Syphilis is still a problem
S Y P H I L I S
remains at the present time
syphilis are commonly insignificant and may be overlooked. It has been estimated from public health surveys that in only about 25 per cent of the new cases in a given community is a definite diagnosis made in the early infectious stage. 1 Every possible effort should be made to find early cases, a task which involves more lay education stressing the mild character of the early manifestations of the disease and urging the need for medical consultation. Physicians, including those caring for children, must be constantly alert for early signs of this infection. In a recent discussion concerning the problem of diagnosis Sciple, Montgomery, and K n o x a describe the case of a schoolboy, 14 years of age, who was referred to the Venereal Disease Clinic because of a "positive" routine serologic test. Physical examination had been negative, and a tentative diagnosis of biologic false positive reaction was made by the referring physician. The patient had been attended by this referring physician for a persistent, nonspecific upper respiratory infection with pharyngitis and sore throat. All information relative to syphilis was negative, and the patient denied exposure of any kind. Serum serologic tests for syphilis at the referral clinic were reported as weakly reactive ( V D R L ) , reactive (Kolmer), and nonreactive (Kahn). The cerebrospinal fluid Kolmer test was reported as nonreactive. Venereal Disease Research Laboratory tests of serum from the mother, father, and 10 siblings were
public health problem of major and increasing proportions. Public health reports 1 published late in 1960 carried the following statements: "cases of infectious syphilis have been increasing alarmingly since 1957. Moreover, there is no indication that the trend is changing . . . . We estimate the reservoir of untreated syphilitics today at 1,200,000 cases, and that the true annual incidence is 60,000 cases. ''1 These reports emphasize the distinction between prevalence and incidence, the total number of cases, and the number of new infections. Effective control measures may bring about marked changes in the incidence which are not reflected rapidly in the prevalence of the disease. Reinfection and recurrence following inadequate treatment complicate the problem of public health control. Emphasis is placed likewise on the need for keeping a high index of suspicion regarding this so-called "dying disease," since a patient with early infectious syphilis may consult specialists about his various complaints without the true nature of the condition being apparent. This is true particularly in the adolescent "teen-age" patient. In one recorded instance the patient was seen over a period of time by 3 specialists before the true condition was suspected by a dermatologistY From the public health standpoint case finding is of great importance. Unfortunately patients with early syphilis are seldom acutely ill, and lesions of primary or even secondary 625
Comments on current literature
all nonreactive, as were cerebrospinal fluid examinations of tile parents. On further interrogation statements made by both parents revealed a suggestive history, and both father and mother admitted infection and treatment before the birth of this son 14 years before. The more sensitive treponemal antibody tests performed after this information was obtained showed the mother's serum and the son's reactive, and the father's weakly reactive. These results together with the family history indicated congenital syphilis in the son. The limited therapy received by the mother during pregnancy was sufficient apparentIy for her "serologic cure," but was inadequate for her fetus. In view of such experiences the authors emphasize the justifiability of persistence in pursuing the history, both individual and family, and state that, in spite of the real problem of biologic false positive reactions, "a positive serologic test for syphilis should suggest a diagnosis of syphilis until proved otherwise. ''~ This policy of high suspicion index was emphasized somewhat earlier by others, notably Perry, Kierland, and Magath ~ in 1956. In the case of congenital syphilis the infection is acquired in utero from the mother after about the fifth month of pregnancy, a The term prenatal syphilis has been suggested as more accurate than congenital syphilis. Pregnancy occurring in women with recent infection results almost invariably in miscarriage, stillbirth, or in congenital syphilis in the child. Women who become pregnant some years after infection give birth to normal children, as a rule. If syphilis can be recognized early in pregnancy and treated adequately, prenatal infection can be prevented in the majority of cases. The most effective case finding procedure for this group consists in the routine blood testing of all pregnant women. Recognition of prenatal syphilis in the living infant born of a syphilitic mother presents a problem, since clinical evidence may not be apparent at birth. Diagnosis depends largely upon tests of cord blood; likewise, a study of the placenta and dark-field examination of tissue scrapings from the urfibilicaI
vein have been recommended. 6 If the mother's serologN is positive at the time of delivery, a passive transfer of reagins to the infant may have occurred in the absence of fetal infection. 7 Relatively few of these infants show manifestations of infection, and many revert to negative in from 1 to 5 months with no treatment. 8 However, a rising or persisting high titer justifies the diagnosis and the institution of treatment. Symptoms and signs of prenatal infection usually appear within the first 3 to 4 weeks of life, and characteristically include a maculopapular rash, snuffles, mucocutaneous fissures, enlarged liver and spleen, and hoarse, aphonic cry. BuIlous lesions on the palms and soles are considered pathognomonic. Bone manifestations include osteochondritis, chondroepiphysitis, and osteomyelitis; pseudoparalysis may be a feature. Osteitis results in the characteristic saddle deformity of the nose. Later manifestations comprise mainly the so-called developmental stigmas: Hutchinsonian teeth, mulberry molars, enlarged frontal bossae, sabre shins, and scaphoid scapulae. Inflammatory lesions are of importance: interstitial keratitis, eighth nerve deafness, hydrarthrosis, etc. The occurrence of neurosyphilis constitutes one of the most serious manifestations leading to taboparesis and mental retardation. Studies in the field of serodiagnosis conducted within the past few years have shown the treponemal tests (Treponema pallidum immobilization, Treponema pallidura complement fixation, Reiter protein complement fixation, and the fluorescent Treponemal antibody tests) more reliable (e.g., more specific) indicators of the presence of asymptomatic syphilis than the reagin tests (Wassermann, Kolmer, VDRL, etc.). Of these more specific procedures, the Reiter protein complement fixation test is gaining wide acceptance because of its good duplicability and easy performance." Since the first use of penicillin in 1943, J~ the effectiveness of this therapy alone, in adequate dosage, has been proved by the absence of serologic and clinical recurrence in cases of early syphiIis, as well as by its
Volume 59 Number 4
efficacy in the prevention of prenatal infection. ;1 Experience with penicillin therapy emphasizes maintenance of continuous effective blood levels for from 7 to 15 days. The form of penicillin employed appears to be an individual matter: water-soluble penicillin G at frequent intervals; twice-weekly administration of procaine pencillin with 2 per cent aluminum monostearate ( P A M ) ; or a single injection of long-acting benzathine penicillin G. The need for convenient or ambulatory~ management has made PAM or benzathine penicillin G the therapy of choice. In infants and young children individualization is the rule. In hospitalized cases aqueous penicillin by frequent injection has been recommended to be continued over a period of 15 days, the total dose being 100,000 units to 400,000 units per kilogram of body weight. This dose may be administered in 120 individual injections 3 hours apart. There appears to be little advantage in total doses higher than 100,000 units per kilogram of body weight. Penicillin readily permeates the placenta from about the tenth week of gestation. This has been shown by studies in experimental animals by the determination of penicillin in fetal tissues and by healing syphilitic lesions in newborn infants following antepartum therapy. While a cure may not be effected in the mother, she may give birth to a normal infant, especially when dosage of the antibiotic is high. The infrequent failures following penicillin treatment usually result from inadequate treatment or from a fetus severely damaged before therapy was instituted, as when infection is discovered late in pregnancy, beyond about 30 weeks. For patients hospitalized during pregnancy a therapeutic regimen of aqueous penicillin is recommended, 40,000 to 50,000 Oxford units every 2 to 3 hours, with a total of 2.4 million units or more over a course of 7 to 12 days. In ambulatory patients, procaine penicillin G has been used successfully, 600,000 units once daily for from 8 to 10 days, with a total of 4.8 to 6.0 million units of penicillin. Sensitivity to penicillin may pose a prob-
Comments on current literature
lem, 12 and in some instances the enzyme penicillinase has been used as a therapeutic agent in the management of reactions. 12 In experimental animals and in human subjects, the parenteral administration of this enzyme results in the rapid disappearance of detectable circulating penicillin. In this connection a recent report by Greaves 1~ is of interest. An objective clinical analysis of the effect of penicillinase was made by determining the degree of spirochetal protection when penicillin and penicillinase were administered concurrently to syphilitic patients with dark-field positive lesions. The author reasoned that "if penicillinase destroys all penicillin, then Treponema pallidum will continue to survive in their chancres or moist eruptions. ''~3 Patients with dark-field lesions were divided into categories, one group receiving 600,000 units of penicillin in aluminum monostearate intramuscularly, preceded by 800,000 units of penicillinase parenterally; the corresponding control group received the same dosage of penicillin alone. Hourly dark-field examinations and penicillin blood levels were carried out. T. pallidurn disappeared from the lesions of both groups of patients with no statistical differences between the two. Penicillin blood levels dropped below the detectable range in the test group, and in some instances failed to rise when penicillin alone was resumed. Nevertheless, organisms disappeared from the lesions and healing occurred. Many patients showed serologic improvement. With respect to peniciltinase as a therapeutic agent in penicillin sensitivity reactions, the author concludes that this enzyme cannot be considered adequate therapy for life-threatening reactions, since penicillin may be suppressed but not neutralized. While the treponemicidal properties of erythromycin have been known for about 10 years, adequate clinical information concerning its oral use has been available only recently. Montgomery, Knox, and their associates ~4 have been interested in the possibilities of this antibiotic for a number of years and have published recently a report concerned with the use of erythromycin
C o m m e n t s on current literature
stearate a n d e r y t h r o m y c i n p r o p i o n a t e in the t r e a t m e n t of early syphilis. :4 Since large doses are r e q u i r e d for effective antisyphilitic t r e a t m e n t , the authors sought m i n i m a l effective dose levels. I n a study of 148 d a r k field positive patients, the use of 20 G m . of either e r y t h r o m y c i n stearate o r e r y t h r o m y cin p r o p i o n a t e distributed over a 10-day p e r i o d a p p e a r e d a d e q u a t e for the t r e a t m e n t of e a r l y syphilis. I n some instances e r y t h r o m y c i n p r o p i o n a t e , 500 mg., 3 times daily for 10 days (15 G m . ) , was effective. A recent composite r e p o r t on " T o d a y ' s V D C o n t r o l P r o b l e m '':~ published in booklet form contains valuable i n f o r m a t i o n a n d urges a g a i n t h a t the p r a c t i c i n g physician be on the alert for early signs of infection a n d t h a t he r e p o r t suspected cases i m m e d i a t e l y , especially a m o n g y o u n g people, since " t h e r e c o n t i n u e d to be outbreaks of syphilis in 25 states a n d 18 cities d u r i n g the present year. ''as R e c e n t statistics compiled in one u r b a n a r e a (Houston, Texas) indicate t h a t in the period, J a n u a r y 1960 t h r o u g h F e b r u a r y 1961, 22.4 p e r cent of the cases of prim a r y a n d s e c o n d a r y syphilis o c c u r r e d in the 15 to 19 y e a r age group, a n d 39.3 p e r cent in the 20 to 24 y e a r age group. :~ RUSSELL J . BLATTNER, M.D.
REFERENCES 1. Conference Report: A Current Look at Venereal Disease, Chicago, 1960: Brown, W. J.: Current Status of Syphilis in the United States, Pub. Health Rep. 75: 990, 1960. Wactor, P. R., Jr.: Case Finding in Chicago, Pub. Health Rep. 75: 993, 1960. Bohan, G. N.: New Haven's Court Clinic: A Casefinding Source, Pub. Health Rep. 75: 997, 1960. 2. Cohen, Morris M.: The Infectious Syphilitic Seeks a Diagnosis, Maryland State M. J. 9: 797, 1960. 3. Sciple, G. W., Montgomery, C. H., and Knox, J. M.: Diagnostic Problem Related to a "Biologic False-Positive" Serologic Test for Syphilis, New England J. Med. 263: 84, 1960. 4. Perry, H. O., Kierland, R. R., and Magath, T. B.: Clinical Problem of Syphilis Today, Minnesota Med. 39:717, 1956. 5. Beck, A. C., and Daily, W. T.: Syphilis in Pregnancy, Lancaster, 1938, Science Press Printing Company, p. 105. ~'
6. Moore, J. E.: The Modern Treatment of Syphilis, Springfield, II1., 1941, Charles C Thomas, Publisher. 7. Vogt, E.: Selective Filtration of Syphilitic Reagins Through the Placenta, Acta paediat. 43: 247, 1954. 8. Shaffer, L. W., and Courville, C. J.: The Effectiveness of Penicillin in the Prevention of Congenital Syphilis With a Note on the Effect of Cowpox Vaccination on the Serologic Tests of Seronegative Infants, Am. J. Syph., Gonor. & Ven. Dis. 36: 457, 1952. 9. Pariser, Harry: Sensitivity of Reiter Protein Complement Fixation and Standard Serologic Tests: Comparison and Correlation With Clinical Findings in Syphilis, South. M. J. 53" 1543, 1960. Portnoy, J., and Carson, W.: New and Improved Antigen Suspension for Rapid Reagin Tests for Syphilis, Pub. Health Rep. 75: 985, 1960. Fiumara, N. J.: Treponemal Tests in Diagnosis of Syphilis and Biologic False Positive Reactors, Pub. Health Rep. 75: 1011, 1960. Montgomery, C. H., Knox, J. M., and Surhland, S.: Fluorescent Antibody Test for Syphilis, J. Invest. Dermat. 35: 95, 1960. 10. Mahoney, J. F., Arnold, R. C., and Harris, A.: Penicillin Treatment of Early Syphilis: Preliminary Rept., J. Ven. Dis. Inform. 24: 355, 1943. 11. Platou, R. V.: Treatment of Congenital Syphilis With Penicillin, in Lcvine, S. Z., et al., editors: Advances in Pediatrics, Vol. IV, New York, 1949, Interscience Publishers Inc., p. 39. Ingraham, Norman, Jr., and Beerman, H.: The Present Siatus in the Treatment of Syphilis in Pregnancy and Infantile Congenital Syphilis, Am. J. M. Sc. 219: 433, 1950. 12. Brown, W. J., Simpson, W. G., and Price, E. V.: Reevaluation of Reactions to Penicillin in Venereal Disease Clinic Patients, Pub. Health Rep. 76: 189, 1961. Zimmerman, M. C.: The Prophylaxis and Treatment of Penicillin Reactions With Penicillinase, Clin. Med. 5: 305, 1958; Antibiotics Annual, N. Y., 1957-1958, p. 312. 13. Greaves, A. B.: Further Observations on Penicillinase, J. A. M. A. 176: 951, 1961. 14. Montgomery, C. H., and Knox, J. M.: Erytbromycin in the Treatment of Early Syphilis, A. M. A. Arch. Dermat. 80: 205, 1959. Montgomery, C. H., Knox, J. M., Sciple, G. W., and Vander Stoep, E. M.: Erythromyein in the Treatment of Early Syphilis, A. M. A. Arch. Int. Med. 107: 732, 1961. 15. Today's VD Control Problem: A Joint Statement: Pamphlet, March, 1961, New York, N. Y., American Social Health Association. 16. Nelson, Paul: Age Distribution in Primary and Secondary Syphilis, Reports From Houston Social Hygiene Clinic, Houston, Texas (personal communication).