Malaria-The Mime Revisited: Fifteen More Years of Experience at a New York City Teaching Hospital ROBERTA. WINTERS,M.D., HENRYW. MURRAY, M.D., New York,New York

PURPOSE AND PATIENT& A previous review of The New York Hospital experience with malaria duing 1966 to 1975 summa&ed clinical and parasitologic features in 24 travelers and highlighted deficiencies in both chemoprophylaxis and diagnosis. To extend this original study, we describe 66 patients with mahuia seen at the same hospital during the subsequent 15 years. RIBULT& Eighty patients were infected with a single PIasmo&zm species, and 60% had P’ modkm fdciparum infection primarily acquired in Africa. Eighty percent were symptomatic while in or within 1 month of departing the mahuious region. All patients described a history of fever, however, 25% were afebrile at the initial hospital visit. A normal white blood cell count, thrombocytopenia, and an increased lactate dehydrogenase level were common laboratory resul& Seventy-five percent of non-native travelers took either no or inadequate chemoprophyhu&. Malaria was not suspected in 16 of the 20 (60%) patients seen initially by local New York City physicians but was initially suspected and confirmed in 49 of 54 (91%) patients fm seen at The New York Hospital. CONCLUSION: In comparison to our 1966 to 1975 experience, these updated results indicate no improvement in either the use of appropriate chemoprophyti or the capacity to properly diagnose mahuia in the community. Improvement is still clearly needed in both areaa

From the Division of Infectious Diseases, Cornell University Medical College and The New York Hospital, New York, New York. Requests for reprints should be addressed to Henry W. Murray, M.D. 1300 York Avenue, New York, New York 10021. Manuscript submitted October 29,1991, and accepted in revised form

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ifteen years ago, Kean and Reilly [l] reported on 24 civilians with malaria seen at The New York Hospital during the 7-year period 1968 to 1975. Two key points emerged from their review. First, nearly 90% of patients had received either no or inadequate antimalarial prophylaxis despite travel to known endemic regions. Second, the diagnosis of malaria was often overlooked by local physicians who instead considered viral syndromes or gastroenteritis as likely diagnoses. Since the majority of infections were caused by Plasmodium falciparum and thus potentially life-threatening, Kean and Reilly [l] appropriately called attention to both the prevention and the early diagnosis of malaria in patients who travel to endemic areas. We now provide a follow-up report and extend this original investigation by describing 86 patients with malaria seen at The New York Hospital since 1975. Our experience with these patients indicates that the majority did not receive appropriate prophylaxis and that community physicians did not often consider the diagnosis of malaria in symptomatic returning travelers. Thus, as in 1976 [l], improvement is still clearly needed in both malaria prevention and diagnosis, especially in view of the increasing number of cases reported in this country

M. PATIENTS AND METHODS A registry of all positive malaria blood smears has been maintained since 1960 in the Parasitology Unit of The New York Hospital Microbiology Laboratory. For the period June 1975 through December 1990,109 patients were recorded as having positive smears. Two patients with thalassemia major had transfusion-acquired malaria and were excluded. Despite an extensive search, records for 21 individuals could not be located. Since our laboratory serves as a referral unit for other local hospitals, we suspect that most of these 21 were patients hospitalized elsewhere but whose smears had been sent for review. Thus, The New York Hospital charts for a total of 86 patients were available for review.

RESULTS Population Sixty-three of the 86 patients were men and 23 were women; the mean age was 32 years (range, 3 to 61 years). Forty-three patients were black, 33 white, 1992

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TABLE I Plasmodium SpeciesAmong 86 Patients Wiih Malaria No.of Patients

Species Single infections P. falciparum

50

Areasof Acquisition*

i

W. Africa-Z& E. Africa-14, C. America-l, S. America-l, Haiti-6 India-g, W. Africa-4, C. America-P; E. Africa, S. America, Thailand, Turkey, New Guinea-l each. W. Africa-4, E. Africa-2. W. Africa-P, Haiti-l, unknown-l.

Mixed infections P. falciparum t P. ova/e P. vivax t P. malafiae

3 1

W. Africa-3. India-l.

Unable to speciate

2

W. Africa- 1, C. America-l.

P. vivax

20

P. ova/e P. malariae

TABLE II Initial PhysicianContact in 86 Patients With Malaria Initial Contact

lve patients who had visited or lkvedin more than one malarious region before becomIngill were assignedto the most likely area of acquisition.

8 Indian, and 2 Hispanic. Of the 86 patients, 42 (49%) were natives of a non-malarious region (primarily the United States) and 28 (32%) were former natives of a malarious area but had moved to a nonmalarious region. Sixteen patients (19%) were natives of and currently living in an endemic area; these patients became symptomatic while visiting New York City. Epidemiology There was one Plasmodium species present on blood smear in 80 patients, 4 had mixed infections, and in 2 patients the species could not be identified (Table I). Fifty-three patients had P. fulciparum infection acquired primarily in Africa. Plasmodium uiuax infection was acquired in India in 10 of 21 patients (48%). Onset of Symptoms Of 77 patients for whom data were available, symptoms developed while still in the endemic area in 14% within 1 month of leaving in 66% and after 1 month of departure in 20%. Ten of these latter 15 patients had P. uiuax infection. One patient, a 61year-old man, had not traveled for more than 11 years; new fever developed and evaluation showed Plasmodium malariae on blood smear. Prophylaxis The records of five patients did not indicate whether or not antimalarial prophylaxis was used. Of the 16 who were current natives of endemic regions, 14 were living in Africa, 12 had not taken any prophylaxis, and 4 had used weekly chloroquine or pyrimethamine. Ten of the 16 natives developed P. falciparum infection. 244

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Malaria Initially Suspected*

Physician in endemic area Local New York City physician Medical service for diplomats The New York Hospital :.?a,.a”, L, n,hs. in&,, Aiannnrsr

86

Total

No.of Patients

Of the remaining 65 travelers who were not current natives of an endemic area, 36 (55%) had not used any prophylaxis, and 24 of the 36 developed P. falciparum malaria (Africa, 18; Haiti, 6). Twentynine patients took prophylactic agents which in 25 consisted of weekly chloroquine alone. Sixteen of these 25 acquired P. falciparum (East Africa, 8; West Africa, 6; South or Central America, 1 each). Two other patients used weekly pyrimethamine, one used chloroquine plus proguanil (all three acquired P. falciparum while in West Africa), and one developed P. uiuax infection while taking chloroquine plus pyrimethamine-sulfadoxine in Thailand. Full compliance with prophylaxis was assumed unless otherwise indicated in the medical record. Overall, of the 29 non-native travelers who took prophylaxis, only 16 were considered to have received adequate therapy appropriate for the region and year of travel. (Weekly chloroquine alone was considered to be inadequate for travel to East Africa beginning in 1982, to West Africa beginning in 1989, and to Southeast Asia and rural South America beginning in 1978 [3-6]). Physician Contact Three patients received their initial care while in the malarious region (Table II). Twenty patients were initially seen one or more times by local New York City physicians; in 16 (80%), malaria was not suspected and blood smears were not obtained. Alternate diagnoses included viral syndromes in four patients and one each with fever of unknown origin, sinusitis, pharyngitis, pneumonia, and urinary tract infection. No diagnosis was assigned to seven patients. Nine of the 16 patients were treated with oral antibacterial agents. Sixty-three patients were first seen either at a medical diagnostic service for diplomats or at The New York Hospital (Table II). All nine seen at the diplomatic medical service were suspected of having malaria, and blood smears were obtained. In 49 of 54 patients (91%) seen initially at this hospital, malaria was suspected by the first physician encountered (emergency room physician, 73%; medical attending physician, 22%; medical ward house-

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officer, 5%). Of the remaining five patients, three were initially thought to have viral syndromes, one had blood smears sent from the emergency room after being admitted for fever, and in one patient malaria was diagnosed during an evaluation for fever that developed after elective admission for lymph node biopsy. In the 86 patients, initial smears were positive in all but 5 patients. Clinical and laboratory Features All 86 patients gave a history of fever, but typical paroxysms were seldom described. Twenty-three patients were afebrile at initial presentation to The New York Hospital; 20 patients had temperatures higher than 40°C. Chills (87%), headache (73%), fatigue (53%), and myalgias (39%) were common. Gastrointestinal symptoms included nausea (44%), vomiting (34%), anorexia (19%), abdominal pain (17%), and diarrhea (16%). Cough, delirium, backache, pharyngitis, lethargy, arthralgias, photophobia, and weight loss were present in 10% or fewer of patients. Signs included systolic hypotension (less than 100 mm Hg) (300/o), jaundice (19%), hepatomegaly (33%), and splenomegaly (29%). Stupor or delirium was present in five individuals. Table III summarizes pertinent laboratory results. A normal white blood cell count, thrombocytopenia, and an elevated serum lactate dehydrogenase level were common results. In the 56 patients for whom the percentage of red cells parasitized was quantitated, 73% had parasitemia of 2% or less, 14% had levels of 2% to 5%, and 13% had greater than 5% of red blood cells infected. The highest level of parasitemia (30%) was seen in an American who had traveled to Kenya in 1982 and took chloroquine alone as prophylaxis.

TABLE III Admission

Laboratory

Data in 86 Patients

Test Result

No. Patients/No.

White blood,cell count I$,;Erra

Tested

9/86 (lo)* 7w& I;:’

Leukqtosis Anemia (Hgb < 12 g/dL) Thrombocytopenia (< 150,000/mm3) Prolonged prothrombin or partial thromboplastin time Creatinine > 1.5 mg/dL SGOT > 50 U/L Alkaline phosphatase > 110 U/L LDH > 225 U/L Bilirubin > 1.2 mg/dL

22/86 (26) 54/80 (68) 14/65 (21) 3174 18177 i5j74 63/76 29173

(4) (23) i2oj (83) (40)

I

Treatment and Outcome Seventy-three patients were hospitalized; 13 were treated as outpatients. All patients with nonfalciparum malaria were treated with chloroquine; primaquine was also given to patients with P. vivax or P. ovale infections. P. falciparum malaria was treated with a variety of different chloroquine- or quinine-based regimens depending upon the area of malaria acquisition, year of travel, and whether the patient was considered partially immune. Side effects of drug therapy were rare: three patients developed nausea, vomiting, tinnitus, or decreased hearing while receiving quinine sulfate. One patient with P. falciparum infection had a generalized seizure. All patients recovered after therapy was completed.

COMMENTS Many difficulties exist when providing pre- and post-travel health care to patients visiting regions September

Hgb = hemoglobin; SGOT = serum glutamic oxaloacehc transaminase: LDH = lacta dehydrogenase. *Numbers in parentheses are percentages.

endemic for malaria, including changing guidelines for chemoprophylaxis, widespread chloroquine-resistant P. falciparum, and the nonspecific signs and symptoms of infection. Several prior reviews have emphasized increasing physician awareness of what constitutes adequate prophylaxis and of recognizing post-travel patients with active infection [1,7-131. In 1976, Kean and Reilly [l], in their original investigation of malaria in civilian travelers seen at The New York Hospital, pointed out several pitfalls in the prevention and diagnosis of this illness. Our current study extends this analysis and indicates that, despite 15 more years of experience, the prevention of malaria and the capacity to recognize infection in the community have not improved substantially. In both New York Hospital series, P. falciparum, responsible for most cases of serious, life-threatening disease [11,12], accounted for approximately two thirds of cases. Whereas 88% of P. falciparum infections were acquired in West Africa in the earlier series [ 11, our study indicates a larger geographic area of acquisition of P. falciparum (Table I). Nearly half of P. vivax infections in our study was associated with travel to India, whereas in the earlier study, P. vivax was primarily acquired in East Africa or Southeast Asia [l]. A recent report from another New York City hospital also demonstrated that most cases of P. vivax infection were acquired in India or Pakistan [7]. Although three quarters of our non-native travelers spent 2 weeks or longer in endemic areas, it is clear that malaria can also be acquired after only transient exposure [14,X]. Indeed, one of our patients stopped in Nigeria for only several hours but subsequently developed P. falciparum infection. Thus, regardless of the duration of stay, obtaining a complete travel history is essential to suggest the diagnosis. A remote travel history in a symptomatic 1992

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patient can also be misleading. One of our patients had not traveled to a malarious region for more than 11 years. In our patients with longer latency periods, P. vivax infection was documented in two thirds of cases, an observation also made by other investigators [7]. The failure to properly prescribe chemoprophylaxis (no drug, inadequate drug) remains a common feature in reviews of malaria [1,7,9-13,161. Our study also indicates that the use of prophylactic agents remains suboptimal: 55% of our non-native patients did not use any agent (representing scant improvement over the 63% figure in our 1968 to 1975 experience [l]), and 25% received inadequate chemoprophylaxis. Since the majority of patients in both New York Hospital studies developed P. falciparum infection, the failure to use adequate prophylaxis is even more noteworthy: three quarters of all P. falciparum-related deaths in the United States from 1959 to 1987 occurred in travelers not receiving any prophylaxis [ll]. Recent Centers for Disease Control guidelines recommend weekly mefloquine when traveling in areas with chloroquine-resistant P. falciparum [16]. In those regions where only chloroquine-sensitive P. falciparum exists (principally Haiti, the Dominican Republic, Central America west of the Panama Canal, the Middle East, and Egypt), weekly chloroquine remains the drug of choice [17]. One objective of this follow-up study was to reevaluate whether physicians properly included malaria in their initial differential diagnosis in the febrile or symptomatic traveler. Since 21 charts could not be located (see Patients and Methods), it is possible that the physicians of some of these 21 patients appropriately considered malaria and utilized our laboratory to review their slides. Nevertheless, for the 20 patients known to have been first cared for by local physicians and then seen at this hospital, malaria was considered and smears were obtained in only 4 (20%). This level of diagnostic capacity is low and represents little improvement over that reported during the 1968 to 1975 period in which 2 of 14 patients (14%) seen initially by community physicians were correctly diagnosed [l]. At The New York Hospital, with Divisions of Infectious Diseases and International Medicine, considerable efforts are made each year to train all medical students, houseofficers, and fellows to recognize malaria. As a likely result of these long-term efforts, New York Hospital physicians had a diagnostic accuracy in 1975 to 1990 of more than 90% in patients with malaria, maintaining the 92% result observed in the original 1968 to 1975 study [l]. No malaria-related deaths have occurred at this hospital during this 23-year period. 246

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In the combined 1968 to 1990 New York Hospital experience, fever was the most common symptom of Plasmodium infection. However, 25% of our recent patients were afebrile when first seen; thus, a history of fever (100% in our study) alone should be sufficient to prompt an evaluation for malaria. Gastrointestinal symptoms, previously reported to be present in up to 75% of patients [1,7,11], were less common in our patients as well as those recently reported from Rhode Island [13]. However, in travelers from endemic regions with fever and gastrointestinal complaints (including nausea alone), malaria should nevertheless be a diagnostic consideration. From our perspective, there should be no hesitation to obtain blood smears in symptomatic travelers even if malaria seems to be a remote possibility.

ACKNOWLEDGMENT We are indebted to Leticia J. Ramos (Parasitology (Medical Records) for their valuable assistance.

Laboratory) and Helen Brown We also wish to acknowledge

Benjamin H. Kean, M.D.. who has taught us and generations of students at Cornell University Medical College and physicians at The New York Hospital all they know about malaria.

REFERENCES 1. Kean BH. Reilly PC. Malaria-the

mime: recent

lessons from a group

of

civilian travelers. Am J Med 1976; 61: 159-64. 2. Centers for Disease Control. Summary of notifiable diseases, United States, 1989. MMWR 1989; 38: I-11. 3. Centers for Disease Control. Chemoprophylaxis of malaria. MMWR 1978; 27 Suppl 10: 81-90. 4. Centers for Disease Control. Follow up on chemoprophylaxis of malaria. MMWR 1978; 27: 221. 5. Centers for Disease Control. Revised recommendations for malaria chemoprophylaxis for travelers to East Africa. MMWR 1982; 31: 328-30. 6. Centers for Disease Control. Health information for international travel, 1989. Atlanta: Centers for Disease Control, 1989; HHS publication no. (CDC) 89-8280. 7. Gordon S. Brennessel DJ, Goldstein JA, Rosner F. Malaria: a city hospital experience. Arch Intern Med 1988; 148: 1569-71. 6. Harris LF, Shastaen WJ, Lampert R. Malaria: recent experience in a community hospital. South Med J 1984; 77: 1121-3. 9. Hilton E, Edwards B. Singer C. Reported illness and compliance in US travelers attending an immunization facility. Arch Intern Med 1989; 149: 178-9. 10. Klingelberger CE. It’s not a viral syndrome, it’s malaria. Ann Emerg Med

1989; 18: 207-9. 11. Greenberg AE. Lobe1 HO. Mortality from Plasmodium falciparum malaria in travelers from the United States, 1959-1987. Ann Intern Med 1990; 113: 326-7. 12. Lobe1 HO, Campbell CC, Robert

JM. Fatal malaria in US civilians [letter].

Lancet 1985; 1: 873. 13. Wiest PM, Opal SM. Romulo RL, Olds GR. Malaria in travelers in Rhode Island: a review of 26 cases. Am J Med 1991; 91: 30-6. 14. Conlon CP. Berendt AR, Dawson K, Peto TE. Runway malaria. Lancet 1990;

335: 472-3. 15. Oswald G. Lawrence

EP. Runway malaria [letter]. Lancet 1990; 335: 1537. 16. Lackritz EM, Lobal HO, Howell BJ. Bloland P, Campbell CC. Imported P/ax+ medium falciparum malaria in American travelers to Africa: implications for prevention strategies. JAMA 1991; 265: 383-5. 17. Centers for Disease Control. Health information for international travel, 1991. Atlanta: Centers for Disease Control, 1991; HHS publication no. (CDC)

91-8280.

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Malaria--the mime revisited: fifteen more years of experience at a New York City teaching hospital.

A previous review of The New York Hospital experience with malaria during 1968 to 1975 summarized clinical and parasitologic features in 24 travelers ...
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