Major. M.P.Vora, M.B.B.S., D.V.D.,
Ex. Hon. Sr. Venereologist, St. George’s Hospital, Bombay
Current Medical Practice
A monthly journal devoted to modern medicine and surgery
Volume .13, Number-4 of April 1969
Syphilis is an endemic disease in all parts of the world and mostly involves the younger age groups between 18 to 35 years of age. For centuries, it has crippled and killed people protected by ignorance, shame, superstition and secrecy. It is like a ‘chameleon’ and can produce symptoms resembling those of numerous other diseases. Again and again it has fooled the public and has shown itself to be the most deceptive of all diseases. In its long history, it has fooled doctors, who thought they had found an answer. And this warning has once again found to be real one.
Penicillin which has been considered specific and effective for syphilis, has now found to have an effect on only growing organisms in early syphilis, when their multiplication is at its maximum, but not so late in syphilis, when Tr.pallidum are few and far between and do not actively multiply. Hence in late syphilis, penicillin has probably no effect Tr.pallidum and they may persist in patients even after adequate treatment. In such patients, the S.T.S. may be negative but Tr.pallidum can be detected by F.A. technique. They may produce lesions or remain stable host parasites until the use of steroids, when this balance may be upset. This is a stunning revealation of the recent work on therapeutics in syphilis. The test of time and experience seldom justify the enthusiasm which new drugs so often arouse.
A challenge to the efficacy of penicillin as a Treponema pallidicidal agent was made by Collort (Ann. Inst. Pasteur 102-693-704, June 1962) and Yob (Arch. Derm. 19: 379-389 April 1965). They showed that Tr.pallidum survive adequate treatment of late syphilis. J.Lawton Smith (J.A.M.A., March 27, 1967, page 980, Vol. 199, No.13) showed the presence of Tr.pallidum in aquous humor and the C.S.F. (though cell count and protein percentage were normal) by Fluoroscent Antibody Technique in cases of neurosyphilis, whose routine blood tests for syphilis were negative but in whom specific treponemal test were positive.
From public health point of view, syphilis should be regarded not one disease but two diseases. Early syphilis with duration of 2 to 4 years represents an acute infectious condition, providing the greatest risk of transmission of infection from one person to another. As the years pass, its infectivity and severity become less & less. Untreated late syphilis which is more than 4 to 5 years old, on the contrary, is not a great problem; it is non-infectious for all practical purposes. A concentrated attack on early syphilis will break the chain of infectiousness and reduce the incidence of syphilis (fresh infection) and ultimately the reservoir of infections in the population. This recognition of division of syphilis into two separate entities is of prime importance from the point of control of syphilis.
Syphilis is due to the entry of a microorganism Tr. pallidum into the skin or mucous membrane. It resembles a cork-screw and has a life cycle of 30 hours. Once the germs have entered the epithelial layer at the site of inoculation, they quickly multiply and spread in the body through lymphatics and blood vessels. The disease becomes generalised in about 24 hours to 3 days, long before any lesion of syphilis become evident. The seeds of potential late syphilis are shown quite early. Hence syphilis is generalised at first, subsequently localised and dispersed. It is unique in the benign character of the illness during the period of blood stream invasion. Despite the slow tempo, the disease if untreated eventually cripples and kills more than 25 percent of the individuals afflicted.
Tr.pallidum organisms are present in early lesions of syphilis and are transferred directly in a liquid vehicle from host to host. Intimate body contacts such as kissing or coitus provide appropriate conditions for the transfer of the liquid infectious material. One comes across occasionally a case of indirect transmission of infection. A person transmitting the disease need not necessarily suffer at that time from obvious syphilitic lesions of the genitalis or the body. Acquired syphilis, after an incubation period of about 2 weeks to 3 months, presents a primary sore called the chancre at the site of the inoculation. In about 50% of the females and 30% of the males, the primary sore either fails to appear or remains unrecognised by the infected person. An unique feature of early syphilitic infection is the fact that it usually produces virtually no symptoms of systemic disease inspite of the presence of Tr.pallidum and wide-spread metastatic lesions. Because of the absence of systemic symptoms, the patient with syphilis may not seek medical care during the period of early infectiousness. As stated, the initial lesion appears any time between 10 to 90 days after the day of infection. There is nothing fundamentally characteristic about the appearance of chancre. The precise diagnosis can only be made and confirmed, not by naked-eye examination but by actual demonstration of Tr.pallidum in the lesion by means of dark-field microscopy or Fluorescent Antibody Technique. Any or all the so-called typical characters of a chancre may be so modified by the location of the lesion, its duration and presence of an additional infection, that no typical picture is consistently available for inference. This is very true in the early stages of a chancre when it must be diagnosed.
The primary lesion usually appears on the skin or mucous membrane of the genitalia. In the female, external genitalia are less frequently involved than the cervix; the primary lesion therefore, often goes unrecognised. It does not itch or pain unless it is secondarily infected. It persists for a few weeks and then heals by itself. It is usually accompanied by moderate enlargement of the regional lymph nodes. The regional lymphadenopathy persists for a few months.
Since early diagnosis and treatment of syphilis is of prime importance from the point of “cure” and the control of the spread of infection, it is of the utmost importance to subject the material from every lesion, as a rule, to the dark-field microscopy or fluorescent antibody technique. However, both the dark-field procedure and F.A.T. are probably the most neglected of all examinations for syphilis. It is unwise to wait for the development of the serologic positivity or the typical clinical picture of the disease. To promote the successful detection of Tr.pallidum in the lesion, application of antiseptics to the sore or the use of antibiotics in any form must be withheld till the necessary formalities are completed. From this point of view, routine use of normal saline as a cleansing agent is of distinct value.
After a period of 4 to 6 weeks of the appearance of the chancre, recurrent attacks of generalization, metastatic lesions in different parts of the body and their resolution continue to occur till the immune forces of the host have attained maximum immunity or effectiveness. The period needed for the development of this state of relative immunity varies greatly from a few months to several years. In the untreated patient, recurrences of infectious episodes seldom occur after the infection has been present for 2 to 4 years and most unusual after the fifth year. Hence the development of infectious state or appearance of new lesions in the previously uninvolved areas is not to be expected or anticipated, subsequent to the first five years of the initial infection. However, administration of subcuartive or irregular antisyphilitic therapy in early syphilis prevents the development of refractoriness to dissemination of the organisms. Dangers of such a therapy therefore will be apparent. Involvement of the cardiovascular and nervous systems is more frequent in syphilitics who receive either irregular or inadequate treatment than those who receive no treatment at all for early syphilis. The process of resolution of metastatic lesions is never complete.
Infectious lesions of early syphilis vary widely in character and extend. The primary lesion is frequently but by no means invariably accompanied or followed by the development of metastatic lesions of the skin and the mucous membrane. Although the cutaneous and mucosal lesions frequently coexist, they may also occur independently of each other. With the exception of a vesicular eruption any type of skin rash may develop. The distribution of eruption is usually generalised and involves palms, soles, and the face in addition or independent of the skin of the trunk and extremities. Mucous membrane shows whitish patches, simple eruptions or moist papules symmetrically especially at the muco-cutaneous junctions. The areas which are warm, moist and subjected to friction are common site for the development of condylomata lata. A solitary lesion at the muco-cutaneous junction i.e. angle of the mouth or anus is likely to be missed or overlooked easily. All the cutaneous and mucosal lesions are teaming with tr. pallidum and highly infectious. Associated with generalised lymphadenitis, the picture is characteristic. By this time, the blood serum of the patient develops antibody-like substance called ‘reagin’ which invariable gives serologic positivity. Syphilis may attack any organ or tissue in the body, but most of the fatalities result from the involvement of the cardiovascular and nervous systems. It is worthwhile to remember that any or all manifestations of syphilis may be omitted or go unrecognised on account of the liberal and wide-spread use of penicillin for many diseases other than syphilis. Now a day’s clinically atypical forms of syphilis are on the increase because of the short-term antibiotic treatment given to the patients during the incubation period of the syphilis. Here-in lies the greatest danger of being misleads unless the practitioner has a high index of suspicion.
The process of resolution metastatic lesions in the body is generally incomplete; one or more foci persist in various locations. When these foci are hidden beyond diagnostic reach, the state of the infection is called “latent” or in apparent. It will be clear that normal cerebrospinal fluid, and the fundi in addition to the absence of any obvious lesions are prerequisites or ‘sina qua non’ for the diagnosis of the latency. The latent syphilis may continue for a decade or more years. There is evidence of the presence but not of the location of the syphilitic foci. As the surface lesions are not present, the individual cannot transmit theoretically the infection at this stage. However, a recurrent generalization of the infection may occur at any time until the forces of resistance have fully developed, such a person is likely to develop metastatic lesions, which may or may not be infectious, depending on whether the surface of the body is involved and the possibility of re-dissemination has been remote. The early latent syphilis may return to the infectious or metastatic variety. Once the infection gets stabilized, the disease enters into either late latent syphilis or asymptomatic neurosyphilis.
The chief features which distinguish early from late syphilis are the presence of numerous Tr.pallidum in the lesions, the wide-spread involvement of the body, intense titer of the S.T.S. and absence of necrosis.
A few weeks after the appearance of a chancre, the host elaborates reagin which can be detected by the S.T.S. The highest dilution of the serum which contains detectable reagin is called titer of reaction. Reagin is not a true antibody and capable of giving non-specific reactions. Hence the S.T.S., though quite reliable, gives only a presumptive evidence of syphilitic infection. The interval between the onset of infection and the appearance of detectable reagin in the serum varies greatly between 4 to 6 weeks and in some cases it may take as long as 3 months. Normally both the V.D.R.L. (flocculation test) and the W.R. (complement fixation test) should be done and one of these should be a quantitative to act as a base line. Because of the distinct value, quantitatively tittered S.T.S. have come in vogue. Once positive, The S.T.S. shows rising or high titer and does not spontaneously revert to negative for many years. When the S.T.S. is positive but not supported by history and clinical findings, it is necessary to repeat the test or use the specific or verification test such as the Reiter Protein Complement Fixation Test (R.P.C.F.T.) or Fluorescent Treponemal Antibody Test (F.T.A.T.). In early syphilis, they may become positive before the S.T.S. They are specific and reliable. The F.T.A. Test is particularly useful in the serologic diagnosis of early syphilis, in the primary stage, when attempts to detect Tr.pallidum in the primary lesion have failed.
The main principles to be observed in the treatment of early syphilis are :- (1) Diagnose early and precisely begin treatment at the very moment. (2) Use adequate dosage over an adequate period. (3) Follow-up every case carefully for at least 18 to 24 months (4) Investigate contacts and treat them.
For the treatment of syphilis, penicillin G is the drug of choice and the most satisfactory agent at present available. Its dosage and duration have been precisely defined. It is recommended that an effective blood level of 0.03 units per ml should be maintained continuously for a minimum period of ten days. With this guide line, the average course for early syphilis consists of giving a single daily dose of 600,000 units of procain penicillin-G I.M. on ten successive days. Some authorities have recommended (a) two I.M. injections of 1.2 mega units of Benzathin penicillin with an interval of 3 to 5 days or (b) 2.4 mega units of Benzathin penicillin I.M. at one session. This is probably the shortest, most intensive and safest course hether-to available for syphilotherapy. In mass treatment, a single session therapy is eminently suitable for the eradication of the disease, provided rigid follow-up is carried out in every case. Results of this one or two shot therapy will need long-term study in a large number of patients to find whether it gives a permanent cure or a temporary one to be followed by a relapse. In these therapies, there is a snag difficulty to come over. It has been found that all patients do not attain effective blood concentration or level relative to the dosage given and the body weight. Wide variations in the blood level and its duration following penicillin administration are common and beyond control.
In view of these facts, it is advisable to err on the safer side and to prolong the treatment of early syphilis for a period more than a few weeks in order to induce “cure” or permanent latency in a small percentage of patients, who do no to attain “cure” following the standard or recommended treatment. Introduction of long-acting penicillin like benzathin and benethamine has made this task very easy and safe.
After the completion of treatment, every patient should be subjected to careful and regular follow-up for over a period of two years. Consistently negative findings on physical health, serology, the C.S.F. etc. must be ascertained before announcing the patient cured from the infection.
A vaccine against syphilis is on the way. Dr. W.J. Brown, the chief of venereal disease section of Atlanta, Georgia has successfully developed a vaccine from Treponema carateum of Pinta. T.carateum is morphologically identical with Tr. pallidum, and capable of inducing cross immunity against syphilis. Tests have shown promising results.