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False-negative syphilis screening: the prozone phenomenon, nonimmune hydrops, and diagnosis of syphilis during pregnancy.

The prevalence of congenital syphilis is rapidly rising in several areas of the United States. Efforts to control the disease depend on the effectiveness of established screening strategies and treatment of infected pregnant women. False-negative test results hinder these efforts and leave the fetus at risk for acquiring congenital syphilis. Recently we encountered four cases of false-negative syphilis serologic results in women who gave birth to infants with congenital syphilis. The false-negative results were caused by the prozone phenomenon. The prozone phenomenon, seen during primary and secondary syphilis, occurs because a higher than optimal amount of antibody in the tested sera prevents the flocculation reaction typifying a positive result in reagin tests. Serum dilution is necessary to make the correct diagnosis. We recommend that for any pregnant woman with apparently negative syphilis serologic results in whom fetal compromise of unknown etiology exists, particularly nonimmune hydrops, nontreponemal testing should be repeated using serum dilutions to prevent a missed diagnosis of syphilis. We further recommend serum dilution as a routine procedure for all pregnant women in areas of high syphilis prevalence.

Adult

Syphilis among parturients at an inner city hospital: association with cocaine use and implications for congenital syphilis rates.

The frequency of positive cord blood rapid plasma reagin (RPR) tests among newborns at an inner city hospital and associations with maternal cocaine use, prenatal care, and adequacy of syphilis therapy were retrospectively assessed. The incidence of positive cord blood RPRs increased from 1.1% of all live births in 1985 to 3.4% in 1988. In 1987, 98 babies were born with positive cord blood RPRs; 86 of their charts were available for review. Four infants had false positive RPRs, and one patient delivered twins, leaving 81 mothers who could be evaluated. Almost 37% of these patients had had no prenatal care. More than 55% had inadequate or not therapy for syphilis. Of these, only 17.4% had prenatal care. Slightly more than 40% of patients acknowledged using drugs during pregnancy, 87.9% of whom used cocaine. Among the patients who used drugs, 75.8% received no prenatal care, in contrast to 10.4% of mothers who did not use drugs (p less than 0.001). It appears that drug use, particularly use of cocaine, is associated with low levels of utilization of prenatal services and inadequate therapy for syphilis. This may lead to increased risk of congenital syphilis in newborns.

Cocaine

Syphilis serology in patients with primary syphilis and non-treponemal sexually transmitted diseases in southern Africa.

The reactivity of a non-specific reagin (RPR) test and a specific treponemal (FTA-ABS) test were determined in 21 patients with primary syphilis, 430 patients with proven non-treponemal genital ulcerations and 719 patients with acute urethritis presenting at a clinic for sexually transmitted diseases in southern Africa. Excluding those 21 cases of primary syphilis, 358 of 1149 tests performed (31%) were found to be reactive by at least one test. The rate of false positive RPR tests was very low (0.02%). Significantly higher rates of seropositivity were detected in patients with genital ulcerations than in patients with acute urethritis. The highest rates were detected among patients with proven lymphogranuloma venereum (34% RPR positive, FTA-ABS positive; 19% RPR negative, FTA-ABS positive). The geometric mean titres (GMT) of positive RPR tests in non-treponemal infections were found to be lower than in darkfield positive cases of genital ulcer disease.

Acute Disease

[Results of modern syphilis serology in blood donors, at the same time a contribution to spontaneous healing of syphilis].

261 out of 336 845 blood donors have been shown to had undergone a syphilitic infection. About 52 per cent of these donors have had knowledge of their infection and of specific treatment of the disease. In about 43 per cent of the investigated cases the T. pallidum infection has had probably an inapparent course and healed without treatment, that means spontaneously. In times with an increasing number of infections by T. pallidum blood banks have to look intensively for donors which are in the first stage of primary syphilis. For identification of these people and for the differentiation between antibodies against T. pallidum and apathogenic treponemes the use of a TPHA-ABS test is discussed.

Antibodies

Role of IgG fractions with high isoelectric points in the thymol turbidity test in syphilis. Evidence for an increase in basic IgG in early syphilis.

It is demonstrated that IgG fractions with isoelectric points above 7.6, isolated from pooled syphilitic sera, are able to elevate the thymol turbidity. The effect increases with increasing isoelectric points of the isolated fraction. IgG from individual syphilitic patients exerts a stronger effect on the thymol turbidity than normal IgG. It is concluded that elevated amounts of these basic immunoglobulins are present in the sera of syphilitic subjects.

Electrophoresis

The syphilis epidemic in Connecticut: relationship to drug use and prostitution.

Syphilis rates in Connecticut increased four-fold between 1986 and 1988. During this time there were also signs of a large increase in cocaine use in the state. We studied links between these parallel trends in drug use and syphilis by examining two sources of data: information collected during syphilis case interviews and information from the syphilis screening program at the state's prison for women. As syphilis rates rose, there were large increases in the percentage of women with syphilis who reported prostitution or illicit drug use. In 1988, 41% of women with syphilis reported cocaine use, and 19% reported prostitution; 21% of male heterosexuals with syphilis reported cocaine use, and 31% reported sexual contact with prostitutes. Among incarcerated women, syphilis infection was frequent: of 113 women incarcerated for possession of illicit drugs in 1987-88, 7% were found to be infected with Treponema pallidum, and of 187 women incarcerated for prostitution in these years, 14% were infected. In both groups of incarcerated women studied, cocaine users had the highest syphilis rates, and those who administered drugs nonintravenously had rates similar to those who administered drugs intravenously. We concluded that the syphilis epidemic in Connecticut is related to the increase in use of illicit drugs (primarily cocaine) and that female drug users are at very high risk of syphilis regardless of whether they administer drugs intravenously or nonintravenously. We recommend that syphilis control efforts focus on wider serologic screening and early treatment of drug users, prostitutes, and their sex partners.

Connecticut

Enzyme-linked immunosorbent assays for detection of immunoglobulin M to nontreponemal and treponemal antigens for the diagnosis of congenital syphilis.

Sera from newborn infants born of mothers with a high risk of syphilis were examined for immunoglobulin M (IgM) antibodies in two different enzyme-linked immunosorbent assays (ELISAs), using either purified flagella from Treponema phagedenis biotype Reiter or the Venereal Disease Research Laboratory (VDRL) antigen as the antigen. All sera were also examined by the fluorescent treponemal antibody absorption (FTA-ABS) test for IgM. Three different groups of patients were studied. Group 1 consisted of 84 women and their newborn infants from a high-risk population for syphilis. Congenital syphilis was diagnosed in one child who had an IgM-positive cord blood specimen in both the ELISA and the FTA-ABS test. Group 2 consisted of 10 mothers and their newborn children. All mothers had positive syphilis-screening tests, and all children had signs of congenital syphilis. All but one child had positive IgM tests. Group 3 consisted of 15 mothers and their newborn children. These mothers had been treated for syphilis late in pregnancy, and all had a positive screening test at delivery. Two of the children had positive IgM tests, probably caused by reactivity after late intrauterine treatment of congenital syphilis. The specificities of the IgM tests were high when evaluated with sera from newborn children without signs of congenital syphilis. Even though IgM rheumatoid factor was found in all of the children tested with definite congenital syphilis, the rheumatoid factor did not cause false-positive results in either the VDRL ELISA or the flagellum ELISA. No significant IgG-IgM competition was noticed in the ELISAs. This study also confirmed that IgA antibodies do not cross the placenta; most newborn children with congenital syphilis were positive in the VDRL ELISA for IgA. Both the VDRL ELISA and the flagellum ELISA are very useful in the diagnosis of congenital syphilis and may be substitute for the FTA-ABS test. The VDRL ELISA for IgM will be especially useful in developing countries with a high incidence of congenital syphilis.

Adult