The biological false positive reaction to serological tests for syphilis.

Acute and chronic biological false positive reactions to serological tests for syphilis are discussed. Three cases are presented, one showing an acute and one a chronic reaction, and one in which it was not possible to determine if the reaction was acute or chronic. Once a biological false positive reaction is found, serum from the patient should be tested at intervals for at least six months to determine if the reaction is acute or chronic. If a chronic reaction is found the patient should then be investigated to find the underlying cause. Problem sera from 753 patients are reviewed. Biological false positive reactions were shown by 47 sera and 257 sera gave results indicating they came from patients infected with syphilis. The reactive sera were divided into four groups: sera from blood donors, antenatal patients, cases of recent vaccination, and a miscellaneous group. It was found that in the first three groups the number of sera from patients showing biological false positive reactions was equalled or exceeded by the number showing syphilitic reactions. Biological false positive reactions in sera from cases of lepromatous leprosy and in sera from the inhabitants of the Okapa region of New Guinea are also discussed. It is concluded that sera which give reactive results to reagin detection tests for syphilis and come from patients known to have conditions which cause acute or chronic biological false positive reactions should never be dismissed as such. Experience has shown that a number of these sera will give reactive Treponema pallidum immobilization test results, that is, they come from patients who have or have had syphilis.

An immunofluorescence method for the diagnosis of primary syphilis using an absorption technique.

An immunofluorescence technique for demonstrating Treponema pallidum in fixed films made from suspected chancre exudate is described. The method used is basically a reversal of the fluorescent treponemal antibody absorption test. It makes use of the fact that by using a syphilitic serum from which group antibody has been absorbed by an extract of Reiter treponemes, leaving only specific antibody, Treponema pallidum can be indentified. Neither the non-pathogenic genital treponemes nor mouth treponemes showed any fluorescence when tested by the technique described. All the reagents used in the test are available commercially, thus placing it within the scope of any laboratory with suitable fluorescence equipment. In the present state of knowledge of the treponematoses, this technique would seen to be the most accurate means of diagnosing primary syphilis because it permits the specific identification of Treponema pallidum in chancre exudate. It has the advantage over the dark-ground method that fixed films can be sent to the laboratory.

Chronic biological false-positive reactions to serological tests for syphilis in blood donors.

Problem sera from 375 blood donors were investigated for biological false-positive reactions to serological tests for syphilis. Problem sera are those sera in which submitting laboratories have found a reactive result to a screening test for syphilis. On each serum a cardiolipin Wassermann reaction, a Venereal Disease Research Laboratory test, a Reiter protein-complement fixation test, a Treponema pallidum immobilization test, and a fluorescent treponemal antibody absorption test were performed. Of the sera 49.9% were found to be non-reactive in all five tests, 28.8% gave results indicating a diagnosis of syphilis, and 21.3% showed biological false-positive reactions. There were 80 sera from blood donors which gave biological false-positive reactions. A further specimen of serum from 67 of these donors was tested after an interval of a minimum of six months. Sixty-six of the sera showed chronic biological false-positive reactions. Some donors were only found reactive for the first time after they had given very many donations of blood. It is concluded that sudden blood loss, as in blood donation, appears to stimulate the production of excess reagin in certain individuals, causing a chronic biological false positive reaction to serological tests for syphilis. This may only appear after several blood donations have been made.

The rapid plasma reagin (circle) card test in biological false positive and leprosy sera.

The rapid plasma reagin (RPR) circle card and the Venereal Disease Reference Laboratory (VDRL) slide test results were compared on a group of sera known to show biological false positive (BFP) reactions to reagin detection tests for syphilis. The RPR test was more specific than the VDRL test on the sera selected, ie, it gave fewer false positive results than the VDRL test. However, in a group of presumed normal sera, the RPR test gave BFP reactions while the VDRL test gave none. The RPR test gave fewer BFP reactions than the VDRL test in 269 sera from patients with lepromatous leprosy.

The Treponema pallidum haemagglutination (TPHA) test in biological false positive and leprosy sera.

The Treponema pallidum haemagglutination (TPHA) test was carried out on 274 sera known to show biological false positive reactions to reagin tests for syphilis. The Treponema pallidum immunization (TPI) and fluorescent treponemal antibody absorption (FTA-ABS) tests were non-reactive on all these sera. Thirty-one or 11.3% showed reactive results in the TPHA test. Sera from 267 people who had lepromatous leprosy were also tested in the TPHA test. Fourteen sera were reactive in the TPHA, TPI, and FTA-ABS tests and were from people who had both syphilis and leprosy. Biological false positive reactions were shown by 26 of the leprosy sera, of which three or 11.5% were also reactive in the TPHA test. A further four sera in the leprosy group were reactive only in the TPHA test. The possible cause of false reactive TPHA test results is discussed. It was concluded that where reagin and TPHA tests are reactive in a person who has no history or clinical signs of syphilis, the serum should be referred for TPI and FTA-ABS testing.

An analysis of 340 cases of syphilis diagnosed in the laboratory in six months in 1973.

Between July and December, 1973, 340 new cases of syphilis previously unknown to the laboratory were diagnosed on the results of serological tests. The male-female ratio was 2-5 : 1. Homosexually acquired infections accounted for 34-3% of cases of syphilis in males. The cases were grouped into primary, secondary, latent and late stages of syphilis according to history, clinical signs and serological test results. Cases in each stage were subdivided into age groups. Primary and secondary syphilis (that is, the early infectious stages) occurred in 56 males and 23 females under 29 years of age. In 41 of the males (73-2%) this infection was homosexually acquired. The figures from this analysis show similar trends to those available in the United Kingdom.

Treponematosis in the eastern highlands of New Guinea.

Serological tests for treponemal disease were undertaken among the inhabitants of 10 census units in the Eastern Highlands of New Guinea. Many sera gave reactive results to some or all of the tests performed. To exclude biological false positive reactions the Treponema pallidum immobilization (TPI) test was carried out on each serum, the results being taken to indicate the presence or absence of treponemal disease in the individual. Clinically, leprosy and malaria were rare and no cases of active yaws were seen. Some middle-aged people showed clinical evidence of old yaws infections. The prevalence of treponemal disease in the census units varied from 3.9% to 79.2%, males having a higher prevalence than females. The children under 15 years showed no serological evidence of treponemal disease in all but 3 units, in which the prevalence ranged from 14.3% to 40%. It is concluded that the treponemal disease involved was yaws. Special interest lies in the non-infected children and adults who have no relative cross-immunity from yaws in a country which is rapidly developing.

Treponemal serology and blood groups on Bali island, Indonesia.

As part of a multidisciplinary study of the population of Bali, Indonesia, 2452 blood samples from people of both sexes were tested for treponemal infection and blood groups. Analysis of blood groups of the 81 patients reactive to the Treponema pallidum immobilisation (TPI) test, who were considered to have latent or inactive yaws, compared with a control group of 552 healthy Balinese, showed that the ratio of MM to MN and NN phenotypes was 2.25 times higher in the patients than in the controls (chi 2(1) = 10.2, p less than 0.005). A speculative hypothesis is that yews infection gives people with the MM phenotype a lower selective fitness. This hypothesis could explain the low prevalence of the M gene in the Australo-Melanesian populations.

Treponemal infection in the Australian Northern Territory aborigines.

For many years, a moderate to high prevalence of positive reactions to standard tests for syphilis (STS) has been found in sera from the aboriginal inhabitants of the Northern Territory of Australia. In the survey reported here, people living in 18 areas of the Northern Territory were sampled to determine if the positive STS results were due to treponemal infection and, if so, to what extent this was endemic syphilis, yaws, or venereal syphilis. The results of the Treponema pallidum immobilization test were taken to indicate the presence or absence of treponemal disease in the subject. Clinically, no cases of active treponemal infection were seen, though findings on old infections were difficult to interpret in the older age groups. The prevalence of treponemal infection varied from 3.4% to 58.0% in the areas tested. No serological evidence of treponemal infection in children under 15 years of age was found in 6 areas, while in 12 areas it varied from 2.2% to 32.6%. Sera from 60 people who had no clinical signs of treponemal infection gave high-titre CWR and VDRL test results. It was concluded that yaws, endemic syphilis, and probably venereal syphilis are to be found in the aboriginal population.

Treponemal serology on Bali Island, Indonesia.

As part of a multidisciplinary study of the population of Bali, Indonesia, treponemal serology was carried out on 2452 serum samples from subjects of both sexes. Sera reactive to the Treponema pallidum immobilisation test (TPI) were found in 81 (3.3%) subjects with a male prevalence of 4% and a female prevalence of 2%. All the reactive sera were from villagers. Of 1118 students sampled in various towns, none had reactive TPI tests. The prevalence of reactive sera varied greatly from one village to another; up to 50% of the sera examined were reactive. Geographical and socioeconomic analyses of the data show a strict correlation between poor socioeconomic status and high reactivity rates to the TPI test. Fifty-seven per cent of all the reactive sera originated from subjects living in two districts where yaws had recently been reported. Only three of the 1406 subjects, aged 15-29 years, had reactive sera. The reactivity rate steadily increased in the age groups 30-44, 45-59, and 60 years and over. Biological false-positive reactions occurred in 3.8% of the sera tested.