February 1978

The Journal o f P E D l A T R I C S

325

Tropical acute rheumatic fever and associated streptococcal infections compared with concurrent acute glomeruionephritis Ninety-three patients with acute rheumatic fever and 195 patients with acute glomerulonephritis were observed in Trinidad during an outbreak of scabies with a high incidence o f secondary streptococcal infections. Clinical and laboratory manifestations o f A R F were the same as those seen in temperate zones, except that antistreptolysin 0 titers were less markedly increased. The patients" with A R F were similar to those with A GN in respect to sex, race, location of residence, and living conditions, but were older and had markedly fewer skin infections. Currently prevalent nephritogenic streptococcal strains never were isolated from patients with A R F even when M55 streptococci appeared and led to an epidemic o f AGN.

E l i z a b e t h V. P o t t e r , M . D . , * M a u r i S v a r t m a n ,

M.D.,

Isahak Mohammed, M.B., M.R.C.P., Reginald Cox, M.B., M.R.C.P., Theo Poon-King, M.B., F.R.C.P., and David P. Earle, M.D., Chicago, Ill.

ACCORDING to early investigators of nonsuppurative streptococcal diseases, acute rheumatic fever was relatively rare 1 or differed clinically2-7 in warm climates from that observed in temperate zones. Although other studies of A R F in tropical and subtropical areas have not shown such differences, 8-18the possibility r e m a i n s that A R F may be missed by rigid application of the Jones criteria in warmer parts of the world, as recently discussed in reports from Egypt 1~and Africa. TM Furthermore, though A R F has not been associated with streptococcal skin infections in temperate or subtropical areas where pyoderma and A R F have divergent seasonal peaks, ~5. 16it may be so associated From the Streptococcal Disease Unit San Fernando General Hospital, Trinidad and Tobago, and Section of Nephrology and Hypertension, Department o f Medicine, Northwestern University-McGaw Medical Center. Supported by the Ministry o f Health o f Trinidad & Tobago, by United States Public Health Service contract P H 108-66-217, by research grants A M 05614 and A I 10980 o f the National Institutes o f Health, and by the Otho S.A. Sprage Memorial Institute. *Reprint address: 303 East Chicago Ave., Chicago, IL 60611.

0022-3476/78/0292-0325500.90/0 9 1978 The C. V. Mosby Co.

in tropical areas where both occur throughout the year. Serum streptococcal antibodies in patients with A R F have been characteristic of this relationship in Trinidad.'7 Abbreviations used ARF: acute rheumatic fever AGN: acute glomerulonephritis CDC: Center for Disease Control AH: antihyaluronidase ADNB: antideoxyribonuclease B In contrast to ARF, acute glomerulonephritis has been associated with streptococcal skin infections in temperate, 1~ subtropical, 16 and tropical areas 17 and with certain streptococcal strains (nephritogenic strains). Furthermore, the rarity of A R F and AGN in the same individual, the same family, or t h e same outbreak of streptococcal disease has led to the hypothesis that nephritogenic strains cannot cause ARF, whereas those which cause A R F cannot cause AGN. 1' ~" Howeve r, few identifiable streptococci have been isolated from A R F and AGN patients concurrently and in the same area to confirm this hypothesis. We have had a unique opportunity to study the above relationships on the island of Trinidad where ARF, AGN,

Vol. 92, No. 2, pp. 325-333

326

Potter et al.

The Journal o f Pediatrics February 1978

9 0 183

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and skin infections occur throughout the year in an area from which all patients are admitted to a single hospital. 1'~ Furthermore, several M-typable streptococcal strains have been established as nephritogenic 2~and thus may be recognized if isolated from patients with ARF. The present report describes observations made in Trinidad when skin infections were more common than usual because of an epidemic of scabies, ~' and the incidence of AGN rose rapidly to epidemic rates after the reappearance of previously epidemic M-type 55 streptococci, lu MATERIALS

AND METHODS

Clinical material. Two hundred thirty-five patients were suspected of having A R F when admitted to the San Fernando General Hospital between November 10, 1970, and June 15, 1971. This large number resulted from the practice of suspecting A R F in most cases of "fever" and malaise of unknown origin. Throat cultures were taken from all of these patients soon after admission to hospital and skin infections were cultured when present. Serum samples were obtained at the time of culture (prior to treatment with antibiotics) for streptococcal antibody, Creactive protein, and complement assays. Ninety-three of the patients fulfilled the revised Jones criteria for guid-

ance in the diagnosis of rheumatic fever 22 and were admitted to the study. Two hundred twenty-two patients suspected of having AGN (usually on the basis of edema or abnormal urine) during the same time period were studied in a similar manner. Criteria for AGN included hematuria or proteinuria or both with evidence of recent streptococcal infection in the absence of previous renal disease and having one or more of the following: edema, hypertension, azotemia, or decreased serum complement; 195 patients fulfilled these criteria. One hundred fifty "well" children attending three schools were examined for skin infections, cultured, and bled for serum samples. Members of the first, second, and then third forms were examined until 50 children six to nine years of age had been seen in each school. Skin infections in additional Children were cultured (34, 29, and 32 in respective schools) in order to obtain enough skin infections for analysis of streptococcal prevalence rates and enough streptococcal strains for identification of prevalent groups and types. The first school was visited at the beginning, the second about one-third of the way through, and the third at the end of the study. Serologic assays. Beta 1C globulin assays were performed by radial immunodiffusion in agar geY 3 on slides prepared in our laboratory with goat anti-fl 1C/fl 1A serum from Hyland Laboratories (Costa Mesa, Calif.). Creactive protein was measured by precipitation in capillary tubes with reagent from Hyland Laboratories. Antistreptolysin O titers were assayed by the microtiter technique described by Edwards 24 with reagents from Hyland Laboratories. Antihyaluronidase titers were assayed by the microtiter adaptation described by Murphy ~ of the clot prevention test described by Harris and associates~6 with reagents from Difco Laboratories (Detroit, Mich.). Antideoxyribonuclease B titers were assayed by the microtiter technique described by Nelson and associates~7 with reagents obtained from Beckman Instruments, Inc. (Fullerton, Calif.). Streptococcal studies. Streptococcal cultures were made with dry cotton swabs on 5% sheep blood agar plates. Subcultures were made in Todd Hewitt Broth (Difco Laboratories) for grouping ~ and M-typing 2'~by the Lancefield technique with antisera from the Center for Disease Control (Atlanta, Ga.). T-typing was performed according to the technique used at the CDC. 3~ Further characterization of some of these strains was achieved by preparing antiserum in rabbits as described by LancefieldY~ The relation of these strains to standard known types and to new strains being isolated by other workers was established by cross-adsorption studies

Volume 92 Number 2

Rheumatic fever, nephritis, and streptococcal infections

o SAN FERNANDO

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Fig. 2. The homes of patients admitted to San Fernando General Hospital during study period are indicated by circles: open circles represent patients with rheumatic fever; closed circles represent those with glomerulonephritis.

employing our antisera and those of CDC, Colindale Laboratory (London, England), and Rockefeller University in precipitin and bactericidal tests. Type specific antibodies were measured by the bacteric i d a l test of Rothbard:" as modified by Stollerman and associates? 2 They were graded according to Potter and associates. 2~ Two- to four-month convalescent serum samples were used for these assays. Production of opacity factor was assayed by the tube method described by Widdowson and associates? :~ RESULTS Seasonal occurrence of ARF and AGN (Fig. 1). Similar minor variations in the monthly incidences of ARF and A G N were Observed until June, 1971, when AGN became epidemic and ARF did not. 1~ The incidence of these diseases during the previous year show that the June, 1971, increase was not an annual seasonal occurrence. Demographic data. Most patients with ARF or AGN lived in the same or similar rural areas (Fig. 2). Only 6% of ARF patients lived in San Fernando whereas 9% of those with AGN lived in this relatively urban area. Patients with AR E generally were older than those with AGN (Table !). Although slightly more ARF patients were female and fewer were East Indian, these differences were not significant. Historical data (Table I). A family history of ARF was more common in patients with ARF than in those with

AGN; a family history of AGN was more common in patients with AGN. Mor,e ARF patients had had previous attacks of ARF whereas previous attacks of AGN had been uncommon in both groups. Neither of the two ARF patients with a history of AGN had been observed in the hospital with AGN during the past six years of our studies, nor could these attacks be confirmed by prior hospital records; two AGN patients had had prior documented attacks of AGN. More Of the ARF than AGN patients had had recent sore throats, whereas more of the AGN patients had had recent skin infections. Nearly all of the ARF patients had had joint pains, in contrast to the AGN patients. Clinical data (Table I). Fewer of the ARF patients had skin infections than the AGN patients or "well" schoolChildren (28% of 150 schoolchildren, P < 0.001). Fewer of the skin infections were associated with scabies in the ARF patients (43%) than in the AGN patients (78%) or the schoolchildren (64%), but these differences were not significant (P > 0.05 and > 0.5, respectively). Polyarthritis, monoarthritis, and polyarthralgia were observed only in patients with ARF. Polyarthralgia was observed in addition to arthritis in 59% of the ARF patients and in the absence of arthritis in 15%. Carditis also was limited to patients with ARF, two of whom had congestive heart failure. The mitral valve was involved in 54~ aortic in 3%, and both in 2% of patients. Chorea was the major criterion in three patients with ARF, none of

328

Potter et al.

The .Journal of Pediatrics February 1978

Table I. Demographic, historical, clinical, and laboratory data concerning 93 patients with acute rheumatic fever (ARF) and 195 patients with acute glomerulonephritis (AGN)

Data

Demographic Less than five years of age More than 15 years of age Female East Indian Negro or mixed Historical Family history of acute rheumatic fever Family history of acute glomerulonephritis Personal history of acute rheumatic fever Personal history of acute glomerulonephritis Recent sore throat Recent skin infection Recent joint pains Clinical Skin infections observed Scabies observed Polyarthritis observed Monoarthritis observed Carditis observed Chorea observed Migratory arthralgia while in hospital Laboratory C-reactive protein of 1 + 3+ /~IC globulin of > 150 mg/dl 120 mg/dl Leukocyte count of >8,000/mm :~ > 10,000/mm ~ Group A streptococcal skin infection ( + ) Group A streptococcal throat culture (+)

ARF patients (%)

A GN patients (%)

p*

8

38

0.05 >0.05

12

1