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In an attempt to develop an assay specific for antibody to capsular polysaccharide (PS) of Streptococcus pneumoniae, the ability of ELISA and Farr (radioactive antigen-binding) assay for antibodies to 6B and 19A PS to be affected by antibodies to C-polysaccharide (C-PS) was compared. Preabsorption with C-PS reduced values obtained by ELISA for anti-6B antibody by >3-fold in 5 of 10 preimmune and 7 of 26 postimmune sera. In contrast, absorption reduced values by >3-fold in 0 of 36 samples studied with the Farr assay. Similar results were observed when the absorption was done with CSR-SCS2 S. pneumoniae. Furthermore, when anti-19A antibody levels were examined, preabsorption with R36a S. pneumoniae reduced ELISA values by 3-fold in 7 of 22 samples, whereas no samples had 3-fold reduction by Farr assay. Thus, the Farr assay for capsular PS is less affected than the ELISA by anti-C-PS antibody.

We examined the ability of sera drawn from rabbits made tolerant to lipopolysaccharide (LPS) from Escherichia coli O18 to inhibit heterologous LPS-induced gelation of Limulus lysate. Compared with a pool of pretolerant sera, a pool of tolerant sera from these rabbits neutralized 5.5-fold more LPS from Salmonella typhimurium, 4.9-fold more LPS from Pseudomonas aeruginosa, and lO.O-fold more LPS from Klebsiella pneumoniae. Because previous studies have found that LPS bound to lipoprotein is less toxic than unbound LPS, we also studied the binding of LPS lipoprotein fractions in the serum pools by using fractionation with a cesium chloride—equilibrium density gradient. Radiolabeled LPS from E. coli O113 bound much more rapidly to lipoprotein fractions in tolerant serum than in pretolerant serum (after 11 min of incubation, 66.1% vs. 16.5% binding, respectively).

Peak concentrations and half-life of gentarrucm in serum were measured after 140 intravenous and 13 intramuscular doses in 52 children and 17 adults with normal levels of creatinine in serum. Marked interpatient variation in peak concentrations and half-life of gentamicin was observed, but individual patients tended to have similar values on repeated determinations. Age markedly affected the peak concentrations: a 1-mg/kg dose produced mean peak concentrations of 1.58, 2.03, and 2.81 µg/ml in the one-half to five, five to 10, and >10 year age groups, respectively. This age-related change in dose response was diminished when the dose was calculated on the basis of body surface area. Patients in whom gentamicin had a short half-life, patients with fever, and adults with a high extracellular fluid volume had low peak concentrations. The mean half-life after intravenous administration was 75 min (range, 26-230 min). The mean half-life was 29 min longer after intramuscular dosage (P < 0.01). A low rate of creatinine clearance was associated with a long half-life; fever and anemia were associated with a short half-life. The dosage of gentamicin necessary to produce mean peak serum concentrations between 4 µg/ml and 6 µg/ml was 60 mg/m-2 per dose for all age groups or 2.5 mg/kg per dose for ages one-half to five years, 2.0 mg kg per dose for ages five to 10 years, and 1.5 mg/kg per dose for ages > 10 years.

A double-antibody, solid-phase enzyme-linked immunosorbent assay was developed for detection of candida antigen(s) in serum and body fluids. The assay detected mannan purified from Candida albicans cells with a sensitivity of 1 ng/ml in buffer, but it was I,OOO-fold less sensitive in pooled human serum. Because antibody appeared to be the major blocking factor in serum, a rapid and efficient heat-extraction method for recovering mannan from antibody-containing serum was devised. The assay detected anti-genemia within 24 hr in all of 30 lethally infected rats, and antigenemia persisted until their deaths. Eight of 15 patients with documented or suspected candidiasis had anti-genemia at levels ranging from 5 to >1,000 ng/ml.

A recombinant endotoxin-neutralizing protein (ENP) from Limuluspolyphemus and a monoclonal IgM anti-lipid A antibody (HA-IA) were compared in a rat model of Escherichia coli sepsis. One hour after intraperitoneal challenge with 106 cfu of E. coli 0 18ac K I, animals were sensitized to endotoxin with lead acetate and treated with ENP, HA-IA, or saline, followed by ceftriaxone and gentamicin. Before treatment, 95% of rats had high-grade bacteremia and high serum endotoxin concentrations, which were similar in all treatment groups (P > .60). One hour after treatment, there was no bacterial growth in any blood sample, and endotoxin concentrations were significantly lower in the ENP group than in the HA-IA and saline groups (P < .01). At 24 h after challenge, survival in the ENP group was significantly higher than in the HA-IA saline group (P < .001). ENP improved survival in a rat model of E. coli sepsis with high mortality despite effective antibiotic therapy.

Antibody to the capsular polysaccharide (CP) of Haemophilus influenzae b (Hib) is bactericidal, opsonic, and protective. Minimum protective levels of primarily IgG antibody to Hib CP, calculated from passive immunization studies, have been found to be ∼.06–.15 µg/ml of serum. The human response to antigenic challenge with the Hib capsule, however, includes production of antibody to Hib CP of different isotypes whose function against Hib is unclear. In order to characterize the function of antibody to Hib CP of different isotypes, we purified human IgG, IgM, and IgA from the serum of an adult donor who had been previously immunized with purified Hib CP vaccine. The globulin preparations were >99% isotypically pure, contained large quantities of anticapsular antibody, and differed in function against Hib. IgG antibody to Hib CP was bactericidal and opsonic for human polymorphonuclear leukocytes (PMNLs) in the presence of complement and protective in infant rats. IgM, although more bactericidal than IgG (P < .01) and equally protective in rats, opsonized Hib poorly for PMNLs. IgA was not bactericidal or opsonic and did not prevent bacteremia and meningitis in rats challenged with Hib. We conclude that antibody directed against the capsule of Hib differs in antibacterial function depending on class. These data may be important to acurately estimate minimum protective levels of anticapsular antibody after vaccination or natural infection and may have implications for the manner in which the host clears Hib from the circulation.

From the pooled plasma of 54 adult donors immunized with Haemophilus influenzae type b capsular polysaccharide (CP), a human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) was prepared. The pharmacokinetics of antibody to H. influenzae type b CP in high-risk children was compared after BPIG and conventional immune serum globulin (ISG) were administered intramuscularly at a dose of 0.5–0.6 ml/kg. The increase in antibody level four to seven days after injection was ninefold higher with BPIG than with ISG and remained higher throughout the three-month follow-up period. The mean half-life of antibody to H. influenzae type b CP was similar after BPIG (27 days) and ISG (29 days). Antibody levels returned to baseline one to two months after ISG but remained significantly above baseline three months after BPIG (mean concentration, 385 ng/ml). Based on the assumption that 150 ng of IgG antibody to H. influenzae type b CP/ml is the minimal protective level, it is concluded that a single intramuscular dose of 0.5 ml of BPIG/kg will protect children for four months.

In studies of the in vivo and in vitro interactions of moxalactam and tobramycin, normal volunteers and anuric patients were given one of the drugs or both drugs simultaneously, and the antibiotics were incubated separately or in combination in pooled human plasma. In both normal volunteers and patients with renal failure, the rate of elimination of tobramycin increased when the drug was given in combination with moxalactam. In patients with normal renal function, the rate of elimination of moxalactam decreased when the drug was given in combination with tobramycin; in contrast, this value did not decrease when the combination was given to anuric patients. In vitro, neither drug was affected by the presence of the other. Thus, the observed changes in elimination rates apparently are not caused by a chemical interaction that can be demonstrated in vitro. However, they are of sufficient magnitude to be of potential clinical significance.

To evaluate the correlation of detection ofhuman immunodeficiency virus (HIV) by polymerase chain reaction (PCR) with detection of HIV antibody, 271 simultaneous serum and peripheral blood mononuclear cell samples were examined from 242 persons whose activities placed them at increased risk for HIV infection: 142 from homosexual men, 86 from hemophilic men, and 43 from heterosexual partners of HIV-infected persons. peR was performed using the gag region primer pair SK38/39 and the env region primer pairs SK68/69 and C071172. Amplified HIV DNA was detected using specific oligomer probes. Of 63 mv antibody-positive samples, 58 (92%) had HIV DNA by PCR. Of 208 HIV antibody-negative samples, 7 (3.4%) had mv DNA by PCR. On follow-up, 4 ofof the latter persons were seropositive when next tested; 2 were well and antibody- and PeR-negative; 1 had died ofa stroke before retesting. Thus, PCR detects mv in most antibody-positive persons; detection is increased by use of multiple primer pairs. PeR-positive antibody-negative specimens may indicate HIV infection in which antibody has not yet developed or may be false-positive PCR results. When PCR is discordant with HIV antibody, testing ofadditional specimens and clinical follow-up are necessary to assess HIV infection status.

The 1-methyl-1 H-tetrazole-5-thiol (MTT) side chain present on several new cephalosporins may be an important factor in coagulopathy observed during therapy with these antibiotics. To determine the plasma kinetics and protein binding of the side chain and to test the hypothesis that renal failure alters these parameters, we gave six normal volunteers and six anuric patients a single iv dose of 15 mg of cefamandole/kg. Plasma concentrations of cefamandole and free MTT were measured by high-performance liquid chromatography 14 times during the 48-hr period after the dose was given. A compartment- independent pharmacokinetic analysis showed that MTT was rapidly removed from the plasma of normal subjects, but that peak concentrations of MTT were nearly three times greater and persisted for 48 hr in patients with renal failure. Further, renal failure caused a significant MTT protein-binding defect. Ifa relation exists between hypoprothrombinemia and plasma concentrations of MTTside chain, patients with reduced renal function may be at increased risk for this adverse effect.

VX-478 is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) protease (Ki, 0.6 nM) and of HIV-1 replication in antiviral assays (IC90, 80 nM). The fractional binding of VX-478 to human plasma and to purified plasma proteins was determined by equilibrium dialysis and difference UV spectrophotometry. Binding to α1-acid glycoprotein (89% at 2 µM total drug concentration, Kd of 4 µM) accounts for its fractional binding in plasma (93%). Stopped-flow spectrophotometry methods showed that binding is a reversible two-step process. The measured dissociation rate constant approaches 100 s−1. The antiviral effect of VX-478 was determined in the presence of 45% human plasma, in which the IC90 increased by 1.5-fold compared with control experiments in the presence of 15% fetal bovine serum. The effects of protein binding on the antiviral activity of VX-478 are minor, as expected for a weak drug-protein interaction.

Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcallipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli 0111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P < .05) and improved 24-h survival (P < .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels,and improved 24-h survival (all, P E. coli .05). In vitro studies confirmed that PMB at 10 µg/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS.

Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcallipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate. Rabbits challenged with an LD90 of LOS (10 μg/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs. 8%, P = ,005) than did rabbits challenged with LOS alone. Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs. 8%, P = .003). Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs. 8% in untreated controls P = .028). LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations. Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock.

To explore the feasibility of preparing a human immune globulin specific for respiratory syncytial virus (RSV) by screening plasma donors, the ability of seven RSV antibody assays to identify plasma-yielding IgG with high virus-neutralizing and animal-protective activities was compared. IgG prepared from plasma units selected by microneutralization assay had significantly higher activity in protecting mice from respiratory RSV challenge than did IgGs prepared from plasmas selected by three direct ELISAs using purified F protein, G protein, or RSV-infected cell lysate, by two competitive ELISAs with RSV neutralizing monoclonal antibodies directed to the F2 or F3 epitopes of the F protein, or by plaque reduction neutralization. Relative to IgG made from unselected plasma, microneutralization-screened IgG was enriched fivefold by plaque-reduction neutralization assays done with or without complement. The microneutralization assay identified RSV antibodies with highest animal protective activity. This assay will be useful for identifying plasma donors for the preparation of a human immune globulin with high protective activity against RSV and deserves further evaluation for prediction of protective antibody concentrations in children.

Eight healthy adults and 48 infants 2 and 4 months old were immunized with Haemophilus injluenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMP) to evaluate antibody kinetics in the first days after immunization. Five adults (63%) had some decrease in antibody, although the geometric mean did not decrease significantly. With one exception, the nadir occurred on postimmunization day 3. Seven had an antibody increase by day 7. Of the children, 6 (75%) of 8 and 17 (77%) of 23 had a decrease in antibody in serum obtained on day 2–3 after the first or second dose, respectively, the magnitude of which directly correlated with the preimmunization antibody concentration. However, the geometric mean did not decrease significantly. Within 1 week of immunization, 85% of infants had an increase in antibody, significantly greater after the second dose than after the first. A high concentration of maternally derived antibody before immunization correlated negatively with antibody response. Thus, a transient decrease in antibody occurs in most adults and infants 2–3 days after immunization with PRP-OMP followed by a prompt increase by day 7.

Pertussis toxin is an important virulence factor of Bordetella pertussis that may also contribute to the toxicity of pertussis vaccines. The effect of low doses of pertussis toxin on response to Haemophilus influenzae type b (Hib) infection was examined in infant rats. Pretreatment of rats with 10 or 100 ng of pertussis toxin increased blood bacterial concentration (P < .01), serum endotoxin levels (P < .01), and mortality (P < .05) relative to saline pretreated controls challenged with 4 × 103 Hib intraperitoneally. The 100-ng dose of pertussis toxin, but not the 10-ng dose, increased the leukocyte count. Thus, doses of pertussis toxin less than the threshold dose for inducing leukocytosis may enhance the susceptibility of infant rats to Hib infections.

Passive transfer of antibody to infants born to women immunized during the third trimester of pregnancy with a Haemophilus influenzae type b (Hib) vaccine (PRP polysaccharide or Hib conjugates PRP-D or HbOC) was studied in 50 mothers and infants and 47 nonimmunized mother-infant pairs. Geometric mean total PRP antibody by RIA was 1.2 µg/mL at delivery in unimmunized women and 21,149, and 171 µg/mL in women who received PRP, PRP-D, and HbOC, respectively. Mean cord PRP antibody levels were 0.29,3.0, 17.5, and 29.3 µg/mL for the corresponding groups. Postimmunization and cord PRP antibody levels were higher after maternal immunization with conjugate vaccines than with PRP vaccine (P < .01).PRP IgG1 subclass was transmitted more efficiently than IgG2 (56% vs. 35%, P < .01). The proportion of anti-PRP IgG transmitted from immunized mothers to infants correlated with time between immunization and delivery. Administration of PRP conjugate vaccines to women during pregnancy resulted in higher levels of PRP antibodies in infants than did polysaccharide or no vaccine.

Plasma samples from 500 blood donors were titrated for diphtheria antitoxin (OAT) by the toxin neutralization (TN) test. Only 1.6% of donors had <0.01 IU/mL OAT, the minimum protective level against diphtheria; 15% had levels between 0.01 and <0.1 IU/mL, indicating basic protection, and 83.4% had levels 0.1 IU, indicating full protection. Three hundred fifty samples were studied by ELISA for diphtheria toxoid IgG antibodies to assess the utility of the assay as a quick, convenient method for evaluating diphtheria immunity. Although the correlation between TN and ELISA titers for the 350 samples was high (r = .80), there was no correlation (r = .07) for samples with antitoxin titers <0.1 IU/mL, the level of special interest for serosurveys for protection. Titration of 62 immune globulin samples (prepared from 1957 to 1994) showed that OAT levels in Massachusetts blood donors increased concurrently with increased use of tetanus-diphtheria vaccine in the state.

Antiserum to rough gram-negative mutants such as Escherichia coli 15 and Salmonella minnesota Re595 is thought to neutralize the toxic effects of lipopolysaccharides (LPSs). Toverify that such antisera are capable of binding heterologous endotoxins, weexamined IgG and IgM class antibodies induced in rabbits to a variety of LPSs. Immunization with rough mutants or lipid A induced high IgG antibody responses to the homologous purified LPS and relatively low but significant responses to heterologous LPSs. Increases in IgM antibodies were also primarily to homologous LPS. Immunization with smooth organisms induced little or no antibody to heterologous LPSs. Soluble LPS, outer membrane vesicles, and whole bacteria produced strong homologous inhibition but little or no heterologous inhibition in enzyme-linked imunosorbent assays. Cross-adsorption of antisera to rough mutants suggested that the IgG and IgM antibodies induced to heterologous LPS were adsorbed by the heterologous LPS and not by the core LPS used to immunize the animals. Rabbit antibody directed to 15 or Re595 LPS fails to bind to any substantial degree to heterologous LPS. Immunization with whole bacterial vaccines, particularly the rough mutants and lipid A, does increase antibody to a wide variety of antigens. The possibilities that the protective effects of antisera to rough mutants are due to a polyclonal antibody response or to the induction of as yet unidentified factor(s) deserve further investigation.

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51 (23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11–20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.

Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children <5 years of age is 5–10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was >90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.

Maternal immunization with the capsular polysaccharide (PRP) vaccine of Haemophilus influenzae type b has been shown to extend the time that protective levels of maternal antibody are detected in infants. In a randomized, blinded trial, PRP or placebo was administered uneventfully to 213 women in the third trimester of pregnancy. Infants born to PRP recipients had significantly higher levels of antibody to PRP than did infants born to placebo recipients: 2.73 µg/ml compared with 0.33 µg/ml. It was estimated that infants of mothers who received the PRP vaccine would be protected for an average of 4 months compared to an average ofonly 2 months for those of mothers who received placebo. Infants were followed for invasive H. influenzae type b disease through the first year of life; none was detected.

A human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) has been prepared from plasma donors immunized with Haemophilus influenzae type b (Rib), pneumococcal, and meningococcal vaccines. At a dose of 0.5 ml/kg, BPIG increased levels of antibody to Rib by > 0.15 µg/ml within 4–6 h and by 2–4 µg/ml at 72 h. Thereafter, antibody declined, with a mean half-life of 27 days. BPIG treatment of Apache infants did not impair their active antibody responses to concurrently administered diphtheria-tetanus-pertussis or Rib oligosaccharide- diptheria CRM197 conjugate vaccines. In high-risk Apache infants, BPIG given at 2, 6, and 10 months of age provided significant protection from invasive Rib infection during infancy. Thus, BPIG may have utility in the prevention of Rib infections in high-risk patients who cannot be immunized adequately with Rib conjugate vaccines.

Relative to conventional immune globulins (IG, 13 lots), IGs prepared from donors with high activity by microneutralization assay to respiratory syncytial virus (RSVIG, 8 lots) had significantly higher neutralizing antibodies to 6 RSV strains (mean enrichment, 5.2-fold; range, 2.6- to 10.0-fold). In contrast, IgG antibody concentrations to whole RSV, fusion protein, or glycoproteins of A and B strains were similar in RSVIG and IG. Treatment of cotton rats with RSVIG at 0.5 g/kg 24 h before RSV challenge reduced RSV by 99% in the lungs (P < .001). RSVIG at 5.0 g/kg reduced RSV by 99% in the nose. IG at 5.0 g/kg had efficacysimilar to that of RSVIG at 0.5 g/kg. Serum plaque-reduction neutralization titers of 1/390 resulted in 99% reduction of lung RSV and titers of 1/3500 resulted in 99% reduction in nose RSV. Relative to IG, RSVIG is enriched selectively in RSV neutralizing antibodies and has ∼10 times greater protective activity in cotton rats.

Massachusetts provides diphtheria-tetanus toxoid-pertussis (DTP) vaccine, and since 1980 has monitored pertussis with a statewide diagnostic service. The incidence of bacteriologically confirmed pertussis was 104.5 per 100,000 person-years in 1-month-old infants and declined progressively thereafter. Infants <6 months old experienced disproportionate morbidity: 44% of bacteriologically confirmed pertussis, 64% of hospitalizations, and 71% of hospital days. Most children with pertussis had received <3 DTP doses during childhood, whereas 87% of adolescents with pertussis had received 4 doses. Serodiagnosis by single serum anti-pertussis toxin antibody ELISA increased the incidence of confirmed pertussis in persons 11–19 years old from 3.0 to 12.9 per 100,000 and in persons 20 years old from 0.16 to 0.56 per 100,000. Bacteriologic methods underestimate pertussis incidence, but a single serum anti-pertussis toxin antibody ELISA is a practical method for population-based diagnosis in adolescents and adults.

Immunoblot analysis showed that enolase is one of a subset of proteins found in cell supernatants of Candida albicans. Enzyme assays on whole cell extracts indicated that enolase is an abundant protein, comprising 0.7% and 2.0% ofthe total protein from yeast and hyphal forms of C. albicans, respectively. Comparison of enolase enzyme activities in whole cell extracts and cell culture supernatants showed the enzyme to belocated primarily within cells. Extracellular glyceraldehyde- 3-phosphate dehydrogenase activity was absent or lower than that of enolase, despite equivalent intracellular levels. The results suggest that enolase, released from fungi in the absence of host factors, may contribute to enolase found circulating in the blood of patients with hematogenously disseminated candidiasis. In addition, the release from cells of highly immunogenic fungal proteins, such as enolase, may be important in defining the selective stimulation of host antifungal responses during infection.

Infant rats were passively immunized to determine the protective capacity of pneumococcal anticapsular antibodies. Animal-passaged strains of Streptococcus pneumoniae serotypes 1, 4, 5, 6b, 7f, 9v, 14, 18c, 19f, and 23f were used as challenge inocula (1–1500 cfu) in a model of pulmonary infection that resulted in bacteremia, meningitis, and death. From untreated control animals, histologic sections of lung demonstrated infiltrative pneumonia and lung homogenate cultures grew S. pneumoniae at concentrations of 103–108 cfu per gram of lung tissue. A type-specific anti-capsular antibody serum concentration of 0.1–1.15 mg/mL resulted in a statistically significant reduction in mortality compared with the reduction in untreated controls, except for serotype 14, which required 2.32 mg/mL for a significant reduction in mortality. The serum antibody level that provided 50% reduction in mortality ranged from 0.1–3.5 mg/mL for all serotypes.

Concentrations of total immunoglobulins bearing κ and λ light chains were measured in the sera of 215 healthy white children aged 6 months to 10 years. Both κ and λ concentrations increased with age. However, the concentration of immunoglobulins bearing κ light chains increased at a greater rate than those bearing λ light chains (P = .01). Thus, the κ:λ ratio of the youngest children (6–24 months) was significantly lower than that of the oldest (25–130 months) (P = .0015). The relationship between the IgG antibody concentration and the light chain composition of the specific antibody directed to Haemophilus influenzae type b (Hib) polysaccharide was also assessed in 62 of 215 serum samples with detectable Hib antibody. The IgG Hib antibody concentration was strongly correlated with the κ:λ Hib antibody ratio (r = .60, P = .001), and this correlation was independent of age. Thus, light chain selection and response to polysaccharides may be regulated by common mechanisms that mature late in ontogeny.

Moxalactam is the first representative of a new class of potent β-lactam antibiotics. To establish dosage recommendations, the kinetics of moxalactam elimination were studied in 20 patients with various degrees of renal dysfunction. After a 1-g intravenous bolus injection, the elimination half-life increased from 2.2 ± 0.1 hr in normal subjects to 22.3 ± 1.7 hr in anuric patients. Similar correlations were shown between the rate ofcreatinine clearance and the rate of plasma clearance, the rate of renal clearance, and the overall elimination rate constant of moxalactam. No changes in the distribution volumes or metabolic clearance rates of moxalactam were detected. A nomogram for adjustment of moxalactam dosage in patients with any level of renal function was generated, and specific recommendations for moxalactam dosage are discussed.

The suitability of paper-absorbed (PA) fingerstick blood specimens for antibody testing of human immunodeficiency virus type 1 (HIV-1) was examined in two populations of intravenous drug users (IVDU): 393 persons from a drop-in counseling and testing clinic and 145 from a methadone treatment clinic. From the first group, the same 66 immunoblot-confirmed enzyme immunoassay (EIA)-positive specimens were identified in sera from venipuncture and parallel fingerstick PA specimens. The latter had slightly higher EIA mean background levels resulting in 10 immunoblot-negative EIA-positive samples versus 6 in the sera group. HIV-1 seroprevalence was 17% of 393 from the drop-in clinic. By category of IVDU, the rates were 34% and 14% for active and recovering IVDU, respectively (P <.001), and 36% in black and Latino compared with 13% in white IVDU (P< .002). Of the 145 participants in the methadone program, 39% had antibody to HIV-1: 49% for blacks and Latinos compared with 30% in whites (P < .01). The data indicate that antibody testing for HIV-1 by PAis equivalent to the serum antibody assay of venipuncture specimens. The fingerstick method appears to have greater use for serosurveysand screening programs because of convenience, safety, and ease of storage, transport, and processing of samples.

The antigenic relationship between prototype and isolate strains of echovirus types 1 and 8 was confirmed by double-diffusion gel-precipitation studies. All strains shared a common antigen. In addition, some strains possessed a second antigen that related them more closely to one or the other of the prototype strains. The prototype and isolate strains failed to show the classical prime relationship described for echovirus type 6. The antigenic variation is similar to that described for echovirus types 4 and 9. For this reason the diagnostic laboratory should consider the use of antisera to both prototype and variant strains.