Biomedical subjects
Publications and source records attributed to E R Alexander.
Sexually transmitted infection may result in serious damage to the reproductive tract of the mother, damage to the fetus, wastage of pregnancy, or illness or death of the infant. The effects of gonorrhea, Chlamydia trachomatis infection, mycoplasmal infections, group B streptococcus infections, syphilis, and viral infections are discussed separately for both mother and infant.
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In a prospective study of chlamydial and mycoplasmal infections in pregnancy, Chlamydia trachomatis occurred in 8.0%, Mycoplasma hominis in 23.5%, and Ureaplasma urealyticum in 72.3% of 1,365 enrollees. By multivariate analysis, C trachomatis was correlated with lower socioeconomic status, age 23 years or younger, and 12 years or less of schooling. Ureaplasma urealyticum was correlated with age 23 years or younger and lower socioeconomic status. Mycoplasma hominis was correlated with more than one recent sexual partner, first intercourse at age 17 years or younger, and higher socioeconomic status. These cervical infections did not predict low birth weight, abortion, stillbirth, prematurity, or premature rupture of membranes. Only M hominis predicted endometritis/fever after vaginal delivery (relative risk, 7.3). IgM-seropositive C trachomatis-infected women had more low-birth-weight infants and more premature rupture of membranes than either IgM-negative C trachomatis-infected women or C trachomatis culture-negative women. Thus, only certain subgroups of infected women may experience adverse pregnancy outcomes.
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In a prospective study of morbidity associated with Chlamydia trachomatis infections during pregnancy, we isolated C trachomatis from the endocervix of 18 (6.7%) of 268 women examined before 19 weeks' gestation. Infected women were significantly younger than noninfected women, and significantly more often unmarried, supported by public assistance, and pregnant for the first time. Among women followed up from 19 weeks' gestation until delivery, the mean duration of gestation was significantly shorter for those with antepartum chlamydial infection. Stillbirth or neonatal death occurred in six (33%) of the 18 pregnancies of infected women compared with eight (3.4%) of the 238 pregnancies of noninfected women followed up from the 19th week of gestation through delivery. Stillbirth or neonatal death occurred ten times more often among Chlamydia-infected women than among uninfected controls matched for age, marital status, socioeconomic status, pregnancy order, and race.
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Thirty-three women were examined on three or more occasions, each at 2-month intervals. The overall recovery rate of cytomegalovirus (CMV) was 28% (60/215). CMV was recovered from 53% of the cases where the local antibody was 1 : 64 or greater but the greatest difference occurred below titers of 1 : 32. Below that level virus was recovered in less than 5%, compared to a prevalence of 35% for cases with a titer of 1 : 32 (P less than 0.001). Twenty-eight cases in whom CMV was sought underwent colposcopy examination and had cytologic smears examined by the papanicolaou method. The external uterine cervix with columnar cells only yield a CMV prevalence of 3/17 (18%). However, if colposcopy showed either atypical transformation or metaplasia the prevalence was 4/11 (36%). Similarly, it is provocative that the prevalence of CMV appears to increase with abnormal cytologic findings to 33% recovery in severe dysplasia or carcinoma in situ.
Thirty five female Cebus albifrons monkeys (16 adolescents and 19 adults) were infected vaginally with herpes simplex virus (HSV) type 2. Fifteen developed spontaneous recurrent genital HSV infections. All 35 were killed for study eight to 12 months after primary infection, and tissue from the vagina, cervix, uterus, ovary, paracervical autonomic plexus, and lumbosacral dorsal root ganglia of eight animals. Host age was the most important variable influencing viral latency; 69% of adolescents and 42% of adults had latent HSV type 2 infections. Animals that developed latent infections were significantly easier to infect, shed virus during the primary infection significantly longer, and had more severe primary disease than those who did not become latently infected.
Management of patients potentially infected with Chlamydia trachomatis has been hampered by the cost and time required to perform Chlamydia cultures. To isolate C. trachomatis, we developed a microtiter method that exhibited equal sensitivity but less frequent contamination than our previously used vial-cover slip culture system. In addition, costs and technician time were substantially reduced with the microtest method. Subsequent studies showed that cycloheximide-treated cells were superior to 5-iodo-2-deoxyuridine-treated cells in the microtest method and that a subpassage significantly enhanced the sensitivity of the method. The microtest method appears to be a sensitive, rapid, and economical method for isolating C. trachomatis.
We treated 289 men who had nongonococcal urethritis with minocycline, 100 mg once or twice daily for 7 to 21 days. After 21 +/- 7 days, urethritis persisted or recurred in 31 (27%) of 114 given 7-day therapy and only nine (8%) of 110 given 21-day therapy (p = 0.0005). However, by 49 +/- 14 days, the cumulative percent rate of failure was 31% for 7-day and 30% for 21-day therapy. Thus, 21-day therapy only delayed recurrence. The higher daily dosage did not improve outcome. Urethritis persisted or recurred in 19% of men with initial Chlamydia trachomatis infection. Among men without C. trachomatis, urethritis persisted or recurred in 32% with and 52% without Ureaplasma urealyticum infection (p = 0.03). At follow-up, 79% of cases of persistent or recurrent urethritis were culture negative for C. trachomatis and U. urealyticum. The cause of C. trachomatis-negative, U. urealyticum-negative nongonococcal urethritis, which was least responsive to minocycline therapy, remains uncertain.
We investigated the relationship of route of delivery and of antepartum Chlamydia trachomatis cervical infection to selected forms of puerperal infectious morbidity, including intrapartum fever, or early (less than 48 hours) postpartum fever not attributable to infections of sites outside the uterus and late (48 hours to 6 weeks) postpartum endometritis. Infectious morbidity occurred in 27 (44%) of 62 women who underwent cesarean section and in 33 (10%) of 329 who underwent vaginal delivery (p less than 0.001). Postsection infectious morbidity was not correlated with C. trachomatis infection and was largely limited to early postpartum fever. Among women who underwent vaginal delivery, infectious morbidity occurred in 10 (34%) of 29 women with and in 23 (8%) of 300 without C. trachomatis infection (p less than 0.001), and chlamydial infection was associated only with intrapartum fever and late postpartum endometritis. Separate matched case-control analyses confirmed that cesarean section was associated with an increased risk of early postpartum fever (p = 4 x 10(-8)); whereas among women who underwent vaginal delivery, antepartum C trachomatis infection was associated with an increased risk of development of intrapartum fever or late postpartum endometritis (p = 0.002).
We compared the efficacy of erythromycin ophthalmic ointment vs 1% silver nitrate drops for the prevention of neonatal conjunctivitis or respiratory tract infection from Chlamydia trachomatis. The organism was isolated from the cervix of 67 (12%) of 572 pregnant women. They gave birth to 559 infants who were randomly assigned to either prophylaxis immediately after birth. Thirty-six of 60 infants born to Chlamydia-positive women received silver nitrate; 24 received erythromycin. Twelve (33%) of the 36 infants who received silver nitrate had chlamydial conjunctivitis, but none of the 24 infants who received erythromycin did. Ten (29%) of 36 infants receiving silver nitrate had chlamydial nasopharyngeal infection (three later had pneumonia), as opposed to five (21%) of 24 who received erythromycin (one had pneumonia). Thus, erythromycin ointment is effective in prevention of chlamydial conjunctivitis, but it may not reduce nasopharyngeal infection or subsequent pneumonia.
To determine the cause of the acute urethral syndrome, we studied 59 women with dysuria and frequent urination without "significant bacteriuria" (defined as greater than or equal to 10(5) organisms per milliliter), 35 women with typical cystitis and 66 women with no symptoms of urinary-tract infection. Although none of the 59 women with urethral syndrome had greater than 3.4 x 10(4) bacteria per milliliter in either of two successive midstream urine specimens, samples of bladder urine obtained by suprapubic aspiration or catheterization from 24 women contained coliforms, and samples from three contained Staphylococcus saprophyticus; all but one of these 27 women also had pyuria. Of the 32 women with sterile bladder urine, 10 of 16 with pyuria and one of 16 without pyuria were infected with Chlamydia trachomatis (P = 0.002). Chlamydial infection was found in 11 of 42 women with urethral syndrome and pyuria, in three of 66 without symptoms, and in one of 35 with cystitis (P less than 0.01 when the group with urethral syndrome is compared with either of the other groups). Thus, 42 of 59 women with urethral syndrome had abnormal pyuria and 37 of these 42 were infected with coliforms, S. saprophyticus, or C. trachomatis, whereas few women without pyuria had demonstrable infection. Bacteriuria of greater than or equal to 10(5) per milliliter may be an insensitive diagnostic criterion when applied to symptomatic lower-urinary-tract infection.
As part of a prospective study of cardiovascular disease (CVD) in middle-aged Chinese men in Taiwan, 1820 Chinese males, aged 40--59 years, from the middle and upper socioeconomic classes, were characterized at study entry by a history and physical examination with particular reference to cardiovascular status and by the Cornell Medical Index (CMI). Disease occurrence in the 1820 participants was observed over a seven-year period. Comparison of CMI test performance by specific disease incidence categories showed no group mean differences. In examining total disease occurrence in the form of prevalence, incidence of major morbidity and mortality and no illness occurrence, however, the authors found significant differences using the CMI. The highest scoring group on the CMI was non-survivors who had chronic illness at study entry, followed closely by those subjects who also had a chronic illness at study entry but who survived. Scoring lower than those with chronic illness at study entry, but significantly higher than the group remaining disease-free, were the subjects who incurred a major illness event and/or developed a chronic disease. The authors conclude that the CMI diffentiated between those who stayed healthy and those who died or incurred a major illness in this study population. Therefore, this study supports the use of the CMI as a measurement of general health, as well as a predictor of future health status, and suggests that it may be used in other cultures than the one in which it was developed.
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