Malaria at the Hospital for Sick Children, Toronto
Table Il-Clinical presentation Symptoms and signs Fever Chills Vomiting Headache Sore throat Malaise Sweats Abdominal pain Hepatomegaly and splenomegaly Splenomegaly only Hepatomegaly only
Patients % No. 100 15 53 8 47 7 47 7 33 5 27 4 27 4 20 3 6 3 1
40 20 7
M.icrodantinE children, both from Africa, most recently in an endemic area. A mild normochromic, normocytic anemia was present in about two thirds of the cases. Leukocyte counts were normal or slightly low and differential counts were unremarkable. When measured, the platelet count was invariably low but returned to normal within 3 days of the start of therapy. One child was tested for, and found to have, antiplatelet antibodies. Glucose-6-phosphate dehydrogenase deficiency was absent in all cases. Four of seven patients tested had positive serum titres of agglutinins against antigens of Salmonella spp., and stools from three of seven contained parasites. Treatment followed the recommendations of the American Academy of Pediatrics.4 Only one patient had side effects, nausea and vomiting, which were thought to be due to primaquine phosphate.
recent arrival from a region where malaria is endemic. Symptoms and signs were vague in many cases and did not always fit the textbook description of malaria. Any child with a febrile illness of no obvious cause who has been in a region where malaria is endemic within the previous 6 months should probably have a blood film examined for parasites. Even those who have received malaria chemoprophylaxis must be considered susceptible since the drugs are not completely effective5 - as evidenced by our patient 1. If the suspicion of malaria remains high despite a negative smear, a blood film should be stained with acridine orange or serologic testing should be performed.6 Accurate identification of species is important because therapy varies according to the causative organism. Resistance to chloroquine has been found in cases due to P. falciparum in Asia and South America and this, too, must be taken into account.7
Discussion Despite heroic attempts to control it, malaria is still endemic in many parts of the world. With an increasing influx of immigrants from endemic regions, it is not surprising that the incidence of malaria in Toronto is increasing. Nearly 65 000 persons immigrated to Canada from endemic regions in 1974, and one third of the approximately 22000 who settled in the metropolitan Toronto area were under the age of 18 years; 5 of these were found to have malaria after admission to this hospital. Thus, a crude estimate of the. proportion of children with malaria in this group would be 1:1500. This proportion is undoubtedly an underestimate, since it does not include patients treated elsewhere or those with undiagnosed chronic disease. The most helpful clue to diagnosis in the 15 children at this hospital was
Addendum Between Aug. 1, 1975 and July 1, 1976 the diagnosis of malaria was made in four more children at the Hospital for Sick Children. These included 3-week-old twins, who had acquired the infection transplacentally. Clinical and laboratory features did not differ from those of the patients discussed above, and all patients came from the Indian subcontinent. References 1. World Health Organization, expert committee on malaria: Sixteenth report. WHO Tech Rep Ser: no 549, 1974 2. RANSOME-KUTI 0: Malaria in childhood. Adv Pediatr 19: 319, 1972 3. Immigration 1974, Ottawa, Department of M4npower and Immipation, 1975 4. American Academy of Pediatrics: Report of the Committee on Infectious DIseases, 17th ed, Evanston, IL, AAP, 1974, pp 104-7 5. BAxanrr-CoNNoR E: Chemoprophylaxis of malaria for travelers. Ann Intern Med 81: 219, 1974 6. SADUN EH: The research and development of serologic tests for malaria. Am I Trop Med Hyg 21: 677, 1972 7. PETERS W: Antimalarial drugs and their actions. Postgrad Med J 49: 573, 1973
Table Ill-Laboratory findings Patient no.
i
Hemoglobin (g/dl)
13.9
Leukocyte count (X 10./l)
5.4
2 9.6 5.5 3 9.1 5.4 4 10.8 5.6 10.5 5.5 5 8.4 15.0 6 11.7 4.5 7 7.0 8 10.0 11.1 5.7 9 10 9.6 5.5 11* 17.8 7.7 12 10.5 5.4 10.7 13 8.6 9.3 3.5 14 10.4 8.4 15 6.7 Mean 10.8 *Patlent with cyanotic congenital heart disease.
Platelet count (X 10911)
35
99 147 90 40 47
89
60 59 99 81 78 77
406 CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115
Parasite identifIed
P. vivax
P. vivax P. falciparum Not identified P. vivax P. vivax P. vivax P. vivax P. falciparum P. uwax P. vivax P. vivax P. vivax P. vivax P. vivax
(Nitrofurancoin Macrocryscals)
References 1. Roth, R.B. et al. The Ruined Kidney, Filmstrip produced with the cooperation of the Hess Urological Foundation, Inc. Erie, Pa., U.S.A. 2. Kunin, CM.: Detection, Prevention and management of urinary tract Infections. Philadelphia, Lea & Febiger, 1972 pg. 18811. 3. Kalowski S., Radford N., Kincaid-Smith P: New Eng. J.M 290: 386, 1974 4. Shirley SW. and Ozog L.S.: Urology Digest 9:8-10, 1970 Action: The large crystal size of Macrodantin (nitorfurantoin macrocrystals) provides the proven clinical efficacy of Furadantin (nitrofurantoin) but with increased gastro intestinal tolerance. In a comparative clinical study the incidence of nausea and/or emesis was appreciably less with Macrodantin than with Furadantin. Patients unable to tolerate Furadantin reported good tolerance of Macrodantin. Indications: Macrodantin is indicated for the treatment of pyelonephritis, pyelitis and cystitis caused by sensitive organisms. Contraindications: Anuria, oliguria or extensive impairment of renal function. Infants under one month. Warnings: Haemolytic anaemia, which disappears on cessation of drug therapy has been reported in sensitive individuals. Usually defined as the 10% of negroes and lower percentages of people of Mediterranean and near Eastern origin who exhibit glucose -6 - phosphate dehydrogenase deficiency of the red blood cells. Safety during pregnancy and lactation has not been established. Precautions: Peripheral neuropathy has been reported with nitrofurantoin. This may become severe and irreversible and one fatality has been reported. Therapy should be discontinued if numbness and tingling occur. Macrodantin should not be co-prescribed with drugs which impair renal function. Adverse Reactions: Nausea, emesis, and less frequently, diarrhea may occur; reduction in dosage may alleviate these symptoms. Sensitization appearing as an erythematous, maculopapular cutaneous eruption, urticaria, eczematoid eruption or pruritus has occurred. Hypersensitivity reactions resulting in nonfatal anaphylaxis, angioedema, pulmonary infiltration with pleural effusion, and eosinophilia have been reported. Other possible reactions are chills, fever, jaundice, asthmatic symptoms, and hypotension. Occasional minor reactions such as headache, dizziness, nystagmus, vertigo, drowsiness, malaise, and muscular aches have occurred. Transient alopecia has been reported. Leukopenia, including granulocytopenia has been reported rarely. Return of the blood picture to normal has followed cessation of therapy. As with other antimicrobial agents, superinfections by resistant organisms may occur. With Macrodantin, however, these are limited to the genitourinary tract because suppression of normal bacterial flora elsewhere in the body does not occur. Administration and Dosage: Dosage: Adult: 50 to 100 milligrams four times a day. Children: Should be calculated on the basis of 5 to 7 milligrams per kilogram (2.2 to 3.2 mg per Ib) of body weight per 24 hours, to be given in divided doses four times a day (contraindicated under one month of age). Administration: Macrodantin (nitrofurantoin macrocrystals) may be given with food or milk to further minimize gastric upset. Therapy should be continued for at least one week and for at least 3 days after sterility of the urine is obtained. Continued infection indicates the need for re-evaluation. If the drug is to be used for long-term suppressive therapy, a reduction of dosage should be considered. How Suppiled: Macrodantin is available in opaque white imprinted capsules of 25 mg. (Eaton 007) in bottles of 30, 100 and 500 capsules; opaque yellow/white imprinted capsules 0150mg. (Eaton 008) in bottles of 30, 100, and 500 captules; opaque yellow, imprinted capsules of 100 mg. (Eaton 009) in bottles of 30, 100, and 500 capsules. Preduct monograph avaiiabie on request. Originators and Developers of the Nitrofurans
. . EATON LABORATORIES Division of Norwich Pharmacal Company Ltd. Paris, Ontario.
Table Il-Clinical presentation Symptoms and signs Fever Chills Vomiting Headache Sore throat Malaise Sweats Abdominal pain Hepatomegaly and splenomegaly Splenomegaly only Hepatomegaly only
Patients % No. 100 15 53 8 47 7 47 7 33 5 27 4 27 4 20 3 6 3 1
40 20 7
M.icrodantinE children, both from Africa, most recently in an endemic area. A mild normochromic, normocytic anemia was present in about two thirds of the cases. Leukocyte counts were normal or slightly low and differential counts were unremarkable. When measured, the platelet count was invariably low but returned to normal within 3 days of the start of therapy. One child was tested for, and found to have, antiplatelet antibodies. Glucose-6-phosphate dehydrogenase deficiency was absent in all cases. Four of seven patients tested had positive serum titres of agglutinins against antigens of Salmonella spp., and stools from three of seven contained parasites. Treatment followed the recommendations of the American Academy of Pediatrics.4 Only one patient had side effects, nausea and vomiting, which were thought to be due to primaquine phosphate.
recent arrival from a region where malaria is endemic. Symptoms and signs were vague in many cases and did not always fit the textbook description of malaria. Any child with a febrile illness of no obvious cause who has been in a region where malaria is endemic within the previous 6 months should probably have a blood film examined for parasites. Even those who have received malaria chemoprophylaxis must be considered susceptible since the drugs are not completely effective5 - as evidenced by our patient 1. If the suspicion of malaria remains high despite a negative smear, a blood film should be stained with acridine orange or serologic testing should be performed.6 Accurate identification of species is important because therapy varies according to the causative organism. Resistance to chloroquine has been found in cases due to P. falciparum in Asia and South America and this, too, must be taken into account.7
Discussion Despite heroic attempts to control it, malaria is still endemic in many parts of the world. With an increasing influx of immigrants from endemic regions, it is not surprising that the incidence of malaria in Toronto is increasing. Nearly 65 000 persons immigrated to Canada from endemic regions in 1974, and one third of the approximately 22000 who settled in the metropolitan Toronto area were under the age of 18 years; 5 of these were found to have malaria after admission to this hospital. Thus, a crude estimate of the. proportion of children with malaria in this group would be 1:1500. This proportion is undoubtedly an underestimate, since it does not include patients treated elsewhere or those with undiagnosed chronic disease. The most helpful clue to diagnosis in the 15 children at this hospital was
Addendum Between Aug. 1, 1975 and July 1, 1976 the diagnosis of malaria was made in four more children at the Hospital for Sick Children. These included 3-week-old twins, who had acquired the infection transplacentally. Clinical and laboratory features did not differ from those of the patients discussed above, and all patients came from the Indian subcontinent. References 1. World Health Organization, expert committee on malaria: Sixteenth report. WHO Tech Rep Ser: no 549, 1974 2. RANSOME-KUTI 0: Malaria in childhood. Adv Pediatr 19: 319, 1972 3. Immigration 1974, Ottawa, Department of M4npower and Immipation, 1975 4. American Academy of Pediatrics: Report of the Committee on Infectious DIseases, 17th ed, Evanston, IL, AAP, 1974, pp 104-7 5. BAxanrr-CoNNoR E: Chemoprophylaxis of malaria for travelers. Ann Intern Med 81: 219, 1974 6. SADUN EH: The research and development of serologic tests for malaria. Am I Trop Med Hyg 21: 677, 1972 7. PETERS W: Antimalarial drugs and their actions. Postgrad Med J 49: 573, 1973
Table Ill-Laboratory findings Patient no.
i
Hemoglobin (g/dl)
13.9
Leukocyte count (X 10./l)
5.4
2 9.6 5.5 3 9.1 5.4 4 10.8 5.6 10.5 5.5 5 8.4 15.0 6 11.7 4.5 7 7.0 8 10.0 11.1 5.7 9 10 9.6 5.5 11* 17.8 7.7 12 10.5 5.4 10.7 13 8.6 9.3 3.5 14 10.4 8.4 15 6.7 Mean 10.8 *Patlent with cyanotic congenital heart disease.
Platelet count (X 10911)
35
99 147 90 40 47
89
60 59 99 81 78 77
406 CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115
Parasite identifIed
P. vivax
P. vivax P. falciparum Not identified P. vivax P. vivax P. vivax P. vivax P. falciparum P. uwax P. vivax P. vivax P. vivax P. vivax P. vivax
(Nitrofurancoin Macrocryscals)
References 1. Roth, R.B. et al. The Ruined Kidney, Filmstrip produced with the cooperation of the Hess Urological Foundation, Inc. Erie, Pa., U.S.A. 2. Kunin, CM.: Detection, Prevention and management of urinary tract Infections. Philadelphia, Lea & Febiger, 1972 pg. 18811. 3. Kalowski S., Radford N., Kincaid-Smith P: New Eng. J.M 290: 386, 1974 4. Shirley SW. and Ozog L.S.: Urology Digest 9:8-10, 1970 Action: The large crystal size of Macrodantin (nitorfurantoin macrocrystals) provides the proven clinical efficacy of Furadantin (nitrofurantoin) but with increased gastro intestinal tolerance. In a comparative clinical study the incidence of nausea and/or emesis was appreciably less with Macrodantin than with Furadantin. Patients unable to tolerate Furadantin reported good tolerance of Macrodantin. Indications: Macrodantin is indicated for the treatment of pyelonephritis, pyelitis and cystitis caused by sensitive organisms. Contraindications: Anuria, oliguria or extensive impairment of renal function. Infants under one month. Warnings: Haemolytic anaemia, which disappears on cessation of drug therapy has been reported in sensitive individuals. Usually defined as the 10% of negroes and lower percentages of people of Mediterranean and near Eastern origin who exhibit glucose -6 - phosphate dehydrogenase deficiency of the red blood cells. Safety during pregnancy and lactation has not been established. Precautions: Peripheral neuropathy has been reported with nitrofurantoin. This may become severe and irreversible and one fatality has been reported. Therapy should be discontinued if numbness and tingling occur. Macrodantin should not be co-prescribed with drugs which impair renal function. Adverse Reactions: Nausea, emesis, and less frequently, diarrhea may occur; reduction in dosage may alleviate these symptoms. Sensitization appearing as an erythematous, maculopapular cutaneous eruption, urticaria, eczematoid eruption or pruritus has occurred. Hypersensitivity reactions resulting in nonfatal anaphylaxis, angioedema, pulmonary infiltration with pleural effusion, and eosinophilia have been reported. Other possible reactions are chills, fever, jaundice, asthmatic symptoms, and hypotension. Occasional minor reactions such as headache, dizziness, nystagmus, vertigo, drowsiness, malaise, and muscular aches have occurred. Transient alopecia has been reported. Leukopenia, including granulocytopenia has been reported rarely. Return of the blood picture to normal has followed cessation of therapy. As with other antimicrobial agents, superinfections by resistant organisms may occur. With Macrodantin, however, these are limited to the genitourinary tract because suppression of normal bacterial flora elsewhere in the body does not occur. Administration and Dosage: Dosage: Adult: 50 to 100 milligrams four times a day. Children: Should be calculated on the basis of 5 to 7 milligrams per kilogram (2.2 to 3.2 mg per Ib) of body weight per 24 hours, to be given in divided doses four times a day (contraindicated under one month of age). Administration: Macrodantin (nitrofurantoin macrocrystals) may be given with food or milk to further minimize gastric upset. Therapy should be continued for at least one week and for at least 3 days after sterility of the urine is obtained. Continued infection indicates the need for re-evaluation. If the drug is to be used for long-term suppressive therapy, a reduction of dosage should be considered. How Suppiled: Macrodantin is available in opaque white imprinted capsules of 25 mg. (Eaton 007) in bottles of 30, 100 and 500 capsules; opaque yellow/white imprinted capsules 0150mg. (Eaton 008) in bottles of 30, 100, and 500 captules; opaque yellow, imprinted capsules of 100 mg. (Eaton 009) in bottles of 30, 100, and 500 capsules. Preduct monograph avaiiabie on request. Originators and Developers of the Nitrofurans
. . EATON LABORATORIES Division of Norwich Pharmacal Company Ltd. Paris, Ontario.
