Tests for treponemal antibody in CSF.

We studied the potential usefulness of CSF treponemal tests in the diagnosis of neurosyphillis. The CSF was tested with the microhemagglutination test for Treponema pallidum (CSF-MHA-TP test) and with the CSF-FTA test by using undiluted CSF and CSF diluted in saline and in sorbent. In a prospective evaluation, of 177 nonsyphilitics, none had reactive CSF-MHA-TP tests and only one had a reactive CSF-FTA test. However, five of 15 syphilitics with no other evidence of neurosyphilis had reactive CSF-FTA tests. The CSF-FTA test reactivity appeared most likely when the titer of the serum FTA test was high. In a retrospective evaluation of syphilitics with reactive CSF-FTA tests, similar patterns of reactivity occurred in patients with and without other evidence of neurosyphilis. Without other supporting clinical or laboratory data, the diagnostic value of a reactive CSF-FTA test is unknown.

Prevalence, incidence, and correlates of syphilis seroreactivity in multiethnic San Francisco neighborhoods.

To examine the extent of infection with syphilis in an inner-city community, we determined the prevalence, incidence, and correlates of syphilis seroreactivity in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. One thousand seven hundred seventy single men and women aged 20 to 44 were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Syphilitic infection was determined by testing specimens with the microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP). Of blood samples available from 1262 participants from the initial survey, 32 (2.5%) were MHA-TP reactive. After adjustment for age, a reactive syphilis serology was significantly predicted (P < 0.05) by African American race, homosexual activity (men), and less education. In homosexually active men, lifetime number of male sex partners and the presence of antibody to the human immunodeficiency virus (HIV) significantly predicted syphilis seroreactivity (P < 0.01). One year later, of 841 specimens available for testing, an additional 13 (1.5%) had become MHA-TP reactive. Eleven (85%) of the new cases were in heterosexual men and women. Although San Francisco citywide incidence data indicate that syphilis may be decreasing for the city as a whole, incidence data on a community level suggests that syphilitic infection is increasing in high-risk heterosexual communities. Thus, syphilis prevention programs should rely on serologic testing at the community level to plan effective intervention strategies.

Pathology of the umbilical cord in congenital syphilis: analysis of 25 specimens using histochemistry and immunofluorescent antibody to Treponema pallidum.

Identification of Treponema pallidum in the placenta is important for diagnosis of congenital syphilis; however, spirochetes are difficult to observe in chorionic villi. To determine the sensitivity of umbilical cord examination for T pallidum, and the association of spirochetes with cord pathology, placentas were prospectively obtained from 25 women with untreated syphilis. The most common finding using hematoxylin-eosin staining was a normal-appearing umbilical cord (48%); necrotizing funisitis was the most frequent pathological lesion (36%). Spirochetes were detected using silver and immunofluorescent staining in 89% of cords, including 92% of histologically normal and 84% of abnormal cords. Three specimens showed subamnionic aggregates of spirochetes, consistent with amniotic fluid infection. Necrotizing funisitis was strongly associated with umbilical artery infection by spirochetes (P = .008). There was a 100% correlation between results of silver and immunofluorescent staining. The umbilical cord is a sensitive site for morphological confirmation of T pallidum; it is significant for the pathologist that spirochetes may often be detected in the absence of overt tissue inflammation or necrosis.

Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area.

The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985.

Adenovirus ELISA for the evaluation of cerebrospinal fluid in patients with suspected neurosyphilis.

An enzyme-linked immunosorbent assay (ELISA) detecting antibodies against the adenovirus group antigen was used to examine cerebrospinal fluid (CSF) of suspected neurosyphilis patients for serum contamination or blood-brain barrier (BBB) leakage. Adenovirus antibodies are ubiquitous, produce high antibody titers, and rarely cause central nervous system (CNS) infections. Of 52 normal adult sera tested with this ELISA, only one lacked antibodies. CSF from 48 healthy individuals did not present a detectable amount of anti-adenovirus antibodies. CSF from 33 suspected neurosyphilis patients with positive results in the fluorescent treponemal antibody-absorption (FTA-ABS)-CSF test were examined. Eighteen showed anti-adenovirus antibodies indicating contamination of the CSF with peripheral blood or damaged BBB by syphilis or other disease, resulting in questionable CSF treponemal results. The remaining 15 of these patients appeared to be producing their anti-treponemal antibodies in the CNS. This procedure may prove to be of considerable help in excluding false positive FTA-ABS results in CSF samples.

Hemagglutination tests for syphilis antibody.

In a study of serodiagnosis of syphilis, the authors compared the specificities and sensitivities of two hemagglutination tests, a sheep-erythrocyte test (MHA-TP) and a trukey-erythrocyte test (TPHA), with those of the Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test. In tests of sera from 935 patients without syphilis, the MHA-TP, TPHA, and FTA-ABS tests were reactive for 0.96, 0, and 1.3% respectively. The false-positive results were usually transient and not associated with underlying illness. For the 68 patients with syphilis, the MHA-TP test was as sensitive as the FTA-ABS test in all stages except untreated primary disease. The TPHA test appeared to be undersensitive, and testing of follow-up sera from persons with latent syphilis showed unexplained conversion of false-negative TPHA results to reactive results. Reproducibilities of the two hemagglutination tests were comparable. The MHA-TP test is a valuable confirmatory test for syphilis. Further study is needed before the use of the TPHA test can be recommended.

Syphilis.

The clinical manifestations of syphilis can resemble many diseases. The diagnosis can be confirmed through serologic tests and by direct microscopic observation of Treponema pallidum, subspecies pallidum in lesion, biopsy, or autopsy specimens. Direct microscopic examination may be carried out by darkfield methods or by immunofluorescent staining. The serologic testing sequence is usually a screening nontreponemal test followed by confirmation with a specific treponemal test. Serologic tests for syphilis have been highly standardized in the past, but today quality control lies in the hands of the laboratorian.

The relative efficacy of imaginal and in vivo desensitization in the treatment of agoraphobia.

Claims have often been made that in vivo procedures are generally superior to imaginal approaches in the clinical management of anxiety and avoidance behavior. Such claims seem unwarranted in that the relevant clinical research appears only to have involved either flooding or rapid exposure techniques. The aim of the present study was specifically to examine the relative efficacy of imaginal and in vivo desensitization in the clinical management of debilitating phobia. Six agoraphobic women participated in the study which employed a multiple-baseline single-subject methodology. Severity of phobia was repeatedly assessed on measures of avoidance behavior and subjective distress, and subjects self-monitored pulse rate. Significant reductions in phobic behavior were observed during both imaginal and in vivo desensitization, but neither treatment was found to be more effective than the other. Moreover, the same pattern of results was observed for both treatment and generalization settings. As such, the results do not support previous suggestions that in vivo exposure is necessarily superior to imaginal desensitization in the treatment of agoraphobia. Encouraging follow-up results provided some confirmation of previous findings indicating the effectiveness of self-management procedures in the long-term control of agoraphobia.

Quality assessment activities in Latin America and the Caribbean.

The Pan American Health Organization (PAHO) supports performance evaluation programs in clinical chemistry, Caribbean. Much more work remains to be done before many labs in this part of the world can be certified as providing accurate results, but PAHO has taken an important first step toward establishing benchmarks and rallying for labs to improve test quality.

Evaluation and standardization of an agglutination test for human listeriosis.

Human sera from patients with culturally confirmed listeriosis were tested for immunoglobulin M (IgM) and immunoglobulin G (IgG) agglutinating antibodies with trypsinized antigens of Listeria monocytogenes, Streptococcus faecalis, and Staphylococcus aureus. The response of humans to listeria infections is mainly IgM rather than IgG as found in animals. The antigens prepared from L. monocytogenes serotypes 1a, 1b, 2, 4b, and 4d were evaluated for specificity with normal sera, sera from patients with various other diseases, and sera from patients with listeriosis. The trypsinized antigens appeared to be specific for listeria antibodies with a cross-reaction rate of from 5.4 to 6%. Cross-reaction with S. aureus can be eliminated by absorption of the serum with S. aureus. This agglutination technique appears to be applicable for diagnostic testing, but, as with all serological procedures, both acute and convalescent sera should be tested.

Relation of breast versus bottle feeding to hospitalization for gastroenteritis in a middle-class U.S. population.

PIP: In an effort to determine the relation of breast versus bottle feeding to hospitalization for gastroenteritis, children hospitalized for gastroenteritis at the Kaiser-Permanente Medical Center in California were compared with a larger normal population of children discharged from the Center's nursery, for incidence of breast feeding. All infants under 12 months of age admitted to the hospital with acute gastroenteritis between January 1, 1973 and December 31, 1975 were identified. All infants had an acute onset of diarrhea and weight loss, some with vomiting. Variable degrees of clinical dehydration also occurred. 107 infants were admitted during the period of study. The type of feeding--breast or bottle--was obtained from the patients' admission history, nursery records, outpatient clinic charts, or by direct contact with parents. Of the 197 patients admitted with acute gastroenteritis during the study period, only 1 was being breast fed at the time of admission. 40 infants were under 6 months of age. Breast feeding accounted for 28 percent of the infant-months in the 0-6 month age group. The lower than predicted incidence of acute gastroenteritis in the breast fed infants was statistically significant. Although about 1/3 of the bottle fed infants had started breast feeding at birth, all had been switched to the bottle at least 1 month prior to hospitalization. The study data strongly indicate that breast feeding plays a major role in protection against intestinal infections.^ieng

Anatomical evidence of synaptic plasticity in the cochlear nuclei of white-deaf cats.

Synapses are dynamic structures reflecting environmental events. It was observed that densities associated with apposing synaptic membranes were altered in response to changing conditions of auditory stimulation (Gulley et al. 1978. J. Comp. Neurol. 180: 707-742). Synapses also exhibit plasticity during early development of the auditory system (Larsen and Pappas, 1985. Proceedings: 43rd Annual Meeting of the Electron Microscopy Society of America, pp. 493-494). Larsen and Pappas reported that, in young kittens, the end bulb of Held (EBH) terminal was distinguished by excessive density at apposing synaptic membranes which assume gradually the pattern observed in adult cats. The maturation of synapses parallels emerging function and may depend upon auditory stimulation (Larsen and Kirchhoff, 1987. Neurosci. Abstr. 13: 1260). Larsen and Kirchhoff found that EBH synapses on large spherical cells of white-deaf cats resembled the immature synapses found in young kittens (Fig. 1). They also found terminals that had an increased number and length of the membrane densities associated with synapses. Because the number of synaptic vesicles in these presynaptic terminals was equivalent to the number of vesicles found in normal-hearing cats, Larsen and Kirchhoff (1987) suggest that this is evidence of synaptic plasticity. We have completed a quantitative study of the synapses of EBH terminals found in adult cats that had been deaf for at least 3 years.

Development of the epithelium of the middle ear. Electron microscopic study of fine structure, including junctional complexes and basal lamina.

A detailed light and electron microscopic study of the development of the middle ear lining epithelium of the rat was undertaken in order to determine whether a portion of the middle ear lining is normally derived from a condensation of mesenchymal connective tissue. We learned that pharyngeal epithelium outpouches early in development and persists during the formation and growth of the ossicles and inner ear structures in a relatively constant anatomic relationship. We found no evidence of a contribution of mesodermal tissue to the lining epithelium itself. Certain features of the junctional complexes between adjacent cells were used as a means of identifying pharyngeal and middle ear epithelial cells. It is concluded that at no time is connective tissue found within the middle ear space (as defined by its epithelial limits); pneumatization occurs by absorption of mesenchymal tissue that occupied the space between the outer part of the epithelium and bone structures.

Laboratory diagnosis and interpretation of tests for syphilis.

The lack of a method for demonstrating the presence of Treponema pallidum by growth necessitates the use of alternative methods. Traditionally, these methods are divided into direct detection methods (animal inoculation, dark-field microscopy, etc.) and serologic tests for the presence of patient antibody against T. pallidum. Serologic methods are further divided into two classes. One class, the nontreponemal tests, detects antibodies to lipoidal antigens present in either the host or T. pallidum; examples are the Venereal Disease Research Laboratory and rapid plasma reagin and tests. Reactivity in these tests generally indicates host tissue damage that may not be specific for syphilis. Because these tests are easy and inexpensive to perform, they are commonly used for screening, and with proper clinical signs they are suggestive of syphilis. The other class of test, the treponemal tests, uses specific treponemal antigens. Confirmation of infection requires a reactive treponemal test. Examples of the treponemal tests are the microhemagglutination assay for antibodies to T. pallidum and the fluorescent treponemal antibody absorption test. These tests are more expensive and complicated to perform than the nontreponemal tests. On the horizon are a number of direct antigen, enzyme-linked immunosorbent assay, and PCR techniques. Several of these techniques have shown promise in clinical trials for the diagnosis of congenital syphilis and neurosyphilis that are presently difficult to diagnose.

Cross-reactivity to Borrelia burgdorferi proteins in serum samples from residents of a tropical country nonendemic for Lyme disease.

Reports of Lyme disease from areas where the disease is not endemic have increased. Eighty-six human serum samples from Papua New Guinea (nonendemic for Lyme disease) were examined for the presence of IgG antibodies that recognize Borrelia burgdorferi antigens, using the currently recommended two-tiered system of analysis (sensitive ELISA with Western blot). The percentage of positive tests dropped from 50% to 10% when individual negative controls were included in the two-tiered analysis. Positive serum samples failed to inhibit the growth of B. burgdorferi in culture and did not yield positive reactions in the fluorescent treponemal antibody-absorption test. These characteristics, together with atypical Western blot antigen recognition patterns and the absence of known vectors, provide evidence that seropositive results for these persons are not the result of exposure to B. burgdorferi. Individual negative controls may minimize false-positive results for serologic tests for Lyme disease, and these tests must be interpreted in the context of clinical and epidemiologic data.

Growth of lactic acid bacteria in waste waters of vegetable-processing plants.

Waters used in washing, blanching, cooling, and conveying vegetables during processing for freezing were filtered, sterilized, and inoculated with Streptococcus faecalis, S. lactis, or Lactobacillus plantarum. The contents of total nitrogen and total solids were determined, and ninhydrin tests and Benedict's tests for reducing sugars were performed. Substances positive to the ninyhydrin tests and also capable of supporting the growth of the bacteria to high levels of population were found in waters used to blanch cut green beans, but not in the cooling or conveying waters. They were found only in waters following slicing of blanched whole beans. They were also present in waters used in processing purple hull peas at all stages, but only in the waters used to blanch and cool lima beans. The substances were present in waters used to wash and blanch squash, but only in the waters used to blanch greens; they were not found in the cooling waters during the handling of either vegetable. No waters used in the processing of okra yielded a positive ninhydrin test, nor did they support the growth of the lactic acid bacteria.

Antigenic variation in group A streptococci: types 11 and 9.

A strain of group A Streptococcus which was virulent but M-nontypable was isolated from patients in a hospital nursery during an epidemic. This strain, Boston 11, reacted in T-agglutination tests with antisera for types 9 and 11, an unusual combination. A comparison of this strain with Lancefield's M-11 strain (NCDC SS-721) and Alabama 11 (Provisional 61) revealed three serologically related but distinct strains. Antiserum produced with the Boston 11 strain exhibited similar reactivity with all three "11" strains as well as with M-9 (SS-501) as demonstrated in precipitin tests. Immunodiffusion studies indicated that the Boston 11 antigen was partially identical with the M-11 and M-9 strains and shared at least one antigen with the Alabama 11 strain. The Boston 11 antiserum could be made specific for precipitin tests, but bactericidal activity for the Alabama 11, M-11, and Boston 11 strains was essentially negative.