SEROLOGIC TESTS FOR SYPHILIS

By

Major. M.P.Vora, M.B.B.S., D.V.D., I.M.S. (Rtd.)

Indian Medical Record

A monthly journal of Public Health, Tropical Medicine and Surgery etc .

Volume LXXXIII, Number-5 of May 1963

Pages 62-65

This article was solely contributed to Indian Medical Record

Serologic tests for syphilis when read in conjunction with the history, clinical signs and symptoms are one of the most helpful aid to diagnosis. However, when the history and clinical evidence are opposed to positive result of serologic test for syphilis, diagnosis for syphilis must not be made at once on this flimsiest evidence. If the patient is suffering from other condition such as yaws, leprosy, scarlet fever, malaria, active tuberculosis, jaundice, acute fever, lymphogranuloma venereum, infectious mononucleosis, hepatic insufficiency or urticaria pigmentosa, it is possible to obtain a positive S.T.S.; but in great majority of cases it is only a weak positive reaction which becomes negative in the course of 2 to 3 months. If one is unable to discover the cause for the non-specific serologic reaction, the cerebrospinal fluid should be examined. If the fluid is normal, patient should be followed for some time with serologic tests. There is only two laboratory procedures i. e. Treponema Pallidum Immunization or Reiter’s Protein Complement Fixation tests, of established value, for the differentiation of true and false serologic reactions for syphilis but they are not freely available in the country.

The serologic test for syphilis does not become positive in the first few weeks of syphilis. It usually becomes positive between 3 to 6 weeks after the syphilitic infection has been contracted. In a small proportion the test may not become positive until three months after the onset of the infection. It is invariably positive in the secondary syphilis. No matter how experienced the doctor nor how characteristic the primary lesion, the diagnosis of early syphilis cannot be made with certainty except by dark field microscopy the value of which lies in its ability to demonstrate Tr.pallidum long before blood reaction becomes positive. Less certain but generally acceptable evidence is the persistently positive serologic test for syphilis in a patient who presents lesions which have the appearance of early syphilis. The proof of diagnosis of early syphilis rests entirely on laboratory procedures. In every patient who has been exposed to the risk of infection or where dark field microscopy for Tr.pallidum is negative, serologic tests for syphilis should be carried out at regular intervals until ninety days after the suspected exposure. The negative S.T.S. during the course of the observation time, do not exclude the presence of early syphilis, but as the follow-up continues from week to week, the significance of negative S.T.S is steadily increased and the chances that the individual is developing syphilis becomes increasingly remote. It is important to remember that a negative S.T.S. in the first few weeks of infection does not prove the absence of syphilis. Similarly a negative test after some treatment does not necessarily indicate that the patient is completely cured or he will not be subjected to a relapse involving vital organs.

Occasionally a negative reaction may be met with in a known case of syphilis. In assessing the diagnostic value of the test, one must carefully differentiate between the treated and untreated cases of syphilis. In treated cases it is important to remember the interval which has elapsed since the last treatment was given. In a treated case, one has to bear in mind the wide variation in the duration of positive reaction; the blood may remain positive as long as six months in some cases. However, quantitative titration of the strength of the reaction, especially when steadily diminishing, is indicative of good response to treatment and encouraging. In an untreated case, little importance can be placed on a weak positive result. It can never be considered diagnostic in the same way as one would be justified in assuming a strong positive reaction in the untreated case, as a definite evidence of syphilis.

Serologic diagnosis of syphilis assumes a great importance depending on the type of syphilis which is under consideration. In the early infectious syphilis, the serologic tests are distinctly secondary in importance to demonstration of Tr.pallidum by dark field microscopy. In certain varieties of cardiovascular syphilis and neurosyphilis the serologic tests are chiefly of value as an additional confirmation of the clinical diagnosis. In the great bulk of infections seen by the practitioner, however, the diagnosis of syphilis can be established only by serologic testing. For, approximately 80% of the syphilitics seen by him are in the latent stage i.e. there is undoubted serologic or historical evidence of syphilis but not the outward evidence of location of syphilitic lesions in the body. It is essential therefore, that S.T.S. be made part of the routine of the initial examination of every patient. It is equally important that the results of such tests be submitted to proper interpretation; for sera from non-syphilitics will occasionally give rise to false positive reactions for syphilis. When the practitioner discovers a positive S.T.S. in a patient who presents no history or clinical evidence of syphilis, certain steps should be taken before the final diagnosis of syphilis is made and the treatment instituted. They are:

• Question the patient in a language which he can understand to find out history, clues pertaining to syphilis or conditions likely to give false positive reactions.

• Examine him carefully for possible manifestations of syphilis. Special attention should be given to the skin, oral cavity, eyes, genitalia, cranial nerves, tendon reflexes, ophthalmoscopy, mucous membrane and mucocutaneous junctions, lymph nodes, joints and bones etc.

• Enquire about the previous serologic tests and antisyphilitic therapy and their results.

• Question him about recent illness, immunization against small-pox, malaria, blood donation or acute fever.

• Make another careful physical examination for detecting prenatal or late acquired syphilis. Special attention is given to cardiovascular and nervous systems, X-ray, C.S.F, Ophthalmoscopy etc.

• Repeat the S.T.S. and send the samples of the same specimen to two different laboratories. Quantitative serologic tests are to be preferred to qualitative serologic tests.

• Examine the partner, contacts and siblings.

• If available employ T.P.I. Test or R.P.C.F. Test to differentiate the false and true positivity.

• Evaluate all the information thus obtained.

All the steps may not be always necessary in every case. If none of these investigations disclose anything definite, it will be justifiable to with-hold the diagnoses till further tests are carried out over a few weeks.

If the S.T.S. is repeatedly reported as strongly positive, and there is no history of recent immunization or conditions which are likely to give rise to false positive reactions, there is sufficient evidence for the diagnosis of syphilis, regardless of the lack of historical or clinical evidence of syphilitic infection. The problem of the individual with recent infection is relatively simple. The performance of quantitatively titrated serologic test for syphilis is of definite value during the period of observation. If the test becomes, especially in the second or third decade of life, consistently positive with steady increase in the titer, it indicates any early infection. In an older individual who presents irregular serologic pattern, the possibility of syphilitic infection of many years’ standing cannot be excluded. Serologic tests for syphilis especially quantitatively tittered, have a distinctive value not only in the diagnosis but also in assessing the response to treatment and predicting the impending relapse. Hence they should have preference over qualitatively tittered S.T.S. In a small proportion of adequately treated syphilitics, minor fluctuations in the titer, due to day-to-day variations in the sensitivity of the serologic tests in the laboratories are not uncommon, and have no significance. Only a change from complete negativity to complete positivity or persistently rising titer can be considered as a definite evidence of sero-relapse or failure of treatment. Although clinical relapse does not invariably accompany or follow serologic relapse, a correlation between the two phenomena is so constant and frequent that they have an identical significance in terms of therapy.

Sero-resistance is a well defines phenomenon especially in the late syphilis where the process of sero reversal may take many years. If the titre gets stabilized at a low level, there is nothing to worry. But it is important to exclude an instance of overlooked neurologic, cardiovascular or other complicating disease. When serologic tests are positive at higher titer, say 1: 64 to 128, or show rising titer, it is an indication of active progressive lesions of syphilis although undetectable by means at one’s disposal. The finding of a negative S.T.S. constitutes a strong evidence against the diagnosis of osseous syphilis or gummata.

The presence of the pregnant state is of importance in the laboratory evaluation of syphilitic infection because of the suppressive effect which pregnancy may exert on the development of syphilitic lesions or serologic titer. The cutaneous lesions of syphilis are rarely observed in a pregnant woman in spite of spirochetemia or generalised infection. The titer of the S.T.S. may be conceivably diminished likewise. Thus a weakly positive S.T.S. in a pregnant woman requires usually intensive investigations before it can be dismissed as non-specific reaction.

A positive S.T.S. on the cord-blood does not necessarily mean that the infant has syphilis. Such a test may be positive due to reagin present in the mother’s blood. Subsequent tests should reveal, if the infant is having an active infection, an increasing amount of reagin in the infant’s blood. IF they show progressive decline in the amount of reagin or become negative, it is evident that the infant is free from infection. Positive S/T.S after the second month are usually regarded as conclusive evidence of infection. If the S.T.S. is negative at birth, it should be repeated at regular intervals till adolescence to make sure that there is no infection. The S.T.S. is usually positive and relatively unaffected by antisyphilitic treatment in children and adults who were infected before birth. Ignorance of this fact i.e. sero-resistance is a usual occurrence in this group, frequently results in over-treatment. The titer of S.T.S. may fall gradually upto 3 rd or 4 th decade of life. Thus one will occasionally come across adults who present clinical evidence suggestive of prenatal syphilis yet whose serologic tests are negative or intermittently positive with low titer. These transient serologic abnormalities may be erroneously classified as biologic false positive reactions unless the residuals of the prenatal syphilitic infection are disclosed by a careful examination. For confirmation one may have to examine the mother and other siblings. When one suspects but cannot prove that the latent infection in an adult patient was acquired before birth, it is advisable to regard it as having been recently acquired.