Sonja Mali, MPH
Stefanie Steele, RN, MPH
Laurence Slutsker, MD, MPH
Paul M. Arguin, MD Division of Parasitic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases
Corresponding author: Sonja Mali, MPH, Division of Parasitic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric
Diseases, CDC, 4770 Buford Hwy., N.E., MS F-22, Atlanta, GA 30341. Telephone: 770-488-7757; Fax: 770-488-4465; E-mail: smali@cdc.gov.
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 mosquito. The majority of malaria infections in the United
States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can
occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria
surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.
Period Covered: This report summarizes cases in persons with onset of illness in 2007 and summarizes trends during
previous years.
Description of System: Malaria cases confirmed by blood film, rapid diagnostic tests, or polymerase chain reaction
are mandated to bereported to local and state health departments by health-care providers or laboratory staff members.
Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the
National Malaria Surveillance System, the National Notifiable Diseases Surveillance System, and direct CDC consultations. Data
from these reporting systems are the basis for this report.
Results: CDC received reports of 1,505 cases of malaria among persons in the United States, including one
transfusion-related case and one fatal case, with onset of symptoms in 2007; 1,564 cases were reported for 2006.
P. falciparum, P. vivax, P.
malariae, and P. ovale were identified in 43.4%, 20.3%, 2.0%, and 3.5% of cases, respectively. Nine patients (0.6%)
were infected by two or more species. The infecting species was unreported or undetermined in 30.2% of cases. Based on
estimated volume of travel, the highest estimated relative case rates of malaria among travelers occurred among those returning
from countries in West Africa. Of 701 U.S. civilians who acquired malaria abroad and for whom chemoprophylaxis
information was known, 441 (62.9%) reported that they had not followed a chemoprophylactic drug regimen recommended by CDC
for the area to which they had traveled. Twenty-four cases were reported in pregnant women; none had adhered to a
complete prevention drug regimen. One death was reported in a person infected with
P. vivax.
Interpretation: No significant change in the number of malaria cases occurred from 2006 to 2007. No change was
observed in the proportion of cases by species causing the infection. U.S. civilians traveling to countries in West Africa had the
highest estimated relative case rates. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered
to a chemoprophylaxis regimen that was appropriate for the country where they acquired malaria.
Public Health Actions: Persons at risk for malaria infection should take one of the recommended chemoprophylaxis
regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has
been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately
and report their travel history to the clinician; investigation should always include blood-film tests for malaria with
immediately available results. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning
malaria prevention are available from CDC at
http://wwwn.cdc.gov/travel/contentdiseases.aspx#malaria or by calling the
CDC Malaria Hotline (telephone: 770-488-7788). Recommendations concerning malaria treatment are available at
http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.
Introduction
Malaria in humans is caused by infection with one or more of several species of
Plasmodium (i.e., P. falciparum, P.
vivax, P. ovale, P. malariae, and occasionally
other Plasmodium species). The infection is transmitted by the bite of an infective
female Anopheles species mosquito. P. falciparum
and P. vivax species cause the most infections worldwide.
P. falciparum is the species
that most commonly causes severe, potentially fatal malaria. Worldwide, an estimated 350--500 million clinical cases
and approximately 1 million deaths caused by malaria occur annually, primarily among children aged <5 years living in
sub-Saharan Africa (1). P. vivax and
P. ovale have dormant liver-stage parasites, which can reactivate and cause malaria
several months or years after the infecting mosquito bite.
P. malariae can result in long-lasting infections that, if untreated, can
persist asymptomatically in the human host for years, even a lifetime
(1). P. knowlesi, a parasite of Old World monkeys, has
been documented as a cause of human infections and some fatalities in Southeast Asia; investigations are ongoing to determine
the extent of transmission to humans (2,3). A total of 49% of the world population lives in areas where malaria is
transmitted (i.e., 109 countries in parts of Africa, Asia, the Middle East, Eastern Europe, Central and South America, Caribbean,
and Oceania). Before the 1950s, malaria was endemic throughout the southeastern United States; an estimated 600,000
cases occurred in the United States in 1914
(4). During the late 1940s, a combination of improved housing and
socioeconomic conditions, environmental 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 resistance to antimalarial drugs.
Anopheline mosquitoes remain seasonally present in all states and territories except Hawaii.
The majority of reported malaria cases diagnosed each year in the United States are imported from regions where
malaria transmission is known to occur, although congenital infections and infections resulting from exposure to blood or
blood products are also reported in the United States. In addition, a limited number of cases are occasionally reported that
might have been acquired through local mosquitoborne transmission
(5).
State and local health departments and CDC investigate malaria cases acquired in the United States, and CDC analyzes
data from reported cases to detect trends in acquisition. This information is used to guide malaria prevention recommendations
for international travelers.
The signs and symptoms of malaria illness vary, but the majority of patients have fever. Other common symptoms
include headache, back pain, chills, increased sweating, myalgia, nausea, vomiting, diarrhea, and cough. The diagnosis of
malaria should always be considered for persons with these symptoms who have traveled to an area with known malaria
transmission. Malaria also should be considered in the differential diagnosis of persons who have fever of unknown origin, regardless of
their travel history. Untreated P.
falciparum infections can rapidly progress to coma, renal failure, pulmonary edema, and
death. This report summarizes malaria cases reported to CDC among persons with onset of symptoms in 2007.
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 because of differences in collection and transmission of data. A substantial difference between 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). Malaria cases can be reported to CDC through
NMSS, NNDSS, or a direct consultation with CDC; cases identified through these various paths are compared and
compiled, duplicates are eliminated, and cases are analyzed. This report presents data on the aggregate of cases reported to CDC
through all reporting systems.
Cases of malaria confirmed by blood film, a rapid diagnostic test (RDT), or polymerase chain reaction (PCR)
among civilians and military personnel are identified by health-care providers or laboratories.* Each confirmed malaria 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 reviews all report forms when received and requests additional information from
the reporting provider or state if necessary (e.g., when no recent travel to a malarious country is reported). Other cases
are reported by telephone to CDC directly by health-care providers, usually when they are seeking assistance with diagnosis
or treatment. Information regarding cases reported directly to CDC is shared with relevant state health departments. All
cases that have been reported as acquired in the United States are investigated further, 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.
An estimated case rate for each country was determined using estimates of travel volume for U.S. travelers to each
country where cases of malaria were acquired and the number of cases among U.S. travelers attributable to each country. Data used
to estimate country-specific relative case rates were extrapolated from World Tourism Organization estimates of annual
numbers of U.S. travelers to specified countries
(7). Estimated relative case rates were determined by dividing the individual
country-specific case rates by the median individual country-specific case rate.
Definitions
The following definitions are used in this report:
U.S. residents: Persons living in the United States; includes both civilians and U.S. military personnel, regardless of
legal citizenship.
U.S. civilians: U.S. residents, excluding U.S. military personnel.
Foreign residents: Persons who have resident status in a country other than the United States.
Laboratory criteria for diagnosis: Demonstration of malaria parasites on blood film, RDT, or PCR.
Confirmed case: Symptomatic or asymptomatic infection that occurs in a person in the United States or one of its
territories who has laboratory-confirmed (by microscopy, PCR, or RDT that is subsequently confirmed by microscopy or
PCR) malaria parasitemia, regardless of whether the person has had previous episodes of malaria while in other countries.
A subsequent episode of malaria is counted as an additional case if the indicated
Plasmodium species 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 indicated
Plasmodium species is the same species identified previously.
This report also uses terminology derived from the recommendations of the World Health Organization
(8). 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 a person with an imported case in an area where malaria
does not occur regularly.
Imported malaria: Malaria acquired outside a specific area. In this report, imported malaria cases are those acquired
outside the United States and its territories.
Induced malaria: Malaria acquired through artificial means (e.g., by blood transfusion, organ transplantation, or
using shared syringes).
Relapsing malaria: Recurrence of malaria after the disease has been apparently cured. True malaria relapses are caused
by reactivation of dormant liver-stage parasites (hypnozoites) found in P. vivax and
P. ovale.
Cryptic malaria: A case of malaria for which epidemiologic investigations fail to identify a plausible mode of
acquisition (primarily cases identified in countries where malaria is not endemic).
Laboratory Diagnosis of Malaria
The early and prompt diagnosis of malaria requires that physicians obtain a travel history from every febrile patient.
Malaria should be included in the differential diagnosis of every febrile patient who has traveled to a malarious area. If malaria
is suspected, a Giemsa-stained film of the patient's peripheral blood should be examined for parasites as soon as possible.
Thick and thin blood films must be prepared correctly because diagnostic accuracy depends on blood-film quality and
examination by experienced laboratory personnel
(9). Some reference laboratories and health departments have the capacity to
perform PCR diagnosis of malaria, although PCR is generally reserved for cases for which blood-film diagnosis of malaria or
species determination is inadequate. PCR results are also often not available quickly enough to be useful in the initial diagnosis of
a patient with malaria.
An RDT, BinaxNOW Malaria, which detects circulating malaria-specific antigens, became available for use in the
United States on June 13, 2007. The test is the first malaria RDT authorized for use in the United States and is only approved for
use
by hospital and commercial laboratories, not by individual clinicians or the general public. Use of RDTs in the United
States can decrease the amount of time required to determine whether a patient is infected with malaria but does not eliminate
the need for the standard tests (10). Positive and negative RDTs must be confirmed by microscopy or PCR. RDTs are
generally less sensitive than blood films and do not quantify malaria parasites
(11).
Results
General Surveillance
For 2007, CDC received 1,505 reports of cases of malaria occurring among persons in the United States and its
territories. A total of 734 cases occurred among U.S. residents, 263 cases among foreign residents and 508 cases among persons
with unknown resident status. Of the 734 cases reported among U.S. residents, 50.1% were among blacks, 27.2% among
whites, 10.9% among Asians, and 4% among Hispanics; 67% of the U.S. resident cases were among males.
The 1,505 cases reported in 2007 is not significantly different from the 1,564 cases reported in 2006
(9) (Table 1) (chi-square test; p = 0.25). After a significant increase in cases from 2003 to 2004 (chi-square test; p = 0.002), the number
of malaria cases appears to have plateaued beginning in 2004; during 2004--2007, no statistically significant change occurred
in the number of reported cases (chi-square test; p = 0.21).
Plasmodium Species
Of the 1,505 cases reported in 2007, the infecting species of
Plasmodium was identified and reported in 1,051
(69.8%) cases. P. falciparum and P.
vivax accounted for the majority of infections and were identified in 62.2% and 29.0% of
infected persons with species identified, respectively. The number of reported cases of
P. falciparum and P. vivax remained stable
during 2005--2007 (Table 2).Among 983 cases for which both the region of acquisition and the infecting species were known,
P. falciparum accounted for 85.1% of infections acquired in Africa, 45.4% in the Americas, 18.2% in Oceania, and 10.7%
in Asia (Table 3). Infections attributed to P.
vivax accounted for 3.9% acquired in Africa, 52.7% in the Americas, 77.3%
in Oceania, and 83.2% in Asia.
Region of Acquisition and Diagnosis
All cases were reported as imported cases, except for one transfusion-related case. Of 1,155 imported cases for which
the region of acquisition was known, 744 (64.4%) were acquired in Africa, 253 (21.9%) in Asia, 131 (11.3%) in the
Americas, and 27 (2.3%) in Oceania. Countries in West Africa accounted for 545 (73.3%) cases acquired in Africa, and India
accounted for 151 (59.7%) cases acquired in Asia. In the Americas, 12 (9.2%) cases were acquired in North America, all of which
were acquired in Mexico. A combined 99 (78.6%) cases were acquired in Central America and the Caribbean (Belize,
Dominican Republic, El Salvador, Guatemala, Haiti, Honduras, Nicaragua, and Panama), of which 66% of the cases were acquired in
the Caribbean. Twenty (17.3%) cases were acquired in South America (Brazil, Guyana, French Guiana, Peru, and
Suriname). Information regarding region of acquisition was missing for 349 (23.2%) imported cases (Table 3).
In the United States, six jurisdictions accounted for 50.7% of the reported cases: New York City (n = 233), California (n
= 157), Texas (n = 136), New York (n = 93), New Jersey (n = 77), and Maryland (n = 67) (Figure 1). Compared with 2006,
the states and regions with the most significant change in reported malaria burden in 2007 were New York City, Georgia,
and Alaska. The number of cases reported in New York City increased from 174 cases in 2006 to 233 cases in 2007. Cases
in Georgia decreased by almost half, from 90 in 2006 to 46 in 2007, and Alaska reported a significant decrease from 23 cases
(all among military personnel) in 2006 to two cases in 2007. No cases from Alaska among military personnel were documented
in 2007.
Imported Malaria by Resident Status
Of 997 imported malaria cases among persons with known resident status, 734 (73.6%) occurred among U.S.
residents, and 263 (26.4%) occurred among residents of other countries. Of the 734 imported malaria cases among U.S. residents,
476
(64.9%) were acquired in Africa, 143 (19.5%) were acquired in Asia, and 75 (10.2%) were acquired in Central American
and Caribbean regions (Table 4). Of the 263 imported cases among foreign residents, 167 (63.5%) were acquired in
Africa. Among the 167 foreign residents who acquired malaria in Africa and for whom purpose of travel was known, 114
(68.3%) reported being recent immigrants or refugees, and 21 (12.6%) reported visiting friends and relatives in the United States.
A total of 61 cases were in foreign residents who traveled from Tanzania and Burundi to the United States; reason for travel
was known for 58 persons, among whom 57 were reported as being recent immigrants or refugees, and one was reported as
visiting friends and relatives. In 2006, no foreign cases were reported from Tanzania or Burundi
(9).
Estimated Relative Case Rates Among U.S. Residents
Using estimates of travel volume for U.S. travelers to each country from which cases of malaria were acquired and
the number of cases among U.S. travelers attributable to each country, a case rate was estimated for each country. In 2007,
the countries with the lowest estimated case rates of malaria among U.S. travelers were China and Thailand (Figure 2).
Other countries with low estimated relative case rates included Mexico, Vietnam, and South Africa. In many of these
countries, malaria risk areas are localized in small geographic areas of the country. Countries with estimated relative case rates in
the middle range included India, Honduras, Angola, and Pakistan, which have more homogenous malaria
transmission throughout the country. Estimated relative case rates were highest in West African countries and Oceania, including
Republic of the Congo, Benin, Papua New Guinea, and Solomon Islands. These high estimated case rates likely reflect not
only widespread transmission areas but also higher transmission intensity
(1).
Interval Between Arrival in the United States and Illness
Both the 1) interval between the date of arrival in the United States and onset of illness and 2) infecting
Plasmodium species were known for 771 (51.2%) of the imported malaria cases (Table 5). Symptoms began before arrival in the United States
in 78 (10.1%) persons and after arrival in 693 (89.9%)
persons.Clinical malaria occurred <30 days after arrival in 398
(80.1%) of the 497 of persons with P.
falciparum infections and in 74 (35.9%) of the 206 persons with
P. vivax infections (Table 5). Six (0.8%) of the 771 persons became ill with a
P. vivax infection >1 year after returning to the United States.
Imported Malaria Among U.S. Military Personnel
In 2007, a total of 33 cases of imported malaria were reported among U.S. military personnel. Nineteen persons
reported travel to Afghanistan, and 10 reported travel to South Korea; the remaining four persons reported travel to Iraq and
two unspecified countries in Africa. Information on infecting species was known for 25 cases; all cases were
P. vivax. Of these 25 cases, 15 were among persons who reported having taken the appropriate primary chemoprophylactic drug; four
reported taking the recommended primaquine for presumptive antirelapse therapy, and five patients reported adherence to
the prescribed drug regimen. These cases were reported by state health departments and do not include all cases reported
through malaria surveillance activities conducted by the U.S. Department of Defense.
Prophylaxis Use Among U.S. Civilians
Information concerning chemoprophylaxis use and travel area was known for 646 (92.2%) of the 701 U.S. civilians
who had imported malaria. Of these 646 persons, 205 (31.7%) had taken chemoprophylaxis. Of the 205 persons who
reported taking malaria chemoprophylaxis, 53 (25.9%) had not taken a CDC-recommended drug for the area visited, and
143 (69.8%) had taken a CDC-recommended medication. Data for the specific drug taken was missing for the remaining
nine (4.4%) travelers. A total of 66 (46.2%) patients taking CDC-recommended chemoprophylaxis reported having
taken mefloquine, 42 (29.4%) doxycycline, and 27 (18.9%) atovaquone/proguanil; four patients (2.8%) who had traveled only
in areas where chloroquine-resistant malaria has not been documented reported having taken
chloroquine.Four patients took a combination of two CDC-recommended malaria prophylactics for the specific travel region.
Malaria Infection After Recommended Prophylaxis Use
A total of 143 U.S. civilians contracted malaria after taking a recommended antimalarial drug for chemoprophylaxis.
Of these, 43 (30.1%) reported complete adherence with the drug regimen, and 85 (59.4%) reported nonadherence;
adherence was unknown for the remaining 15 (10.5%). Information regarding infecting species was available for 113 (79%)
patients who had taken a recommended antimalarial drug and undetermined for the remaining 30 patients.
Cases Caused by P. vivax or P.
ovale
Of the 143 patients who had malaria diagnosed after recommended chemoprophylaxis use, 39 (27.3%) had cases that
were caused by P. vivax, and 12 (8.4%) had cases caused by
P. ovale.Of the 51 total cases of
P. vivax or P. ovale, 42 (82.3%) occurred >45 days after arrival in the United States. These cases were consistent with relapsing infections and do not
indicate primary prophylaxis failures. Information on four cases was insufficient to assess a relapse infection because of missing
data regarding symptom onset or return date. A total of five cases occurred
<45 days after the patient returned to the United
States; all were caused by P. vivax. Four of the five patients did not adhere to their malaria chemoprophylaxis regimen. The
patient who contracted malaria but reported adherence to the chemoprophylaxis regimen had traveled to Papua New Guinea and
had taken atovaquone/proguanil for malaria chemoprophylaxis. Possible explanations for this case include inappropriate
dosing, unreported nonadherence, malabsorption of the drug, an early relapse from hypnozoites established at the start of this trip,
or emerging parasite resistance.
Cases Caused by P. falciparum or P.
malariae
Sixty of the 143 patients who had malaria diagnosed after recommended chemoprophylaxis use included 48 cases of
P. falciparum and 12 of P. malariae.
Of the 48 P. falciparum cases, all except two cases were acquired in Africa; one was
acquired in Vietnam and one in India. Forty-two (87.5%) patients reported nonadherence to the antimalarial drug regimen, and
three persons had no adherence information available. Three (6.3%) patients who had all contracted malaria and had traveled
to Africa reported adherence with antimalarial chemoprophylaxis; one patient took doxycycline, one patient took
atovaquone/proguanil, and one took mefloquine. Of the 12
P. malariae cases, 10 were acquired in Africa, and one was acquired in
Asia (Indonesia). Six of the patients reported nonadherence to the antimalarial drug regimen, and two had no
adherence information available. The remaining four patients reported drug regimen adherence; two took mefloquine, and two
took atovaquone-proguanil
Cases of Mixed Species Infection
Of the 143 patients who had taken a recommended malaria chemoprophylaxis, two reported a mixed
Plasmodium species infection. One patient who traveled to Nigeria acquired a mixed infection of
P. falciparum and P. ovale, and one patient
who traveled to Indonesia acquired a mixed infection of
P. falciparum and P. vivax. Both patients reported taking mefloquine
for malaria chemoprophylaxis; however, neither patient adhered completely to the drug regimen.
Clinical Complications
Clinical complications associated with malaria were reported for 358 (23.8%) of the total 1,505 reported cases. One
case was fatal. Although patients can have multiple clinical complications associated with malaria, the largest proportion
(53.4%) of patients experienced anemia (hemoglobin <11 g/dL or hematocrit <33%). Of the 358 cases with clinical complications,
57 (15.9%) cases were classified as severe malaria, because one or more of the following manifestations were reported:
cerebral malaria, renal failure, acute respiratory distress syndrome (ARDS), jaundice, or >5% parasitemia. Severe anemia
(hemoglobin <7 g/dL) is also a characteristic of severe malaria
(12); however, because data for severe anemia are not collected on
the surveillance form, the percentage of severe malaria cases might have been
higher.† Of the 57 patients with severe malaria,
four (7%) reported taking chemoprophylaxis; however, none reported complete adherence to the drug regimen. Of the 57
patients with severe malaria cases, seven were treated using an investigational new drug protocol for intravenous artesunate; all
seven patients recovered after treatment.
Purpose of Travel
Purpose of travel to areas where malaria is endemic was reported for 599 (85.4%) of the 701 U.S. civilians with
imported malaria. Though travelers could report multiple reasons for travel, the largest proportion (62.8%) was persons who had
visited friends or relatives in malarious areas; the second and third highest proportions (10.2% and 8.5%) were persons who
had traveled as tourists or missionaries, respectively (Table 6). Proportions of various reasons for travel remained stable
during 2005--2007.
Malaria by Age
Among the 1,464 cases among patients for whom age was known, 295 (20.2%) cases occurred in persons aged <18
years, 1,115 (76.2%) in persons aged 18--64 years, and 54 (4.6%) in persons aged
>65 years. Although the majority of cases
occur in persons aged 18--64 years, pediatric cases are of particular interest because the preventive care of most children is
controlled by parents or guardians. Of the 295 (20.2%) cases among persons aged <18 years, 100 (33.9%) cases occurred among
U.S. civilian children, 105 (35.6%) cases among children of foreign citizenship, and for 90 (30.5%) children, resident status
was unknown.
Seventy-one (71.0%) of the cases among U.S. civilian children for whom country of exposure was known were
attributable to travel to Africa. Of the 100 cases among U.S. civilian children, two (2.0%) children were aged <24 months, 22
(22.0%) were aged 24--59 months, 41 (41.0%) were aged 5--12 years, and 35 (35.0%) were aged 13--17 years. Of the 87 children
for whom reason for travel was known, 73 (83.9%) were reported as visiting friends and relatives; the remaining 14 cases
were attributed to tourist, missionary, and student travel. Thirty-one (33.3%) of the 93 children for whom
chemoprophylaxis information was known were reported as having taken chemoprophylaxis, of whom 28 (90.3%) had taken an
appropriate regimen; however, eight (28.6%) reported complete adherence.
Malaria During Pregnancy
A total of 24 cases of malaria were reported among pregnant women in 2007, representing 4.5% of cases among all
women. Fourteen (58.3%) of the 24 cases occurred among U.S. civilian pregnant women; 21 of these patients reported travel to
Africa, and three reported travel to Central and South American countries. Thirteen women reported visiting friends and
relatives, and one reported missionary-related travel. Of the 14 cases of malaria reported among U.S. civilian pregnant women,
three (21.4%) women reported taking malaria chemoprophylaxis. One woman reported taking an appropriate medication;
however, she did not complete the drug regimen. No information was available on the birth outcomes of these women.
Selected Malaria Case Reports
Malaria Associated with Blood Transfusion
One case of induced malaria, caused by blood transfusion in the United States, was reported in 2007. A black woman
aged 25 years with transfusion-dependent sickle cell disease and no previous travel history was admitted to a Houston,
Texas, hospital on August 12, 2007, with complaints of abdominal pain. Treatment was provided for sickle cell crisis. On August
16, 2007, the woman became febrile and was evaluated for causes of fever. On August 20, 2007,
P. falciparum malaria with 16% parasitemia was diagnosed, and quinidine and doxycycline were administered. A retrospective review of blood
samples obtained on hospital admission revealed that the woman was parasitemic on the date of admission. The patient
tolerated quinidine well and by August 24, 2007, her physician reported resolution of parasitemia. However, on August 28, 2007,
the patient, who was still hospitalized, developed ARDS and acute renal failure, requiring mechanical ventilation
and hemodialysis. After prolonged hospitalization, she recovered and was discharged.
During the year before admission, the woman had 66 units of red blood cells transfused; her most recent transfusions
had occurred on June 12, 2007, and July 18, 2007. All of the units that she had received during June 12--July 18 had come
from the same blood distribution facility. The hospital's transfusion services department was contacted to initiate an investigation
of the donors of the units and identify the infected donor, thus preventing additional transfusion-related infections.
Serologic
testing using indirect immunofluoresence antibody identified one donor with elevated titers of antibodies to malaria
consistent with previous malaria infection at an indeterminate time. All other donors' serologic tests were negative. The implicated
donor was located and questioned regarding malaria history. The donor reported immigrating to the United States from Nigeria
in 2001 and indicated that he had not traveled abroad since that time. The donor reported that in 1988, he was hospitalized
for a severe febrile illness that was presumed to be a malaria infection. He did not recall the infecting species or the
treatment provided. Investigators explained to the donor that his donated blood was likely to be the source of a malaria infection
in another patient. He understood the findings but chose not to undergo any type of malaria therapy because he did not feel
ill; however, he understood that he should be alert for any future episodes. The implicated donor was counseled not to
donate blood until 3 years after undergoing an appropriate malaria therapy.
Imported Malaria Possibly Associated with Organ Transplantation
On January 18, 2007, a man aged 53 years returned to California after a 3-week trip to Pakistan for a kidney transplant;
he did not take malaria chemoprophylaxis before his trip. During his stay in Pakistan, the man reported spending most of
his time indoors. The transplant surgery was performed on January 7, 2007; the transplanted kidney came from India. During
the transplant surgery, no transfusions were administered. On January 25, 2007, the man developed a fever and sought
medical attention. Infection with P. vivax was diagnosed. Although the patient might have acquired the infection naturally in
Pakistan, the kidney transplant procedure might have been the source.
Death Attributed to Malaria
One death attributable to malaria was reported in 2007. A man aged 67 years from India was visiting the United States
to attend a wedding. He had a history of type 2 diabetes mellitus and hyperlipidemia. On October 17, 2007, the man
was admitted to a U.S. hospital with fever, and
P. vivax malaria infection was diagnosed. He was treated with quinine sulfate
and doxycycline and subsequently had a negative blood smear. However, the man then developed respiratory failure and
ARDS, which eventually resulted in severe hypoxia. The man developed oliguric renal failure and multisystem organ failure. He
died on November 21, 2007.
Discussion
A total of 1,505 cases of malaria were reported to CDC for 2007, which is not significantly different from the number
of cases reported in 2006. The number of cases reported with no information regarding residence status or clinical
findings decreased from 634 in 2006 to 508 in 2007
(9). Excluding cases with no information on residence status, the percentage
of U.S. resident cases during 2000--2007 remained stable.
During 2002--2007, the proportion of cases from Asia increased. The number of cases acquired in a specific region can
be affected by many factors, including the amount of transmission occurring in the region, adherence to preventive
measures (including mosquito avoidance and chemoprophylaxis) by travelers, the style of travel that occurs in that country
(e.g., business or adventure travel), and the volume of travel to those countries.
Of the 1,504 imported cases, 508 (33.8%) cases did not have information on residential status. In addition, 350
(23.3%) cases did not have information describing travel history. High numbers of cases with no reported residential and
clinical information compromises the ability of the data to accurately reflect trends in malaria surveillance in the United
States. Continued vigilance is needed by local and state health departments, health-care providers, and other health personnel
in providing essential information regarding malaria cases when submitting cases through the various reporting systems to CDC.
Malaria cases acquired in Africa continue to account for the largest number of U.S. cases acquired from a specific
region. The West African region accounts for almost 74% of the cases acquired in the continent; however, the number of
cases acquired in Tanzania and Burundi increased. In 2006, only eight cases were acquired from Tanzania, and no persons with
a malaria infection reported travel to or from Burundi
(9). In 2007, a combined total of 61 cases were acquired in
either Tanzania or Burundi. Among these, 57 persons were identified as resettling refugees or immigrants as their reason for travel
to the United States.
CDC recommends presumptive treatment of P.
falciparum malaria in refugees who are from areas where malaria is
endemic before entering the United States to resettle. To ensure adequate presumptive treatment, the treatment regimen must
be completed no sooner than 3 days before departure to the United States
(13). This strategy decreases risk for symptoms,
severe complications, or death associated with a malaria infection that could occur after arriving in the United States.
Because refugees might settle in areas where access to health care is difficult to obtain or health-care providers are not familiar
with malaria diagnosis or treatment, treating possible malaria infections in refugees before they immigrate to the United States
is optimal to prevent ongoing infections from progressing to severe disease after arrival in the United States.
Presumptive treatment also can reduce the risk for malaria reintroduction in the United States because the malaria vector, the
female Anopheles mosquito, is found throughout the continental United States.
The International Organization for Migration (IOM) is an intergovernmental agency that
evaluatesmost refugees bound for the United States and provides treatment for certain infectious diseases. To reduce the incidence of malaria among
refugees after they arrive in the United States, IOM administered presumptive malaria treatment against
P. falciparum to Burundi refugees resettling from Tanzania. In 2005, CDC recommended artemisinin-based combination therapy (ACT)
as presumptive P. falciparum treatment for refugees resettling to the United States from sub-Saharan Africa
(14). However, until July 2007, IOM continued to implement sulfadoxine-pyrimethamine (SP) treatment for malaria to refugees before arrival
in the United States; P. falciparum infections in sub-Saharan Africa have considerable resistance to SP
(15). Therefore, SP resistance is a possible explanation for the increase of cases in Burundi refugees who immigrated to the United States in
2007. In response to such cases, IOM is now implementing ACT treatment as presumptive
P. falciparum treatment for refugees resettling in the United States
(14). A total of 7,545 Burundian refugees from Tanzania resettled to the United States
during 2007--2008 (16). Health-care providers in the United States caring for refugees resettling from malaria-endemic
regions should remain aware of the possibility of malaria in this population, regardless of previous treatment.
One reason malaria surveillance is conducted is to monitor for prophylaxis failures that might indicate emergence of
drug resistance. However, approximately 82% of imported malaria cases among U.S. residents for whom prophylaxis use
was known occurred among persons who were not taking prophylaxis, were taking prophylaxis but not the regimen
recommended for the region to which they were traveling, or were taking a recommended prophylactic regimen incorrectly. The majority
of patients for whom appropriate prophylaxis was reported and who did not have a relapsing infection reported
nonadherence with the recommended regimen or provided insufficient information to determine whether they adhered to an
appropriate antimalarial chemoprophylaxis regimen. In the small subset of patients who reported choosing and adhering to
the recommended prophylactic drug regimen, subsequent malaria might have been a result of malabsorption of the
antimalarial drug or emerging drug resistance. Because CDC does not routinely evaluate blood drug levels among patients with
malaria who report adherence with a recommended regimen, determining whether adherence reporting is inaccurate, the
antimalarial drug was malabsorbed, or the patient was experiencing emerging drug resistance is not possible. No conclusive evidence
exists 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 who suspect chemoprophylaxis failure should contact CDC quickly,
which will enable CDC to measure patient antimalarial blood drug levels and assess the parasite in vitro for genetic
resistance characteristics to evaluate for possible drug resistance.
Severe malaria is characterized by one or more of the following clinical complications: prostration, impaired
consciousness or coma, respiratory distress, seizures, shock, ARDS, jaundice, severe anemia, acute renal failure, disseminated
intravascular coagulation, acidosis, hemoglobinuria, and >5% parasitemia
(17). Intravenous quinidine gluconate, principally used as
an antiarrhythmic medicine, also has antimalarial properties and is the only parenteral drug approved by the Food and
Drug Administration for treatment of severe malaria that is available in the United States. However, quinidine has cardiotoxic
effects and has become less available in U.S. hospitals with the advent of newer antiarrhythmic drugs
(18,19). Since 2000, the World Health Organization has recommended artemisinins such as artesunate rather than quinidine for treatment of severe
malaria; artesunate has been used outside the United States for many years
(17). On June 21, 2007, CDC's investigational new
drug (IND) protocol for intravenous artesunate became effective, allowing the use of intravenous artesunate for the treatment
of severe malaria. The medication is stocked at eight quarantine stations around the United States and can be shipped
quickly when needed. Precise guidelines must be followed and eligibility requirements must be met to enroll a patient in the
treatment protocol. Artesunate is provided free of charge to hospitals on request and on an emergency basis by the CDC Drug Service
or by one of the CDC quarantine stations. Physicians who administer the drug to patients must notify CDC of any
resulting
adverse effects and comply with the IND protocol
(20). To enroll a patient with severe malaria in this treatment
protocol, health-care providers should call CDC's Malaria Hotline (Table 7).
As in previous years, the majority of malaria cases in 2007 were among persons who traveled to visit friends and
relatives. Foreign-born U.S. civilians need to be aware that acquired immunity wanes quickly when exposure to malaria is
interrupted and that they should take prophylaxis when returning to malarious areas. In addition, children of foreign-born U.S.
civilians who are born in the United States have no immunity to malaria and are vulnerable to infection
(21). In this report, approximately three fourths of the children who were visiting friends and relatives and contracted malaria had not been
taking any chemoprophylaxis or had been taking an incorrect medication for chemoprophylaxis.
Twenty-four cases were reported in pregnant women, which is a 41% increase from 2006. Among the 14 U.S.
civilian women who were pregnant and contracted malaria, three (21.4%) women reported taking chemoprophylaxis, and none
of these three completely adhered to the drug regimen. The proportion of pregnant women taking chemoprophylaxis is
lower than the percentage of total U.S. civilians with malaria who took chemoprophylaxis. Malaria during pregnancy poses a
high risk for both maternal and perinatal morbidity and mortality
(22). Pregnant women should be counseled to avoid travel
to malarious areas. If deferral of travel is impossible, pregnant women should be informed that the risks for malaria
greatly outweigh those associated with prophylaxis, and chemoprophylaxis should be used. Information for pregnant women
is available at
http://www.cdc.gov/malaria/travel/drugs_pregnant_public.htm.
Appropriate chemoprophylaxis, promptly seeking medical care if symptoms develop, and consideration of malaria in
the differential diagnosis of fever in a traveler who has returned to the United States will help ensure malaria is properly
managed and controlled in the United States. In addition, because induced malaria infections are possible, health professionals
and blood donation and collection staff members must be attentive and thorough in their blood deferment protocols.
FDA screening guidelines indicate that residents of countries where malaria is not endemic who then travel to areas where malaria
is endemic should not be accepted as blood donors until 1 year after their departure from the malarious area. Former residents
of areas where malaria is endemic should be deferred from blood donation until 3 years after their departure from the
malarious area. Persons who receive a diagnosis of malaria should not donate blood until 3 years after treatment, during which time
they must have remained asymptomatic (23).
Signs and symptoms of malaria are often nonspecific, but fever usually is 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 international visitors, immigrants, refugees, migrant laborers, and
other international travelers.
Prompt treatment of suspected malaria is essential because persons with
P. falciparum infection are at risk for
experiencing life-threatening complications soon after onset of illness. Ideally, therapy for malaria should be initiated immediately after
the diagnosis has been made. 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
(22). If a diagnosis of malaria is
suspected and cannot be confirmed, or if a diagnosis of malaria is confirmed but species determination is not possible,
antimalarial treatment should be initiated that is effective against
P. falciparum. Resistance of P.
falciparum to chloroquine is worldwide, with the exception of a limited number of geographic regions (e.g., Mexico and Central America); therefore, therapy
for presumed P. falciparum malaria should include a drug effective against such resistant strains
(24).
Health-care providers should be familiar with prevention, recognition, and treatment of malaria and are encouraged
to consult appropriate sources for malaria prevention and treatment recommendations (Table 7). Physicians seeking
assistance with the diagnosis or treatment of patients with suspected or confirmed malaria should call CDC's Malaria Hotline (Table 7) during regular business hours; during evenings, weekends, and holidays, physicians should call CDC's Emergency
Operations Center (Table 7) and ask the staff member to page the person on call for the Malaria Branch. These resources are intended
for use by health-care providers only.
Detailed recommendations for preventing malaria are available to the general public online at
http://www.cdc.gov/travel/diseases.htm/malaria. In addition, CDC biannually publishes recommendations in
Health Information for International Travel (commonly referred to as
The Yellow Book) (1), which is available for purchase from Elsevier
(http://www.elsevierhealth.com
or telephone: 800-545-2522); the publication is also available and updated more frequently on the CDC Travelers' Health site
at http://wwwn.cdc.gov/travel. Additional information on malaria prevention recommendations is available through the
online
CDC malaria map application (http://www.cdc.gov/malaria/risk_map). The application is an interactive map that
provides information on malaria risk throughout the world. Users can search for or browse through countries, cities, and place
names and obtain information about malaria and recommended malaria prevention medications in particular locations. The
malaria map application complements resources currently available on the CDC Travelers' Health website.
CDC provides assistance for diagnostic parasitology through DPDx, CDC's Division of Parasitic Diseases
diagnostic website. DPDx (available at http://www.dpd.cdc.gov/dpdx) provides free Internet-based laboratory diagnostic assistance
(i.e., telediagnosis) to laboratorians and pathologists who are investigating suspected parasitic disease cases, such as malaria.
Digital images captured from diagnostic specimens can be submitted by e-mail for consultation. Telediagnosis assistance from CDC
is available during regular business hours (Monday--Friday, 8 a.m.--4:30 p.m. EST). Because laboratories can transmit images
to CDC and obtain a rapid response (average time: minutes to several hours) to their inquiries, DPDx allows efficient
diagnosis of challenging cases and rapid dissemination of information. As of January 2007, approximately 49 public health
laboratories in 46 states and Puerto Rico had the ability to perform telediagnosis. Implementation of telediagnosis at public
health laboratories is supported by CDC, including training of personnel in digital imaging techniques and diagnostic
identification of parasites. The DPDx Internet site is CDC's reference for the telediagnosis of parasitic diseases and also serves as an
online guide for diagnostic parasitology. The DPDx website contains reference material with images, text, and videos
on approximately 100 different species of parasites, covering information on laboratory diagnosis, geographic
distribution, clinical features, treatment, and life cycles.
Acknowledgments
The authors acknowledge the state, territorial, and local health departments; health-care providers; and laboratories for reporting
this information to CDC.
References
World Health Organization. World malaria report 2008. WHO Press. 2008.
Cox-Singh J, Davis TM, Lee KS, et al.
Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect
Dis 2008 46:165--71.
Pan American Health Organization. Report for registration of malaria eradication from United States of America. Washington, DC: Pan
American Health Organization; 1969.
World Tourism Organization. Yearbook of tourism statistics; 2008. Available at
http://data.un.org.
World Health Organization. Terminology of malaria and of malaria eradication: report of a drafting committee. Geneva, Switzerland: World
Health Organization; 1963:32.
CDC. Presumptive treatment of P.
falciparum malaria in refugees relocating from sub-Saharan Africa to the United States. Atlanta, GA:
US Department of Health and Human Services, CDC; 2008. Available at
http://www.cdc.gov/ncidod/dq/refugee/rh_guide/domestic.htm.
US Department of State, US Department of Homeland Security, US Department of Health and Human Services. Proposed refugee admissions
for fiscal year 2009. Report to Congress. Available at
http://www.state.gov/documents/organization/113507.pdf.
World Health Organization. WHO guidelines for the treatment of malaria. Geneva, Switzerland: WHO Press; 2006.
Baird JK. Effectiveness of antimalarial drugs. N Engl J Med 2005;352:1565--77.
* To confirm malaria diagnosed by blood films from questionable cases and to obtain appropriate treatment recommendations, contact either the state or
local health department or CDC's Malaria Hotline (telephone: 770-488-7788).
† Data on severe anemia (hemoglobin <7 mg/dL) will be reported in subsequent malaria surveillance summaries.
Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of
Health and Human Services.References to non-CDC sites on the Internet are
provided as a service to MMWR readers and do not constitute or imply
endorsement of these organizations or their programs by CDC or the U.S.
Department of Health and Human Services. CDC is not responsible for the content
of pages found at these sites. URL addresses listed in MMWR were current as of
the date of publication.
All MMWR HTML versions of articles are electronic conversions from typeset documents.
This conversion might result in character translation or format errors in the HTML version.
Users are referred to the electronic PDF version (http://www.cdc.gov/mmwr)
and/or the original MMWR paper copy for printable versions of official text, figures, and tables.
An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S.
Government Printing Office (GPO), Washington, DC 20402-9371;
telephone: (202) 512-1800. Contact GPO for current prices.
**Questions or messages regarding errors in formatting should be addressed to
mmwrq@cdc.gov.
