Volume 121 Number 4

Clinical and laboratory observations


Prevention of rheumatic fever in Costa Rica A d r i a n o A r g u e d a s , MD, a n d E d g a r Mohs, MD From the Department of Pediatric Infectious Diseases,National Children's Hospital, the Universidad Autonoma de Ciencias Medicas, and the Universidad de Costa Rica, San Jos~, Costa Rica

During the beginning of the 1970s, major changes occurred in Costa Rica in the treatment of streptococcal throat infections. Because of poor c o m p l i a n c e with regimens using orally administered agents, intramuscular administration of benzathine penicillin was selected as the standard treatment and throat cultures were eliminated as a prerequisite for prescribing antibiotics. A decline in the incidence of rheumatic fever then occurred. We believe that similar health intervention could be applied in other developing countries. (J PEDIATR1992; 421:569-72)

Rheumatic fever follows nasopharyngeal infection caused by group A S-hemolytic streptococcus in about 2% to 3% of individuals; in a substantial number of cases the infection may be subclinical.~ Thus a systematic approach toward early detection and treatment of GABS infection is considered the best method to decrease the incidence of rheumatic fever. Costa Rica has been an excellent example of this preventive approach; with an established health program we have been able to eliminate rheumatic fever, a disease that was one of the major causes of hospitalization and cardiac sequelae in our country during the 1950s and 1970s. 2 We believe that our program may have potential applications for developing countries that continue to have a high incidence of the disease and its sequelae. METHODS During the 1970s a program of primary health care and an extension of other health programs were launched with the idea of providing comprehensive medical care in Costa Rica. The concept of prevention through professional dedication (increase in the number of daily working hours, better community health programs) and good medical care organization (increase in the number of peripheral clinics and improvement in organization and therapeutic decisions) was implemented; this new concept included secondary prevention of complications of diseases that could be prevented primarily.l, 3 In the case of rheumatic fever, although giving supportSubmitted for publication Jan. 23, 1992; accepted May 4, 1992. Reprint requests: Adriano G. Arguedas, MD, National Children's Hospital, PO Box 1654-1000, San Jos6, Costa Rica, Central America. 9/22/39179

ive therapy to the population that already had heart disease was important, it was considered more important to establish feasible programs for the treatment of GABS throat infections. Two important decisions were taken: the selection of benzathine penicillin as the standard treatment and the elimination of throat cultures as a prerequisite for prescribing antibiotics. At that time, considering the poor compliance with a 10-day oral or parenteral penicillin regimen,2, 4 it was decided to implement the use of intramuscularly administered benzathine penicillin as the drug of choice for the treatment of GABS throat infection. Multiple educational programs around the country were organized to inform health care workers (physicians, nurses, health technicians, medical students) of this new campaign; at the same time, all health care centers were provided with sufficient amounts of benzathine penicillin to cover their needs.2, 5 GABS

Group A ~-hemolytic streptococcus


Throughout the nation the diagnosis of GABS throat infection is now based only on clinical grounds. The national health authorities recommend treatment with benzathine penicillin for every patient who consults because of fever or sore throat and whose physical examination shows halitosis, redness of the pharynx, and hypertrophy of the tonsils with a white exudate. The dosage of penicillin used is 300,000 units for patients less than 3 years of age, 600,000 units for patients between 3 and 5 years of age, and 1,200,000 units for patients older tl~an 5 years. A penicillin skin test is placed in every patient older than 3 years of age; for patients with a history of allergy to penicillin or with a positive skin test result, the use of orally administered erythromycin at a dosage of 30 to 40 mg/kg per day, divided in four doses for 10 days, is sUggested. 3


Clinical and laboratory observations


The Journal of Pediatrics October 1992







YEARS Fig. t. Incidence of rheumatic fever in Costa Riea from 1985 to 1990. (From the Mfnistry of Health, Costa Rica.)

RESULTS A major decline in the incidence of rheumatic fever has occurred in Costa Rica (Fig. 1). In 1950 the attack rate was 120 cases per 100,000 inhabitants, and no major changes were observed until the beginning of the 1970s (90/ 100,000). Furthermore, acute rheumatic fever and associated mitral valve disease represented 25% of all deaths in children 5 tO 14 years of age in 1968. Associated with the increased use of benzathine penicillin, a sharp decrease in the national incidence of rheumatic fever occurred (Fig. 2). This therapeutic approach has been maintained during subsequent years, and a continuous decline in the incidence of rheumatic fever has been observed both nationwide and at the National Children's Hospital, San Jos6, the only Costa Rican children's tertiary care hospital (94 vs 4 new cases in 1970 and 1991, respectively). Rheumatic fever is no longer included in the list of common causes of morbidity or death in Costa Rican children. 5 Nationwide, no deaths have been due to the use of penicillin, and major penicillin-related side effects (anaphylaetic reactions or local site abscesses) have been reported only sporadically. The most commonly reported side effects have been a transitory painful sensation at the site of the injection and a transient rash (Statistics Department, National Children's Hospital, San Jos6, C~)sta Rica). A major concern with our national policy has been the possibility of selection of resistance to penicillin. However, this phenomenon has not been observed in Costa Rica. During recent years (including 1991), 100% of the GABS strains isolated at the National Children's Hospital have

been susceptible, by the Kirby-Bauer method, to penicillin. Furthermore, cross-selection of resistance by other microorganisms to penicillin has not occurred; Streptococcus pneumoniae remains 100% susceptible to penicillin and Haemophilus influenzae is 100% susceptible to ampicillin (Kirby-Bauer method and/3-1actamase testing, Microbiology Department, National Children's Hospital, San Jos6, Costa Rica). DISCUSSION The prevalence of rheumatic fever in schoolchildren in developed countries is 0.1 per 1000 and is much higher (1 to 22 per 1000) in developing countries.6 Although lately a resurgence in rheumatic fever has been noted in developed countries,7]2~eo reasons for these overall differences between developing and developed countries remain unclear. A few hypotheses have been postulated, among which are inadequate provision of health care services and the delays observed in obtaining medical attention. These are supported by the Baltimore experience showing that prompt diagnosis and treatment of streptococcal infection were direct!y related to a decline in the incidence of rheumatic fever. During 1966 the attack rate in Baltimore was 27 new cases per 100,000 inhabitants. At that time, the establishment of a neighborhood health care clinic in the inner part of the city was associated with a decrease in the incidence to 1 l new cases per 100,000. In another section of the city, with a similar population but not served by neighborhood health care centers, the attack rate remained unchanged. Citywide comprehensive medical services were then ex-

Volume 121 Number 4

Clinical and laboratory observations






.35 80 3O 26


20 40

18 10


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Fig. 2. C•rr••ati•nb•tw•ennewcas•s•frh•umaticf•verandth•use•fb•nzathin•penici•••natth•Nati•na•Chi•dr•n•s Hospital, San Jos6, Costa Rica.

panded, and by 1980 the attack rate of rheumatic fever in the entire city of Baltimore had fallen to 0.5/100,000.13 Although we recognize that our approach may result in overuse of benzathine penicillin, including overuse in some patients with viral tonsillitis (e.g., adenovirus, coxsackievirus, Epstein-Barr virus), rapid agglutination tests and throat cultures are not recommended for use in Costa Rica because they are unavailable and expensive and because patient follow-up cannot be ensured in a national program. Another advantage of benzathine penicillin over orally administered penicillin V potassium is the lower cost of the parenteral preparation. Presently the cost of a single treatment (in Costa Rica) for a 7-year-old patient (weight 24 kg) with a GABS throat infection with benzathine penicillin (1,200,000 units) is $6.66 ($3.33/600,000 units per vial), whereas the total cost of a 10-day course of oral penicillin therapy (50 mg/kg per day) is $42.72 (250 mg tablet costing $0.89). A vial of benzathine penicillin is stable under regular refrigeration (20 ~ C) for 24 hours, and therefore one vial may be used for two 3-year-old or younger patients during the same day. Furthermore, 0.1 ml of penicillin diluted in 20 ml of sterile water may be used for skin testing in 20 individuals, adding to the cost of the parenteral treatment only $0.18 for the syringe. Although this difference in cost is not important for a single patient, it does represent a significant budgetary consideration in a nationwide program (Pharmacy Department, National Children's Hospital, San Jos6, Costa Rica). On the basis of the experience accumulated in Costa Rica

with the control of rheumatic fever in children, we believe that a similar health plan could be applied in other developing countries. Our program is not expensive, has not resulted in selection of resistance, ensures 100% patient compliance, and is easily implemented by health care workers. We believe that if orally administered antimicrobial drugs with strong activity against GABS and with improved pharmacokinetic properties (longer half-life with shorter dosing intervals and shorter treatment duration) become available in the future, our strategy could be reconsidered because fewer side effects are seen with the oral route than with parenterally administered medications. We thank Dr. Harris R. Stutman for his helpful comments during the writing of this manuscript.

REFERENCES I. AyoubEM. Immune response to group A streptococcal infections. Pediatr Infect Dis J 1991;10:S15-9. 2. Mohs E. La fiebre reumatica en Costa Rica. Revista Medica del Hospital Nacional de Nifios [Costa Rica] 1985;20:77-85. 3. Mohs E, Arguedas J, Arguedas A. Management of the pediatric patient in the outpatient clinic. Ministry of Health, Costa Rica, 1987. 4. Marbello JR. Factors influencing pediatric compliance.Pediatr Infect Dis 1985;4:579-83. 5. Mohs E. Infectious diseases and health in Costa Rica: the development of a new paradigm. Pediatr Infect Dis J 1982; 1:212-6. 6. Rotta J, Tikhomirov E. Streptococcal diseases worldwide: present status and prospects. Bull World Health Organ 1987;65:769-77.

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Clinical and laboratory observations

7. Veasey LG, Wiedmeier SE, Orsmond GS, et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 1987;316:421-7. 8. Hosier DM, Craenen JM, Teske DW, et al. Resurgence of acute rheumatic fever. Am J Dis Child 1987;141:730-3. 9. Congeni B, Rizzo C, Congeni J, et al. Outbreak of acute rheumatic fever in northeast Ohio. J PEDIATR1987;111:176-9. 10. Westlake RM, Graham TP, Edwards KM, et al. An outbreak of acute rheumatic fever in Tennessee. Pediatr Infect Dis J 1990;9:97-100.

The Journal of Pediatrics October 1992

11. Wald ER, Dashefsky B, Feidt C, et al. Acute rheumatic fever in western Pennsylvania and the tristate area. Pediatrics 1987;80:371-4. 12. Zangwill KM, Wald ER, Londino AV. Acute rheumatic fever in western Pennsylvania: a persistent problem into the 1990s. J PEDIATR1991;118:561-3. 13. Gordis L. Effectiveness of comprehensive-care programs in preventing rheumatic fever. N Engl J Med 1973;289:331-5.

Chronic hepatitis B in adopted Romanian children R o b e r t J. Z w i e n e r , MD, B a r b a r a A. F i e l m a n , RN, ANP, a n d R o b e r t H. Squires, Jr., MD From the Center for Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, and Children's Medical Center of Dallas, Dallas, Texas

Four of five Romanian orphans a d o p t e d by U.S. families were found to have chronic hepatitis B virus (HBV) infection after negative test results were reported in Romania before adoption. Another child with known HBV infection was found to be coinfected with hepatitis D virus. There is a high incidence of HBV infection in Romanian orphans, and results of tests for HBV are unreliable in Romania. (J PEDIATR1992;424:572-4)

Changing political conditions in Romania have resulted in relaxation of the Romanian government's emigration policies. Consequently, since October 1990, more than 2000 Romanian orphans have been adopted by families in the United States (Blanet Shanks, U.S. Immigration and Naturalization Service: personal communication, January 1992). These children were generally retrieved from squalid, overcrowded, understaffed facilities in a country where the prerevolution health care institutions were isolated from the international medical community. As a result, practices such as "routine" neonatal transfusion of well babies and the frequent use of parenteral medications administered with improperly sterilized needles were common.l Infection with hepatitis B virus is highly endemic to Romania, and no Submitted for publication March 10, 1992;accepted May 13, 1992. Reprint requests: Robert J. Zwiener, MD, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235. 9/22/39308

effective screening and immunization programs exist; these children are at high risk for infection with parenterally transmitted organisms, most importantly HBV and human immunodeficiency virus.2 We report four adopted Romanian children, represented to be free of infection with HIV and HBV before adoption, who were found to have chronic hepatitis B on arrival in the ALT HBV HDV HIV

Alanine aminotransferase Hepatitis B virus Hepatitis D virus Human immunodeficiencyvirus

United States, and another child known at the time of adoption to have HBV infection who was later found to have eoinfection with hepatitis D virus. METHODS The families of five adopted Romanian children with chronic HBV infection were interviewed. The medical his-

Prevention of rheumatic fever in Costa Rica.

During the beginning of the 1970s, major changes occurred in Costa Rica in the treatment of streptococcal throat infections. Because of poor complianc...
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