Management strategies for infectious diseases in pregnancy.

This review presented the clinical manifestations, diagnostic and therapeutic options, and preventive strategies for several congenital infections. The infections discussed show the spectrum of modes of vertical transmission and severity of fetal disease encountered, in addition to the successes and limitations of the current medical interventions. Further improvements in diagnostic techniques and therapies for managing the infected fetus are likely to occur during the next decade. Similarly, the widespread adaptation of new and sensitive diagnostic assays, such as the polymerase chain reaction, is likely to further improve our ability to identify infectious agents as the primary cause of certain abnormal fetal conditions. Where specific diagnostic tests and therapies have proven successful in preventing or treating fetal infections, universal screening programs should be given serious consideration. Of paramount importance, however, is the active research on the development of preventive interventions designed to prevent maternal infections and vertical transmission. Although specific immunotherapies, vaccines, and drug therapies hold great promise for controlling the spread of some infections, it cannot be overemphasized that some serious infectious complications of pregnancy may be avoided by simple preconception or early antenatal maternal counseling.

Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. The New England Regional Toxoplasma Working Group.

BACKGROUND: Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. METHODS: In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. RESULTS: Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three). CONCLUSIONS: Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.

Heterologous protection against invasive Escherichia coli K1 disease in newborn rats by maternal immunization with purified mannose-sensitive pili.

Heterologous protection against Escherichia coli K1 bacteremia with antibody to purified mannose-sensitive (MS) pili was demonstrated in a neonatal rat model. The serological relatedness of purified MS pili from 17 E. coli K1 clinical isolates was examined by an enzyme-linked immunosorbent assay. Five pilus serogroups were identified, with the pili in each group showing 50% or greater cross-reactivity with the typing serum of the group. The MS pili from 12 of 17 (70%) strains belonged to just two serogroups. Pregnant Sprague-Dawley rats (dams) were immunized with purified pili, and their newborns (pups) were challenged with heterologous E. coli. Bacteremia was significantly reduced when the pili used for immunization were from the same serogroup as the pili expressed by the challenge bacteria. Thus, immunization with C94 pili and challenge with E03 (71% cross-reactivity) or E04 (50% cross-reactivity) resulted in bacteremia rates of 12 of 17 (17%) versus 51 of 79 (65%) in controls and 0 of 75 (0%) versus 28 of 70 (40%) in controls, respectively (P less than 0.001 for each comparison). With lower cross-reactivity, less protection was observed (P less than 0.05 for 22 to 37% pilus serological relatedness). No protection was seen in pups suckled by dams immunized with MS pili having only 5% serological relatedness to the pili on the challenge strain.

Comparison of 7S nerve growth factor and nerve growth factor I from mouse submandibular glands.

7S nerve growth factor (7S NGF) and nerve growth factor I (NGFI) are NGF-containing protein complexes isolated from mouse submandibular glands by different protocols, and reports suggest that the molecules differ chemically. In this study, we compared the molecular properties and subunit compositions of the two proteins. Purified 7S NGF and NGFI electrophoresed to identical positions on polyacrylamide gels in nondissociating buffers, with electrophoretic mobilities indistinguishable from that of unpurified NGF in salivary gland extracts. Ultraviolet absorption curves were identical, and sedimentation coefficients were similar (7.3 +/- 0.25 S for 7S NGF; 7.2 +/- 0.2 S for NGFI) as determined by sedimentation velocity analysis. By sedimentation equilibrium analysis, molecular weights of 135 000-140 000 were obtained for both complexes at protein concentrations in the centrifuge cell greater than 85 micrograms/mL; when protein concentrations within the centrifuge cell ranged from approximately 30 to 100 micrograms/mL at equilibrium, both complexes dissociated. Molecular weight values determined by gel filtration on Bio-Gel P300 and Sephadex G200 resins were similar for both proteins, and the values determined on Sephadex agreed with those obtained by ultracentrifugation. The subunit compositions of the complexes were also similar as determined by nonequilibrium isoelectric focusing, NGFI being composed of proteins that migrated to positions identical with those of the alpha, beta, and gamma subunits of 7S NGF. Furthermore, the stoichiometry of the subunits was similar in the two complexes as determined by radioimmunoassays to each of the subunits and by densitometric analysis of electrophoretic gels. Both methods showed that the complexes contain approximately 2 mol of the alpha and gamma subunits per mole of beta-NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Purification and characterization of Haemophilus influenzae pili, and their structural and serological relatedness to Escherichia coli P and mannose-sensitive pili.

Haemophilus influenzae pili were purified, and their physical and serological properties were examined. The solution properties of the pili were determined, and then a purification scheme involving repeated cycles of precipitation and solubilization was developed. The purified pili from one type b isolate (A02) were found to consist of multiple copies of a 25,000 mol wt subunit. Amino-terminal sequence analysis of A02 pili was carried out to 40 amino acid residues, and a remarkable degree of sequence homology was found with E. coli P and mannose-sensitive (MS) pili (27.5 and 25% homology, respectively). Purified A02 pili were found to be highly immunogenic, and serological analysis by enzyme-linked immunosorbent assay and whole piliated cell agglutination revealed significant cross-reactivity between A02 pilus antiserum and the pili of seven other H. influenzae strains tested (heterologous titers = 2-100% of the homologous titer). Cross-reactivity was also observed between the H. influenzae pili (five of eight strains tested) and the P pili from E. coli strains HU849 and 3669; no cross-reactivity was detected with MS pili from E. coli strain H10407 and C94. The structural similarities between H. influenzae and E. coli P and MS pili suggest a common gene ancestry.

Cardiac effects of noncardiac neoplasms.

Clinically significant cardiovascular abnormalities may occur as secondary manifestations of noncardiac neoplasms. The principal cardiac effects of noncardiac tumors include the direct results of metastases to the heart or lungs, the indirect effects of circulating tumor products (causing nonbacterial thrombotic endocarditis, myeloma-associated amyloidosis, pheochromocytoma-associated cardiac hypertrophy and myofibrillar degeneration, and carcinoid heart disease), and the undesired cardiotoxicities of chemotherapy and radiotherapy.

The role of pili and capsule in the pathogenesis of neonatal infection with Escherichia coli K1.

The role of pili and capsule was studied in neonatal infection with Escherichia coli K1. E coli strains were selectively cultured into three phases: mannose-sensitive (MS) piliated, non-mannose-sensitive (NMS) piliated, and nonpiliated. A high percentage of neonatal rats fed each phase of K1 strains developed bacteremia; there was no bacteremia with non-K1 strains or an acapsular mutant of K1 strain C94 (C94K-). Oral cavity colonization was noted in nearly 100% of rats fed K1 strains, non-K1 strains, or C94K-, regardless of the phase of piliation at feeding. Only MS piliated bacteria were found on oral cavity culture, indicating a rapid shift of NMS piliated and nonpiliated bacteria to the MS piliated phase. Conversely, only nonpiliated bacteria were found on blood culture when neonatal rats were fed piliated bacteria. Colonization of ileal epithelium was not observed. Thus, in vivo phase variation may be important in colonization and bacteremia with E coli K1.

Comparison of virulence and colonizing capacity of Escherichia coli K1 and non-K1 strains in neonatal rats.

Neonatal rats fed three strains of Escherichia coli K1 at birth had bacteremia rates of 29 to 81%; negligible bacteremia was seen with K92 and an unencapsulated strain. Despite this marked difference in virulence, K1, K92, and the unencapsulated strain all promptly, reliably, and stably colonized the entire alimentary tract, from pharynx to colon.

Host-dependent phosphorylation and kinase activity associated with vesicular stomatitis virus.

Among the protein kinases associated with vesicular stomatitis virus (VSV), one was identified by immunoprecipitation to be pp60src, the transformation-specific product coded for by avian sarcoma virus, or its endogenous cellular homolog. This activity phosphorylated only tyrosine. pp60src was enriched in the membranes, whereas the serine- and threonine-specific kinases were concentrated with viral cores. The content of pp60src in VSV can be manipulated by growing VSV in different host cells. Monolayer baby hamster kidney cells transformed by an avian sarcoma virus produced VSV progeny which contained 7-fold greater pp60src activity than progeny produced by control untransformed or revertant cells. In contrast, suspension cultures of baby hamster kidney cells which produced VSV with increased tyrosine-specific kinase activity did not affect the content of pp60src. When pp60src was specifically increased in cells, the endogenous phosphorylation of tyrosine residues in the VSV matrix M protein was also enhanced, to as much as 20-fold. The phosphorylation of serine or threonine in this protein or in the other VSV phosphoprotein NS was not affected. Cellular tyrosine-specific kinases other than pp60scr did not change the overall phosphorylation pattern of any VSV phosphoproteins. Experiments designed to test the effects of endogenous phosphorylation on the various functions of the M protein failed to detect any significant alterations.