Sepsis in previously healthy neonates discharged home after delivery in Soweto, South Africa.

BACKGROUND: There is a paucity of data on the aetiology of neonatal sepsis in sub-Saharan Africa. OBJECTIVES: To investigate the incidence, aetiology and outcomes of physician-diagnosed sepsis in hospitalised neonates who had previously been discharged home after delivery in Soweto, South Africa. METHODS: A retrospective review using data abstracted from clinical and laboratory databases identified physician-diagnosed sepsis cases in neonates admitted to the general paediatric wards at Chris Hani Baragwanath Academic Hospital from January 2015 to September 2016. Neonates with physician-diagnosed sepsis were categorised into two groups based on putative pathogens recovered from blood and/or cerebrospinal fluid specimens: (i) culture-confirmed sepsis; and (ii) culture-negative sepsis. RESULTS: Of 1 826 neonatal admissions, 1 025 (56.2%) had physician-diagnosed sepsis: 166 (16.2%) with culture-confirmed sepsis and 859 (83.8%) with culture-negative neonatal sepsis. The commonest pathogens causing culture-confirmed neonatal sepsis were Streptococcus viridans (n=53; 26.5%), S. agalactiae (n=38; 19.0%), and Staphylococcus aureus (n=25; 12.5%). The case fatality rates for culture-confirmed sepsis and culture-negative sepsis were 10.8% (18/166) and 2.6% (22/859), respectively. The odds of death occurring during hospitalisation was 10-fold (95% confidence interval 3.7 - 26.9) higher in neonates with culture-confirmed sepsis compared with culture-negative sepsis. CONCLUSIONS: In our setting, physician-diagnosed sepsis represents a huge disease burden in previously healthy neonates hospitalised from home. Most sepsis cases were attributed to S. viridans, S. agalactiae and S. aureus.

Maternal and neonatal vitamin D status at birth in black South Africans.

BACKGROUND: Vitamin D deficiency (VDD) in pregnant women has been associated with adverse pregnancy and neonatal outcomes. 25-hydroxyvitamin D (25(OH)D) levels are affected by numerous factors, including vitamin D intake, skin pigmentation, latitude and season of the year; they therefore vary by race and country. Vitamin D status in pregnant women and their offspring in South Africa (SA) is not well established. OBJECTIVES: To assess vitamin D status by measuring serum 25(OH)D in pregnant black SA women and their offspring in Johannesburg (latitude 26°S) and to assess whether vitamin D status is affected by maternal HIV infection. METHODS: We prospectively enrolled pregnant women and their healthy neonates, and measured 25(OH)D in maternal and cord blood at delivery. Pregnant women were stratified by their HIV status. Predictors of maternal and neonatal VDD (levels <30 nmol/L) were assessed using multiple logistic regression analysis. RESULTS: A total of 291 pregnant women and their healthy neonates were enrolled over a 21-month period. Mean (standard deviation) maternal and cord blood 25(OH)D levels were 57.0 (29.7) and 41.9 (21.0) nmol/L and the prevalence of VDD was 15.9% and 32.8%, respectively. On average, concentrations of 25(OH)D in cord blood were ~80% of those in the mother. There was no association between cord 25(OH)D and gestational age, but levels were associated with birth weight (p<0.001). There were no differences in maternal or cord blood 25(OH)D levels between those HIV-infected or uninfected. The predictor of VDD in mothers was giving birth in winter (odds ratio (OR) 2.87, 95% confidence interval (CI) 1.47 - 5.61), and in neonates the predictors were maternal age (OR 16.5, 95% CI 1.82 - 149), being born in winter (OR 3.68, 95% CI 2.05 - 6.61), being born by caesarean section (OR 4.92, 95% CI 1.56 - 15.57) and being of low birth weight (OR 1.99, 95% CI 1.13 - 3.50). CONCLUSIONS: Among black SA women delivering in Johannesburg, about one in six mothers and one in three neonates have 25(OH)D levels indicative of VDD. Maternal HIV status appears not to affect levels of 25(OH)D in either the mother or her neonate. Research on the effects of VDD on the outcomes of pregnancy and the best methods to combat the high prevalence of VDD in women of childbearing age in the SA context is required.

Empyema in children hospitalised at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa: A retrospective study.

BACKGROUND: There is a paucity of information on empyema in children from low- and middle-income countries since the introduction of the pneumococcal conjugate vaccine. OBJECTIVES: To describe the aetiology and management of empyema in a setting of high HIV and tuberculosis (TB) prevalence. METHODS: A retrospective descriptive study was undertaken between January 2012 and December 2016 in children aged <14 years at a large secondary-tertiary referral hospital in Soweto, South Africa. Cases of empyema were identified through administrative databases. Clinical, laboratory and radiological data were extracted from patient records. RESULTS: We identified 65 cases of protocol-defined empyema, including 22 (33.8%) referred from surrounding hospitals. The median age at presentation was 53.2 months (interquartile range (IQR) 19.5 - 103.6). Thirteen patients (20.0%) were HIV-infected and 6 (9.2%) were HIV-exposed but uninfected. A bacterial pathogen was identified in 36 cases (55.3%). The commonest causative organisms were Staphylococcus aureus (14/65, 21.5%) and Streptococcus pneumoniae (5/65, 7.7%). Treatment for TB, initiated in 28 children (43.1%), was more frequent in HIV-infected children (10/13, 76.9%) (p=0.011); however, microbiological evidence of TB was present in only 5 cases (7.7%). Forty-three children (66.2%) had an intercostal drain (ICD) inserted and 16 (24.6%) a pigtail percutaneous catheter, while a fibrinolytic was only used in 6 (10.2%). Eight children (12.3%) had a thoracotomy and 7 (10.7%) had video-assisted thorascopic drainage, all of whom had a prior ICD inserted, a median of 20 days (IQR 10 - 33) before surgery. Overall, 7 children (10.8%) were mechanically ventilated and 1 (1.5%) died. CONCLUSIONS: Our study showed a dominance of S. aureus as a cause of empyema. A high proportion of HIV-infected children with empyema were initiated on TB treatment, highlighting challenges in managing TB-HIV co-infection. Although fibrinolytics or early surgery are recommended, neither practice was common in this setting.

Incidence of tuberculosis meningitis in a high HIV prevalence setting: time-series analysis from 2006 to 2011.

SETTING: This study was undertaken at a tertiary hospital in Soweto, a peri-urban low-middle income setting. Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis. OBJECTIVE: To describe the incidence, mortality and clinical features of TBM in human immunodeficiency virus (HIV) infected and non-infected children in South Africa from 2006 to 2011. DESIGN: A retrospective, cross-sectional descriptive study. METHODS: Electronic databases and individual patient records of all children with a discharge diagnosis of TBM were reviewed to yield incidence rate ratios (IRR) in HIV-infected and non-infected children. Clinical, laboratory and radiological characteristics were compared between HIV-infected and non-infected children with TBM. RESULTS: Overall TBM incidence per 100 000 population in 2006 was 6.9 (95%CI 4.4-10.3) and 9.8 (95%CI 6.9-13.6) in 2009, but had subsequently declined to 3.1 (95%CI 1.6-5.5) by 2011. There was a significant reduction in the IRR of TBM among HIV-infected children (IRR 0.916, P = 0.036). The overall case fatality ratio was 6.7%. Clinical features, cerebrospinal fluid and computed tomography brain findings were similar in HIV-infected and non-infected children. CONCLUSION: TBM incidence decreased over the study period from 2006 to 2011, and was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

Focal segmental glomerulosclerosis and partial deletion of chromosome 6p: a case report.

We treated a patient with 6p partial deletion syndrome diagnosed after proteinuria was detected during developmental examination 3 years after birth. External anomalies included ocular hypertelorism, saddle nose, elongated philtrum, tent-like lips, and low-set auricles. Mental retardation was evident. The karyotype was 46,XX,del(6) (p.22.1-p22.3) with an interstitial deletion. The kidneys showed no abnormality on imaging such as hydronephrosis, atrophy, or malformation. Examination of a renal biopsy specimen disclosed focal segmental glomerulosclerosis. No cardiac anomaly or Rieger anomaly, which often are present in this syndrome, were noted.

Phylogeny of Litsea and related genera (Laureae-Lauraceae) based on analysis of rpb2 gene sequences.

The relationship between Litsea and related genera is currently unclear. Previous molecular studies on these taxa using cpDNA and nrITS were unable to produce well-resolved phylogenetic trees. In this study, we explored the potential of the rpb2 gene as a source of molecular information to better resolve the phylogenetic analysis. Although rpb2 was believed to be a single-copy gene, our cloning results showed that most species examined possessed several copies of these sequences. However, the genetic distance among copies from any one species was low, and these copies always formed monophyletic groups in our molecular trees. Our phylogenetic analyses of rpb2 data resulted in better resolved tree topologies compared to those based on cpDNA or nrITS data. Our results show that monophyly of the genus Litsea is supported only for section Litsea. As a genus, Litsea was shown to be polyphyletic. The genera Actinodaphne and Neolitsea were resolved as monophyletic groups in all analyses. They were also shown to be sisters and closer to the genus Lindera than to the genus Litsea. Our results also revealed that the genus Lindera is not a monophyletic group.

Effectiveness of sodium hypochlorite in preventing inoculation of periapical tissues with contaminated patency files.

The aim of this study was to analyze the effectiveness of 5.25% sodium hypochlorite (NaOCI) in preventing inoculation of periapical tissues with contaminated patency files. Twenty-eight extracted human permanent teeth with single canals were used in the study. Group I teeth were filled with NaOCl, and #15 stainless steel files contaminated with Streptococcus sanguis (ATCC #10556) were allowed to pass through the NaOCI into the culture medium. The teeth in group II were also filled with NaOCl, but the contaminated files used in group II canals were immersed in NaOCl for 10 s prior to being placed into the canals and cultured. The negative control group used sterile files (0% growth), the first positive control group used contaminated patency files in teeth with empty canals (100% growth), and the second positive control group placed contaminated files into broth next to teeth filled with NaOCl (to evaluate potential chlorine leakage; 100% growth). The experimental results showed no positive growth of S. sanguis for groups I and II, indicating that the NaOCl present in the canal after irrigation was sufficient to kill the test organism.

Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women.

CONTEXT: Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections in the United States. No prospective study has shown the ability of condoms to reduce transmission of HSV-2. OBJECTIVE: To evaluate risk factors for HSV-2 acquisition and efficacy of condoms in prevention of HSV-2 transmission. DESIGN: Analysis of data from a randomized, double-blind, placebo-controlled trial conducted December 13, 1993, to June 28, 1996, of an ineffective candidate HSV-2 vaccine with 18 months of follow-up. SETTING: Eighteen clinical trial centers in the United States. PARTICIPANTS: A total of 528 monogamous couples discordant for HSV-2 infection, including an HSV-2-susceptible population of 261 men and 267 women. MAIN OUTCOME MEASURE: Acquisition of HSV-2 infection by susceptible partners, compared with those remaining free of HSV-2 with regard to demographic characteristics, sexual activity, and condom use. RESULTS: Twenty-six women (9.7%) vs 5 men (1.9%) acquired HSV-2, for a rate per 10 000 sex acts (episodes of sexual intercourse) of 8.9 vs 1.5, respectively (P<.001). In multivariable analysis, younger age (adjusted hazard ratio [HR] per 5 years, 1.57; 95% confidence interval [CI], 1.22-2.04), seropositivity for HSV-1 and HSV-2 vs HSV-2 alone in the source partner (adjusted HR, 2.34; 95% CI, 1.14-4.82), and more frequent sexual activity (adjusted HR per additional sex act per week, 1.10; 95% CI, 1.01-1.19) were associated with higher risk of HSV-2 acquisition. Condom use during more than 25% of sex acts was associated with protection against HSV-2 acquisition for women (adjusted HR, 0.085; 95% CI, 0.01-0.67) but not for men (adjusted HR, 2.02; 95% CI, 0.32-12.50). Risk of HSV-2 transmission declined from 8.5 per 100 person-years in the initial 150-day interval to 0.9 per 100 person-years in the final 150-day interval (P =.002 for trend), concurrent with a decrease in sexual activity and proportion of sex acts occurring when the source partner had genital lesions. CONCLUSIONS: Condom use offers significant protection against HSV-2 infection in susceptible women. Changes in sexual behavior, correlated with counseling about avoiding sex when a partner has lesions, were associated with reduction in HSV-2 acquisition over time. These data suggest that identification of discordant couples can reduce transmission of HSV-2, especially for heterosexual couples in which the male partner has HSV-2 infection.

Effects of antigen dose and immunization regimens on antibody responses to a cytomegalovirus glycoprotein B subunit vaccine.

The purpose of this phase I study was to evaluate the safety and immunogenicity of 2 doses of cytomegalovirus glycoprotein B (CMV gB)/MF59 vaccine at 3 different immunization schedules. Ninety-five volunteers were randomized to 6 groups. Antibodies to gB represent the majority of the CMV-specific neutralizing response. Three groups received 5 microgram of gB antigen combined with MF59 (a proprietary adjuvant) and 3 groups received a 30-microgram dose at 0, 1, and 2 months; 0, 1, and 4 months; or 0, 1, and 6 months. The vaccine was well tolerated, and there was no significant difference in antibody production between the 2 doses. The vaccine induced highest antibody titers when given at 0, 1, and 6 months. A low dose of CMV gB/MF59 may be the preferred dose for future studies.

An acellular pertussis vaccine in healthy adults: safety and immunogenicity. Pennridge Pediatric Associates.

Recent data indicate that Bordetella pertussis can be an important cause of illness in adolescents and adults. In a randomized observer- and subject-blinded study, adults (> or = 18 years of age) received an acellular pertussis (aP) vaccine containing genetically inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), or a saline placebo, and were monitored for safety and immunogenicity. IgG antibodies to PT, FHA, and PRN were measured by enzyme-linked immunosorbent assay (ELISA) and PT neutralization by a Chinese hamster ovary (CHO) cell assay. Local reactions, more common in the aP group, were mild and transient. One month after immunization, geometric mean ELISA antibody concentrations for the aP and placebo groups, respectively, were: anti-PT, 463 and 7.6; anti-FHA, 417 and 18; and anti-PRN, 855 and 14. The anti-PT neutralization titers for the aP and placebo groups were 1:3439 and 1:58 respectively. This aP vaccine is a safe and immunogenic candidate booster vaccine against pertussis for adults.

A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant.

The safety and immunogenicity of a novel hepatitis B virus (HBV) vaccine containing recombinant PreS2 and S antigens combined with MF59 adjuvant (HBV/MF59) was evaluated in healthy adults (N=230) who were randomized to receive 2 or 3 immunizations of either the study vaccine or a licensed control vaccine (Recombivax HB). After a single immunization, 105 of 118 (89%) recipients of HBV/MF59 achieved protective serum levels of anti-HBs antibody (> 10 mIU/ml), compared with 13 of 110 (12%) recipients of licensed vaccine (P < 0.001). The geometric mean titer (GMT) after 2 doses of HBV/MF59 given 2 months apart (13,422 mIU/ml) was more than 5-fold higher than that following 3 doses of licensed vaccine given over 6 months (2,346 mIU/ml; P < 0.001). The GMT following 3 injections of HBV/MF59 (249,917 mIU/ml) was 100-fold higher than licensed vaccine (P < 0.001). Anti-PreS2 antibodies were elicited in over 90% of the subset of HBV/MF59 recipients tested. Both vaccines were well tolerated; transient, mild-to-moderate local inflammation was the major postinjection reaction.

Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group.

CONTEXT: In the last 3 decades, herpes simplex virus type 2 (HSV-2) infection seroprevalence and neonatal herpes have increased substantially. An effective vaccine for the prevention of genital herpes could help control this epidemic. OBJECTIVE: To evaluate the efficacy of a vaccine for prevention of HSV-2 infection. DESIGN: Two randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 microg each of 2 major HSV-2 surface glycoproteins (gB2 and gD2) against which neutralizing antibodies are directed, administered at months 0, 1, and 6. Control subjects were given a citrate buffer vehicle. Participants were followed up for 1 year after the third immunization. SETTING AND PARTICIPANTS: We enrolled 2393 persons from December 10, 1993, to April 4, 1995, who were HSV-2 and human immunodeficiency virus seronegative. One trial with 18 centers enrolled 531 HSV-2-seronegative partners of HSV-2-infected persons; the other, with 22 centers, enrolled 1862 persons attending sexually transmitted disease clinics. A total of 2268 (94.8%) met inclusion criteria and were included in the analysis with 1135 randomized to placebo and 2012 to vaccine. MAIN OUTCOME MEASURE: Time to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group. RESULTS: Time-to-event curves indicated a 50% lower acquisition rate among vaccine vs placebo recipients during the initial 5 months of the trial; however, overall vaccine efficacy was 9% (95% confidence interval, -29% to 36%). Acquisition rates of HSV-2 were 4.6 and 4.2 per 100 patient-years in the placebo and vaccine recipients, respectively (P =.58). Follow-up of vaccine recipients acquiring HSV-2 infection showed vaccination had no significant influence on duration of clinical first genital HSV-2 episodes (vaccine, median of 7.1 days; placebo, 6.5 days; P>.10) or subsequent frequency of reactivation (median monthly recurrence rate with vaccine, 0.2; with placebo, 0.3; P>.10). The vaccine induced high levels of HSV-2-specific neutralizing antibodies in vaccinated persons who did and did not develop genital herpes. CONCLUSIONS: Efficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.

Immunotherapy of recurrent genital herpes with recombinant herpes simplex virus type 2 glycoproteins D and B: results of a placebo-controlled vaccine trial.

To determine the safety, immunogenicity, and efficacy of a recombinant herpes simplex virus type 2 glycoprotein D and B vaccine in the treatment of recurrent genital herpes, a randomized, placebo-controlled trial was held at two referral centers. Healthy patients with 4-14 recurrences per year received injections of both glycoproteins in MF59 adjuvant or of MF59 alone at 0, 2, 12, and 14 months. For 18 study months, the rate and number of recurrences, the duration and severity of the first confirmed recurrence, vaccine immunogenicity, and rates of local and systemic reactions were determined. The monthly rate of recurrences was not significantly improved, but the duration and severity of the first study outbreak was reduced significantly by vaccination. Glycoprotein-specific and neutralizing antibodies were boosted by vaccination for the duration of the study. This vaccine is safe and immunogenic and ameliorated an observed first postvaccination genital recurrence, but it does not reduce recurrence frequency.

Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers.

OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY DESIGN: This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except for a higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product.

Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G by intravenous bolus in AIDS and AIDS-related complex.

To assess the safety, pharmacokinetics, and antiviral effects of intravenous recombinant CD4 immunoglobulin G (CD4-IgG), a 12-week Phase One study with an optional maintenance phase was performed. Twenty-two subjects with advanced human immunodeficiency virus (HIV) infection were enrolled; 15 subjects completed the initial 12 weeks. CD4-IgG doses were 30, 100, or 300 micrograms/kg weekly; 1,000 micrograms/kg once, twice, or three times per week; or 3,000 micrograms/kg twice weekly. Serum concentrations of CD4-IgG increased linearly with dose, with average peak serum concentrations of 22 micrograms/ml with 1,000 micrograms/kg. CD4-IgG was well tolerated; one patient had self-limited tachycardia and flushing associated with CD4-IgG therapy. No changes were seen in CD4 cell counts, hematologic or coagulation studies, serum chemistries, HIV p24 antigen titers, or plasma HIV titers. No subject developed anti-CD4 antibodies. HIV isolates from five patients had IC90 values that were higher than the peak concentrations of CD4-IgG achieved in those patients. Additional studies that achieve higher CD4-IgG concentrations are necessary to evaluate the antiviral activity of this compound.

Transport of recombinant human CD4-immunoglobulin G across the human placenta: pharmacokinetics and safety in six mother-infant pairs in AIDS clinical trial group protocol 146.

Recombinant CD4-immunoglobulin G (rCD4-IgG) is a 98-kDa human immunoglobulin-like protein that is produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain. This hybrid molecule was given to human immunodeficiency virus (HIV)-infected pregnant women at the onset of labor by intravenous bolus at 1 mg/kg of body weight (group A; n = 3) and 1 week prior to and at the onset of labor by the same route and at the same dose (group B; n = 3). In addition to pharmacokinetic studies, safety in the mothers and infants was determined through routine chemistries, hematology, and urinalysis; immunologic and HIV infection statuses in the infants were assessed through lymphocyte cultures, p24 antigen level determination, culture of HIV from plasma, PCR, lymphocyte subset enumeration, quantitative immunoglobulin analysis, and lymphocyte proliferation. Thirty minutes after the rCD4-IgG injection, concentrations in maternal serum were 12 to 23 micrograms/ml. These concentrations declined slowly, with initial and terminal half-lives (mean +/- standard deviation) of 9.95 +/- 3.23 and 47.6 +/- 22.3 h, respectively. Infants were born 2.6 to 46.5 h after rCD4-IgG administration; concentrations of rCD4-IgG in cord blood ranged from 28 to 107 ng/ml. The half-life of rCD4-IgG in infants ranged from 5 to 29 h. These data demonstrate that the transfer of rCD4-IgG from the mother to the fetus is rapid and that newborns do not appear to have any difficulty eliminating rCD4-IgG. No safety concerns in mothers or infants were encountered. Although the study did not address the question of efficacy, none of the infants was HIV type 1 infected 36 months later. In summary, these findings document that bifunctional immune molecules can be transported across the placenta, and this general approach may be used in the future to block vertical transmission of HIV type 1.

Treatment of steroid-dependent asthma with recombinant interferon-gamma.

We have recently reported that treatment of patients with severe atopic dermatitis with recombinant interferon-gamma (rIFN-gamma) resulted in clinical improvement as well as a reduction of circulating eosinophils. Since IgE-dependent late phase allergic reactions and eosinophilic infiltration are thought to play an important role in the pathogenesis of asthma, we conducted a two centre randomized double-blind placebo-controlled trial of rIFN-gamma in the treatment of steroid-dependent asthma. Patients were treated with daily subcutaneous injections of either 0.05 mg/m2 rIFN-gamma (n = 9) or placebo (n = 11) for 90 days. All patients completed the study without significant drug toxicity noted. Oral prednisone dose, forced expiratory volume in 1 second (FEV1), peak expiratory flow rates (PEFR) and circulating eosinophil counts were monitored throughout the trial. There was no significant difference between the two treatment groups in per cent reduction from baseline of daily prednisone (P = 0.51). There was also no significant difference between the two treatment groups in per cent change from baseline in FEV1 (P = 0.54) or in PEFR (P = 0.75). Total circulating eosinophil counts decreased by 31% in the rIFN-gamma group and increased by 8.5% in the placebo group (P = 0.09). We conclude that this treatment regimen was not effective in patients with steroid-dependent asthma.

Induction of HIV-1-neutralising and syncytium-inhibiting antibodies in uninfected recipients of HIV-1IIIB rgp120 subunit vaccine.

A recombinant human immunodeficiency virus 1 IIIB (HIV-1IIIB) gp120 subunit vaccine (IIIB-rgp120/HIV-1, Genentech) was tested for safety and immunogenicity in a randomised, double-blind, placebo-controlled phase-I trial. HIV-1-seronegative adult volunteers received three 100 micrograms or 300 micrograms doses of IIIB-rgp120/HIV-1 in alum adjuvant (10 vaccinees in each group), or alum adjuvant alone (8 vaccinees), at 0, 4, and 32 weeks by intramuscular injection. The three injections were well tolerated in both vaccine groups. Antibodies that neutralised homologous HIV-1IIIB were induced in 9 of 10 recipients after three 300 micrograms doses, and 6 of these 9 sera also neutralised heterologous HIV-1SF2. A dose response was evident, since three 100 micrograms injections induced lower titres of HIV-1IIIB neutralising antibodies and in fewer recipients (5 of 9) than the higher dose, with no neutralisation of HIV-1SF2. Similarly, syncytia-inhibiting, CD4-rgp120-blocking, and HIV-1IIIB V3-binding antibodies were induced in a dose dependent manner. Response to the 300 micrograms per dose vaccination occurred in a larger proportion of volunteers and at higher mean titres than seen in previous human trials with other recombinant envelope subunit vaccines or live vaccinia-env priming followed by envelope subunit boosting.