Malaria results in over 650 000 deaths each year; thus, there is an urgent need for an effective vaccine. Pre-clinical studies and recently reported human trials suggest that pre-erythrocytic stage ...vaccines can provide protection against infection. A Phase 1, randomized, placebo-controlled, dose-escalation study was conducted with a vaccine composed of a replication-deficient adenovirus-35 backbone with P. falciparum circumsporozoite (CS) surface antigen (Ad35.CS.01). Healthy adult subjects received three doses of 10
8
, 10
9
, 10
10
, or 10
11
vp/mL Ad35.CS.01 vaccine or saline placebo intramuscularly at 0, 1, and 6-mo intervals. Adverse events were assessed and anti-CS antibody responses were determined by ELISA. Seventy-two individuals were enrolled, with age, gender, and ethnicity similar across each study arm. While the vaccine was generally well tolerated, adverse events were more frequent in the highest dose groups (10
10
and 10
11
vp/mL). More robust humoral responses were also noted at the highest doses, with 73% developing a positive ELISA response after the three dose series of 10
11
vp/mL. The Ad35.CS.01 vaccine was most immunogenic at the highest dosages (10
10
and 10
11
vp/mL). Reactogenicity findings were more common after the 10
11
vp/mL dose, although most were mild or moderate in nature and resolved without therapy.
C(6), a Borrelia burgdorferi-derived peptide, is used as the antigen in the C(6)-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative ...value in anti-C(6) antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans EM; n=93) or early disseminated (multiple EM; n=27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C(6) negative or had a >or=4-fold decrease in C(6) antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C(6) negative) for all of the multiple-EM patients (P<0.0001) and in 89% of the single-EM patients (P<0.0001). These results indicate that a decline in anti-C(6) antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis.
To determine the least worsening of a visual field (VF) and the least number of confirming tests needed to identify progression of glaucomatous VF defects.
Cohort study of participants in a clinical ...trial.
Seven hundred fifty-two eyes of 565 patients with advanced glaucoma.
Visual field tests were quantified with the Advanced Glaucoma Intervention Study (AGIS) VF defect score and the Humphrey Field Analyzer mean deviation (MD). Follow-up was 8 to 13 years.
Two measures based on the AGIS VF defect score: (1) sustained decrease of VF (SDVF), a worsening from baseline by 2 (alternatively, 3 or 4) or more units and sustained for 2 (alternatively, 3) consecutive 6-month visits and (2) after the occurrence of SDVF, the average percent of eyes with worsening by 2 (alternatively, 3 or 4) or more units from baseline. Two similar measures based on MD.
Based on the original AGIS criteria for SDVF (a worsening of 4 units in the AGIS score sustained during 3 consecutive 6-month visits), 31% of eyes had an SDVF. The percent of eyes with a sustained event increases by approximately 10% when either the minimum number of units of field loss or the minimum number of 6-month visits during which the loss is sustained decreases by 1. During 3 years of follow-up after a sustained event, a worsening of at least 2 units was found in 72% of eyes that had a 2-visit sustained event. The same worsening was found in 84% of eyes that had a 3-visit sustained event. Through the next 10 years after a sustained event, based on worsening of 2, 3, or 4 units at 2 or 3 consecutive tests, the loss reoccurred, on average, in >/=75% of study eyes. Results for MD are similar.
In patients with advanced glaucoma, a single confirmatory test 6 months after a VF worsening indicates with at least 72% probability a persistent defect when the worsening is defined by at least 2 units of AGIS score or by at least 2 decibels of MD. When the number of confirmatory tests is increased from 1 to 2, the percentage of eyes that show a persistent defect increases from 72% to 84%.
PURPOSE: To examine the relationships between baseline risk factors and sustained decrease of visual field (SDVF) and sustained decrease of visual acuity (SDVA).
DESIGN: Cohort study of participants ...in the Advanced Glaucoma Intervention Study (AGIS).
METHODS: This multicenter study enrolled patients between 1988 and 1992 and followed them until 2001; 789 eyes of 591 patients with advanced glaucoma were randomly assigned to one of two surgical sequences, argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy (ATT) or trabeculectomy-ALT-trabeculectomy (TAT). This report is based on data from 747 eyes. Eyes were offered the next intervention in the sequence upon failure of the previous intervention. Failure was based on recurrent intraocular pressure elevation, visual field defect, and disk rim criteria. Study visits occurred every 6 months; potential follow-up ranged from 8 to 13 years. For each intervention sequence, Cox multiple regression analyses were used to examine the baseline characteristics for association with two vision outcomes: SDVF and SDVA. The magnitude of the association is measured by the hazard ratio (HR), where HR for binary variables is the relative change in the hazard (or risk) of the outcome in eyes with the factor divided by the hazard in eyes without the factor, and HR for continuous variables is the relative change in the hazard (or risk) of the outcome in eyes with a unit increase in the factor.
RESULTS: Characteristics associated with increased SDVF risk in the ATT sequence are: less baseline visual field defect (hazard ratio HR = 0.86,
P < .001, 95% CI = 0.82–0.90), male gender (HR = 2.23,
P < .001, 1.54–3.23), and worse baseline visual acuity (HR = 0.96,
P = .001, 0.94–0.98); in the TAT sequence: less baseline visual field defect (HR = 0.93,
P = .001, 0.89–0.97) and diabetes (HR = 1.87,
P = .007, 1.18–2.97). Characteristics associated with increased SDVA risk in both treatment sequences are better baseline acuity (ATT: HR = 1.05,
P < .001, 1.02–1.09; TAT: HR = 1.06,
P < .001, 1.03–1.08), older age (ATT: HR = 1.05,
P = .001, 1.02–1.08; TAT: HR = 1.04,
P = .002, 1.01–1.06), and less formal education (ATT: HR = 1.92,
P = .001, 1.29–2.88; TAT: HR = 1.77,
P = .002, 1.22–2.54).
CONCLUSIONS: For SDVF, risk factors were better baseline visual field in both treatment sequences, male gender, and worse baseline visual acuity in the ATT sequence, and diabetes in the TAT sequence. For SDVA, risk factors in both treatment sequences were better baseline visual acuity, older age, and less formal education.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PURPOSE: To investigate the association of pre-intervention and post-intervention patient and eye characteristics with failure of argon laser trabeculoplasty (ALT) and trabeculectomy.
DESIGN: Cohort ...study of participants in the Advanced Glaucoma Intervention Study.
METHODS: This multicenter study took place between 1988 and 2001. Between 1988 and 1992, 789 eyes of 591 patients aged 35 to 80 years with advanced glaucoma were randomized into one of two surgical treatment sequences: argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy or trabeculectomy-ALT-trabeculectomy. Upon study-defined failure (based on maximum medications, sustained intraocular pressure (IOP) elevation, visual field defect, and disk rim deterioration) of each intervention, patients were offered the subsequent intervention. Potential follow-up was 8 to 13 years. This report is based on data from 779 eyes that had at least 3 months of follow-up. The main outcome measures are failure of ALT and trabeculectomy, whether as first or second interventions. Effect size is measured by the hazard ratio (HR) and its corresponding 95% confidence interval (CI) obtained from Cox multiple regression analysis, where HR corresponds to the coefficient of change in risk associated with a unit increase in a factor. For binary factors, this corresponds to the change in risk in eyes with the factor relative to the risk in eyes without the factor.
RESULTS: Pre-intervention factors associated with failure of ALT are younger age (HR = 0.98, CI = 0.96–0.99,
P = .009) and higher IOP (1.11, 1.08–1.15,
P < .001). Pre-intervention factors associated with failure of trabeculectomy are younger age (HR = 0.97, CI = 0.95–0.99,
P = .005) and higher IOP (1.04, 1.01–1.06,
P = .002), as well as diabetes (2.86, 1.88–4.36,
P < .001) and any postoperative complication (1.99, 1.35–2.93,
P < .001). Individual postoperative complications significantly associated with increased risk of failure of trabeculectomy are elevated IOP (3.4, 1.9–6.1,
P < .001) and marked inflammation (2.4, 1.3–4.6,
P = .006).
CONCLUSIONS: In this study, ALT failure was associated with younger age and higher pre-intervention IOP. Trabeculectomy failure was associated with younger age, higher pre-intervention IOP, diabetes, and one or more postoperative complications, particularly elevated IOP and marked inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Despite significant rises in total CD4 T cells, the process of immune reconstitution in adults with HIV infection treated with potent antiretroviral treatment results in a rather slow increase in ...phenotypically naive lymphocytes. In children more than in adults, thymic function may be at least partly restored when disease-induced immunosuppression is attenuated by pharmacological means.
Twenty-five vertically infected and antiretroviral-experienced zidovudine (ZDV)/ZDV plus didanosine (ddl) children were prospectively followed during 12 months of treatment with lamivudine (3TC), stavudine (d4T) and indinavir (IDV). The plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined. The relationship between the degree of immune reconstitution and thymus volume assessed by nuclear magnetic resonance was also examined.
An early and steep increase in CD45RA+62L+ T cells was observed in parallel with a sustained decrease in plasma HIV RNA levels and a significant rise in total CD4 T cells. This increase was significantly greater than that observed in CD4+CD45RO+ T cells. Analysis of the CD4 T cell receptor (TCR) beta repertoire and T helper function showed the ability to reconstitute families almost completely absent at baseline, and a substantial improvement of antigen-specific responses by peripheral blood lymphocytes. The rise in CD4 cells and in CD4+CD45RA+62L+ T cells was statistically associated with changes in thymus size observed over time.
These data suggest a relevant contribution of the thymus to reconstitution of the peripheral pool of T cells in vertically HIV-infected children treated with potent antiretroviral regimens.
OBJECTIVEThe purpose of this study was to characterize auditory function in patients diagnosed with post-treatment Lyme disease syndrome (PTLDS).
DESIGNEighteen patients with PTLDS were evaluated and ...compared to a normal population. Evaluations consisted of pure tone and speech thresholds, word recognition (WRS), acoustic immittance battery, auditory brain stem response (ABR), and loudness discomfort level (LDL). Both seropositive and seronegative patients were evaluated. Audiologists were blinded to patient status.
RESULTSForty four percent of the patients had one or more abnormal pure tone thresholds compared to gender- and age-adjusted norms. Thirty-one percent showed abnormally reduced LDLs, and 17% had abnormal acoustic reflexes at one or more frequencies.
CONCLUSIONSThis paper catalogs previously unstudied long-term auditory system sequelae resulting from PTLDS. Our most significant finding was the dramatically reduced loudness tolerance in the presence of either normal or minimally impaired hearing. The clinician is encouraged to consider PTLDS when confronted with these or similar findings in patients having history of Borrelia burgdorferi infection and continued complaints.
To investigate the occurrence of AIDS dementia complex (ADC) in Italy and its incidence over time, examining possible correlations between this condition and some demographic and immunological ...variables.
Inception cohort. Data collected from the case notification forms of the Italian National AIDS Registry.
16813 consecutive AIDS cases reported to the National AIDS Registry from August 1, 1987 through October 31, 1993 were included.
All data refer to the time of AIDS diagnosis as reported on the case notification forms. Main analyses of the monthly proportion of ADC cases were by multiple logistic regression.
1364 subjects (8.1%) were reported with a diagnosis of ADC as the first AIDS defining disease, either as the only manifestation or associated with other AIDS defining conditions. At the time of AIDS diagnosis, the observed ADC/AIDS proportion was significantly higher among intravenous drug users (IVDU), 9.1%, compared to heterosexuals, 6.3%, and homo-bisexual men, 5.2%. Simple logistic regression analysis showed a significant (p < 0.0001) quadratic trend in the monthly ADC/AIDS proportion, peaking in March 1990 and decreasing thereafter. Multiple logistic regression, adjusting for month of diagnosis, showed that IVDUs have consistently the highest risk and homo-bisexual men the lowest, although differences tended to decrease with increasing age. Older age, in fact, was highly associated with an increased risk, especially within the homo-bisexual and heterosexual transmission categories. CD4 + cells counts proved to have no significant effect on the risk of progressing to AIDS with ADC rather than with any other AIDS indicative disease.
ADC is a relatively frequent manifestation at diagnosis of AIDS among Italian patients, and particularly in IVDUs. Differences in its occurrence were found according to time of diagnosis, transmission category and age.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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