• View in gallery

    Cases of malaria (n = 684) reported to the Office of Medical Services, Department of State, 1988–2004. This figure appears in color at www.ajtmh.org.

  • View in gallery

    Estimated incidence of malaria among U.S. government personnel at diplomatic posts in Africa, 1995–2004. For 1995–1999, the number of authorized personnel at posts was used as the denominator. For 2000–2004, the number of employees and eligible family members counted in the medical program by the health units was used. This figure appears in color at www.ajtmh.org.

  • View in gallery

    Sum of cases of malaria reported by month in sub-Saharan Africa, 1988–2004. This figure appears in color at www.ajtmh.org.

  • 1

    World Health Organization, 2006. Global Malaria Program. Accessed June 29, 2006. Available from http://www.who.int/malaria/epidemicsandemergencies.html

  • 2

    World Health Organization, 1997. World malaria situation in 1994. Wkly Epidemiol Rec 72 :269–274, 277–283.

  • 3

    Berman JG, 2001. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg 64 (Suppl 1–2):1–11.

    • Search Google Scholar
    • Export Citation
  • 4

    Sachs JD, 2005. Achieving the millennium development goals—The case of malaria. N Engl J Med 352 :115–117.

  • 5

    Centers for Disease Control and Prevention, 2006. Malaria Surveillance—United States, 2004. MMWR Morb Mortal Wkly Rep 55 :23–37

  • 6

    Newman RD, Parise ME, Barber AM, Steketee RW, 2004. Malaria-related deaths among U.S. Travelers, 1963–2001. Ann Intern Med 141 :547–555.

    • Search Google Scholar
    • Export Citation
  • 7

    Jelinek T, Schulte C, Behrens R, Grobusch MP, Couland JP, Bisoffi Z, Matteelli A, Clerinx J, Corachan M, Puente S, Gjorup I, Harms G, Kollaritsch H, Kotlowski A, Bjorkmann A, Delmont JP, Knobloch J, Nielsen LN, Cuadros J, Hatz C, Beran J, Schmid ML, Schulze M, Lopez-Velez R, Fleischer K, Kapaun A, McWhinney P, Kern P, Atougia J, Fry G, da Cunha S, Goecken B, for the European Network on Surveillance of Imported Infectious Diseases (TropNetEurop), 2002. Imported falciparum malaria in Europe: sentinel Surveillance data from the European Network on surveillance of imported infectious diseases. Clin Infect Dis 34 :572–576.

    • Search Google Scholar
    • Export Citation
  • 8

    World Health Organization, 2006. Malaria in Travelers. Accessed April 27, 2006. Available from www.who.int/malaria/malariaandtravellers.html

  • 9

    Frame JD, Lange WE, Frankenfield DL, 1992. Mortality trends of American missionaries in Africa, 1945–1985. Am J Trop Med Hyg 46 :686–690.

    • Search Google Scholar
    • Export Citation
  • 10

    Beadle C, Hoffman SL, 1993. History of malaria in the United States Naval Forces at war: World War I through the Vietnam conflict. Clin Infect Dis 16 :320–329.

    • Search Google Scholar
    • Export Citation
  • 11

    Newton JA, Schnepf GA, Wallace MR, Lobel HO, Kennedy CA, Oldfield EC, 1994. Malaria in U.S. Marines returning from Somalia. JAMA 272 :397–399.

    • Search Google Scholar
    • Export Citation
  • 12

    Kotwal RS, Wenzel RB, Sterling RA, Porter WD, Jordan NN, Petruccelli BP, 2005. An outbreak of malaria in U.S. Army Rangers returning from Afghanistan. JAMA 293 :212–216.

    • Search Google Scholar
    • Export Citation
  • 13

    Wallace MR, Sharp TW, Smoak B, Iriye C, Rozmajzl P, Thornton SA, Batchelor R, Magill AJ, Lobel JO, Longer CF, Burans JP, 1996. Malaria among United States Troops in Somalia. Am J Med 100 :49–55.

    • Search Google Scholar
    • Export Citation
  • 14

    Susi B, Whitman T, Blazes DL, Burgess TH, Martin GJ, Freilich D, 2005. Rapid diagnostic test for Plasmodium falciparum in 32 Marines medically evacuated from Liberia with a febrile illness. Ann Intern Med 142 :476–477.

    • Search Google Scholar
    • Export Citation
  • 15

    Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC, 1993. Long-term malaria prophylaxis with weekly mefloquine. Lancet 341 :848–851.

    • Search Google Scholar
    • Export Citation
  • 16

    Centers for Disease Control and Prevention, 2006. Malaria in multiple family members—Chicago, Illinois. MMWR Morb Mortal Wkly Rep 55 :645–648.

    • Search Google Scholar
    • Export Citation
  • 17

    Centers for Disease Control and Prevention, 2005. Health Information for International Travelers, 2005–2006. Accessed August 1, 2006. Available from www.cdc.gov/travel/destinat.htm

  • 18

    Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, Keystone JS, Pandey P, Cetron MS for the GeoSentinel Surveillance Network, 2006. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 354 :119–130.

    • Search Google Scholar
    • Export Citation
  • 19

    Marx A, Pewsner D, Egger M, Nuesch R, Bucher HC, Genton B, Hatz C, Juni P, 2005. Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas. Ann Intern Med 142 :836–846.

    • Search Google Scholar
    • Export Citation
  • 20

    Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA, 2006. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis 42 :377–382.

    • Search Google Scholar
    • Export Citation
  • 21

    Muhlberger N, Jelinek T, Behrens RH, Gjorup I, Couland JP, Clerinx J, Puente S, Burchard G, Gascon J, Grobusch MP, Weitzel T, Zoller T, Kollaritsch H, Beran J, Iversen J, Hatz C, Schmid ML, Bjorkman A, Fleischer K, Bisoffi Z, Guggemos W, Knobloch J, Matelli A, Schulze H, Laferi H, Kapaun A, McWhinney P, Lopez-Velz R, Fatkenheuer G, Kern P, Zieger BW, Kotlowski A, Fry G, Cuadros J, Myrvang B for the Trop-NetEurop and Surveillance Importierter Infectionen in Deutschland (SIMPID) Surveillance Networks, 2003. Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: Observations from the TropNetEurop and SSIMPID surveillance data. Clin Infect Dis 36 :990–995.

    • Search Google Scholar
    • Export Citation
  • 22

    Remme JHE, Binka E, Nabarro D, 2001. Toward a framework and indicators for monitoring Roll Back Malaria. Am J Trop Med Hyg 64 (Suppl 1–2):76–84.

    • Search Google Scholar
    • Export Citation
  • 23

    Centers for Disease Control and Prevention, 1995. Malaria Surveillance United States—1992. MMWR CDC Surveill Summ 44 (SS-5):1–15. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00039398.htm.

    • Search Google Scholar
    • Export Citation
  • 24

    Willaims HA, Roberts J, Kachur SP, Barber AM, Barat LM, Bloland PB, Ruebush TK II, Wolfe EB, 1999. Malaria Surveillance–United States, 1995. MMWR CDC Surveill Summ 48 :1–23.

    • Search Google Scholar
    • Export Citation
  • 25

    Askling HH, Nilsson J, Tegnell A, Janzon R, Ekdahl K, 2005. Malaria risk in travelers. Emerg Infect Dis 11 :436–441.

  • 26

    Ling J, Baird JK, Fryauff DJ, Sismadi P, Bangs MJ, Lacy M, Barcus MJ, Gramzinski R, Maguire JD, Kumusumangsih M, Miller GB, Jones TR, Chulay JD, Hoffman SL, and the Naval Medical Research Unit 2 Clinical Trial Team, 2002. Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia. Clin Infect Dis 35 :e25–e35.

    • Search Google Scholar
    • Export Citation
  • 27

    Schwartz E, Parise M, Kozarsky P, Cetron M, 2003. Delayed onset of malaria—Implications for chemoprophylaxis in travelers. N Engl J Med 349 :1510–1516.

    • Search Google Scholar
    • Export Citation
  • 28

    Baird JK, Fryauff DJ, Hoffman SL, 2003. Primaquine for prevention of malaria in travelers. Clin Infect Dis 37 :1659–1667.

  • 29

    Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, Primaquine: report from CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg 75 :402–415.

    • Search Google Scholar
    • Export Citation
  • 30

    Centers for Disease Control, 1987. Chloroquine-resistant Plasmodium falciparum malaria in west Africa. MMWR Morb Mortal Wkly Rep 36 :13–14.

    • Search Google Scholar
    • Export Citation
  • 31

    Centers for Disease Control and Prevention, 1988. Current trends. Recommendations for the prevention of malaria in travelers. MMWR Morb Mortal Wkly Rep 37 :277–284.

    • Search Google Scholar
    • Export Citation
  • 32

    Adera T, Wolfe MS, McGuire-Rugh K, Calhoun N, Marum L, 1995. Risk factors for malaria among expatriates living in Kampala, Uganda: the need for adherence to chemoprophylactic regimens. Am J Trop Med Hyg 52 :206–212.

    • Search Google Scholar
    • Export Citation
  • 33

    Centers for Disease Control and Prevention, 1991. Notice to readers: change in dosing regimen for malaria prophylaxis with mefloquine. MMWR Morb Mortal Wkly Rep 40 :72–73.

    • Search Google Scholar
    • Export Citation
  • 34

    Anonymous, 2000. Atovaquone/proguanil (Malarone) for malaria. The Medical Letter 42 :109–111

  • 35

    Centers for Disease Control and Prevention, 2003. Health Information for International Travel, 2003–2004. Atlanta: Centers for Disease Control and Prevention.

  • 36

    Krause G, Schöneberg I, Altmann D, Stark K, 2006. Chemoprophylaxis and malaria death rates. Emerg Infect Dis 12 :447–451.

  • 37

    World Health Organization Study Group, 2006. Malaria vector control and personal protection. World Health Organ Tech Rep Ser 936 :1–62.

  • 38

    Maguire JD, Krisin, Marwoto H, Richie TL, Fryauff DJ, Baird JK, 2006. Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria in Papua, Indonesia. Clin Infect Dis 42 :1067–1072.

    • Search Google Scholar
    • Export Citation
  • 39

    Molle I, Christensen K, 2000. Use of medical chemoprophylaxis and anti-mosquito precautions in Danish malaria patients and their traveling companions. J Travel Med 7 :253–258.

    • Search Google Scholar
    • Export Citation
  • 40

    Kain KC, Shanks GD, Keystone JS, 2001. Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens. Clin Infect Dis 33 :226–234.

    • Search Google Scholar
    • Export Citation
  • 41

    Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, Herold M, Krebs B, Veit O, Allwinn R, Steffen R, 2003. Tolerability of malaria chemoprophylaxis in non-immune travelers to sub-Saharan Africa: Multicentre, randomized, double blind, four arm study. BMJ 327 :1078–1083.

    • Search Google Scholar
    • Export Citation
  • 42

    Centers for Disease Control and Prevention, 1984. Revised recommendations for preventing malaria in travelers to areas with chloroquine-resistant Plasmodium falciparum. MMWR Morb Mortal Wkly Rep 34 :185–190.

    • Search Google Scholar
    • Export Citation
  • 43

    Centers for Disease Control, 1986. Agranulocytosis associated with the use of amodiaquine for malaria prophylaxis. MMWR Morb Mortal Wkly Rep 35 :165–166.

    • Search Google Scholar
    • Export Citation
  • 44

    Farcas GA, Soeller R, Zhong K, Zahirieh A, Kain KC, 2006. Real-time polymerase chain reaction assay for the detection and characterization of chloroquine-resistant Plasmodium falciparum malaria in returned travelers. Clin Infect Dis 42 :622–627.

    • Search Google Scholar
    • Export Citation
  • 45

    Guyatt HL, Snow RW, 2001. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 64 (Suppl 1–2):36–44.

    • Search Google Scholar
    • Export Citation
  • 46

    Centers for Disease Control and Prevention, Information for Health Care Providers: Preventing Malaria in Pregnant Woman. Accessed August 1, 2006. Available form http://www.cdc.gov/travel/mal_preg_hc.htm

  • 47

    Fischer PR, Bialek R, 2002. Prevention of malaria in children. Clin Infect Dis 34 :493–498.

  • 48

    Centers for Disease Control and Prevention, 2006. Prevention of Malaria in Children. Accessed June 29, 2006. Available from www.cdc.gov/malaria and www.cdc.gov/travel

 
 
 
 
 
 
 
 

 

 

 

 

EPIDEMIOLOGY OF MALARIA AMONG UNITED STATES GOVERNMENT PERSONNEL ASSIGNED TO DIPLOMATIC POSTS

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  • 1 Office of Medical Services, United States Department of State, Washington, District of Columbia

The epidemiology of malaria among U.S. government personnel attached to diplomatic posts has not been reported. We reviewed malaria surveillance reports on persons with onset of symptoms between January 1988 and December 2004. Among 684 slide-proven cases, the median age was 36 years. There were 565 (82.6%) cases of Plasmodium falciparum malaria and 56 (8.2%) of P. vivax malaria. A total of 89.9% were infected in Africa and 5.8% were infected in Asia; 95% of the P. falciparum cases originated in sub-Saharan Africa. One-fourth of all cases were reported in 1990–1991. The average annual incidence (per 1,000 personnel) of Plasmodium between 1995 and 1999 was highest in west Africa (8.96), followed by central Africa (8.08), and east Africa (4.27). No or irregular chemoprophylaxis was reported by 58.5%. Among those who indicated regular prophylaxis, 78% took regimens no longer considered adequate. In sub-Saharan Africa, cases were reported in every month. There were three deaths. Prevention of malaria among U.S. Government employees attached to diplomatic posts should particularly focus on those serving in sub-Saharan Africa and malarious areas of Asia.

INTRODUCTION

Malaria is a parasitic disease causing a public health problem in more than 100 countries and threatening roughly 40% of the world’s population.1,2 Each year, malaria causes more than 500 million clinical cases and more than three million deaths worldwide.3,4 In the United States, there are 1,000–1,500 cases and up to 12 deaths from malaria annually.5,6 Many additional cases and deaths are reported in Europe.7 The World Health Organization estimates 30,000 travelers acquire malaria each year.8

There is little published information regarding malaria risk among persons who live or work overseas.9 Malaria is a significant risk for military personnel deployed to Asia and Africa.1014 United States Peace Corps volunteers15 and persons that visit friends and relatives in malarious areas, especially in Africa, are at increased risk.16

The U.S. Department of State (DOS) Medical Program plays an important role in the prevention and treatment of illness among Foreign Service and other government personnel and their families stationed at overseas diplomatic posts. For patients with suspected or confirmed malaria, data forms are completed by DOS health care providers and sent to the Office of Medical Services of the DOS in Washington, DC. We evaluated these reports of malaria to describe the demographics of the affected population, determined the regions most affected by malaria infections, describe the frequency of Plasmodium species, identify the most common clinical complications associated with infection, assess prophylaxis usage by personnel with malaria, estimate the average annual incidence of malaria, and investigate malaria seasonality in Africa to better prevent this common and serious parasitic disease.

METHODS

Project clearance and patient confidentiality.

The protocol for the study was prepared as part of the requirements for a Masters in Public Health degree by Priya Joy Rathnam in consultation with Dr. Joe P. Bryan. Prior to accessing State Department medical records, the Office of Medical Services of the DOS reviewed and approved the protocol and the George Washington University Institutional Review Board (IRB) judged the study exempt from IRB review.

Case report forms.

A case report form (CRF) for malaria is requested for each case of suspected malaria under the care of the DOS medical program. The CRF contains demographic and laboratory data including the results of the malaria blood smear. Health care providers note clinical symptoms, presence of malaria-associated complications, reported use of chemoprophylaxis, and therapy prescribed.

The CRF, along with blood films, are forwarded to the Office of Medical Services in Washington, DC. The blood films are reviewed microscopically by a team of technologists experienced in malaria diagnosis as part of a laboratory quality improvement program.

To ensure patient confidentiality, a unique identifier was assigned to each patient. No personal identifiers were entered. Patient demographic characteristics and information on case reports were analyzed using Microsoft (Redmond, WA) Excel® and frequency tables were generated using SAS (Cary, NC) software applications.

Estimates of malaria incidence in African regions were calculated using number of new cases within each region17 divided by the number of persons assigned to posts during this period. For 1995–1999, the State Department Personnel and Staffing Division provided information on the authorized population at posts with health units for 1997. For 2000–2004, the total population at posts reported by health units for 2002 was used to estimate incidence. The latter included the number of adults and children. Because reporting from southern African posts is incomplete for 2002, the authorized number for 1999 is used.

Definition of terms.

The following definitions were used in this report. Laboratory criteria for diagnosis was the demonstration of malaria parasites in blood smears determined to be P. falciparum, P. vivax, P. ovale, P. malariae, or Plasmodium species. A presumptive case is a person with symptoms compatible with malaria and treated without blood smear microscopic confirmation.

RESULTS

Analysis of case characteristics.

There were 781 reports of malaria between 1988 and 2004. Of these, there were 97 reports of persons treated presumptively for malaria for whom the malaria smear was negative or not done. These presumptive cases were reported from Africa (85%), were primarily male (65%) and had a median age of 33.7 years. Forty-seven patients reported regular prophylaxis (48%). There was one death in this group, a 67-year-old family member of a government contractor. However, because malaria was not shown microscopically in this group, they will not be considered further. Therefore, there were 684 slide-proven cases of malaria.

Among 684 cases with slide-demonstrated malaria parasites, the median age was 36 years (range = 9 months to 72 years). Most patients (64.8%) were 20–49 years of age, 11.1% were 50–59 years of age, and 2% were ≥60 years of age. Children less than five years of age comprised 4.1% and persons 5–19 years of age comprised 13.4%. For 4.5%, the age was not reported. There were 443 male (65%) and 235 female (34%) cases. For six cases, sex was not reported.

Patients with malaria worked for 11 different U.S. government agencies (Table 1). The DOS, along with the U.S. Information Agency, which is now part of the DOS, accounted for 36.3% of cases. Personnel of the U.S. Agency for International Development (USAID) accounted for 30% of cases. Marine Security Guards make up the largest group of military personnel attached to posts and comprised at least 47 of 87 reports among Department of Defense personnel. U.S. Peace Corps staff and their eligible family members receive care from Department of State Health Units and Peace Corps volunteers generally receive care at Peace Corps Health Units.

The peak number of cases reported occurred in 1990 and 1991 (Figure 1). These two years accounted for 172 (25%) of all reports during the 17-year period. There has been a gradual decrease in the number of reports since 1991 when weekly mefloquine was introduced as a recommended regimen for chemoprophylaxis in sub-Saharan Africa.

Plasmodium falciparum infections caused 82.6% of the total cases (Figure 1 and Table 2). Africa and Asia accounted for 95.7% of reported cases (Table 2). West Africa alone reported 42.2% of all cases, followed by east Africa (26.9%) and central Africa (18.4%). In Asia, all cases (5.8% of the total cases) were acquired in south or southeast Asia. Only 2.0% of cases were reported from the Americas and the Australia/South Pacific regions combined.

By Plasmodium species, 95.4% of P. falciparum infections were acquired in Africa, 1.9% in Asia, and 1.6% in the Middle East (Table 2). Among 56 cases of P. vivax, 41% were acquired in Asia, 28.6% in Africa, 14.3% in the Americas, and 7.1% in the Middle East. Cases of Plasmodia that were not further speciated were reported primarily from Africa and Asia. Although most cases were diagnosed and treated in areas endemic for malaria, 19 cases were diagnosed outside malaria-endemic areas.

Incidence of malaria.

The estimated incidence of malaria by regions of the world was highest in sub-Saharan Africa (Table 3). The incidence in sub-Saharan Africa (Figure 2) was more than 10 times higher than Asia, the area with the next highest rate. The number of cases and incidence during 2000–2004 was generally lower than 1995–1999. When we combined data from west, central and east Africa, the average incidence for 2000–2004 was higher in adults (average = 6.2/1,000/year) compared with 3.0/1,000/year for children less than 19 years of age.

Seasonality.

Of the 610 infections acquired in sub-Saharan Africa over the 17-year period, cases were reported each month of the year, except in southern Africa (Figure 3). Interestingly, the peak of cases in west Africa occurred in January during the dry season. Cases in central, east, and southern Africa paralleled average rainfall (data not shown).

Clinical complications.

Complications were reported on 72 (10%) CRFs and included hemolysis (40 cases), mental status changes (10 cases), respiratory symptoms (6 cases), and death (3 cases). Other complications included thrombocytopenia (8 cases), renal failure (2), elevated liver enzyme levels (5), hematemesis (2), hyponatremia (2), and gram-negative sepsis (1).

Three deaths were reported (Table 4). Two were more than 50 years of age (age was not reported for one). Only the Department of Defense employee was part of the DOS medical care system. Two patients reportedly had cerebral malaria. One was taking what is now considered inadequate prophylaxis, one took prophylaxis erratically, and one was not using chemoprophylaxis.

Prophylaxis.

Of 684 microscopically proven cases, 58.5% were not taking prophylaxis or were using it on an irregular basis (Table 5). No or irregular use of chemoprophylaxis was reported by 57.7% of cases with P. falciparum and 83.9% with P. vivax malaria.

There were 221 persons who were diagnosed with P. falciparum malaria in Africa who indicated they used regular prophylaxis. These regimens included chloroquine alone, 71; chloroquine plus proguanil, 68; chloroquine plus primaquine, 4; pyrimethamine alone or in combination with dapsone or sulfadoxine, 5; doxycycline, 8; proguanil alone, 12; mefloquine, 49; a natural product, 1; or unknown, 3. Therefore, 171 (78%) of the 221 cases were taking chemoprophylaxis regimens that are no longer recommended in Africa to prevent P. falciparum malaria. Among those reportedly taking mefloquine, levels were not detectable in one person. Some others may have been taking one tablet every other week as originally recommended.

Comparison of results of microscopy and relationship to chemoprophylaxis.

Among 677 slides submitted to the Laboratory of the Office of Medical Services in Washington, DC over the 17 years, the Washington laboratory agreed with the local laboratory results for 552 (81.5%), including 486 positive and 66 negative. The Washington laboratory found parasites on 12 (1.8%) read as negative by the local laboratory. However, the major discrepancy was in slides read as positive for malaria parasites by local laboratories that could not be confirmed in Washington (n = 113). The Washington laboratory confirmed malaria parasites less frequently among those reportedly taking mefloquine (23 [51%] of 45 cases) compared with those taking chloroquine-based regimens (105 [87%] of 121 cases; P ≤ 0.001 by chi-square test).

DISCUSSION

This report provides important information on the risk and impact of malaria on U.S. government employees working overseas. It defines who is at risk, the types of Plasmodium causing infection, the seasonality of malaria, and the regions of greatest risk. Using post-population data, we estimate the incidence by region and among adults and children. Knowledge of these parameters will improve education of government workers and their medical care providers and provide data for policy makers to formulate prophylaxis strategies. In addition, it highlights the need for better diagnostic testing and continued reporting.

Among 97 cases classified presumptively as malaria without slide-proven malaria, some were likely true cases and were therefore treated appropriately. However, an important alternative diagnosis may have been missed,18 patients may have been exposed unnecessarily to potentially toxic malaria treatment, and importantly, doubt about the effectiveness of chemoprophylaxis may have been introduced. Definitive diagnosis in resource-poor areas, continued quality improvement, and training of laboratory personnel are urgently needed.19,20

Although male adults were the group most affected by malaria, there were no available data on the distribution of sex, agency, or duration of exposure in the total post-population to make conclusions on infection and demographics. In west, central, and east Africa, the rate of malaria in children from 2000 through 2004 was less than half that of adults. One could theorize that workers who spend much time in the field such as USAID, Peace Corps staff, and agriculture-related Foreign Service personnel would be at greater risk, but data are lacking. Because most deaths from malaria in travelers occur in persons ≥50 years of age, increased education and prompt medical therapy for these persons may help reduce mortality caused by malaria.5,21

Plasmodium falciparum caused 83% of all cases of malaria reported in the present study. It is also responsible for the greatest number of reported infections worldwide, and causes the highest rate of complications and death.22 In contrast to our study, the proportion of cases of P. falciparum diagnosed and reported in the United States is lower, but has gradually increased from 30% at the beginning of the study period to 50% of the cases diagnosed in 2003 and 2004.5,23 Plasmodium vivax comprised 8.1% of cases in the present study, but 22–24% of infections reported in the United States in 2003 and 2004. This may reflect the greater number of travelers from the United States to rural areas of Central and South America and the Indian sub-continent where P. vivax is more common. Among cases reported in the United States, P. malariae and P. ovale each make up approximately 3% of cases annually5 but were surprisingly uncommon among government personnel.

In the present study, 89.9% of cases were reportedly acquired in Africa. The proportion of cases acquired in Africa and diagnosed in the United States has increased from 37% in 1992 to 61% in 2004.5,23,24 In a recent study, Africa was the site of acquisition of malaria for 91.1% of European travelers.7 The proportion of patients with malaria was highest among those who had traveled to sub-Saharan Africa.18 Malaria rates in the present study and among Swedish travelers highlight the risk of malaria in Africa.25

Understanding the predominant species in various parts of the world is important in prescribing the most effective anti-malarial prophylaxis. For example, although atovaquone/proguanil is effective in preventing and treating P. falciparum infections, it appears to be less effective in preventing or treating P. vivax infections.26 Likewise, it is not effective in preventing hypnozoite-related relapses of P. vivax and P. ovale if used alone for treatment.27 One of our cases with P. vivax acquired in southeast Asia was treated with atovaquone/proguanil. Plasmodium vivax then relapsed some weeks later apparently from inadequate treatment for hypnozoites. Therefore, in areas with substantial P. vivax or P. ovale, primaquine, either as primary or terminal prophylaxis, might be a better choice, after testing for glucose-6-phosphate dehydrogenase.28,29

The number of patients with P. vivax who indicated they were not taking prophylaxis highlights two issues with P. vivax malaria. Cases with P. vivax and P. ovale malaria often occur weeks to months after leaving a malarious area.11,12,27 Second, and related, terminal prophylaxis or treatment with an 8-aminoquinoline such as primaquine is necessary to prevent late onset or relapses of these malarias.28

The study indicates that malaria cases peaked in the early 1990s among embassy personnel. Many of those cases occurred in Africa as chloroquine resistance developed across this continent.30,31 A study in Kampala, Uganda in 1992 in response to more cases among embassy personnel indicated one of the major problems was non-compliance with antimalarial medication.32 Furthermore, the study suggested chloroquine alone was no longer effective.32 The introduction of weekly mefloquine as the recommended prophylactic medication beginning in 199133 was temporally associated with a major decrease of cases across Africa in government personnel. The addition of atovaquone/proguanil in 200034 and primaquine in 200335 provide alternatives to mefloquine and doxycycline in these areas with chloroquine resistance.

Malaria risk in Africa changes seasonally. Although the months with greatest risk can often be predicted on the basis of increased temperature and rainfall, there is risk of malaria in every month in west, central, and east Africa. We speculate the reason for the high number of cases of malaria in January in west Africa may relate to prophylaxis irregularities during the end of year holidays, travel to rural areas, and increased outdoor activity in the dry season.

This study indicates the importance of preventing malaria to avoid complications and death. Cerebral malaria was reported in two of three of those cases with fatal outcomes. Prompt medical attention to those with fever and appropriate therapy are key to prevention of severe complications associated with malaria, especially for P. falciparum infections. Use of chemoprophylactic medication also reduces the risk of death.36 Additionally, our data confirm that persons more than 50 years of age may be at increased risk for complications including death.5,6

There are probably many reasons for the high numbers of cases of malaria in Foreign Service personnel. The increase in infected Anopheles mosquitoes and resistance to insecticides are probably the most important reasons for malaria risk, especially in Africa.37 The increase in resistance to chloroquine by P. falciparum and more recently by P. vivax in other areas is likely another.38 The underuse of personal anti-mosquito measures such as effective mosquito repellents, insecticide-impregnated bed nets, and protective clothing may be other contributing factors. Finally, the lack of proper and consistent use of chemoprophylactic measures is strongly suggested by this study.

In 2004, 75% of civilians with imported malaria in the United States had used an inappropriate or no chemoprophylactic regimen.5 Likewise, most Foreign Service persons with malaria were not taking regular chemoprophylaxis. Furthermore, in at least one instance, measurement of blood levels detected no mefloquine in someone who claimed regular use of the drug. Primary prevention (avoidance of Anopheles mosquito bites) and improved compliance to chemoprophylaxis are key.5,8,15,39 Effective, generally well-tolerated regimens of mefloquine, doxycycline, atovaquone/proguanil, and primaquine4042 have replaced ineffective30 and less safe prophylactic agents such as sulfadoxine/pyrimethamine42 and amodiaquine.43

Although trained health care workers completed case report forms, data on prophylaxis use were self-reported. In general, the use of self-reported data presents limitations for accuracy and validity. Few blood samples from malaria cases reporting use of mefloquine to detect blood drug and metabolite levels were available to confirm compliance and absorption. Study of P. falciparum isolates for drug sensitivity may be helpful.44 In addition, semi-quantitative information on patient use of personal protective measures (bed nets, insecticides, insect repellent, behavioral measures) as well as chemoprophylaxis may enable better detection of chemoprophylaxis failures and assist with compliance.

Another shortcoming is the lack of information gathered on vulnerable persons such as pregnant women and children. Because of concerns about the potential effects of chemoprophylaxis and the effects of malaria on pregnancy,45 additional information should be collected about chemoprophylaxis during pregnancy and pregnancy outcomes after malaria.46 Attention should also be given to the prevention of malaria in children of all ages through personal protective measures and an effective chemoprophylactic regimen.47,48

Another limitation is that only 89.5% of the 781 case reports reported to the Office of Medial Services were accompanied by blood smears. Some of these slides were of poor quality making confirmation difficult. A further study limitation is underreporting of cases and missing data on reports. We encourage reporting by giving feedback to providers and promoting the use of an updated form. Calculating incidence is complicated by the fact that the denominator of persons at risk for malaria at posts changes almost daily. The use of the actual number of persons at post as reported by health units monthly is probably a more accurate denominator than personnel authorization.

In conclusion, the study indicates those serving in sub-Saharan Africa are at the highest risk for malaria, especially P. falciparum. Many of the cases were taking what we now know was inadequate chemoprophylaxis because of parasite resistance. However, most persons who were infected with malaria did not take chemoprophylaxis, or took it irregularly. Recent drug development now provides four effective preventive drugs for those serving in Africa. Improved mosquito repellents and permethrin-treated bed nets and clothing are also now available. Continued training of laboratory personnel, ongoing laboratory quality improvement programs, field-adapted diagnostic technologies, and ongoing disease surveillance will improve the diagnosis of malaria. Proper and rapid diagnosis ensures all cases of malaria are promptly treated, cases of febrile illness that are not malaria are further investigated for preventable and treatable causes, and appropriate confidence is placed in properly used chemoprophylactic and personal protective regimens.

Table 1

Cases of malaria by agency reported by health units at U.S. diplomatic posts to the U.S. Department of State, 1988–2004

AgencyNo. of Cases%
* Includes one Coast Guard member, 49 Marine Security Guards, 8 Defense Attaché personnel, and 3 attached to a US Naval Medical Research Unit. The other 27 personnel were not further differentiated.
† Persons granted privileges to a health unit by the ambassador including teachers, missionaries, High Commission officers, private contractors, Fulbright scholars, and others.
Department of State22432.7
U.S. Agency for International Development20530.0
Department of Defense*8812.9
Unofficial†608.8
U.S. Peace Corps547.9
United State Information Agency253.6
Not stated81.2
Voice of America71.0
Drug Enforcement Agency60.9
Centers for Disease Control and Prevention40.6
Department of Treasury or Justice30.4
    Total684100
Table 2

Cases of malaria by region of exposure, U.S. Department of State, 1988–2004

Continent/regionPlasmodium falciparumP. vivaxP. malariaeP. ovaleP. speciesRegion totalRegion %
Africa89.9
    North Africa2114
    West Africa25522030289
    Central Africa11050011126
    East Africa16391110184
    South Africa11010012
Asia5.8
    South Asia91510328
    Southeast Asia2900112
Central America
    Caribbean, Mexico1800091.5
South Pacific1100020.3
Middle East73000101.5
South America0300030.4
Unknown4000150.7
    Total565 (82.6%)56 (8.1%)5 (0.7%)2 (0.3%)56 (8.2%)684100
Table 3

Average annual incidence of malaria per 1,000 persons at diplomatic posts, 1995–1999 and 2000–2004

1995–19992000–2004
RegionPersonnel*CasesFive-year average incidencePersonnel†CasesFive-year average incidence
* Authorized persons at posts.
†Actual number of persons at posts reported by Health Units.
Central Africa396168.0851672.71
West Africa1,718778.961,231508.12
East Africa1,780384.271,597313.88
South Africa86040.93860*10.23
South Asia1,62060.741,69930.35
Southeast Asia2,58320.152,84530.21
South America3,39110.064,08800.00
Central America/Caribbean3,73400.003,56220.11
Middle East2,48810.083,22120.12
Unknown40
    Total cases14999
Table 4

Deaths reported from malaria by diplomatic post health units, 1988–2004

Age, yearsSexAgency*StatusDate of onsetLocationPlasmodium speciesProphylaxis
* DoD = Department of Defense.
† Cases of malaria and all deaths among Peace Corps volunteers are officially investigated and recorded by the Office of Medical Services of the US Peace Corps. Peace Corps staff are under the medical program of the Office of Medical Services of the Department of State. In a few posts, there are Joint Peace Corps/Department of State Health Units.
52MaleDoDEmployee1/24/90Lilongwe, MalawifalciparumNone
UnknownPeace Corps†Volunteer4/1/90Nairobi, KenyafalciparumChloroquine/proguanil
65MaleUnofficial6/15/97Guinea-BissaufalciparumMefloquine erratically
Table 5

Number of cases reporting chemoprophylaxis use on malaria case report forms, 1988–2004 (n = 684)

Plasmodium speciesTaking regular chemoprophylaxisNo or irregular use of chemoprophylaxisProphylaxis usage unknownTotal
falciparum229 (40.5%)326 (57.7%)10 (1.8%)565
vivax9 (16.1%)47 (83.9%)0 (0.0%)56
malariae4 (80.0%)1 (20.0%)0 (0.0%)5
ovale1 (50.0%)1 (50.0%)0 (0.0%)2
Species undetermined28 (50.0%)25 (44.6%)3 (5.3%)56
    Total271 (39.6%)400 (58.5%)13 (1.9%)684 (100.0%)
Figure 1.
Figure 1.

Cases of malaria (n = 684) reported to the Office of Medical Services, Department of State, 1988–2004. This figure appears in color at www.ajtmh.org.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 76, 2; 10.4269/ajtmh.2007.76.260

Figure 2.
Figure 2.

Estimated incidence of malaria among U.S. government personnel at diplomatic posts in Africa, 1995–2004. For 1995–1999, the number of authorized personnel at posts was used as the denominator. For 2000–2004, the number of employees and eligible family members counted in the medical program by the health units was used. This figure appears in color at www.ajtmh.org.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 76, 2; 10.4269/ajtmh.2007.76.260

Figure 3.
Figure 3.

Sum of cases of malaria reported by month in sub-Saharan Africa, 1988–2004. This figure appears in color at www.ajtmh.org.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 76, 2; 10.4269/ajtmh.2007.76.260

*

Address correspondence to Joe P. Bryan, 1421 Mayflower Drive, McLean, VA 2210. E-mail: joe.p.bryan@earthlink.net

Authors’ addresses: Priya Joy Rathnam, U.S. Food and Drug Administration, Silver Spring, MD 20903. Joe P. Bryan, 1421 Mayflower Drive, McLean, VA 22101 Telephone: 703-356-8450, E-mail: joe.p.bryan@earthlink.net. Martin Wolfe, Traveler’s Medical Service, 2141 K Street, NW, Suite 408, Washington, DC 20037, Telephone: 202-466-8109.

Acknowledgments: We thank Dr. Cedric Dumont (Director, Office of Medical Services, U.S. Department of State) for initiating the study, the medical technologists in Washington who reviewed the malaria slides, the technologists at overseas diplomatic posts who prepared and interpreted the malaria slides under field conditions, the medical providers who complete the case report forms and send the slides and reports for review, Dr. Robert Burney (Chief, Quality Improvement, U.S. Department of State) for support of monthly health unit reports from which the numbers of persons at post in 2002 are derived, the Department of Epidemiology and Biostatistics, The George Washington University (Washington, DC), Dr. Virginia Foster and Ann Goldman for their assistance.

Financial support: This study was supported by the United States Government. The American Society of Tropical Medicine and Hygiene (ASTMH) and the American Committee on Clinical Tropical Medicine and Travelers’ Health (ACCTMTH) assisted with publication expenses.

Disclaimer: The opinions expressed herein are those of the authors and are not to be construed as official nor necessarily represent the views or official policies of the Department of State or U.S. Government.

Disclosure: Martin Wolfe is a consultant for GlaxoSmithKline, the makers of atovaquone and proguanil (Malarone®). This statement is made in the interest of full disclosure and not because the author considers this to be a conflict of interest.

REFERENCES

  • 1

    World Health Organization, 2006. Global Malaria Program. Accessed June 29, 2006. Available from http://www.who.int/malaria/epidemicsandemergencies.html

  • 2

    World Health Organization, 1997. World malaria situation in 1994. Wkly Epidemiol Rec 72 :269–274, 277–283.

  • 3

    Berman JG, 2001. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg 64 (Suppl 1–2):1–11.

    • Search Google Scholar
    • Export Citation
  • 4

    Sachs JD, 2005. Achieving the millennium development goals—The case of malaria. N Engl J Med 352 :115–117.

  • 5

    Centers for Disease Control and Prevention, 2006. Malaria Surveillance—United States, 2004. MMWR Morb Mortal Wkly Rep 55 :23–37

  • 6

    Newman RD, Parise ME, Barber AM, Steketee RW, 2004. Malaria-related deaths among U.S. Travelers, 1963–2001. Ann Intern Med 141 :547–555.

    • Search Google Scholar
    • Export Citation
  • 7

    Jelinek T, Schulte C, Behrens R, Grobusch MP, Couland JP, Bisoffi Z, Matteelli A, Clerinx J, Corachan M, Puente S, Gjorup I, Harms G, Kollaritsch H, Kotlowski A, Bjorkmann A, Delmont JP, Knobloch J, Nielsen LN, Cuadros J, Hatz C, Beran J, Schmid ML, Schulze M, Lopez-Velez R, Fleischer K, Kapaun A, McWhinney P, Kern P, Atougia J, Fry G, da Cunha S, Goecken B, for the European Network on Surveillance of Imported Infectious Diseases (TropNetEurop), 2002. Imported falciparum malaria in Europe: sentinel Surveillance data from the European Network on surveillance of imported infectious diseases. Clin Infect Dis 34 :572–576.

    • Search Google Scholar
    • Export Citation
  • 8

    World Health Organization, 2006. Malaria in Travelers. Accessed April 27, 2006. Available from www.who.int/malaria/malariaandtravellers.html

  • 9

    Frame JD, Lange WE, Frankenfield DL, 1992. Mortality trends of American missionaries in Africa, 1945–1985. Am J Trop Med Hyg 46 :686–690.

    • Search Google Scholar
    • Export Citation
  • 10

    Beadle C, Hoffman SL, 1993. History of malaria in the United States Naval Forces at war: World War I through the Vietnam conflict. Clin Infect Dis 16 :320–329.

    • Search Google Scholar
    • Export Citation
  • 11

    Newton JA, Schnepf GA, Wallace MR, Lobel HO, Kennedy CA, Oldfield EC, 1994. Malaria in U.S. Marines returning from Somalia. JAMA 272 :397–399.

    • Search Google Scholar
    • Export Citation
  • 12

    Kotwal RS, Wenzel RB, Sterling RA, Porter WD, Jordan NN, Petruccelli BP, 2005. An outbreak of malaria in U.S. Army Rangers returning from Afghanistan. JAMA 293 :212–216.

    • Search Google Scholar
    • Export Citation
  • 13

    Wallace MR, Sharp TW, Smoak B, Iriye C, Rozmajzl P, Thornton SA, Batchelor R, Magill AJ, Lobel JO, Longer CF, Burans JP, 1996. Malaria among United States Troops in Somalia. Am J Med 100 :49–55.

    • Search Google Scholar
    • Export Citation
  • 14

    Susi B, Whitman T, Blazes DL, Burgess TH, Martin GJ, Freilich D, 2005. Rapid diagnostic test for Plasmodium falciparum in 32 Marines medically evacuated from Liberia with a febrile illness. Ann Intern Med 142 :476–477.

    • Search Google Scholar
    • Export Citation
  • 15

    Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC, 1993. Long-term malaria prophylaxis with weekly mefloquine. Lancet 341 :848–851.

    • Search Google Scholar
    • Export Citation
  • 16

    Centers for Disease Control and Prevention, 2006. Malaria in multiple family members—Chicago, Illinois. MMWR Morb Mortal Wkly Rep 55 :645–648.

    • Search Google Scholar
    • Export Citation
  • 17

    Centers for Disease Control and Prevention, 2005. Health Information for International Travelers, 2005–2006. Accessed August 1, 2006. Available from www.cdc.gov/travel/destinat.htm

  • 18

    Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, Keystone JS, Pandey P, Cetron MS for the GeoSentinel Surveillance Network, 2006. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 354 :119–130.

    • Search Google Scholar
    • Export Citation
  • 19

    Marx A, Pewsner D, Egger M, Nuesch R, Bucher HC, Genton B, Hatz C, Juni P, 2005. Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas. Ann Intern Med 142 :836–846.

    • Search Google Scholar
    • Export Citation
  • 20

    Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA, 2006. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis 42 :377–382.

    • Search Google Scholar
    • Export Citation
  • 21

    Muhlberger N, Jelinek T, Behrens RH, Gjorup I, Couland JP, Clerinx J, Puente S, Burchard G, Gascon J, Grobusch MP, Weitzel T, Zoller T, Kollaritsch H, Beran J, Iversen J, Hatz C, Schmid ML, Bjorkman A, Fleischer K, Bisoffi Z, Guggemos W, Knobloch J, Matelli A, Schulze H, Laferi H, Kapaun A, McWhinney P, Lopez-Velz R, Fatkenheuer G, Kern P, Zieger BW, Kotlowski A, Fry G, Cuadros J, Myrvang B for the Trop-NetEurop and Surveillance Importierter Infectionen in Deutschland (SIMPID) Surveillance Networks, 2003. Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: Observations from the TropNetEurop and SSIMPID surveillance data. Clin Infect Dis 36 :990–995.

    • Search Google Scholar
    • Export Citation
  • 22

    Remme JHE, Binka E, Nabarro D, 2001. Toward a framework and indicators for monitoring Roll Back Malaria. Am J Trop Med Hyg 64 (Suppl 1–2):76–84.

    • Search Google Scholar
    • Export Citation
  • 23

    Centers for Disease Control and Prevention, 1995. Malaria Surveillance United States—1992. MMWR CDC Surveill Summ 44 (SS-5):1–15. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00039398.htm.

    • Search Google Scholar
    • Export Citation
  • 24

    Willaims HA, Roberts J, Kachur SP, Barber AM, Barat LM, Bloland PB, Ruebush TK II, Wolfe EB, 1999. Malaria Surveillance–United States, 1995. MMWR CDC Surveill Summ 48 :1–23.

    • Search Google Scholar
    • Export Citation
  • 25

    Askling HH, Nilsson J, Tegnell A, Janzon R, Ekdahl K, 2005. Malaria risk in travelers. Emerg Infect Dis 11 :436–441.

  • 26

    Ling J, Baird JK, Fryauff DJ, Sismadi P, Bangs MJ, Lacy M, Barcus MJ, Gramzinski R, Maguire JD, Kumusumangsih M, Miller GB, Jones TR, Chulay JD, Hoffman SL, and the Naval Medical Research Unit 2 Clinical Trial Team, 2002. Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia. Clin Infect Dis 35 :e25–e35.

    • Search Google Scholar
    • Export Citation
  • 27

    Schwartz E, Parise M, Kozarsky P, Cetron M, 2003. Delayed onset of malaria—Implications for chemoprophylaxis in travelers. N Engl J Med 349 :1510–1516.

    • Search Google Scholar
    • Export Citation
  • 28

    Baird JK, Fryauff DJ, Hoffman SL, 2003. Primaquine for prevention of malaria in travelers. Clin Infect Dis 37 :1659–1667.

  • 29

    Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, Primaquine: report from CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg 75 :402–415.

    • Search Google Scholar
    • Export Citation
  • 30

    Centers for Disease Control, 1987. Chloroquine-resistant Plasmodium falciparum malaria in west Africa. MMWR Morb Mortal Wkly Rep 36 :13–14.

    • Search Google Scholar
    • Export Citation
  • 31

    Centers for Disease Control and Prevention, 1988. Current trends. Recommendations for the prevention of malaria in travelers. MMWR Morb Mortal Wkly Rep 37 :277–284.

    • Search Google Scholar
    • Export Citation
  • 32

    Adera T, Wolfe MS, McGuire-Rugh K, Calhoun N, Marum L, 1995. Risk factors for malaria among expatriates living in Kampala, Uganda: the need for adherence to chemoprophylactic regimens. Am J Trop Med Hyg 52 :206–212.

    • Search Google Scholar
    • Export Citation
  • 33

    Centers for Disease Control and Prevention, 1991. Notice to readers: change in dosing regimen for malaria prophylaxis with mefloquine. MMWR Morb Mortal Wkly Rep 40 :72–73.

    • Search Google Scholar
    • Export Citation
  • 34

    Anonymous, 2000. Atovaquone/proguanil (Malarone) for malaria. The Medical Letter 42 :109–111

  • 35

    Centers for Disease Control and Prevention, 2003. Health Information for International Travel, 2003–2004. Atlanta: Centers for Disease Control and Prevention.

  • 36

    Krause G, Schöneberg I, Altmann D, Stark K, 2006. Chemoprophylaxis and malaria death rates. Emerg Infect Dis 12 :447–451.

  • 37

    World Health Organization Study Group, 2006. Malaria vector control and personal protection. World Health Organ Tech Rep Ser 936 :1–62.

  • 38

    Maguire JD, Krisin, Marwoto H, Richie TL, Fryauff DJ, Baird JK, 2006. Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria in Papua, Indonesia. Clin Infect Dis 42 :1067–1072.

    • Search Google Scholar
    • Export Citation
  • 39

    Molle I, Christensen K, 2000. Use of medical chemoprophylaxis and anti-mosquito precautions in Danish malaria patients and their traveling companions. J Travel Med 7 :253–258.

    • Search Google Scholar
    • Export Citation
  • 40

    Kain KC, Shanks GD, Keystone JS, 2001. Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens. Clin Infect Dis 33 :226–234.

    • Search Google Scholar
    • Export Citation
  • 41

    Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, Herold M, Krebs B, Veit O, Allwinn R, Steffen R, 2003. Tolerability of malaria chemoprophylaxis in non-immune travelers to sub-Saharan Africa: Multicentre, randomized, double blind, four arm study. BMJ 327 :1078–1083.

    • Search Google Scholar
    • Export Citation
  • 42

    Centers for Disease Control and Prevention, 1984. Revised recommendations for preventing malaria in travelers to areas with chloroquine-resistant Plasmodium falciparum. MMWR Morb Mortal Wkly Rep 34 :185–190.

    • Search Google Scholar
    • Export Citation
  • 43

    Centers for Disease Control, 1986. Agranulocytosis associated with the use of amodiaquine for malaria prophylaxis. MMWR Morb Mortal Wkly Rep 35 :165–166.

    • Search Google Scholar
    • Export Citation
  • 44

    Farcas GA, Soeller R, Zhong K, Zahirieh A, Kain KC, 2006. Real-time polymerase chain reaction assay for the detection and characterization of chloroquine-resistant Plasmodium falciparum malaria in returned travelers. Clin Infect Dis 42 :622–627.

    • Search Google Scholar
    • Export Citation
  • 45

    Guyatt HL, Snow RW, 2001. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 64 (Suppl 1–2):36–44.

    • Search Google Scholar
    • Export Citation
  • 46

    Centers for Disease Control and Prevention, Information for Health Care Providers: Preventing Malaria in Pregnant Woman. Accessed August 1, 2006. Available form http://www.cdc.gov/travel/mal_preg_hc.htm

  • 47

    Fischer PR, Bialek R, 2002. Prevention of malaria in children. Clin Infect Dis 34 :493–498.

  • 48

    Centers for Disease Control and Prevention, 2006. Prevention of Malaria in Children. Accessed June 29, 2006. Available from www.cdc.gov/malaria and www.cdc.gov/travel

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