142
6.
7.
8. 9.
10. 11.
Clinical and laboratory observations
change in a severely iron-poisonedchild treated with deferoxamine [Letter]. Vet Hum Toxicol 1981;23:351. Perrotta G. Iron and iron-bindingcapacity. In: Pesce AJ, Kaplan LA eds. Methods in clinical chemistry. St Louis: CV Mosby, 1987:1258-61. Tesoro A, Leeder JS, Bentur Y, Klein J, Freedman M, Koren G. A high performance liquid chromatographic method for the measurement of deferoxaminein bodyfluids.Ther Drug Monit 1989;11:463-70. Keberle H. The biochemistry of desferrioxamine and its relation to iron metabolism. Ann N Y Acad Sci 1964;119:758-68. Herbert V. Drugs effective in iron-deficiencyand other hypochromic anemias. In: Goodman L, Gilman A, eds. The pharmacological basis of therapeutics. 5th ed. New York: Macmillan, 1975:1309-23. Hershko C, Weatherall DJ. Iron chelation therapy. CRC Crit Rev Clin Lab Sci 1988;26:303-45. Peters G, Keberle H, Schmid K, Brunner H. Distribution and renal excretion of desferrioxaMineand ferrioxamine in the dog and the rat. Biochem Pharmacol 1966;15:93-109.
The Journal of Pediatrics January 1991
12. Porter JB, Huehns ER, Hider RC. The development of iron chelating drugs. Bailliere's Clin Haematol 1989;2:257-92. 13. Whitten CF, Gibson GW, Good MH, Goodurin JF, Brough AJ. Studies in acute iron poisoning. I. Desferrioxaminein the treatment of acute iron poisoning:clinical observations,experimental studies and theoretical considerations. Pediatrics 1965;36:322-35. 14. Koren G, Bentur Y, Strong D, ct al. Acute changes in renal function associated with deferoxamine therapy. Am J Dis Child 1989;143:1077-80. 15. Hershko C, Graham G, Bates GW, Rachmilewitz EA. Nonspecific serum iron in thalassemia: an abnormal serum iron fraction of potential toxicity. Br J Haematol 1978;40:255-63. 16. Kruck TPA, Kalow W, Crapper-McLaughlin DR. Determination of desferroxamine and a major metabolite by HPLC: application to the treatment of aluminum-related disorders. J Chromatogr 1985;341:123-30.
Long-term chloroquine-proguanil malaria prophylaxis in a nonimmune pediatric population D a v i d Gozal, MD, Giles F a d a t , MD, a n d C l a u d e Hengy, MD From the Laboratory Division, Organisation contre les Endemies en Afrique Centrale (OCEAC), Yaound6, Cameroon
The appearance in Africa of strains of Plasmodium falciparum resistant to chloroquine during the late 1970s 1 prompted a revision of the recommendations on adequate chemoprophylaxis to short-term travelers to those areas.2, 3 Few if any data are currently available, however, on the efficacy and safety of these drug regimens in nonimmune children living for prolonged periods in areas where malaria is endemic. Moreover, some of these medications have been associated with severe side effects. 2, 4-7 We conducted a prospective long-term study in a pediatric population residing in a chloroquine-resistant malaria area in West Africa, 8 comparing prophylactic use of a combination of weekly chloroquine and daily proguanil (CH-PR) with no prophylaxis in a similar population.
METHODS Sixty-one healthy children of Israeli nationality participated in the study. They and their families were temporary
Submitted for publication May 31, 1990; accepted Aug. 7, 1990. Reprint requests: David Gozat, MD, Divisionof Neonatology and Pediatric Pulmonology, Childrens Hospital of Los Angeles, 4650 Sunset Blvd., PO Box 54700, Los Angeles, CA 90054-0700.
9/26/24453
residents in Yaound6, Cameroon, for the entire study (Aug. 1, 1988, to April 1, 1990). A series of lectures on malaria and its prevention and treatment was delivered by one of us to the whole Israeli community before the study started. Malaria transmission in this part of Cameroon is stable throughout the year; two peaks coincide with the rainy seasons. 9 In vivo and in vitro studies have shown that approximately 30% of strains isolated from symptom-free carriers are chloroquine resistant. 8 A recent survey at our laboratory of 100 consecutive patients with malaria showed in vitro chloroquine resistance to be present in 53 patients (Hengy C: personal communication, 1990), resistance to amodiaquine in 13%, and a decrease in sensitivity to mefloquine in 2%. CH-PR
Chloroquine (weekly) and proguanil (daily)
I
After parental informed consent was received, 42 children enrolled in a chemoprophylactic regimen consisting of chloroquine base (5 mg/kg weekly) and proguanil (3.5 mg/kg daily); the parents of the remaining 19 chose no prophylaxis. In all families, however, the regular application of insect repellents, especially during sunset hours, and the use of window screens are the rule.
Volume 118 Number 1
Clinical and laboratory observations
14 3
Table CH-PR g r o u p (n = 4'I)
Age (yr)* Gender (%) Time in Africa (too)* Time in Yaound6 (too)* Malaria cases Parasite counts (No./#l)* Recovery time (days)* Side effects (%) Anorexia Nausea Vomiting Abdominal pain Headache Recurrent aphtbous stomatitis Pruritus Rash Visual disturbances
No-prophylaxis group (n = 48)
7.1 _+ 3.6 51.2 37 _+ 25 31.4 _+ 16.4 7 67 _+ 72 1.4 _+ 0.4
7.2 _+ 3.5 44.4 41 + 34 30.8 _+ 16.1 11 3237 _+ 2021 3.9 _+ 1.2
p
NS NS NS NS
6.
7.
8. 9.
10. 11.
Clinical and laboratory observations
change in a severely iron-poisonedchild treated with deferoxamine [Letter]. Vet Hum Toxicol 1981;23:351. Perrotta G. Iron and iron-bindingcapacity. In: Pesce AJ, Kaplan LA eds. Methods in clinical chemistry. St Louis: CV Mosby, 1987:1258-61. Tesoro A, Leeder JS, Bentur Y, Klein J, Freedman M, Koren G. A high performance liquid chromatographic method for the measurement of deferoxaminein bodyfluids.Ther Drug Monit 1989;11:463-70. Keberle H. The biochemistry of desferrioxamine and its relation to iron metabolism. Ann N Y Acad Sci 1964;119:758-68. Herbert V. Drugs effective in iron-deficiencyand other hypochromic anemias. In: Goodman L, Gilman A, eds. The pharmacological basis of therapeutics. 5th ed. New York: Macmillan, 1975:1309-23. Hershko C, Weatherall DJ. Iron chelation therapy. CRC Crit Rev Clin Lab Sci 1988;26:303-45. Peters G, Keberle H, Schmid K, Brunner H. Distribution and renal excretion of desferrioxaMineand ferrioxamine in the dog and the rat. Biochem Pharmacol 1966;15:93-109.
The Journal of Pediatrics January 1991
12. Porter JB, Huehns ER, Hider RC. The development of iron chelating drugs. Bailliere's Clin Haematol 1989;2:257-92. 13. Whitten CF, Gibson GW, Good MH, Goodurin JF, Brough AJ. Studies in acute iron poisoning. I. Desferrioxaminein the treatment of acute iron poisoning:clinical observations,experimental studies and theoretical considerations. Pediatrics 1965;36:322-35. 14. Koren G, Bentur Y, Strong D, ct al. Acute changes in renal function associated with deferoxamine therapy. Am J Dis Child 1989;143:1077-80. 15. Hershko C, Graham G, Bates GW, Rachmilewitz EA. Nonspecific serum iron in thalassemia: an abnormal serum iron fraction of potential toxicity. Br J Haematol 1978;40:255-63. 16. Kruck TPA, Kalow W, Crapper-McLaughlin DR. Determination of desferroxamine and a major metabolite by HPLC: application to the treatment of aluminum-related disorders. J Chromatogr 1985;341:123-30.
Long-term chloroquine-proguanil malaria prophylaxis in a nonimmune pediatric population D a v i d Gozal, MD, Giles F a d a t , MD, a n d C l a u d e Hengy, MD From the Laboratory Division, Organisation contre les Endemies en Afrique Centrale (OCEAC), Yaound6, Cameroon
The appearance in Africa of strains of Plasmodium falciparum resistant to chloroquine during the late 1970s 1 prompted a revision of the recommendations on adequate chemoprophylaxis to short-term travelers to those areas.2, 3 Few if any data are currently available, however, on the efficacy and safety of these drug regimens in nonimmune children living for prolonged periods in areas where malaria is endemic. Moreover, some of these medications have been associated with severe side effects. 2, 4-7 We conducted a prospective long-term study in a pediatric population residing in a chloroquine-resistant malaria area in West Africa, 8 comparing prophylactic use of a combination of weekly chloroquine and daily proguanil (CH-PR) with no prophylaxis in a similar population.
METHODS Sixty-one healthy children of Israeli nationality participated in the study. They and their families were temporary
Submitted for publication May 31, 1990; accepted Aug. 7, 1990. Reprint requests: David Gozat, MD, Divisionof Neonatology and Pediatric Pulmonology, Childrens Hospital of Los Angeles, 4650 Sunset Blvd., PO Box 54700, Los Angeles, CA 90054-0700.
9/26/24453
residents in Yaound6, Cameroon, for the entire study (Aug. 1, 1988, to April 1, 1990). A series of lectures on malaria and its prevention and treatment was delivered by one of us to the whole Israeli community before the study started. Malaria transmission in this part of Cameroon is stable throughout the year; two peaks coincide with the rainy seasons. 9 In vivo and in vitro studies have shown that approximately 30% of strains isolated from symptom-free carriers are chloroquine resistant. 8 A recent survey at our laboratory of 100 consecutive patients with malaria showed in vitro chloroquine resistance to be present in 53 patients (Hengy C: personal communication, 1990), resistance to amodiaquine in 13%, and a decrease in sensitivity to mefloquine in 2%. CH-PR
Chloroquine (weekly) and proguanil (daily)
I
After parental informed consent was received, 42 children enrolled in a chemoprophylactic regimen consisting of chloroquine base (5 mg/kg weekly) and proguanil (3.5 mg/kg daily); the parents of the remaining 19 chose no prophylaxis. In all families, however, the regular application of insect repellents, especially during sunset hours, and the use of window screens are the rule.
Volume 118 Number 1
Clinical and laboratory observations
14 3
Table CH-PR g r o u p (n = 4'I)
Age (yr)* Gender (%) Time in Africa (too)* Time in Yaound6 (too)* Malaria cases Parasite counts (No./#l)* Recovery time (days)* Side effects (%) Anorexia Nausea Vomiting Abdominal pain Headache Recurrent aphtbous stomatitis Pruritus Rash Visual disturbances
No-prophylaxis group (n = 48)
7.1 _+ 3.6 51.2 37 _+ 25 31.4 _+ 16.4 7 67 _+ 72 1.4 _+ 0.4
7.2 _+ 3.5 44.4 41 + 34 30.8 _+ 16.1 11 3237 _+ 2021 3.9 _+ 1.2
p
NS NS NS NS
