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Epidemics of Kawasaki syndrome
Volume 101 Number 4
tions present on /3-cells, leading to preferential restriction, followed by uncontrolled virus-mediated cytolysis. Finally, the importance of the destruction of insulin-secreting cells could also be explained by an impaired immune response to the viral infection, due to deficiencies in factors of the complement pathway, C2, C4, Bf (complement variation hypotheses), or to inadequate action of Ir or Is determinants. These models have important implications for research. H. Champsaur, M.D. Centre Hospitalo-Universitaire Bicktre 94270 Paris, France REFERENCES 1.
Notkins AL, and Yoon JW: Virus-induced diabetes in mice prevented by a live attenuated vaccine, N Engl J Med 25:486, 1982. 2. Asplund K: Diabetes, mumps and H L A antigens, Lancet 10:807, 1981. 3. Vague P, Vialettes B, Prince MA, and de Micco P: Coxsackie B viruses and autoimmune diabetes, N Engl J Med 19:1157, 1981. 4. Toniolo A, Onodera T, Yoon JW, and Notkins AL: Induction of diabetes by cumulative environmental insults from viruses and chemicals, Nature 288:383, 1980. 5. Notkins AL: The causes of diabetes, Sci Am 241:56, 1979.
Editorial correspondence
from typical upper UTI diagnosed on strictly defined clinical and laboratory data such as ESR and CRP and in 15 patients in whom the site of infection was considered uncertain. Of course, experience with infants or with hospitalized children (who are more severely ill!) may be quite different, tn fact, the clinical usefulness of localization of the level of UTI in children may be questioned. As pointed out in a recent work, 5 the degree of inflammatory invasion of uroepithelium, in lower as well as in upper UT or renal parenchyma, could be more important than the site of infection itself. Claude Godard Pierre Girardet Groupe Romand d'Etudes de Pbdiatrie Ambulatoire Hopital du District CH 1870 Monthey Lausanne, Switzerland REFERENCES 1.
2. 3. 4.
Short treatment of urinary tract infections To the Editor." We have been most interested in the articles by Lohr et al 1 Shapiro and Wald, 2 and Khan et aP published simultaneously, in the December, 1981, issue of T~E JOURNAI_~which advocated short treatment of uncomplicated urinary tract infection (UTI) in children. Our experience in Switzerland is similar, three days of cotrimoxazole therapy being as successful as conventional therapy (cure rate 97.8 vs. 100%) but more successful than one-day therapy (cure rate 67%). 4 These studies have important practical consequences for pediatric practice. Several points need comment: 1. The lack of uniformity in the definition of cure rate ("sterile urine on day 3 of therapy," "sterile urine two days after therapy," "absence of recurrence for two months") hinders any comparison between the presented results and others. 2. The recurrence rate seems to us not a reliable index for judging the efficacy of different courses, as the frequency of previous episodes of UTI is not taken into consideration. We have shown that the more often the child has had UTI in the past, the more frequent the recurrence of infection within three months after the index episode? 3. The authors either discarded 1'2 or included 3 upper UTI (renal bacteriuria?) in their material, based only on clinical criteria. In ambulatory practice we have been able to obtain a cure of infection with three days' treatment in seven patients suffering
649
5.
Lohr JA, Hayden GF, and Kesler RW: Three-day therapy of lower urinary tract infection with nitrofurantoin macrocrystals: A randomized clinical trial, J PEDIATR 99:980, 1981. Shapiro ED and Wald ER: Single-dose amoxycillin treatment of urinary tract infections, J PED1ATR 99:989, 1981. Khan A J, Kumar E, and Evans HE: Three-day antimicrobial therapy of urinary tract infection, J PEDIATR 99:992,1981. Godard C, Girardet P, Frutiger P, Hynek R, Delarue C, and Christen JP: Short treatment of urinary tract infections in children, Pediatrician 9:309, 1980. Riedasch G, Ritz E, M6bring K, and Bommer J: Antibody coating of urinary bacteria: Relation to site of infection and invasion of uroepithelium, Clin Nephrol 10:239, 1978.
Epidemics of Kawasaki syndrome To the Editor: Dean et al 1 indicate that they report the "first documented epidemic of Kawasaki syndrome [KS] which occurred outside of Japan," although they acknowledge prior reports of recent epidemics in Rochester, N.Y., and Massachusetts. The first "epidemic" of KS in the United States was reported by us in 1978 and 19792,3 and occurred in the New York City area in late 1977. We immediately reported this to the Centers for Disease Control (CDC) and ultimately obtained their joint participation in an epidemiologic investigation. The New York City Department of Health announced the outbreak," and the CDC study s confirmed a rate as high as 17 per 100,000 children under age 5 years during the epidemic period. As subsequently reported by the CDC, 6 this study led to the design and prompt investigation of the subsequent epidemics in Rochester and Massachusetts. Salicylate treatment, described in our 1978 and 1979 reports, is now recommended by all authors. 7,s Salicylate malabsorption, documented frequently during the 1977 epidemic, has been seen less frequently in sporadic cases but has occurred sufficiently frequently in our series of 94 patients to warrant our continuing
650
E d i t o r i a l correspondence
alertness to its potential to interfere with the efficacy of symptomatic control. Jerry C. Jacobs, M.D. Professor o f Clinical Pediatrics Director, Section o f Pediatric Rheumatology College o f Physicians & Surgeons o f Columbia University New York, N Y 10032
The Journal of Pediatrics October 1982
their sporadic localized occurrence argue against this hypothesis. We are grateful to Dr. Jacobs for drawing our attention to the unpublished report. Andrew G. Dean, M.D., M.P.H., Director Division o f Disease Prevention and Control Minnesota Department o f Health 717 S.E. Delaware St. P.O. Box 9441 Minneapolis, M N 55440
REFERENCES 1. 2. 3. 4. 5. 6.
7.
8.
Dean AG, Melish ME, Hicks R, et al: An epidemic of Kawasaki syndrome in Hawaii, J PEDIATR 100:552, 1982. Jacobs JC: Successful treatment of Kawasaki disease with high-dose aspirin, Pediatr Res 12:494, 1978. Jacobs JC: Salicylate treatment of epidemic Kawasaki disease in New York City, Ther Drug Monit 1:123, 1979. New York City Department of Health: Communicable Disease Newsletter 4(6), June, 1978. Anderson L J, Jacobs JC, and Durand C: Unpublished CDC data. Bell DM, Brink EW, Nitzkin JL, et al: Kawasaki syndrome: description of two outbreaks in the United States, N Engl J Med 304:1568, 1981. Meade RH, and Bran& L: Manifestations of Kawasaki disease in New England outbreak of 1980, J PEOIATR 100:558, 1982. Melish ME: Kawasaki syndrome: An update, Hosp Pract 17:99, 1982.
Reply To the Editor: "Documentation" of an epidemic, as we view it, requires demonstration that population-based disease rates are significantly elevated above usual levels. Referral patterns and reporting habits change erratically with public or professional interest in a problem t, 2; an increase in numbers of cases at a particular medical center 3 or of reports to a health department is not sufficient evidence unless active surveillance of a defined population for unreported cases is carried out. We have recently obtained a copy of the unpublished study by the Centers for Disease Control that included the cases Dr. Jacobs mentions. Although one county did have the high case rate mentioned, this was based on a total of four cases. The report concluded that Kawasaki disease was "at least several times more common" in Japan than in metropolitan New York, but provides evidence that the 26 cases during November and December were an "epidemic" by contrast with usual rates in New York City. The biologic point is that initial recognition of Kawasaki syndrome proceeded from Japan to Hawaii to the mainland United States4; "epidemic" Kawasaki syndrome seems to have followed a similar temporal sequence, possibly with an early focus in New York City. This of course would be consistent with spread of an infectious agent (possibly with a high prevalence but low rate of disease production). Although it might also represent spread of a toxic product or social custom from Asia to the United states, the failure to find such a factor in the United States epidemics and
REFERENCES 1.
2.
3.
4.
Osterholm MT, and Forfang JC: Toxic-shock syndrome in Minnesota: Results of an active-passive surveillance system, J Infect Dis 145:458, 1982. Davis JP, and Vergeront JM: The effect of publicity on the reporting of toxic-shock syndrome in Wisconsin, J Infect Dis 145:449, 1982. Jacobs JC: Case report: Salicylate treatment of epidemic Kawasaki disease in New York City, Ther Drug Monit 1:123, 1979. Melish ME, Hicks RM, and Larson E J: Mucocutaneous lymph node syndrome in the United States, Am J Dis Child 130:599, 1976.
Prognosis of infantile spasms To the Editor: In their article "The value of neuroradiology in infantile spasms, ''1 Singer et al claim that their finding "suggests that early treatment of children who have a normal neuroradiologic study and normal development at onset of spasms prevents mental retardation." 1 do not believe that a favorable influence of the early treatment on the mental outcome is demonstrated by the data of this work. With the criteria used by the authors, or~ly eight patients were classified as having idiopathic spasms. All eight were in the early treatment group, and only those patients had normal mental development at follow-up. So one may well wonder if the apparent role of early treatment is not the result of selection, as if spasms and mental alterations were diagnosed sooner in idiopathic than in symptomatic patients. We ourselves have already mentioned this phenomenon z A possible influence of the time between onset of spasms and treatment on mental development remains to be proved. Jean-Jacques Chevrie, M.D. Unitb de Recherches de Gbnbtique Mbdicale I N S E R M U. 12 Hbpital des Enfants-Malades 149 rue de Sbvres F-75743 Paris, France REFERENCES 1. Singer WD, Hailer JS, Sullivan LR, et al: The value of neuroradiology in infantile spasms, J PEmATR 100:47, 1982.
tions present on /3-cells, leading to preferential restriction, followed by uncontrolled virus-mediated cytolysis. Finally, the importance of the destruction of insulin-secreting cells could also be explained by an impaired immune response to the viral infection, due to deficiencies in factors of the complement pathway, C2, C4, Bf (complement variation hypotheses), or to inadequate action of Ir or Is determinants. These models have important implications for research. H. Champsaur, M.D. Centre Hospitalo-Universitaire Bicktre 94270 Paris, France REFERENCES 1.
Notkins AL, and Yoon JW: Virus-induced diabetes in mice prevented by a live attenuated vaccine, N Engl J Med 25:486, 1982. 2. Asplund K: Diabetes, mumps and H L A antigens, Lancet 10:807, 1981. 3. Vague P, Vialettes B, Prince MA, and de Micco P: Coxsackie B viruses and autoimmune diabetes, N Engl J Med 19:1157, 1981. 4. Toniolo A, Onodera T, Yoon JW, and Notkins AL: Induction of diabetes by cumulative environmental insults from viruses and chemicals, Nature 288:383, 1980. 5. Notkins AL: The causes of diabetes, Sci Am 241:56, 1979.
Editorial correspondence
from typical upper UTI diagnosed on strictly defined clinical and laboratory data such as ESR and CRP and in 15 patients in whom the site of infection was considered uncertain. Of course, experience with infants or with hospitalized children (who are more severely ill!) may be quite different, tn fact, the clinical usefulness of localization of the level of UTI in children may be questioned. As pointed out in a recent work, 5 the degree of inflammatory invasion of uroepithelium, in lower as well as in upper UT or renal parenchyma, could be more important than the site of infection itself. Claude Godard Pierre Girardet Groupe Romand d'Etudes de Pbdiatrie Ambulatoire Hopital du District CH 1870 Monthey Lausanne, Switzerland REFERENCES 1.
2. 3. 4.
Short treatment of urinary tract infections To the Editor." We have been most interested in the articles by Lohr et al 1 Shapiro and Wald, 2 and Khan et aP published simultaneously, in the December, 1981, issue of T~E JOURNAI_~which advocated short treatment of uncomplicated urinary tract infection (UTI) in children. Our experience in Switzerland is similar, three days of cotrimoxazole therapy being as successful as conventional therapy (cure rate 97.8 vs. 100%) but more successful than one-day therapy (cure rate 67%). 4 These studies have important practical consequences for pediatric practice. Several points need comment: 1. The lack of uniformity in the definition of cure rate ("sterile urine on day 3 of therapy," "sterile urine two days after therapy," "absence of recurrence for two months") hinders any comparison between the presented results and others. 2. The recurrence rate seems to us not a reliable index for judging the efficacy of different courses, as the frequency of previous episodes of UTI is not taken into consideration. We have shown that the more often the child has had UTI in the past, the more frequent the recurrence of infection within three months after the index episode? 3. The authors either discarded 1'2 or included 3 upper UTI (renal bacteriuria?) in their material, based only on clinical criteria. In ambulatory practice we have been able to obtain a cure of infection with three days' treatment in seven patients suffering
649
5.
Lohr JA, Hayden GF, and Kesler RW: Three-day therapy of lower urinary tract infection with nitrofurantoin macrocrystals: A randomized clinical trial, J PEDIATR 99:980, 1981. Shapiro ED and Wald ER: Single-dose amoxycillin treatment of urinary tract infections, J PED1ATR 99:989, 1981. Khan A J, Kumar E, and Evans HE: Three-day antimicrobial therapy of urinary tract infection, J PEDIATR 99:992,1981. Godard C, Girardet P, Frutiger P, Hynek R, Delarue C, and Christen JP: Short treatment of urinary tract infections in children, Pediatrician 9:309, 1980. Riedasch G, Ritz E, M6bring K, and Bommer J: Antibody coating of urinary bacteria: Relation to site of infection and invasion of uroepithelium, Clin Nephrol 10:239, 1978.
Epidemics of Kawasaki syndrome To the Editor: Dean et al 1 indicate that they report the "first documented epidemic of Kawasaki syndrome [KS] which occurred outside of Japan," although they acknowledge prior reports of recent epidemics in Rochester, N.Y., and Massachusetts. The first "epidemic" of KS in the United States was reported by us in 1978 and 19792,3 and occurred in the New York City area in late 1977. We immediately reported this to the Centers for Disease Control (CDC) and ultimately obtained their joint participation in an epidemiologic investigation. The New York City Department of Health announced the outbreak," and the CDC study s confirmed a rate as high as 17 per 100,000 children under age 5 years during the epidemic period. As subsequently reported by the CDC, 6 this study led to the design and prompt investigation of the subsequent epidemics in Rochester and Massachusetts. Salicylate treatment, described in our 1978 and 1979 reports, is now recommended by all authors. 7,s Salicylate malabsorption, documented frequently during the 1977 epidemic, has been seen less frequently in sporadic cases but has occurred sufficiently frequently in our series of 94 patients to warrant our continuing
650
E d i t o r i a l correspondence
alertness to its potential to interfere with the efficacy of symptomatic control. Jerry C. Jacobs, M.D. Professor o f Clinical Pediatrics Director, Section o f Pediatric Rheumatology College o f Physicians & Surgeons o f Columbia University New York, N Y 10032
The Journal of Pediatrics October 1982
their sporadic localized occurrence argue against this hypothesis. We are grateful to Dr. Jacobs for drawing our attention to the unpublished report. Andrew G. Dean, M.D., M.P.H., Director Division o f Disease Prevention and Control Minnesota Department o f Health 717 S.E. Delaware St. P.O. Box 9441 Minneapolis, M N 55440
REFERENCES 1. 2. 3. 4. 5. 6.
7.
8.
Dean AG, Melish ME, Hicks R, et al: An epidemic of Kawasaki syndrome in Hawaii, J PEDIATR 100:552, 1982. Jacobs JC: Successful treatment of Kawasaki disease with high-dose aspirin, Pediatr Res 12:494, 1978. Jacobs JC: Salicylate treatment of epidemic Kawasaki disease in New York City, Ther Drug Monit 1:123, 1979. New York City Department of Health: Communicable Disease Newsletter 4(6), June, 1978. Anderson L J, Jacobs JC, and Durand C: Unpublished CDC data. Bell DM, Brink EW, Nitzkin JL, et al: Kawasaki syndrome: description of two outbreaks in the United States, N Engl J Med 304:1568, 1981. Meade RH, and Bran& L: Manifestations of Kawasaki disease in New England outbreak of 1980, J PEOIATR 100:558, 1982. Melish ME: Kawasaki syndrome: An update, Hosp Pract 17:99, 1982.
Reply To the Editor: "Documentation" of an epidemic, as we view it, requires demonstration that population-based disease rates are significantly elevated above usual levels. Referral patterns and reporting habits change erratically with public or professional interest in a problem t, 2; an increase in numbers of cases at a particular medical center 3 or of reports to a health department is not sufficient evidence unless active surveillance of a defined population for unreported cases is carried out. We have recently obtained a copy of the unpublished study by the Centers for Disease Control that included the cases Dr. Jacobs mentions. Although one county did have the high case rate mentioned, this was based on a total of four cases. The report concluded that Kawasaki disease was "at least several times more common" in Japan than in metropolitan New York, but provides evidence that the 26 cases during November and December were an "epidemic" by contrast with usual rates in New York City. The biologic point is that initial recognition of Kawasaki syndrome proceeded from Japan to Hawaii to the mainland United States4; "epidemic" Kawasaki syndrome seems to have followed a similar temporal sequence, possibly with an early focus in New York City. This of course would be consistent with spread of an infectious agent (possibly with a high prevalence but low rate of disease production). Although it might also represent spread of a toxic product or social custom from Asia to the United states, the failure to find such a factor in the United States epidemics and
REFERENCES 1.
2.
3.
4.
Osterholm MT, and Forfang JC: Toxic-shock syndrome in Minnesota: Results of an active-passive surveillance system, J Infect Dis 145:458, 1982. Davis JP, and Vergeront JM: The effect of publicity on the reporting of toxic-shock syndrome in Wisconsin, J Infect Dis 145:449, 1982. Jacobs JC: Case report: Salicylate treatment of epidemic Kawasaki disease in New York City, Ther Drug Monit 1:123, 1979. Melish ME, Hicks RM, and Larson E J: Mucocutaneous lymph node syndrome in the United States, Am J Dis Child 130:599, 1976.
Prognosis of infantile spasms To the Editor: In their article "The value of neuroradiology in infantile spasms, ''1 Singer et al claim that their finding "suggests that early treatment of children who have a normal neuroradiologic study and normal development at onset of spasms prevents mental retardation." 1 do not believe that a favorable influence of the early treatment on the mental outcome is demonstrated by the data of this work. With the criteria used by the authors, or~ly eight patients were classified as having idiopathic spasms. All eight were in the early treatment group, and only those patients had normal mental development at follow-up. So one may well wonder if the apparent role of early treatment is not the result of selection, as if spasms and mental alterations were diagnosed sooner in idiopathic than in symptomatic patients. We ourselves have already mentioned this phenomenon z A possible influence of the time between onset of spasms and treatment on mental development remains to be proved. Jean-Jacques Chevrie, M.D. Unitb de Recherches de Gbnbtique Mbdicale I N S E R M U. 12 Hbpital des Enfants-Malades 149 rue de Sbvres F-75743 Paris, France REFERENCES 1. Singer WD, Hailer JS, Sullivan LR, et al: The value of neuroradiology in infantile spasms, J PEmATR 100:47, 1982.