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While enteroviruses have been the most commonly identified cause of aseptic meningitis in the United States, the role of the emerging, neurotropic West Nile virus (WNV) is not clear. In summer 2001, an aseptic meningitis epidemic occurring in an area of a WNV epizootic in Baltimore, Maryland, was investigated to determine the relative contributions of WNV and enteroviruses. A total of 113 aseptic meningitis cases with onsets from June 1 to September 30, 2001, were identified at six hospitals. WNV immunoglobulin M tests were negative for 69 patients with available specimens; however, 43 (61%) of 70 patients tested enterovirus-positive by viral culture or polymerase chain reaction. Most (76%) of the serotyped enteroviruses were echoviruses 13 and 18. Enteroviruses, including previously rarely detected echoviruses, likely caused most aseptic meningitis cases in this epidemic. No WNV meningitis cases were identified. Even in areas of WNV epizootics, enteroviruses continue to be important causative agents of aseptic meningitis.

Ureaplasma urealyticumrespiratory tract colonization in preterm infants has been associated with a high incidence of pneumonia and the development of bronchopulmonary dysplasia. However, study of this human pathogen has been hampered by the absence of animal models. We have developed the first juvenile mouse model ofUreaplasmapneumonia and characterized the histopathology during the month following inoculation. C3H/HeN mice were inoculated intratracheally with a mouse-adapted clinicalUreaplasmaisolate (biovar 2) or sham inoculated with 10B broth. Culture of lung homogenates and PCR of DNA from bronchoalveolar lavage fluid (BAL) confirmed the presence ofUreaplasmain 100% of inoculated animals at 1 day, 60% at 2 days, 50% at 3 days, and 25% at 7 and 14 days.Ureaplasmawas undetectable 28 days postinoculation. There were marked changes in BAL and interstitial-cell composition with increased number of polymorphonuclear leukocytes 1 to 2 days and 14 days postinoculation and macrophages at 2 and 14 days postinoculation. TheUreaplasmainfection caused a persistent focal loss of airway ciliated epithelium and a mild increase in interstitial cellularity. There were no differences in BAL protein concentration during the first 28 days, suggesting that pulmonary vascular endothelial barrier integrity remained intact. Comparison of BAL cytokine and chemokine concentrations revealed low levels of tumor necrosis factor alpha (TNF-α) at 3 days and monocyte chemoattractant protein 1 at 7 days inUreaplasma-infected mice but a trend toward increased TNF-α at 14 days and increased granulocyte-macrophage colony-stimulating factor and interleukin-10 at 28 days. These data suggest thatUreaplasmaalone may cause limited inflammation and minimal tissue injury in the early phase of infection but may promote a mild chronic inflammatory response in the later phase of infection (days 14 to 28), similar to the process that occurs in human newborns.

Antenatal Chlamydia trachomatis infections are associated with both maternal and neonatal morbidity. Erythromycin, the only drug recommended for treatment during pregnancy, is often poorly tolerated, thus preventing successful cure. We have done a prospective, randomized, double-blind, placebo-controlled trial to compare the efficacy of clindamycin with that of erythromycin base in eradication of antenatal chlamydia. A total of 126 patients with documented cervical infection were enrolled before 24 weeks' gestation to receive clindamycin (450 mg), erythromycin (333 mg), or placebo orally four times daily for 14 days. Partners received doxycycline, 100 mg, twice daily for 7 days. Both clindamycin and erythromycin were effective agents with cure rates of 92.7% and 83.8%, respectively. Erythromycin therapy was associated with significantly more gastrointestinal complaints than was placebo therapy (23.1% (9/39) vs. 2.4% (1/41), p less than 0.02) whereas clindamycin was not. Patients who experienced side effects were more likely to be poorly compliant (p less than 0.03) and patients with moderate-to-good compliance were more likely to be cured than were women who were poorly compliant (p less than 0.002). Results of test of cure cultures performed immediately on completion of therapy did not differ significantly from those taken 4 weeks later.

The cost-effectiveness of screening for pharyngeal gonorrhea (PG) in an adolescent clinic population was examined in the context of dramatically decreasing prevalence. Chart review revealed that the apparent PG prevalence had decreased from 15/555 (2.7%) 8 years ago to 0/319 (0.0%) recently in the clinic population studied. The earlier high prevalence of PG probably represented poor laboratory test specificity. Cost analysis showed that only at very high prevalence of PG (greater than 8%) would pharyngeal screening be cost-effective unless PG can be shown to be an important source of genital infection. We concluded that continued pharyngeal screening is not justified in our clinic because prevalence is so low.

We previously observed thatUreaplasma urealyticumrespiratory tract colonization in infants with a birth weight of ≤1,250 g was associated with increases in the tracheal aspirate proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) relative to the counterregulatory cytokine IL-6 during the first week of life (A. M. Patterson, V. Taciak, J. Lovchik, R. E. Fox, A. B. Campbell, and R. M. Viscardi, Pediatr. Infect. Dis. J. 17:321–328, 1998). We hypothesized thatU. urealyticumalters the host immune response in the presence of a coinflammatory stimulus (e.g., bacterial infection or hyperoxia) by shifting the balance of cytokine expression towards the proinflammatory cytokines. To test this hypothesis, we compared the release of TNF-α, IL-8, IL-6, and IL-10 in vitro by unstimulated andU. urealyticum(with or without lipopolysaccharide [LPS])-stimulated human monocytes from adult peripheral blood and from term and preterm cord blood.U. urealyticumalone and in combination with LPS induced concentration- and development-dependent changes in cytokine release. In vitro inoculation with low-inoculumU. urealyticum(103color-changing units [CCU]) (i) partially blocked the LPS-stimulated IL-6 release by all cells and reduced LPS-stimulated IL-10 release by preterm cells, (ii) stimulated TNF-α and IL-8 release by preterm cells, and (iii) augmented LPS-stimulated TNF-α release in all cells. In preterm cells, high-inoculumU. urealyticum(106CCU) (i) stimulated TNF-α and IL-8, but not IL-6 or IL-10, release and (ii) augmented LPS-stimulated TNF-α and IL-8 release. High-inoculumU. urealyticum(i) stimulated release of all four cytokines in term cells and IL-8 release in adult cells and (ii) augmented LPS-induced TNF-α, IL-10, and IL-8 release in term cells but did not significantly affect LPS-induced cytokine release in adult cells. We speculate thatU. urealyticumenhances the proinflammatory response to a second infection by blocking expression of counterregulatory cytokines (IL-6 and IL-10), predisposing the preterm infant to prolonged and dysregulated inflammation, lung injury, and impaired clearance of secondary infections.

A cultured cell line was derived from a hemangiopericytoma obtained at surgery from a 9 year-old boy with hypophosphatemic rickets. Hypophosphatemia and metabolic bone disease were cured in the patient after tumor removal. Cells from passage 5 were transplanted into 8 week-old athymic female mice. Additional animals received innocula of cells thawed from the stored original tumor tissue, as well as MRC-5 fibroblasts. Serum phosphate levels 3-7 months post-transplantation were lowest in mice which received the cultured cell line (n = 5) 6.1 +/- 0.6 mg/dl (p < 0.05 compared to the other groups), thawed tumor cells (n = 8) 7.2 +/- 0.7 mg/dl, MRC fibroblasts (n = 4) 8.1 +/- 1.0 mg/dl, no transplant (n = 10) 8.7 +/- 1.9 mg/dl. Repeat of the experiment with cultured tumor cells from passage 12 no longer altered phosphate levels. A substance produced and release by the tumor in situ and by tumor-derived cultured cells is capable of producing hypophosphatemia. Experimental manipulation of functional tumor-derived cell lines may help elucidate the factor(s) causing hypophosphatemia in oncogenic osteomalacia/rickets.

The prevalence of Chlamydia trachomatisgenital infection was studied in a sexually active urban Baltimore adolescent population. Possible risk factors such as age, past history of sexually transmitted disease, number of sexual partners, contact with sexually transmitted disease, oral contraceptive use, and concomitant gonococcal infection were also evaluated. The prevalence of chlamydial infection in the 280 adolescents studied was 26%: 35% in male adolescents, 27% in pregnant female adolescents, and 23% in nonpregnant female adolescents. Chiamydia was almost three times as prevalent as gonorrhea in the same population. Age, past history of sexually transmitted disease, oral contraceptive use, and concomitant gonorrhea were not significantly associated with chlamydial infection. However, multiple current sexual partners, contact with sexually transmitted disease, genitourinary symptoms, and cervical ectopy were significantly associated with chlamydial infection. Testing for chlamydial infection in sexually active urban teenagers is recommended for those with genitourinary symptoms, those with cervical ectopy, or those who are contacts of persons with sexually transmitted disease. Considering the reservoir of infection in the asymptomatic female adolescents, screening for chlamydial infections in family planning clinics warrants consideration.

An infant with severe combined immunodeficiency had normal numbers of lymphocytes which bore E rosette and surface Ig markers in an appropriate distribution. However, only minimal responsivity to in vitro stimulation by mitogens and allogeneic cells, and none to antigens could be elicited; functional antibody responses were also nil, except to cytomegalovirus. Intrauterine-acquired cytomegalovirus may have caused his immune dysfunction, although the possibility of a postnatal infection cannot be excluded. Therapy with transfer factor and thymus transplantation was unsuccessful in restoring immunity and may have aggravated a pre-existing monoclonal gammopathy. It is possible that the monoclonal protein was derived from B-cells transplacentally received from the patient's mother.

There is conflicting evidence regarding a possible causal role for Chlamydia trachomatis in the development of preterm premature rupture of the membranes. We investigated the relative prevalence of endocervical infection with C. trachomatis and group B streptococci in patients with preterm premature rupture of membranes compared with a control group taken from the same obstetric population. C. trachomatis was isolated from 23/52 (44%) patients with preterm premature rupture of membranes versus 13/84 (15%) women in the control group (p less than 0.001). This association was independent of infection with group B streptococci or Neisseria gonorrhoeae. Group B streptococci were isolated from 16% of the patients with preterm premature rupture of membranes versus 4% of the control population (p less than 0.05). The risk of preterm premature rupture of membranes associated with group B streptococcal infection was independent of infection with C. trachomatis and N. gonorrhoeae. Endocervical infection with C. trachomatis did not significantly affect early maternal complication rates after delivery.

The finding that the relationship of the in vitro and in vivo responses of different strains of mice is under genetic control indicates that at least two mechanisms must operate under in vivo conditions to control 19S antibody synthesis. One is involved in the termination of 19S antibody synthesis; the other has a regulatory role on the magnitude of the response. In light of these findings, various concepts based on other genetically controlled immune responses and on the limiting dilution technique should be reassessed. Furthermore, the suppressive in vivo mechanism may be an important type of control in the resistance or susceptibility to the establishment or maintainance of neoplasms.

The prevalence of Chlamydia trachomatis genital infection was studied in a sexually active urban Baltimore adolescent population. Possible risk factors such as age, past history of sexually transmitted disease, number of sexual partners, contact with sexually transmitted disease, oral contraceptive use, and concomitant gonococcal infection were also evaluated. The prevalence of chlamydial infection in the 280 adolescents studied was 26%: 35% in male adolescents, 27% in pregnant female adolescents, and 23% in nonpregnant female adolescents. Chlamydia was almost three times as prevalent as gonorrhea in the same population. Age, past history of sexually transmitted disease, oral contraceptive use, and concomitant gonorrhea were not significantly associated with chlamydial infection. However, multiple current sexual partners, contact with sexually transmitted disease, genitourinary symptoms, and cervical ectopy were significantly associated with chlamydial infection. Testing for chlamydial infection in sexually active urban teenagers is recommended for those with genitourinary symptoms, those with cervical ectopy, or those who are contacts of persons with sexually transmitted disease. Considering the reservoir of infection in the asymptomatic female adolescents, screening for chlamydial infections in family planning clinics warrants consideration.