Malaria in Travelers in Rhode Island: A Review of 26 Cases PETERM. WIEST,M.D., Providence, Rhode Island, STEVENM. OPAL, M.D., Pawtucket, Rhode /s/and, RODRIGOL. ROMULO, M.D., G. RICHARDOLDS, M.D., Providence, Rhode/s/and
PURP0SE We reviewed our experience with malaria in two community hospitals in Rhode Island from 1986 to 1990. RESULTS: Twenty-six patient8 with malaria were identified. Fifteen patients were immigrants who had acquired malaria while visitiug their country of orisin, particularly West Afria Fever was present in 67% of cams and gastrointestinal complain& were prominent in 26 % . Individuals with a past history of malaria could accurately dieting&b current malarial infections from other febrile illnesses. Two patients developed cerebral malark PJasmodium f&iparum was identified in 77% of the Casey CONCLUSIONS:
hhhria
is an impm’tfmt
dia@O-
sis that United States physicians must consider in the medical evaluation of returning travelers. A significant increase in the number of cases of R fdcipmum acquired iu East Africa has been report8d in recent years. I? fdci@rum infection must be rapidly diagnosed aud treated since delays may remIt in complications of malaria that may lead to death. Mefloquine is currently recommended by the Centers for Disease Control for prevention of malaria in travelers visiting count&a endemic for chloroquine-resistant malaria, This change may alter the epidemiology of malaria in the United Statea in the future.
From the Program in Geographic Medicine (PMW, RLR. GRO), Department of Medicine, The Miriam Hospital, Brown University, Providence, Rhode Island, and Division of Infectious Diseases (‘&IO), Department of Medicine, Memorial Hospital, Brown University, Pawtucket, Rhode Island. Requests for reprints should be addressed to Peter M. Wiest. Program in Geographic Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906. Manuscript submitted August 21, 1990, and accepted in revised form March 13, 1991.
30
July 1991 The American Journal of Medicine
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alaria is a protozoaldiseasethat infects more M than 200 million individuals in underdevelopedcountriesthroughoutthe world Moreover, [l].
it is estimated that over 1 to 2 million individuals die from malaria each year [l-3]. In the United States,malaria is acquiredprimarily by immigrants and travelers who visit endemic areas. Approximately 1,000casesper year were reported to the Centers for DiseaseControl (CDC) for the past 5 years,but the actualnumber of casesmay besignificantly higher [4]. Furthermore, in recent years, a significant increasein the number of casesof infection with Plasmodium falciparum acquiredin East Africa has beenreported to the CDC [5]. A similar increasewas also reportedin Canada[6]. This may reflect resistanceof the parasiteto chloroquine,the main chemoprophylacticdrug usedto prevent malaria in travelers to endemic countries. With increased travel of American citizens to areaswhere malaria is endemic and the spread of chloroquine-resistantmalaria, we were interested in reviewing our experiencewith malaria in two community hospitals in RhodeIsland from 1986to 1990.Thesehospitalsarethe major regionalcenters for tropical medicine and operatethe largesttravel clinics in the state. PATIENTS AND METHODS Charts werereviewedof all patients with a diagnosis of malaria at The Miriam Hospital in Providence,Rhode Island, and The Memorial Hospital, Pawtucket, Rhode Island, from January 1986to June 1990.Recordswere identified by a computer searchof all patients with a dischargediagnosisof malaria. Furthermore, all casesof malaria seenat the travel clinics at The Miriam Hospital and The Memorial Hospital were reviewed. Approximately 3,000 individuals are seen yearly at these clinics. Malaria was diagnosedby demonstration of malarial parasites on peripheral blood films. In one case,thick and thin blood smearswerenegative,but a clinical diagnosisof malaria wasmade basedon a travel history to an endemic area, symptoms and signs consistent with infection, and a rapid responseto antimalarial treatment. No casesof congenital transmission, transfusion-inducedmalaria,
MALARIA
IN TRAVELERS
IN RHODE
ISLAND
/ WIEST ET AL
TABLE I Casesof Malaria Diagnosedin Rhode Island from 1986to 1990 Patient Number/Age/Sex 1/29/M 2/-IM ;;z;; 51-IM 6/-/M 7/37/M 8142/M 9/44/M :$&: ::;;;;i 14/35/F
Native of
Countries Acquired
Nigeria Nigeria Nigeria Nigeria Nigeria Nigeria Liberia Ghana Ghana Ghana Ghana Angola Senegal India
Nigeria Nigeria Nigeria Nigeria Nigeria Nigeria Liberia, Sierra Leone, Nigeria Ghana Ghana Ghana Ghana Angola Senegal India
E
India Sierra Leone, Kenya, India Papua New Guinea Liberia, Nigeria, Ghana Mexico Kenya, Tanzania Papua New Guinea
22/22/F
us
Kenya
%kF
If us US
Thailand Kenya Kenya Mexico
‘1E17/19/M :;%Y 20/20/F 2 1/20/M
25/38/M 26/44/M
F” l-2 us
Species f. falciparum P. fa/ciparum P. falciparum ? ? ? P. falcipafum P. falciparum P. falciparum P. falciparum f. falciparum P. falciparum P. falcipafum P. falciparum P. vivax f. falciparum P. falciparum P. vivax P. falciparum ? P. falciparum P. falcipafum P. vivax P. falcipafum P. vivax (?I f. ova/e (?I P. falciparum P. fa/c!parum M&parum
Malaria Prophylaxis Taken Given E No ? 1 E Yes No No No No No C
fro No No ? ? Yes No No No No No No Yes
No
i
vN,“s Yes Yes 2 weeks Yes Yes
c, F No
E E
C;F
?i%Zf Yes No No ? Yes 1 Yes Yes ? Yes Yes Yes No No No Yes Yes Yes No
Treatment Fi,F ;’ ;. s E,F ;, ;’ ; Q:T’ 9, PI s Q,P, S ;, p, s Q, p, s ;, ; c , i,T
vN,“s
::TD
Yes
No
Q,D
No Yes Yes No
ii No No
= chlorcquine; F = pyrimethamine/suiiadoxine;Q = qumine; D = doxcycline; P = pyrimethamine; S = sutiadiezine;T = tetracycline
or malaria associatedwith intravenousdrug abuse cation as recommended.Two individuals (Patients were observed. 14 and 19) used chloroquine while traveling overseas but discontinued prophylaxis prematurely RESULTS upon return to the United States. Ninety-one perCharts of 26 patients with a diagnosisof malaria cent of travelersborn in the United Statesand 36% were reviewed (Table I). Ages of the patients of individuals born overseaswere recommendedto rangedfrom 15to 48 years,with a meanof 29years. take malarial prophylaxis. It was not possible to Of these, 19 were males and sevenwere females. determine from a review of the charts why individFifteen were foreign-born, with six from Nigeria, uals did not take malaria prophylaxis or, for indifour from Ghana, two from India, and one each viduals who took chemoprophylaxis,who initially from Senegal,Angola, and Liberia. These individ- recommendedtheseprecautionsto thesetravelers. uals were infected in the countries in which they Malaria wassuspectedin 23 of the 26 casesupon were born, except for Patient 7 who was born and presentationto a medical carefacility. Of those intraveled to Liberia but who may havealso acquired dividuals for whom malaria was not initially susmalaria in Nigeria or Sierra Leone.For citizens of pected,one patient was treated initially with penithe United States, six individuals were infected in cillin for pharyngitis. A second patient was Africa, one in Thailand, two in Papua New Guinea, diagnosedas having a viral syndrome. The third and two in Mexico. Reasonsfor travel werepleasure patient was a female and complained of lower ab(sightseeing,visiting families) in 68%of the patients dominal pain. Initial evaluationconsistedof a gyneand businessin 32%. cologicexamination for suspectedpelvic inflammaMalaria prophylaxis was recommendedto 14 in- tory disease, the results of which were dividuals (Table I). Weekly chloroquinewasrecom- unremarkable. Persistent fevers in all patients mended to 13 individuals. One was given chloro- prompted evaluation for malaria. quine plus weekly pyrimethamine/sulfadoxine The major presenting complaints were fever, (Patient 22).Of these,11individuals usedthe medi- chills, headache, fatigue, and gastrointestinal
July 1991
The American
Journal
of Medicine
Volume
91
31
MALARIA
IN TRAVELERS
IN RHODE
ISLAND
/ WIEST ET AL
TABLE II Presenting Symptomsof Malaria in 26 Patients Number of
Symptoms Fever and chills Headache Fatigue Nausea, vomiting, diarrhea hlyalgias Anorexia Abdominal pain Pharyngitis Shortness of breath Neck stiffness Low back pain
Patients
%
:
TABLE Ill Signs of Malaria on Presentation of 26 Patients Sign
Numberof Patients
Te;pe:,)rre 99-1°0o”F lOO-101°F lOl-102°F 102-103°F > 103°F Splenomegaly Orthostatic hypotension Abdominal tenderness Neurologic symptoms
symptoms (Table II). Other symptoms reported included myalgias, low back pain, neck stiffness, sorethroat, shortnessof breath, forgetfulness,and confusion. Fever and chills were common in patients infected with all three species of malaria identified. Low backpain and myalgiaswereprominent in Patient 17 who was infected with P. uiuax malaria (Table I). Patient 21 complained of neck stiffness as well as fever, chills, and headacheand was infected with both P. falciparum and P. uiuax. All other symptoms of malaria, including gastrointestinal symptoms, werefound in patients infected with P. falciparum. A history of a previous episode of malaria was found in 11 of 26 individuals. Each person with a history of malaria stated that their current illness was malaria since the symptomatology was similar to that of previousepisodes.They all thought that their current illness was clearly distinguishable from other febrile illnesses. Fever was documentedin 14 patients upon presentationto a medical carefacility (Table III). Seven individuals wereafebrile. Other findings included orthostatic hypotension, lower abdominal
32
July 1991 The American Journal of Medicine
Volume 91
tenderness,and a palpablespleentip. Two patients had difficulty rememberingrecent eventsand were disoriented.Fever was common in all patients regardlessof which species of malaria was found. Splenomegalywas found in one patient with P. uiuax and two patients infected with P. falciparum. All other signswere found in patients infected only with P. falciparum. The white blood cell count wasnormal in 12 and decreasedin six. An increasedpercentageof bands was found in 14 of 18 cases.Thrombocytopenia (normal 150,000to 400,000/mm3)wasfound in 14of 20 individuals with platelet counts ranging from 46,000to 136,000/mm3.Three patients wereanemic upon presentation.Total bilirubin levels were elevated in three of nine patients tested,and increased lactate dehydrogenaselevels were found in four of six patients. Thin smearswere positive for malaria in 22 patients. In two patients, malaria was presenton the thick smearbut not the thin smear (Patients 2 and 3). In Patient 5, malaria wasnot found on multiple thin and thick smears;however,her symptomswere consistentwith malaria and sherespondedpromptly to treatment with chloroquine. P. falciparum was the most common species identified, beingfound in 20of the 26cases.Sixteen patients were infected in Africa, while of the remaining patients, two wereinfected in India, onein Thailand, and one in Papua New Guinea.P. uiuax wasidentified in four patients: two who visited Papua New Guinea and one eachwho visited Mexico and India, respectively.In four cases,the speciesof malaria could not be positively identified. Mixed infections werefound in three individuals. P. falciparum and either P. ouale or P. uiuax were identified in Patient 22.Two patients wereinfected with P. falciparum and P. uiuax (Patients 14 and 21). Twenty of the 26infected patients werehospitalized. P. falciparum infections were treated with a variety of regimens including chloroquine alone (Patient 13 who visited Senegalin 1986),quinine plus tetracycline or doxycycline in eight, quinine plus pyrimethamine plus sulfadiazinein seven,quinine plus pyrimethamine/sulfadoxine and chloroquine in two, and quinine plus pyrimethamine/sulfadoxine in one. Two patients were treated for P. uiuax with chloroquine.Unidentified speciesof malaria were treated with chloroquine alone in two patients, chloroquine plus pyrimethamine/sulfadoxine in two, and quinine plus doxycycline in one. Pyrimethamine/sulfadoxinefailed to cure malaria in three individuals. Oneindividual (Patient 20) ac-
MALARIA
IN TRAVELERS
IN RHODE
ISLAND
/ WIEST ET AL
quired malaria while traveling in Kenya and Tanxa- peraxine,and dystonic reactionsdeveloped.Sympnia. Shedevelopeda febrileepisodeto 102OF(38.9OC) toms resolvedafter discontinuation of prochlorperandtook threetabletsof pyrimethamine/sulfadoxine. azine.A third patient developedesophagealulcers Her symptoms persisted.Three days later, a physi- attributed to doxycycline therapy. This resolved cian in Kenya found P. fdciparum in her peripheral with treatment with antacids and discontinuation bloodsmear.Shewastreated with oral quinine for 3 of doxycyline. days and her symptoms gradually improved. One weekafter her arrival in the United States,shedevel- COMMENTS opedfever.P. falciparum was identified in her peMalaria is a potentially fatal diseaseencountered ripheral blood smear.She was treated with quinine by travelers to endemic countries. It is therefore and tetracyclineand her symptomsand parasitemia necessarythat physicians in the United States resolved. be able to diagnose and to treat patients with The secondcase(Patient18)occmredin anIS-year- malaria rapidly and effectively. This was exempliold man who traveledin Liberia, Ghana,and Nigeria. fied by a tragic caseseen at another hospital in Despitetakingweeklychloroquineprophylaxis,hede- RhodeIsland.A 48year-old black man from Ghana velopedseveralfebrileepisodesthat werediagnosedas presentedafter a recent visit to Ghana to a local malariaon bloodsmear.Symptomspromptly resolved emergencyroom complaining of fevers,chills, and aftertreatmentwith pyrimethamine/sulfadoxine, Sev- diarrhea. The patient told the physician that he enweeksafterhis return to the United States,heagain thought he had malaria since his symptomatology developeda febrileillness.Malarial parasiteswereseen was similar to that of a previous episode.A comin his peripheralbloodsmear,andhe wastreatedwith plete blood cell count was sent to the laboratory, three tablets of pyrimethaminelsulfadoxinefollowed but parasiteswerenot detected.He was discharged by a singledoseof weeklypyrimethaminelsulfadoxine from the emergencyroom with a diagnosisof colitis. for 3 weeks.Upon his arrival in RhodeIsland, pyri- Two days later, he was found dead.Autopsy findmethamine/sulfadoxinewas discontinuedafter two ings demonstratedcerebralmalaria. Retrospective doses.Two weeks later, he developedP. falciparum examination of the peripheral blood smear malariaandwassuccessfuhy treatedwith quinineand obtained in the emergencyroom demonstratedP. fulciparum malaria. doxycycline. The third patient (Patient 25) wasa 3%year-old In RhodeIsland, a recentreviewof casesreported physician who developed P. falciparum malaria to the Rhode Island State Health Department rewhile working in a medical mission in Kenya. He vealed that 52 casesof malaria occurredin Rhode took three tablets of pyrimethamine/sulfadoxine Island from 1984to 1989 [7]. One patient died of and his symptoms resolved.Symptoms reappeared malaria, the only deathin the 6-yearperiod.Studies 3 weekslater after he returned to the United States. haveshownthat malaria is important in major metHe againtook pyrimethamine/sulfadoxinewith res- ropolitan medical centers [2,3]. Our review indiolution of his symptoms. Four weekslater, hedevel- catesthat malaria is alsoan important problem that opedfever, chills, and fatigue associatedwith peri- physicians need to be aware of in community ods of confusion and difficulty concentrating. hospitals. Reviewof his peripheral blood smeardemonstrated In our review, 42%of the patients were United P. falciparum with a parasitemia of 5%. He was States citizens who traveled to countries where treated with quinine and doxycycline with perma- malaria was endemic. The remaining 58% were nent resolution of his symptoms and clearanceof immigrants from foreign countries who visited his parasitemia. countries wherethey wereborn. Our data indicate The only complication of malaria that devel- that the majority of individuals who took malaria oped in two patients (Patients 20 and 25) was prophylaxis while traveling overseaswere born in cerebral malaria. Both individuals were confused the United States, while only 36%of foreign-born and disoriented. No focal neurologic abnormali- travelers took preventive measures.This decrease ties were observed. Symptoms resolved quickly in the number of travelers born overseaswho did with treatment and no residual neurologic deficits not take preventive measures may reflect dewere noted. No patients died during this time creasedaccessto medical care and pretravel adperiod. vice, languageor cultural barriers, or the mistakComplications due to treatment for malaria oc- en impression that they possess“immunity” to curred in three patients. Severenauseaand vomit- malaria. It is therefore important that immiing secondaryto quinine therapy developedin two grants from countries where malaria is endemic patients. Individuals were treated with prochlor- be advised that they are susceptible to malaria
July 1991
The American
Journal
of Medicine
Volume
91
33
MALARIA IN TRAVELERS IN RHODE ISLAND / WIEST ET AL
and should receive chemoprophylaxis when visiting their country of origin. The majority of casesof malaria imported into the United Statesin our study wereacquiredduring travel in Africa. This is consistent with a recent review of casesof malaria reportedto the CDC from 1983to 1986[8]. Of 634casesof P. fuZciparum malaria amongAmerican civilians, 80%were acquired in sub-Saharan Africa. The remaining were acquired in SoutheastAsia, the Caribbean,and South America. This occurreddespitethe fact that an estimated 90,000Americans travel to sub-SaharanAfrica each year, while 900,000Americans travel to SoutheastAsia and South America yearly. Travelers to Africa are at an increasedrisk for acquiring malaria in most rural and urban areas.In contrast, most travelers to SoutheastAsia and South America spend the majority of their time in urban and resort areaswherethe risk of exposureto malaria is limited. The majority of our caseswereinfections with P. falciparum. P. fatciparum was also seenin 70%of casesby Kean et al [2] but in only 25%reportedby Gordonet al [3]. These differencesmay reflect the regionswherethe travelersvisited. In our study and that of Kean and co-workers,the majority of individuals visited Africa, while in Gordon’sstudy, only 17%visited Africa [2,3].Of thoseinfected in Africa, all had P. falciparum malaria [2].P. uiuax predominates in India, Pakistan, Bangladesh,and Central America, while P. falciparum predominatesin Africa and Haiti [9]. P. ouale also occurs primarily in Africa, while P. malariae is cosmopolitan [9]. The typical symptoms of malaria-fever and chills, associatedwith myalgia, fatigue, anorexia, and headache-are often mistaken for more common illnesses in the United States such as viral syndromes [2]. In addition, patients with malaria may be afebrile in the early phasesof infection and thus the suspicion of malaria by the physician is lessened.Furthermore, gastrointestinal symptoms and signsmay be prominent in patients with malaria, and again,this may mislead the physician [2,3]. In our review,gastrointestinalcomplaints werepresenting symptoms in 26%of patients, all of whom were infected with P. falciparum. Gastrointestinal symptoms are common in P. falciparum infections, but are alsofrequently seenwith casesof non-falciparum malaria [2,3]. It is therefore necessarythat physicians consider malaria in any symptomatic patient returning from travel overseas. A critical point not often emphasizedis that individuals who havehad a previousepisodeof malaria are ableto distinguish current infections of malaria from other febrile illnesses.In our review, all indi-
34
July 1991 The American Journal of Medicine
Volume 91
viduals with a history of malaria indicated to the physicianthat they thought they wereinfectedwith malaria again.The reasonsfor thesecharacteristic symptoms of malarial infection are not known. Alternatively, individuals with a history of malaria may suspectthat any fever is againdue to malaria. Nevertheless, this history indicates to physicians that they must seriously consider this diagnosis. The diagnosisof malaria currently restsupon the demonstration of parasites in thin- and thickstained peripheral blood smears. Newer methods such as DNA probes and acridine orangefluorescencemay provide more sensitive and rapid techniques to diagnosemalaria in the future but are currently only researchtools [lO,ll]. Prevention of malaria has becomea particularly difficult problem in recent years. One important way to prevent malaria is to reduce contact with mosquitoes [8]. This can be accomplished by remaining within well-screenedareasat night, using mosquito nets, wearing clothes that cover most of the body, and using an insect repellent on exposed skin. An additional measureto prevent malaria is chemoprophylaxis [8]. The major difficulty has beenthe developmentof resistanceby malarial parasites to different chemotherapeuticagentsin recent years [12].Chloroquinewas the drug of choice to prevent malaria for many years,but resistanceto this agent developed in Southeast Asia, South America, and East Africa and has recently spread into West Africa [13]. Previous recommendationsby the CDC for malarial prophylaxis werefor individuals to take chloroquine to prevent infection with susceptible strains of P. falciparum and non-falciparum malaria [13]. It was also suggestedthat individuals take weekly pyrimethamine/sulfadoxinefor prophylaxis against chloroquine-resistant malaria. Between 1982and 1985,24casesof erythemamultiform, Stevens-Johnsonsyndrome, and toxic epidermal necrolysisweredocumentedin American travelersusing weekly pyrimethamine/sulfadoxine [14]. Seven caseswere fatal. Recommendationswere changed suchthat individuals should carry pyrimethamine/ sulfadoxinefor presumptivetreatment of malaria if a personcould not obtain immediate medical attention [8,12,14]. Resistance to pyrimethamine/sulfadoxine has alsodevelopedand is currently found in Southeast Asia, South America, and recently in Africa [8,15,16].In our series,three individuals who traveled to Africa may havehad chloroquine-and pyrimethamine/sulfadoxine-resistant P. falciparum malaria. Two patients acquired probable chloro-
MALARIA IN TRAVELERS IN RHODE ISLAND / WIEST ET AL
quine- and pyrimethamine/sulfadoxine-resistant malaria while traveling in Kenya. This has been described previously in East Africa [16]. The third patient (Patient 18) developed chloroquine-resistant and probable pyrimethaminel sulfadoxine-re-sistant malaria while in West Africa. Serum levels to determine if therapeutic levels of pyrimethamine/sulfadoxine were achieved were not performed. Nevertheless, the clinical response to treatment of previous episodes of malaria with pyrimethamine/sulfadoxine suggests that adequate serum levels were obtained. This latter case suggests that resistance to pyrimethamine/sulfadoxine may have emerged in West Africa. Current recommendations by the CDC, which we agree with, suggest that travelers to sub-Saharan Africa, Southeast Asia, and South America use mefloquine prophylactically to prevent malaria [8]. This drug is highly effective in the prevention of chloroquine-resistant and pyrimethamine/sulfadoxine-resistant P. fdciparum malaria as well as malaria caused by non-falciparum species [16,17]. Mefloquine has recently been approved for use in the United States. Several problems exist with the use of mefloquine [8]. First, careful patient selection is required. Mefloquine is not recommended for individuals taking drugs that alter cardiac conduction or who have a history of psychiatric or seizure disorders. This is particularly important since many older individuals with cardiac disease visit the game parks in East Africa each year. Furthermore, various neurologic side effects such as vertigo, dizziness, restlessness, or other neuropsychiatric problems may occur, and patients need to be warned about these potential reactions [8,18]. Despite the relatively recent introduction of mefloquine, resistance to this agent has been reported in Africa, Thailand, Indonesia, and the Philippines [19-241. It is therefore critical that all travelers be advised that no chemoprophylactic agent is 100% effective in the prevention of malaria. Furthermore, these medications are not a substitute for other measures that can be used to prevent malaria. In addition, all travelers must understand that any febrile illness, either in an area in which malaria is endemic or after departure from such an area, may represent malaria, and they should seek immediate medical attention. Recommendations for malaria chemoprophylaxis and treatment are constantly changing. Up-to-date information can be obtained from the CDC Malaria Hotline (404-332-4555) or from Health Informa-
tion for International Travel published by the CDC or local travel clinics. In summary, physicians in the United States must be aware that malaria is still a major medical problem throughout the world. Symptoms of malaria are nonspecific and often present as a viral syndrome. It is therefore necessary that a high index of suspicion be maintained by physicians in the medical evaluation of returning travelers. Furthermore, malaria must be seriously considered in individuals with a history of malaria who now indicate that they have malaria again. Lastly, attempts to prevent malaria should be utilized by all travelers in areas where malaria is endemic. It is therefore essential that physicians either provide proper up-todate information regarding malarial prophylaxis to travelers or refer these individuals to local tropical disease specialists for assistance.
ACKNOWLEDGMENT We wish to thank Valerie Sears for her expert preparation of this manuscript.
secretarial
assistance
in the
REFERENCES 1. Wyler DJ. Malaria-resurgence,
308:8?5-8,
resistance
and research.
N Engl J Med 1983;
934-40.
2. Kean BH, Reilly PC. Malaria-the mime: recent lessons from a group of travellers. Am J Med 1976; 61: 159-64. 3. Gordon S, Brennessel DJ, GoldsteIn JA, Rosner F. Malaria, a city hospital experience. Arch Intern Med 1988; 148: 1569-71. 4. Finn L. Reports of notifiable diseases. MMWR 1985; 34: 589-95. 5. Lobe1 HO. Campbell CC, Schwartz IK, Roberts JM. Recent trends in the importation of malaria caused by Plasmodium falciparium into the United States from Africa. J Infect Dis 1985; 152: 613-7. 6. Recent Canadian deaths from malaria in Africa. Can Dis Wkly Rep 1989; 15: 199-204. 7. Gilbert TT. Malaria In Rhode Island. Rhode Island Medical Journal 1990; 73:
220. 6. Centers for Disease Control. Recommendation for the prevention of malaria among travelers. MMWR 1990; 39: l-10. 9. Wyler DJ. Plasmodium species (malaria). In: Mandel GL. Douglas RG. Bennett JE. eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone. 1990: 205665. 10. Lanar DE, McLaughlin GL, Wirth DF, Barker RJ, Zolg JW, Chulay JD. Comparison of thick films, in vitro culture and DNA hybridization probes for detecting Plasmodium falciparum malaria. Am J Trop Med Hyg 1989; 40: 3-6. 12. Spielman A, Perrone JB, Teklehaimanot A, Balcha F, Wardlaw SC, Levine RA. Malaria diagnosis by direct observation of centrifuged samples of blood. Am J Trop Med Hyg 1988; 39: 337-42. 13. Krogstad DJ, Herwaldt EL. Chemoprophylaxis and treatment of malaria. N Engl J Med 1988; 319: 1538-40. 14. Moran JS, Bernard KW. The spread of chloroquine resistant malaria in Africa. JAMA 1989; 262: 245-8.
15. Pearson RD. Hewlett EL Use of pyrimethamine-sulfadoxine (Fansidar) in prophylaxis against chloroquine-resistant Plasmodium falciparum and Pneumo cystic carinii. Am J Med 1987; 106: 714-8. 16. Bjorkman A, Phillips-Howard PA. The epidemiology of drug-resistant malaria. Trans R Sot Trop Med Hyg 1990: 84: 177-80.
July 1991
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35
MALARIA IN TRAVELERS IN RHODE ISLAND / WIEST ET AL 17. Centers for Disease Control. Malaria in travelers returning from Kenya: failure of self-treatment with pyrimethamine/sulfadoxine. MMWR 1989; 38: 363-4. 18. Jiang JB. Li GQ, Guo XB. Kong YC, Arnold K. Antimalarial activity of mefloquine and quinghaosu. Lancet 1982; 2: 285-8. 19. Sturchler D, Handschin J, Kaiser D, et al. Neuropsychiatric side effects of mefloquine. N Engi J Med 1990; 322: 1752-3. 20. Odulola AMJ, Michols WK, Salaro LA, Walker 0. Desjardin RE. Reduced in vitro susceptibility to mefloquine in West African isolates of Plasmodium fa/cC parum. Lancet 1987; 1: 1304-5.
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21. Smrkovshi LL. Buck RL. Alcantara AK, Rodriguez CS. Uylanco CV. h vitro mefloquine resistant Plasmodium falciparumfrom the Philippines. Lancet 1982; 1: 322. 22. Boudreau FF. Webster HK. Pavanaud K. Thosingham L. Type II mefloquine resistance in Thailand. Lancet 1982; 2: 1335. 23. Bygbjerg IC. Scharira A, Flachs H, Gomme G, Jepsen S. Mefloquine resistance of falciparum malaria from Tanzania enhanced by treatment. Lancet 1983; 1: 774-5. 24. Salako LA, Aderounmu AF. In vitro chloroquine and mefloquine resistant Plasmodium fakiparum in Nigeria. Lancet 1987; 2: 572-3.
PURP0SE We reviewed our experience with malaria in two community hospitals in Rhode Island from 1986 to 1990. RESULTS: Twenty-six patient8 with malaria were identified. Fifteen patients were immigrants who had acquired malaria while visitiug their country of orisin, particularly West Afria Fever was present in 67% of cams and gastrointestinal complain& were prominent in 26 % . Individuals with a past history of malaria could accurately dieting&b current malarial infections from other febrile illnesses. Two patients developed cerebral malark PJasmodium f&iparum was identified in 77% of the Casey CONCLUSIONS:
hhhria
is an impm’tfmt
dia@O-
sis that United States physicians must consider in the medical evaluation of returning travelers. A significant increase in the number of cases of R fdcipmum acquired iu East Africa has been report8d in recent years. I? fdci@rum infection must be rapidly diagnosed aud treated since delays may remIt in complications of malaria that may lead to death. Mefloquine is currently recommended by the Centers for Disease Control for prevention of malaria in travelers visiting count&a endemic for chloroquine-resistant malaria, This change may alter the epidemiology of malaria in the United Statea in the future.
From the Program in Geographic Medicine (PMW, RLR. GRO), Department of Medicine, The Miriam Hospital, Brown University, Providence, Rhode Island, and Division of Infectious Diseases (‘&IO), Department of Medicine, Memorial Hospital, Brown University, Pawtucket, Rhode Island. Requests for reprints should be addressed to Peter M. Wiest. Program in Geographic Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906. Manuscript submitted August 21, 1990, and accepted in revised form March 13, 1991.
30
July 1991 The American Journal of Medicine
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alaria is a protozoaldiseasethat infects more M than 200 million individuals in underdevelopedcountriesthroughoutthe world Moreover, [l].
it is estimated that over 1 to 2 million individuals die from malaria each year [l-3]. In the United States,malaria is acquiredprimarily by immigrants and travelers who visit endemic areas. Approximately 1,000casesper year were reported to the Centers for DiseaseControl (CDC) for the past 5 years,but the actualnumber of casesmay besignificantly higher [4]. Furthermore, in recent years, a significant increasein the number of casesof infection with Plasmodium falciparum acquiredin East Africa has beenreported to the CDC [5]. A similar increasewas also reportedin Canada[6]. This may reflect resistanceof the parasiteto chloroquine,the main chemoprophylacticdrug usedto prevent malaria in travelers to endemic countries. With increased travel of American citizens to areaswhere malaria is endemic and the spread of chloroquine-resistantmalaria, we were interested in reviewing our experiencewith malaria in two community hospitals in RhodeIsland from 1986to 1990.Thesehospitalsarethe major regionalcenters for tropical medicine and operatethe largesttravel clinics in the state. PATIENTS AND METHODS Charts werereviewedof all patients with a diagnosis of malaria at The Miriam Hospital in Providence,Rhode Island, and The Memorial Hospital, Pawtucket, Rhode Island, from January 1986to June 1990.Recordswere identified by a computer searchof all patients with a dischargediagnosisof malaria. Furthermore, all casesof malaria seenat the travel clinics at The Miriam Hospital and The Memorial Hospital were reviewed. Approximately 3,000 individuals are seen yearly at these clinics. Malaria was diagnosedby demonstration of malarial parasites on peripheral blood films. In one case,thick and thin blood smearswerenegative,but a clinical diagnosisof malaria wasmade basedon a travel history to an endemic area, symptoms and signs consistent with infection, and a rapid responseto antimalarial treatment. No casesof congenital transmission, transfusion-inducedmalaria,
MALARIA
IN TRAVELERS
IN RHODE
ISLAND
/ WIEST ET AL
TABLE I Casesof Malaria Diagnosedin Rhode Island from 1986to 1990 Patient Number/Age/Sex 1/29/M 2/-IM ;;z;; 51-IM 6/-/M 7/37/M 8142/M 9/44/M :$&: ::;;;;i 14/35/F
Native of
Countries Acquired
Nigeria Nigeria Nigeria Nigeria Nigeria Nigeria Liberia Ghana Ghana Ghana Ghana Angola Senegal India
Nigeria Nigeria Nigeria Nigeria Nigeria Nigeria Liberia, Sierra Leone, Nigeria Ghana Ghana Ghana Ghana Angola Senegal India
E
India Sierra Leone, Kenya, India Papua New Guinea Liberia, Nigeria, Ghana Mexico Kenya, Tanzania Papua New Guinea
22/22/F
us
Kenya
%kF
If us US
Thailand Kenya Kenya Mexico
‘1E17/19/M :;%Y 20/20/F 2 1/20/M
25/38/M 26/44/M
F” l-2 us
Species f. falciparum P. fa/ciparum P. falciparum ? ? ? P. falcipafum P. falciparum P. falciparum P. falciparum f. falciparum P. falciparum P. falcipafum P. falciparum P. vivax f. falciparum P. falciparum P. vivax P. falciparum ? P. falciparum P. falcipafum P. vivax P. falcipafum P. vivax (?I f. ova/e (?I P. falciparum P. fa/c!parum M&parum
Malaria Prophylaxis Taken Given E No ? 1 E Yes No No No No No C
fro No No ? ? Yes No No No No No No Yes
No
i
vN,“s Yes Yes 2 weeks Yes Yes
c, F No
E E
C;F
?i%Zf Yes No No ? Yes 1 Yes Yes ? Yes Yes Yes No No No Yes Yes Yes No
Treatment Fi,F ;’ ;. s E,F ;, ;’ ; Q:T’ 9, PI s Q,P, S ;, p, s Q, p, s ;, ; c , i,T
vN,“s
::TD
Yes
No
Q,D
No Yes Yes No
ii No No
= chlorcquine; F = pyrimethamine/suiiadoxine;Q = qumine; D = doxcycline; P = pyrimethamine; S = sutiadiezine;T = tetracycline
or malaria associatedwith intravenousdrug abuse cation as recommended.Two individuals (Patients were observed. 14 and 19) used chloroquine while traveling overseas but discontinued prophylaxis prematurely RESULTS upon return to the United States. Ninety-one perCharts of 26 patients with a diagnosisof malaria cent of travelersborn in the United Statesand 36% were reviewed (Table I). Ages of the patients of individuals born overseaswere recommendedto rangedfrom 15to 48 years,with a meanof 29years. take malarial prophylaxis. It was not possible to Of these, 19 were males and sevenwere females. determine from a review of the charts why individFifteen were foreign-born, with six from Nigeria, uals did not take malaria prophylaxis or, for indifour from Ghana, two from India, and one each viduals who took chemoprophylaxis,who initially from Senegal,Angola, and Liberia. These individ- recommendedtheseprecautionsto thesetravelers. uals were infected in the countries in which they Malaria wassuspectedin 23 of the 26 casesupon were born, except for Patient 7 who was born and presentationto a medical carefacility. Of those intraveled to Liberia but who may havealso acquired dividuals for whom malaria was not initially susmalaria in Nigeria or Sierra Leone.For citizens of pected,one patient was treated initially with penithe United States, six individuals were infected in cillin for pharyngitis. A second patient was Africa, one in Thailand, two in Papua New Guinea, diagnosedas having a viral syndrome. The third and two in Mexico. Reasonsfor travel werepleasure patient was a female and complained of lower ab(sightseeing,visiting families) in 68%of the patients dominal pain. Initial evaluationconsistedof a gyneand businessin 32%. cologicexamination for suspectedpelvic inflammaMalaria prophylaxis was recommendedto 14 in- tory disease, the results of which were dividuals (Table I). Weekly chloroquinewasrecom- unremarkable. Persistent fevers in all patients mended to 13 individuals. One was given chloro- prompted evaluation for malaria. quine plus weekly pyrimethamine/sulfadoxine The major presenting complaints were fever, (Patient 22).Of these,11individuals usedthe medi- chills, headache, fatigue, and gastrointestinal
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91
31
MALARIA
IN TRAVELERS
IN RHODE
ISLAND
/ WIEST ET AL
TABLE II Presenting Symptomsof Malaria in 26 Patients Number of
Symptoms Fever and chills Headache Fatigue Nausea, vomiting, diarrhea hlyalgias Anorexia Abdominal pain Pharyngitis Shortness of breath Neck stiffness Low back pain
Patients
%
:
TABLE Ill Signs of Malaria on Presentation of 26 Patients Sign
Numberof Patients
Te;pe:,)rre 99-1°0o”F lOO-101°F lOl-102°F 102-103°F > 103°F Splenomegaly Orthostatic hypotension Abdominal tenderness Neurologic symptoms
symptoms (Table II). Other symptoms reported included myalgias, low back pain, neck stiffness, sorethroat, shortnessof breath, forgetfulness,and confusion. Fever and chills were common in patients infected with all three species of malaria identified. Low backpain and myalgiaswereprominent in Patient 17 who was infected with P. uiuax malaria (Table I). Patient 21 complained of neck stiffness as well as fever, chills, and headacheand was infected with both P. falciparum and P. uiuax. All other symptoms of malaria, including gastrointestinal symptoms, werefound in patients infected with P. falciparum. A history of a previous episode of malaria was found in 11 of 26 individuals. Each person with a history of malaria stated that their current illness was malaria since the symptomatology was similar to that of previousepisodes.They all thought that their current illness was clearly distinguishable from other febrile illnesses. Fever was documentedin 14 patients upon presentationto a medical carefacility (Table III). Seven individuals wereafebrile. Other findings included orthostatic hypotension, lower abdominal
32
July 1991 The American Journal of Medicine
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tenderness,and a palpablespleentip. Two patients had difficulty rememberingrecent eventsand were disoriented.Fever was common in all patients regardlessof which species of malaria was found. Splenomegalywas found in one patient with P. uiuax and two patients infected with P. falciparum. All other signswere found in patients infected only with P. falciparum. The white blood cell count wasnormal in 12 and decreasedin six. An increasedpercentageof bands was found in 14 of 18 cases.Thrombocytopenia (normal 150,000to 400,000/mm3)wasfound in 14of 20 individuals with platelet counts ranging from 46,000to 136,000/mm3.Three patients wereanemic upon presentation.Total bilirubin levels were elevated in three of nine patients tested,and increased lactate dehydrogenaselevels were found in four of six patients. Thin smearswere positive for malaria in 22 patients. In two patients, malaria was presenton the thick smearbut not the thin smear (Patients 2 and 3). In Patient 5, malaria wasnot found on multiple thin and thick smears;however,her symptomswere consistentwith malaria and sherespondedpromptly to treatment with chloroquine. P. falciparum was the most common species identified, beingfound in 20of the 26cases.Sixteen patients were infected in Africa, while of the remaining patients, two wereinfected in India, onein Thailand, and one in Papua New Guinea.P. uiuax wasidentified in four patients: two who visited Papua New Guinea and one eachwho visited Mexico and India, respectively.In four cases,the speciesof malaria could not be positively identified. Mixed infections werefound in three individuals. P. falciparum and either P. ouale or P. uiuax were identified in Patient 22.Two patients wereinfected with P. falciparum and P. uiuax (Patients 14 and 21). Twenty of the 26infected patients werehospitalized. P. falciparum infections were treated with a variety of regimens including chloroquine alone (Patient 13 who visited Senegalin 1986),quinine plus tetracycline or doxycycline in eight, quinine plus pyrimethamine plus sulfadiazinein seven,quinine plus pyrimethamine/sulfadoxine and chloroquine in two, and quinine plus pyrimethamine/sulfadoxine in one. Two patients were treated for P. uiuax with chloroquine.Unidentified speciesof malaria were treated with chloroquine alone in two patients, chloroquine plus pyrimethamine/sulfadoxine in two, and quinine plus doxycycline in one. Pyrimethamine/sulfadoxinefailed to cure malaria in three individuals. Oneindividual (Patient 20) ac-
MALARIA
IN TRAVELERS
IN RHODE
ISLAND
/ WIEST ET AL
quired malaria while traveling in Kenya and Tanxa- peraxine,and dystonic reactionsdeveloped.Sympnia. Shedevelopeda febrileepisodeto 102OF(38.9OC) toms resolvedafter discontinuation of prochlorperandtook threetabletsof pyrimethamine/sulfadoxine. azine.A third patient developedesophagealulcers Her symptoms persisted.Three days later, a physi- attributed to doxycycline therapy. This resolved cian in Kenya found P. fdciparum in her peripheral with treatment with antacids and discontinuation bloodsmear.Shewastreated with oral quinine for 3 of doxycyline. days and her symptoms gradually improved. One weekafter her arrival in the United States,shedevel- COMMENTS opedfever.P. falciparum was identified in her peMalaria is a potentially fatal diseaseencountered ripheral blood smear.She was treated with quinine by travelers to endemic countries. It is therefore and tetracyclineand her symptomsand parasitemia necessarythat physicians in the United States resolved. be able to diagnose and to treat patients with The secondcase(Patient18)occmredin anIS-year- malaria rapidly and effectively. This was exempliold man who traveledin Liberia, Ghana,and Nigeria. fied by a tragic caseseen at another hospital in Despitetakingweeklychloroquineprophylaxis,hede- RhodeIsland.A 48year-old black man from Ghana velopedseveralfebrileepisodesthat werediagnosedas presentedafter a recent visit to Ghana to a local malariaon bloodsmear.Symptomspromptly resolved emergencyroom complaining of fevers,chills, and aftertreatmentwith pyrimethamine/sulfadoxine, Sev- diarrhea. The patient told the physician that he enweeksafterhis return to the United States,heagain thought he had malaria since his symptomatology developeda febrileillness.Malarial parasiteswereseen was similar to that of a previous episode.A comin his peripheralbloodsmear,andhe wastreatedwith plete blood cell count was sent to the laboratory, three tablets of pyrimethaminelsulfadoxinefollowed but parasiteswerenot detected.He was discharged by a singledoseof weeklypyrimethaminelsulfadoxine from the emergencyroom with a diagnosisof colitis. for 3 weeks.Upon his arrival in RhodeIsland, pyri- Two days later, he was found dead.Autopsy findmethamine/sulfadoxinewas discontinuedafter two ings demonstratedcerebralmalaria. Retrospective doses.Two weeks later, he developedP. falciparum examination of the peripheral blood smear malariaandwassuccessfuhy treatedwith quinineand obtained in the emergencyroom demonstratedP. fulciparum malaria. doxycycline. The third patient (Patient 25) wasa 3%year-old In RhodeIsland, a recentreviewof casesreported physician who developed P. falciparum malaria to the Rhode Island State Health Department rewhile working in a medical mission in Kenya. He vealed that 52 casesof malaria occurredin Rhode took three tablets of pyrimethamine/sulfadoxine Island from 1984to 1989 [7]. One patient died of and his symptoms resolved.Symptoms reappeared malaria, the only deathin the 6-yearperiod.Studies 3 weekslater after he returned to the United States. haveshownthat malaria is important in major metHe againtook pyrimethamine/sulfadoxinewith res- ropolitan medical centers [2,3]. Our review indiolution of his symptoms. Four weekslater, hedevel- catesthat malaria is alsoan important problem that opedfever, chills, and fatigue associatedwith peri- physicians need to be aware of in community ods of confusion and difficulty concentrating. hospitals. Reviewof his peripheral blood smeardemonstrated In our review, 42%of the patients were United P. falciparum with a parasitemia of 5%. He was States citizens who traveled to countries where treated with quinine and doxycycline with perma- malaria was endemic. The remaining 58% were nent resolution of his symptoms and clearanceof immigrants from foreign countries who visited his parasitemia. countries wherethey wereborn. Our data indicate The only complication of malaria that devel- that the majority of individuals who took malaria oped in two patients (Patients 20 and 25) was prophylaxis while traveling overseaswere born in cerebral malaria. Both individuals were confused the United States, while only 36%of foreign-born and disoriented. No focal neurologic abnormali- travelers took preventive measures.This decrease ties were observed. Symptoms resolved quickly in the number of travelers born overseaswho did with treatment and no residual neurologic deficits not take preventive measures may reflect dewere noted. No patients died during this time creasedaccessto medical care and pretravel adperiod. vice, languageor cultural barriers, or the mistakComplications due to treatment for malaria oc- en impression that they possess“immunity” to curred in three patients. Severenauseaand vomit- malaria. It is therefore important that immiing secondaryto quinine therapy developedin two grants from countries where malaria is endemic patients. Individuals were treated with prochlor- be advised that they are susceptible to malaria
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33
MALARIA IN TRAVELERS IN RHODE ISLAND / WIEST ET AL
and should receive chemoprophylaxis when visiting their country of origin. The majority of casesof malaria imported into the United Statesin our study wereacquiredduring travel in Africa. This is consistent with a recent review of casesof malaria reportedto the CDC from 1983to 1986[8]. Of 634casesof P. fuZciparum malaria amongAmerican civilians, 80%were acquired in sub-Saharan Africa. The remaining were acquired in SoutheastAsia, the Caribbean,and South America. This occurreddespitethe fact that an estimated 90,000Americans travel to sub-SaharanAfrica each year, while 900,000Americans travel to SoutheastAsia and South America yearly. Travelers to Africa are at an increasedrisk for acquiring malaria in most rural and urban areas.In contrast, most travelers to SoutheastAsia and South America spend the majority of their time in urban and resort areaswherethe risk of exposureto malaria is limited. The majority of our caseswereinfections with P. falciparum. P. fatciparum was also seenin 70%of casesby Kean et al [2] but in only 25%reportedby Gordonet al [3]. These differencesmay reflect the regionswherethe travelersvisited. In our study and that of Kean and co-workers,the majority of individuals visited Africa, while in Gordon’sstudy, only 17%visited Africa [2,3].Of thoseinfected in Africa, all had P. falciparum malaria [2].P. uiuax predominates in India, Pakistan, Bangladesh,and Central America, while P. falciparum predominatesin Africa and Haiti [9]. P. ouale also occurs primarily in Africa, while P. malariae is cosmopolitan [9]. The typical symptoms of malaria-fever and chills, associatedwith myalgia, fatigue, anorexia, and headache-are often mistaken for more common illnesses in the United States such as viral syndromes [2]. In addition, patients with malaria may be afebrile in the early phasesof infection and thus the suspicion of malaria by the physician is lessened.Furthermore, gastrointestinal symptoms and signsmay be prominent in patients with malaria, and again,this may mislead the physician [2,3]. In our review,gastrointestinalcomplaints werepresenting symptoms in 26%of patients, all of whom were infected with P. falciparum. Gastrointestinal symptoms are common in P. falciparum infections, but are alsofrequently seenwith casesof non-falciparum malaria [2,3]. It is therefore necessarythat physicians consider malaria in any symptomatic patient returning from travel overseas. A critical point not often emphasizedis that individuals who havehad a previousepisodeof malaria are ableto distinguish current infections of malaria from other febrile illnesses.In our review, all indi-
34
July 1991 The American Journal of Medicine
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viduals with a history of malaria indicated to the physicianthat they thought they wereinfectedwith malaria again.The reasonsfor thesecharacteristic symptoms of malarial infection are not known. Alternatively, individuals with a history of malaria may suspectthat any fever is againdue to malaria. Nevertheless, this history indicates to physicians that they must seriously consider this diagnosis. The diagnosisof malaria currently restsupon the demonstration of parasites in thin- and thickstained peripheral blood smears. Newer methods such as DNA probes and acridine orangefluorescencemay provide more sensitive and rapid techniques to diagnosemalaria in the future but are currently only researchtools [lO,ll]. Prevention of malaria has becomea particularly difficult problem in recent years. One important way to prevent malaria is to reduce contact with mosquitoes [8]. This can be accomplished by remaining within well-screenedareasat night, using mosquito nets, wearing clothes that cover most of the body, and using an insect repellent on exposed skin. An additional measureto prevent malaria is chemoprophylaxis [8]. The major difficulty has beenthe developmentof resistanceby malarial parasites to different chemotherapeuticagentsin recent years [12].Chloroquinewas the drug of choice to prevent malaria for many years,but resistanceto this agent developed in Southeast Asia, South America, and East Africa and has recently spread into West Africa [13]. Previous recommendationsby the CDC for malarial prophylaxis werefor individuals to take chloroquine to prevent infection with susceptible strains of P. falciparum and non-falciparum malaria [13]. It was also suggestedthat individuals take weekly pyrimethamine/sulfadoxinefor prophylaxis against chloroquine-resistant malaria. Between 1982and 1985,24casesof erythemamultiform, Stevens-Johnsonsyndrome, and toxic epidermal necrolysisweredocumentedin American travelersusing weekly pyrimethamine/sulfadoxine [14]. Seven caseswere fatal. Recommendationswere changed suchthat individuals should carry pyrimethamine/ sulfadoxinefor presumptivetreatment of malaria if a personcould not obtain immediate medical attention [8,12,14]. Resistance to pyrimethamine/sulfadoxine has alsodevelopedand is currently found in Southeast Asia, South America, and recently in Africa [8,15,16].In our series,three individuals who traveled to Africa may havehad chloroquine-and pyrimethamine/sulfadoxine-resistant P. falciparum malaria. Two patients acquired probable chloro-
MALARIA IN TRAVELERS IN RHODE ISLAND / WIEST ET AL
quine- and pyrimethamine/sulfadoxine-resistant malaria while traveling in Kenya. This has been described previously in East Africa [16]. The third patient (Patient 18) developed chloroquine-resistant and probable pyrimethaminel sulfadoxine-re-sistant malaria while in West Africa. Serum levels to determine if therapeutic levels of pyrimethamine/sulfadoxine were achieved were not performed. Nevertheless, the clinical response to treatment of previous episodes of malaria with pyrimethamine/sulfadoxine suggests that adequate serum levels were obtained. This latter case suggests that resistance to pyrimethamine/sulfadoxine may have emerged in West Africa. Current recommendations by the CDC, which we agree with, suggest that travelers to sub-Saharan Africa, Southeast Asia, and South America use mefloquine prophylactically to prevent malaria [8]. This drug is highly effective in the prevention of chloroquine-resistant and pyrimethamine/sulfadoxine-resistant P. fdciparum malaria as well as malaria caused by non-falciparum species [16,17]. Mefloquine has recently been approved for use in the United States. Several problems exist with the use of mefloquine [8]. First, careful patient selection is required. Mefloquine is not recommended for individuals taking drugs that alter cardiac conduction or who have a history of psychiatric or seizure disorders. This is particularly important since many older individuals with cardiac disease visit the game parks in East Africa each year. Furthermore, various neurologic side effects such as vertigo, dizziness, restlessness, or other neuropsychiatric problems may occur, and patients need to be warned about these potential reactions [8,18]. Despite the relatively recent introduction of mefloquine, resistance to this agent has been reported in Africa, Thailand, Indonesia, and the Philippines [19-241. It is therefore critical that all travelers be advised that no chemoprophylactic agent is 100% effective in the prevention of malaria. Furthermore, these medications are not a substitute for other measures that can be used to prevent malaria. In addition, all travelers must understand that any febrile illness, either in an area in which malaria is endemic or after departure from such an area, may represent malaria, and they should seek immediate medical attention. Recommendations for malaria chemoprophylaxis and treatment are constantly changing. Up-to-date information can be obtained from the CDC Malaria Hotline (404-332-4555) or from Health Informa-
tion for International Travel published by the CDC or local travel clinics. In summary, physicians in the United States must be aware that malaria is still a major medical problem throughout the world. Symptoms of malaria are nonspecific and often present as a viral syndrome. It is therefore necessary that a high index of suspicion be maintained by physicians in the medical evaluation of returning travelers. Furthermore, malaria must be seriously considered in individuals with a history of malaria who now indicate that they have malaria again. Lastly, attempts to prevent malaria should be utilized by all travelers in areas where malaria is endemic. It is therefore essential that physicians either provide proper up-todate information regarding malarial prophylaxis to travelers or refer these individuals to local tropical disease specialists for assistance.
ACKNOWLEDGMENT We wish to thank Valerie Sears for her expert preparation of this manuscript.
secretarial
assistance
in the
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308:8?5-8,
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2. Kean BH, Reilly PC. Malaria-the mime: recent lessons from a group of travellers. Am J Med 1976; 61: 159-64. 3. Gordon S, Brennessel DJ, GoldsteIn JA, Rosner F. Malaria, a city hospital experience. Arch Intern Med 1988; 148: 1569-71. 4. Finn L. Reports of notifiable diseases. MMWR 1985; 34: 589-95. 5. Lobe1 HO. Campbell CC, Schwartz IK, Roberts JM. Recent trends in the importation of malaria caused by Plasmodium falciparium into the United States from Africa. J Infect Dis 1985; 152: 613-7. 6. Recent Canadian deaths from malaria in Africa. Can Dis Wkly Rep 1989; 15: 199-204. 7. Gilbert TT. Malaria In Rhode Island. Rhode Island Medical Journal 1990; 73:
220. 6. Centers for Disease Control. Recommendation for the prevention of malaria among travelers. MMWR 1990; 39: l-10. 9. Wyler DJ. Plasmodium species (malaria). In: Mandel GL. Douglas RG. Bennett JE. eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone. 1990: 205665. 10. Lanar DE, McLaughlin GL, Wirth DF, Barker RJ, Zolg JW, Chulay JD. Comparison of thick films, in vitro culture and DNA hybridization probes for detecting Plasmodium falciparum malaria. Am J Trop Med Hyg 1989; 40: 3-6. 12. Spielman A, Perrone JB, Teklehaimanot A, Balcha F, Wardlaw SC, Levine RA. Malaria diagnosis by direct observation of centrifuged samples of blood. Am J Trop Med Hyg 1988; 39: 337-42. 13. Krogstad DJ, Herwaldt EL. Chemoprophylaxis and treatment of malaria. N Engl J Med 1988; 319: 1538-40. 14. Moran JS, Bernard KW. The spread of chloroquine resistant malaria in Africa. JAMA 1989; 262: 245-8.
15. Pearson RD. Hewlett EL Use of pyrimethamine-sulfadoxine (Fansidar) in prophylaxis against chloroquine-resistant Plasmodium falciparum and Pneumo cystic carinii. Am J Med 1987; 106: 714-8. 16. Bjorkman A, Phillips-Howard PA. The epidemiology of drug-resistant malaria. Trans R Sot Trop Med Hyg 1990: 84: 177-80.
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MALARIA IN TRAVELERS IN RHODE ISLAND / WIEST ET AL 17. Centers for Disease Control. Malaria in travelers returning from Kenya: failure of self-treatment with pyrimethamine/sulfadoxine. MMWR 1989; 38: 363-4. 18. Jiang JB. Li GQ, Guo XB. Kong YC, Arnold K. Antimalarial activity of mefloquine and quinghaosu. Lancet 1982; 2: 285-8. 19. Sturchler D, Handschin J, Kaiser D, et al. Neuropsychiatric side effects of mefloquine. N Engi J Med 1990; 322: 1752-3. 20. Odulola AMJ, Michols WK, Salaro LA, Walker 0. Desjardin RE. Reduced in vitro susceptibility to mefloquine in West African isolates of Plasmodium fa/cC parum. Lancet 1987; 1: 1304-5.
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21. Smrkovshi LL. Buck RL. Alcantara AK, Rodriguez CS. Uylanco CV. h vitro mefloquine resistant Plasmodium falciparumfrom the Philippines. Lancet 1982; 1: 322. 22. Boudreau FF. Webster HK. Pavanaud K. Thosingham L. Type II mefloquine resistance in Thailand. Lancet 1982; 2: 1335. 23. Bygbjerg IC. Scharira A, Flachs H, Gomme G, Jepsen S. Mefloquine resistance of falciparum malaria from Tanzania enhanced by treatment. Lancet 1983; 1: 774-5. 24. Salako LA, Aderounmu AF. In vitro chloroquine and mefloquine resistant Plasmodium fakiparum in Nigeria. Lancet 1987; 2: 572-3.
