poor oral intake and pallor. On examination, the baby was irritable and pale, with a heart rate of 95 beats/minute and mild hepatosplenomegaly. Laboratory examination revealed a hemoglobin of 2.5 g/dL, and a malaria blood film indicated P. vivax. The infant was treated with oral chloroquine and recovered without complications.

  The infant was born by normal spontaneous vaginal delivery to a Guatemalan mother, who reported a history of malaria in Guatemala in November 1999, for which she was treated with proguanil. She immigrated to the United States in March 2000, where she continued to do well until April. At that time, she reportedly experienced fever and chills and self-medicated with an unknown oral medication. The mother's thick and thin blood smears were negative, as was PCR. Immunofluorescent assay titers performed on the mother's serology were 1:256 to P. vivax, 1:64 to P. falciparum, 1:64 to P. malariae, and 1:64 to P. ovale, indicating prior infection with malaria.

Induced Malaria

Two cases of induced malaria were reported in 2000 and are described in the following case reports:

• Case 1. On August 4, 2000, a female nurse aged 55 years, sustained a needle-stick injury while caring for a patient in a Massachusetts hospital emergency department. The patient had returned recently from Cote d'Ivoire and had a fever. Infection with P. falciparum was diagnosed, and the patient responded well to treatment with quinine and doxycycline.

  On September 11, the nurse experienced fever, chills, and vomiting. Infection with P. falciparum was diagnosed, and the nurse was admitted to the hospital and treated successfully with quinine and doxycycline. She reported no travel to malaria-endemic areas nor transfusion of blood products.
  
  

• Case 2. On September 23, 2000, a man aged 71 years who had a history of hypertension, hypercholesterolemia, diabetes mellitus, and endocarditis was admitted to a Massachusetts hospital because of progressive weakness, nausea, and vomiting. Acalculous cholecystitis was diagnosed. Review of the complete blood count was suspicious for Babesia. The patient was administered a single dose of intravenous doxycycline and started on intravenous clindamycin at a dosage of 600 mg every 8 hours. Blood films sent to CDC revealed P. falciparum. Therapy was changed to quinine and doxycycline and the patient improved.

  The patient reported no recent travel, having been house-bound for the previous 4--5 months because of his chronic illnesses. He had received 1 unit of packed red blood cells (PRBC) on July 7 and 13; he had also received 1 unit of PRBC, 6 units of platelets, and 6 units of fresh frozen plasma during coronary artery bypass graft and mitral valve repair on August 8, and 1 unit of PRBC for gastrointestinal bleeding on September 8. Five of the six platelet donors and all four PRBC donors were traced, and their blood films, PCR, and serology did not indicate malaria. One donor refused to cooperate with the trace-back investigation.

  Investigation revealed that a nurse, who had cared for this patient during his emergency room visit on September 8, had previously experienced P. falciparum malaria (see case 1 in this section). The nurse's exposure was thought to be from a needle-stick injury sustained at another local hospital on August 4. At that time, she had been caring for a patient who was diagnosed with P. falciparum after a trip to Cote d'Ivoire.

  PCR analysis demonstrated that the parasite identified in induced cases 1 and 2 are clonal (i.e., related). These results strongly imply that malaria was transmitted between the two persons. Technical difficulties with specimens from the Cote d'Ivoire patient prohibited PCR analysis to determine clonal identity.

Deaths Attributed to Malaria

Six deaths attributable to malaria were reported during 2000 and are described in the following case reports:

• Case 1. On January 16, 2000, a female aged 91 years who was a resident of a long-term care facility in California was evaluated by her physician and determined to have microcytic anemia (hemoglobin 8.3 g/dL), thrombocytopenia (platelet count: 53,000/µL), and renal insufficiency (blood urea nitrogen: 39 mg/dL and creatinine: 1.4 mg/dL). A blood film indicated P. malariae, and she was treated with chloroquine. Years had passed since she had traveled to a malarious area (China). Her course was complicated by pneumonia, and she died on January 26.
  
  
• Case 2. On May 5, 2000, a female aged 47 years and a resident of Kenya arrived in California to visit family. She visited a physician on May 16 with complaints of nausea and abdominal pain; a urinary tract infection was diagnosed, and she was treated with nitrofurantoin. She was examined at a California hospital the following day; she was jaundiced, and hepatitis was diagnosed. She refused hospitalization and insisted on continuing her travels to Canada on May 18. She required a wheelchair for transport in the airport but was able to walk onto the airplane. While on the airplane she felt ill, vomited, and collapsed in the airplane's bathroom. The airplane was diverted to an airport in Nevada, and she was transported to an emergency department where she was found to be comatose and in acute respiratory failure. Her laboratory examinations revealed P. falciparum malaria (9.3% parasitemia) as well as metabolic acidosis, thrombocytopenia (platelet count: 13,000/µL), and abnormal liver function (aspartate aminotransferase: 117 U/L; alanine aminotransferase: 71U/L; total bilirubin: 8.2 mg/dL). Computerized tomography of the head indicated probable cerebral edema. Therapy with intravenous quinidine gluconate was begun. Her condition deteriorated, necessitating assisted ventilation. Her course was further complicated by supraventricular tachycardia and later bradycardia and hypotension unresponsive to therapy with intravenous fluids and vasopressors, and she died in the emergency department. Blood cultures, taken on arrival at the hospital, later grew both Staphylococcus aureus and coagulase-negative staphylococcus.
  
  
• Case 3. On November 7, 2000, a woman aged 24 years was examined in the emergency department of a Vermont hospital and was prescribed antibiotics. She was not admitted to the hospital and was found deceased 4 days later. She had recently been on a 3-month trip to Ghana, and she had begun experiencing symptoms within days after returning to the United States. She did not take prophylaxis during her travel in Africa. Her blood films revealed P. falciparum, and the state medical examiner reported the cause of death as cerebral malaria secondary to P. falciparum.
  
  
• Case 4. On September 22, 2000, a Senegalese man aged 39 years who reported a history of congestive heart failure (CHF), peptic ulcer disease, and hepatitis, was treated at a Georgia hospital. The patient had arrived in the United States approximately 2 months earlier to visit friends. On examination, he was diaphoretic, but without fever, and in moderate respiratory distress; he also had signs and symptoms consistent with CHF. The patient was admitted with a diagnosis of CHF and was treated with intravenous diuretics and inotropic agents. After admission, he became nauseated and febrile. Laboratory studies demonstrated abnormal liver function, although viral hepatitis serology tests were negative. Plasmodium parasites were identified on a malaria blood film (September 24), and treatment with quinine and doxycycline was begun. The species was subsequently identified as nonfalciparum malaria, and the treatment was changed to chloroquine. On September 26, the patient was lethargic with altered mental status, and he was transferred to the medical intensive care unit. On September 27, the patient suffered a cardiac arrest and was unable to be resuscitated. Species confirmation of blood films, taken during his admission, occurred postmortem and revealed P. ovale.
  
  
• Case 5. On April 3, 2000, a man aged 55 years with multiple medical problems was examined at an emergency department of a Florida hospital. He complained of generalized weakness, cough, and fever, and on examination, he was hypotensive and febrile (105ºF). Malaria was diagnosed (species undetermined), and the patient was admitted to the intensive care unit. He was initially treated with oral chloroquine and then oral quinine sulfate.

  His medical history included atrial fibrillation, sleep apnea, liver disease, and morbid obesity. The patient had been noncompliant with his regular medications before hospitalization. Moreover, the patient, a U.S. civilian, had recently traveled to Mexico, Nicaragua, Honduras, and Ecuador, and he had not taken any prophylaxis during this 6-week trip. He returned to the United States on March 30, a total of 4 days before admission to the hospital. His course was complicated by pulmonary embolism, cardiac arrhythmia (supraventricular tachycardia and atrial fibrillation), congestive cardiac failure, disseminated intravascular coagulation, renal failure, retroperitoneal bleeding, and malignant hyperthermia. He received multiple transfusions of blood products. On April 20, as he was being prepared for insertion of an inferior vena cava filter, he suffered a cardiac arrest and died. Species confirmation of blood films taken during his admission occurred postmortem and demonstrated P. falciparum.
  
  

• Case 6. On December 17, 2000, a male sailor from West Africa, aged 37 years, was admitted to a Florida hospital after a fall onboard his ship. He complained of generalized weakness, cough, and loss of appetite during the previous weeks. He had recently traveled from Liberia through Ghana and the Cape Verde Islands and arrived in Baltimore, Maryland, on December 12. While in Baltimore, he was seen by a physician and was prescribed erythromycin for his symptoms. He had not been taking any prophylaxis for malaria.

  On examination, he was febrile (101.6ºF), tachycardic (138 beats/minute) and jaundiced. His laboratory test results revealed a normal white blood cell count (8,100/µL), thrombocytopenia (platelets: 68,000/µL), and anemia (hemoglobin: 12.2 g/dL). He was admitted with a diagnosis of malaria (P. falciparum) and acute renal failure, and treated with quinine and doxycycline. His hospital course was further complicated by respiratory failure and gastrointestinal (GI) bleeding. He was placed on assisted ventilation, and he received multiple blood transfusions for anemia secondary to malaria and GI bleeding. Subsequent malaria blood films, on December 20 and 21, did not indicate malaria parasites. However, the patient's condition continued to deteriorate and he experienced multiorgan failure. Despite supportive therapy, the patient died on January 5, 2001.

  Discussion

A total of 1,402 cases of malaria were reported to CDC for 2000, representing a 9.0% decrease from the 1,540 cases reported for 1999. This change primarily resulted from a decrease in cases acquired in Africa and the Americas. Beginning in 2000, CDC routinely contacts state health departments to ask for outstanding reports from the previous reporting year or for a statement that reporting is complete. The decrease in cases in 2000, compared with 1999, possibly is a result of expected variation in the reporting system, although other possibilities include decreased international travel, changing patterns of travel (e.g., immigration from malarious areas or adventure tourism), or an increased use of effective antimalarial chemoprophylaxis.

One reason for conducting malaria surveillance is to monitor for prophylaxis failures that might indicate emergence of drug resistance; however, >70% of imported malaria among U.S. civilians occurred among persons who were either not taking prophylaxis or were taking nonrecommended prophylaxis for the region to which they were traveling. Among the 117 cases where appropriate prophylaxis was reported, 60 (i.e., 37 P. falciparum, 10 P. vivax, and 13 P. malariae) had insufficient information to determine whether these represented problems with adherence while using correct antimalarial chemoprophylaxis or emerging drug resistance. No conclusive evidence existed to indicate a single national or regional source of infection among this group of patients or the failure of a particular chemoprophylactic regimen. Health-care providers are encouraged to contact CDC rapidly whenever they suspect chemoprophylaxis failure, thus enabling measurement of serum drug levels of the antimalarial drugs in question.

In 2001, to be better able to evaluate chemoprophylaxis failures, CDC revised the NMSS case report form to facilitate collection of more thorough data regarding chemoprophylaxis. The current form solicits more detailed information regarding the prescribed regimen, the degree of compliance with the regimen, and the reasons for noncompliance, if any. Data gathered from the responses will be useful in generating public health messages to improve use of antimalarial chemoprophylaxis, and therefore decrease malaria-associated morbidity and mortality among U.S. civilians.

The importance of taking correct precautions and chemoprophylaxis is underscored by the six fatal cases of malaria that occurred in the United States in 2000. An earlier review of deaths attributed to malaria in the United States identified certain risk factors for fatal malaria, including failure to take recommended antimalarial chemoprophylaxis, refusal of or delay in seeking medical care, and misdiagnosis (11).

The occurrence of 15 cases of malaria among pregnant U.S. civilians is cause for concern also. Malaria during pregnancy among nonimmune women is more likely to result in severe disease or contribute to an adverse outcome for the woman than malaria in a nonpregnant woman (12); the fetus might be adversely affected as well (13). Pregnant travelers should be counseled to avoid travel to malarious areas, if possible. If deferral of travel is impossible, pregnant women should be informed that the risks for malaria outweigh those associated with prophylaxis and that safe chemoprophylaxis regimens are available. Specific guidance for pregnant travelers is available from CDC's website at http://www.cdc.gov/travel/mal_preg_pub.htm.

Signs and symptoms of malaria are often nonspecific, but fever is usually present. Other symptoms include headache, chills, increased sweating, back pain, myalgia, diarrhea, nausea, vomiting, and cough. Prompt diagnosis requires that malaria be included in the differential diagnosis of illness in a febrile person with a history of travel to a malarious area. Clinicians should ask all febrile patients for a travel history, including when evaluating febrile illnesses among international visitors, immigrants, refugees, migrant laborers, and international travelers.

Treatment for malaria should be initiated immediately after the diagnosis has been confirmed by a positive blood film. Treatment should be determined on the basis of the infecting Plasmodium species, the probable geographic origin of the parasite, the parasite density, and the patient's clinical status (14). Although nonfalciparum malaria rarely causes complications, persons with P. falciparum infection are at risk for developing life-threatening complications.

Health-care workers should be familiar with prevention, recognition, and treatment of malaria and are encouraged to consult appropriate sources (Table 7) for malaria treatment recommendations or call CDC's National Center for Infectious Diseases, Division of Parasitic Diseases at 770-488-7788. Detailed recommendations for preventing malaria are available 24 hours/day from CDC by telephone at 877-394-8747 (toll-free voice information system) or 888-232-3299 (toll-free facsimile request line), or on the Internet at http://www.cdc.gov/travel/diseases.htm#malaria. In addition, CDC biannually publishes recommendations in the Health Information for International Travel (9), which is available for purchase from the Public Health Foundation at 877-252-1200 or 301-645-7773; it is also available and updated more frequently on CDC's Internet site at http://www.cdc.gov/travel.

CDC provides support for the diagnosis of malaria through DPDx, a program that enhances diagnosis of parasitic diseases throughout the world. It includes an Internet site, http://www.dpd.cdc.gov/dpdx, that contains information regarding laboratory diagnosis, geographic distribution, clinical features, treatment, and life cycles of >100 parasite species. The DPDx Internet site is also a portal for diagnostic assistance for health-care providers through telediagnosis. Digital images captured from diagnostic specimens are submitted for diagnostic consultation through electronic mail. Because laboratories can transmit images to CDC and rapidly obtain answers to their inquiries, this system allows more efficient diagnosis of difficult cases and more rapid dissemination of information. Approximately 36 laboratories in 34 states have or are in the process of acquiring the hardware to perform telediagnosis.

Acknowledgments

The authors acknowledge the state, territorial, and local health departments, health-care providers, and laboratories for reporting this information to CDC.

References

1. World Health Organization. World malaria situation in 1994. Wkly Epidemiol Rec 1997;72:269--76.
2. Bremen JG. Ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg 2001;64(S1):1--11.
3. Pan American Health Organization. Report for registration of malaria eradication from United States of America. Washington, DC: Pan American Health Organization, 1969.
4. Zucker JR. Changing patterns of autochthonous malaria transmission in the United States: a review of recent outbreaks. Emerg Infect Dis 1996;2:37--43.
5. Lackritz EM, Lobel HO, Howell J, Bloland P, Campbell CC. Imported Plasmodium falciparum malaria in American travelers to Africa: implications for prevention strategies. JAMA 1991;265:383--5.
6. Stroup DF. Special analytic issues. In: Teutsch SM, Churchill RE, ed. Principles and practice of public health surveillance. New York, NY: Oxford University Press, 1994;143--5.
7. World Health Organization. Terminology of malaria and of malaria eradication: report of a drafting committee. Geneva, Switzerland: World Health Organization, 1963;32.
8. Newman RD, Barber AM, Roberts J, Holtz TH, Steketee RW, Parise ME. Malaria surveillance---United States, 1999. In: CDC Surveillance Summaries. MMWR 2002; 51(No. SS-1):15--28.
9. CDC. Health information for international travel, 2001--2002. Atlanta, GA: US Department of Health and Human Services, Public Health Service, CDC, National Center for Infectious Diseases, 2001.
10. CDC. Congenital malaria as a result of Plasmodium malariae---North Carolina, 2000. MMWR 2002;51:164--5.
11. Greenberg AE, Lobel HO. Mortality from Plasmodium falciparum malaria in travelers from the United States, 1959 to 1987. Ann Intern Med 1990;113:326--7.
12. Luxemburger C, Ricci F, Nosten F, Raimond D, Bathet S, White NJ. Epidemiology of severe malaria in an area of low transmission in Thailand. Trans R Soc Trop Med Hyg 1997;91:256--62.
13. Nosten F, ter Kuile F, Maelankirri L, Decludt B, White NJ. Malaria during pregnancy in an area of unstable endemicity. Trans R Soc Trop Med Hyg 1991;85:424--9.
14. Zucker JR, Campbell CC. Malaria: principles of prevention and treatment. Infect Dis Clin North Am 1993;7:547--67.

* To obtain confirmation diagnosis of blood films from questionable cases and to obtain appropriate treatment recommendations, contact either your state or local health department or CDC's National Center for Infectious Diseases, Division of Parasitic Diseases, Malaria Epidemiology Branch at 770-488-7788.

^† East, West, and Central Africa: Angola, Benin, Burkina Faso, Burundi, Cameroon, Cape Verde Islands, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Djibouti, Equatorial Guinea, Eritrea, Ethiopia, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Niger, Nigeria, Réunion, Rwanda, São Tomé and Príncipe, Senegal, Seychelles, Sierra Leone, Somalia, Sudan, Togo, Uganda, Tanzania, Zambia, and Zimbabwe.

^§ Southern Africa: Botswana, Lesotho, Namibia, Saint Helena, South Africa, and Swaziland.

* In Figures A-1 and A-2, the hands are illustrated ungloved to better indicate their placement during the procedures. However, wearing gloves while processing blood specimens is recommended to prevent transmission of bloodborne pathogens (MMWR 1988;37:377--82, 387--8 and MMWR 1987;36[No. S2]).

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