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Biomedical subjects

J Todd

Publications and source records attributed to J Todd.

At least 91 records · Page 5Linked to original sources
PubMed1996

Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection. AIDS Clinical Trials Group (ACTG) 116B/117 Study Team. ACTG Virology Committee Resistance and HIV-1 RNA Working Groups.

Human immunodeficiency virus (HIV)-1 RNA level in plasma was evaluated as a surrogate marker for disease progression in a clinical trial of advanced HIV-1 infection. Baseline HIV-1 RNA level was an independent predictor of disease progression (relative hazard [RH] for each doubling of HIV-1 RNA level, 1.26; 95% confidence interval [CI], 1.03-1.54; P = .02), after adjusting for the week 4 change in HIV-1 RNA level, baseline CD4 cell count, syncytium-inducing phenotype, clinical status at study entry, and therapy randomization. A 50% reduction in HIV-1 RNA level was associated with a 27% decrease in the adjusted risk of disease progression during the study (RH, 0.73; 95% CI, 0.52-1.02; P = .07). The partial validation of HIV-1 RNA as a predictor for clinical end points has implications for the use of HIV-1 RNA in clinical trials and practice.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

Clinical Protocols↗
PubMed1996

An enhanced-sensitivity branched-DNA assay for quantification of human immunodeficiency virus type 1 RNA in plasma.

The quantification of human immunodeficiency virus type 1 (HIV-1) RNA has facilitated clinical research and expedited the development of antiretroviral drugs. The branched-DNA (bDNA) assay provides a reliable method for the quantification of HIV-1 RNA in human plasma and is considered one of the most reproducible assays ready for use in clinical trials. A series of oligonucleotide probe design and solution changes have been developed to enhance the sensitivity of the bDNA assay while maintaining its performance characteristics. Among the changes incorporated into the enhanced-sensitivity bDNA (ES bDNA) assay to reduce the background level and enhance the signal are the use of shorter overhang sequences of target probes for capture, the cruciform design of target probes for amplification, and the addition of preamplifier molecules. The ES bDNA assay is at least 20-fold more sensitive than the first-generation bDNA assay, yet it maintains a high level of accuracy, linearity, and reproducibility. Further, quantification values obtained with the ES bDNA assay and the first-generation bDNA assay are highly correlated, thus allowing for meaningful comparisons of HIV-1 RNA levels in specimens tested with either assay. The ES bDNA assay may be useful in determining the prognostic value of HIV-1 RNA levels of below 10,000 copies per ml and in assessing the clinical benefit of antiretroviral therapy-induced decreases in plasma HIV-1 RNA sustained at levels of below 10,000 copies per ml.

Anti-HIV Agents↗
PubMed1995

Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.

A randomised trial was done to evaluate the impact of improved sexually transmitted disease (STD) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania. HIV incidence was compared in six intervention communities and six pair-matched comparison communities. A random cohort of about 1000 adults aged 15-54 years from each community was surveyed at baseline and at follow-up 2 years later. Intervention consisted of establishment of an STD reference clinic, staff training, regular supply of drugs, regular supervisory visits to health facilities, and health education about STDs. 12,537 individuals were recruited. Baseline HIV prevalences were 3.8% and 4.4% in the intervention and comparison communities, respectively. At follow-up, 8845 (71%) of the cohort were seen. Of those initially seronegative, the proportions seroconverting over 2 years were 48 of 4149 (1.2%) in the intervention communities and 82 of 4400 (1.9%) in the comparison communities. HIV incidence was consistently lower in the intervention communities in all six matched pairs. Allowing for the community-randomised design and the effects of confounding factors, the estimated risk ratio was 0.58 (95% CI 0.42-0.79, p = 0.007). No change in reported sexual behaviour was observed in either group. We conclude that improved STD treatment reduced HIV incidence by about 40% in this rural population. This is the first randomised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population.

Adolescent↗
PubMed1995

Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma.

Quantification of HIV-1 RNA in human plasma has provided unique insight into AIDS pathogenesis and promises to hasten progress in antiretroviral therapy and vaccine research. However, no generally available HIV-1 RNA assay has yet been subjected to rigorous clinical testing or to comparative evaluation with research-based RNA assays using large numbers of well-characterized clinical specimens. In this study, the Chiron Quantiplex branched DNA (bDNA) signal amplification assay was used to measure viral RNA in the plasma of 152 HIV-1-positive individuals at all stages of infection and in 12 patients before and after initiating zidovudine therapy. Eighty-six percent of patients had bDNA assay results above the 10,000-RNA Eq/ml sensitivity cutoff. Branched DNA values were significantly correlated with plasma viral RNA levels determined by quantitative competitive polymerase chain reaction (QC-PCR) assay (Spearman rank correlation, r = 0.89), infectious plasma virus titers (r = 0.72), p24 antigen levels (r = 0.51), immune complex dissociated p24 antigen levels (r = 0.56), and CD4+ lymphocyte counts (r = -0.72; p < 0.0001 for all comparisons). Plasma viral RNA determinations by bDNA and QC-PCR assays were quantitatively similar in the range of 10(4) to 10(7) RNA molecules/ml [log bDNA = 0.93 + 0.80 (log QC-PCR); R2 = 0.81, p < 0.0001] and declined identically following the institution of zidovudine therapy (68-73% decrease from baseline). The close quantitative correlation between bDNA and QC-PCR results, and their significant association with other viral markers and CD4+ counts, support the use of plasma viral RNA measurement in HIV-1 clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants.

The safety and immunogenicity of a group A plus group C meningococcal polysaccharide-CRM197 conjugate vaccine was evaluated in 304 8- to 10-week-old Gambian infants. Infants were immunized with one, two, or three doses of conjugate vaccine or with two doses of a meningococcal A plus C polysaccharide vaccine. The conjugate vaccine produced few systemic side effects, and local reactions were similar to those produced by the polysaccharide vaccine. Postvaccination group A meningococcal polysaccharide antibody levels, measured by ELISA, increased progressively after one, two, or three doses of conjugate vaccine. However, one dose of conjugate vaccine given at the age of 6 months induced a higher group C meningococcal antibody response than did two doses of conjugate vaccine given at 2 and 6 months. Two doses of conjugate vaccine induced higher levels of antibody than did two doses of polysaccharide vaccine. Thus, this new meningococcal conjugate vaccine proved to be safe and immunogenic.

Antibodies, Bacterial↗
PubMed1995

A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 1. Design.

OBJECTIVE: To describe the rationale and design of a randomized trial of the impact of improved services for the treatment of sexually transmitted diseases (STD) on the incidence of HIV infection in Mwanza Region, Tanzania. METHODS: The likely impact of improved STD treatment services on HIV incidence, and the need for empirical information on the effectiveness of this intervention strategy, are discussed. The rationale and design of such an intervention programme in Mwanza Region, and of a community-randomized trial to measure the impact of the programme on HIV and other STD, are presented. Problems in the design and interpretation of the trial are reviewed. RESULTS: Results of the baseline survey of the cohort of over 12,000 adults in 12 communities are presented in a companion paper. CONCLUSION: There is an urgent need for effective preventive measures against the HIV epidemic in sub-Saharan Africa and other developing regions. Improved STD treatment has been promoted as a potentially effective strategy, but there is little empirical information on its impact. The trial in Mwanza Region is the first randomized study of this intervention and should provide valuable data for health policy makers.

Adult↗
PubMed1995

A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 2. Baseline survey results.

OBJECTIVES: To determine baseline HIV prevalence in a trial of improved sexually transmitted disease (STD) treatment, and to investigate risk factors for HIV. To assess comparability of intervention and comparison communities with respect to HIV/STD prevalence and risk factors. To assess adequacy of sample size. SETTING: Twelve communities in Mwanza Region, Tanzania: one matched pair of roadside communities, four pairs of rural communities, and one pair of island communities. One community from each pair was randomly allocated to receive the STD intervention following the baseline survey. METHODS: Approximately 1000 adults aged 15-54 years were randomly sampled from each community. Subjects were interviewed, and HIV and syphilis serology performed. Men with a positive leucocyte esterase dipstick test on urine, or reporting a current STD, were tested for urethral infections. RESULTS: A total of 12,534 adults were enrolled. Baseline HIV prevalences were 7.7% (roadside), 3.8% (rural) and 1.8% (islands). Associations were observed with marital status, injections, education, travel, history of STD and syphilis serology. Prevalence was higher in circumcised men, but not significantly after adjusting for confounders. Intervention and comparison communities were similar in the prevalence of HIV (3.8 versus 4.4%), active syphilis (8.7 versus 8.2%), and most recorded risk factors. Within-pair variability in HIV prevalence was close to the value assumed for sample size calculations. CONCLUSIONS: The trial cohort was successfully established. Comparability of intervention and comparison communities at baseline was confirmed for most factors. Matching appears to have achieved a trial of adequate sample size. The apparent lack of a protective effect of male circumcision contrasts with other studies in Africa.

Adolescent↗
PubMed1995

A randomized trial of chloramphenicol vs. trimethoprim-sulfamethoxazole for the treatment of malnourished children with community-acquired pneumonia.

Children in developing countries who present with malnutrition often have infections, particularly pneumonia, at the time of presentation. We evaluated the initial antibiotic management of 144 Gambian children who presented for the first time with malnutrition and who had clinical or radiologic evidence of pneumonia. They were enrolled in a double blind trial of trimethoprim-sulfamethoxazole vs. chloramphenicol. Most children in the study underwent detailed investigations of bacterial and viral etiology as part of another study. The study drug was administered for a week along with oral metronidazole, vitamins and standardized nutritional therapy. Treatment failure was defined as the need for change to parenteral antibiotics during treatment, failure to respond to a week of treatment with the study drug or relapse during the following 2 weeks. There were no differences between the treatment groups in the clinical indicators of severity, etiology or radiologic findings. Thirty-three children were excluded from the analysis because of tuberculosis, inappropriate enrollment or inadequate follow-up. Of the 111 children remaining, 32 (16 in each arm of the study) failed treatment. Clinical failure was not related to in vitro antimicrobial resistance in the 20 cases in which invasive bacterial isolates were obtained. Those who failed treatment were more likely to have had lower chest wall indrawing and positive bacterial cultures than those who were successfully treated. In an area with infrequent antimicrobial resistance of common respiratory pathogens, oral chloramphenicol and trimethoprim-sulfamethoxazole were equally effective in the initial management of malnourished children with community-acquired pneumonia.

Administration, Oral↗
PubMed1995

Movement of Anopheles gambiae s.l. malaria vectors between villages in The Gambia.

Movement of mosquitoes belonging to the Anopheles gambiae complex (mixed wild populations of An.arabiensis, An.gambiae and An.melas) between three neighbouring rural villages in The Gambia was investigated by mark-release-recapture. A total of 12,872 mosquitoes were collected in bednets, marked with a magenta fluorescent powder and released over a 15-day period in one of the villages. A further 15,507 mosquitoes were collected in exit traps, marked with a yellow powder and released over the same period. Mosquitoes were captured daily in all three villages using pyrethrum spray catches, as well as bednet and exit trap catches. The catching period extended for 6 days after the last day of release. Of the mosquitoes released, 372 (1.3%) were recaptured 2-21 days later. Of these recaptures, 272 were caught in the release village, and 98 were caught in other villages situated 1-1.4 km away. The 'movement index' between villages was calculated as 17.2% (12.2-22.4% confidence limits) for mosquitoes released after feeding and 20.1% (14.7-25.3%) for those released unfed. These results suggest that movement of mosquitoes between neighbouring villages in The Gambia seriously affects the entomological evaluation of pyrethroid-impregnated bednet programmes in areas where treated and untreated villages are interspersed.

Animals↗
PubMed1995

Comparison of BioStar Strep A OIA optical immune assay, Abbott TestPack Plus Strep A, and culture with selective media for diagnosis of group A streptococcal pharyngitis.

We directly compared three techniques for the diagnosis of group A streptococcal pharyngitis in 500 symptomatic children seen in the Emergency Department or Child Care Clinic of The Children's Hospital of Denver. Throats were vigorously swabbed with two rayon swabs, which were transported immediately to the Microbiology Laboratory. Each swab was cultured aerobically on Strep A Isolation Agar (Remel) and then tested for antigen-one swab by the Strep A OIA optical immune assay (BioStar) and the other by the TestPack Plus Strep A (Abbott) technique. Each test was performed blind to the others. The refrigerated pledget was cultured in Todd-Hewitt broth if an antigen test was positive and both direct plate cultures were negative (the "gold standard" was any culture positive). All isolates were serologically grouped. Of 500 complete patient cultures, 151 (30%) were positive for group A streptococcal growth. The two antigen tests gave comparable results with an average sensitivity of 83%. Each was significantly (P < 0.02) less sensitive than its corresponding culture. The BioStar Strep A OIA optical immune assay produced significantly (P < 0.003) more false-positive results than did the Abbott test. Rapid antigen testing is not sensitive enough to eliminate the need for backup cultures.

Antigens, Bacterial↗
PubMed1995

Comparative stabilities of quantitative human immunodeficiency virus RNA in plasma from samples collected in VACUTAINER CPT, VACUTAINER PPT, and standard VACUTAINER tubes.

This study compared the levels of human immunodeficiency virus (HIV) virion RNA in plasma from whole blood collected in VACUTAINER CPT (cell preparation tube), VACUTAINER PPT (plasma preparation tube), VACUTAINER SST (serum separation tube), and standard VACUTAINER tubes with sodium heparin, acid citrate dextrose, sodium citrate, and potassium EDTA used as anticoagulants. Quantitative plasma HIV RNA levels were measured by branched-DNA signal amplification. Blood from all tubes was either processed within 1 to 3 h after collection or stored at room temperature or at 4 degrees C for analysis at 6 to 8 and 30 h postdraw. Immediately separated plasma from sodium citrate CPT tubes held at 4 degrees C maintained better stability of HIV RNA equivalents than whole blood held at room temperature or 4 degrees C. The highest number of HIV RNA equivalents was seen with EDTA VACUTAINER tubes. HIV RNA equivalents in all types of plasma were significantly higher than in SST tubes. Although a decline in HIV RNA equivalents was seen in all collection devices after 30 h, a significantly greater decline in plasma HIV RNA equivalents occurred in acid citrate dextrose VACUTAINER tubes than in citrate CPT, PPT, and standard EDTA VACUTAINER tubes. In order to minimize the variability of quantitative HIV RNA test results, our data suggest that samples collected for a particular assay should be processed at the same time postdraw using a particular tube type throughout a given study.

Anticoagulants↗
PubMed1995

Performance characteristics for the quantitation of plasma HIV-1 RNA using branched DNA signal amplification technology.

Highly sensitive assays that quantitate human immunodeficiency virus type 1 (HIV-1) RNA may be valuable for clinical research and the treatment of HIV-1-infected patients. In this study we evaluated the reproducibility and accuracy of the first-generation branched DNA (bDNA-1.0) signal amplification assay under conditions that are relevant to routine use in a clinical context. We show that the bDNA-1.0 assay was able to discern two- to three-fold changes in plasma HIV-1 RNA levels as significant. Reverse transcription coupled to polymerase chain reaction (RT-PCR) was less reproducible and required a 3.7- to 5.8-fold change in plasma HIV-1 RNA levels to be statistically significant. The accuracy of the bDNA-1.0 assay in RNA quantitation was not affected by HIV-1 genotypic variation or by the presence of hemoglobin, bilirubin, lipemia, or any of a dozen therapeutic drugs. Using the bDNA-1.0 assay, we show that HIV-1 RNA levels in plasma specimens were stable when stored at -80 degrees C and were able to withstand at least three freeze-thaw cycles without significant loss. We also examined the performance of an ultrasensitive bDNA assay with improvements to the signal amplification technology. The ultrasensitive bDNA assay displayed a quantitation limit of approximately 500 RNA Eq/ml, yet maintained a dynamic quantitation range up to 1.6 x 10(6) RNA Eq/ml. Like the bDNA-1.0 assay, the ultrasensitive bDNA assay was not affected by HIV-1 genotype variability.

Anticoagulants↗
PubMed1995

Acromioclavicular joint injuries.

Acromioclavicular joint injuries, including sprains and dislocations, are common shoulder problems treated by orthopaedic surgeons. The classification of acromioclavicular joint injuries comprises six grades, according to the degree of ligamentous disruption and displacement. Grades I and II are generally treated nonoperatively, whereas types IV, V, and VI are treated surgically. Treatment for grade III injuries remains controversial. Fractures of the distal aspect of the clavicle have been divided into three types. Type I fractures are stable and require brief immobilization. Type II fractures are unstable and require surgical fixation. Type III fractures often require late surgery for acromioclavicular arthritis.

Acromioclavicular Joint↗
PubMed1995

Risk assessment and other screening options for gonorrhoea and chlamydial infections in women attending rural Tanzanian antenatal clinics.

Sexually transmitted diseases (STDs) are a major cause of morbidity and mortality in developing countries and may play a key role in enhancing the heterosexual transmission of human immunodeficiency virus (HIV). Treatment of STDs is one of the most cost-effective of all health interventions in developing countries; however, STDs among women in rural populations have received little attention. In this study, we report that prevalences of STDs among 964 women attending antenatal clinics in a rural area of the United Republic of Tanzania. A total of 378 (39%) of these women were infected with at least one STD pathogen, 97 (10%) had syphilis, and 81 (8%) has Neisseria gonorrhoeae (NG) and/or Chlamydia trachomatis (CT) infection. The recommended syndromic approach to screening for NG/CT infection, based on reported genital symptoms, had a low sensitivity (43%) and failed to discriminate between infected and uninfected women. A risk score approach that we developed, based on sociodemographic and other factors associated with NG/CT infection, had a higher sensitivity and lower cost per true case treated than other approaches, although its positive predictive value was only about 20%.

Adult↗
PubMed1994

The immunogenicity and safety of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in Gambian infants.

In developing countries, Haemophilus influenzae type b is a major cause of meningitis and pneumonia in the 1st year of life. The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) were evaluated in two studies of Gambian infants. In the first study, 131 infants were recruited and randomized into three groups to receive PRP-T at 1 and 3 months (group A), PRP-T at 2 and 4 months (group B) or no PRP-T (group C). The liquid form of PRP-T was used. The geometric mean titre (GMT) of anti-PRP antibody 1 month after the second dose was 0.26 microgram/ml in group A and 0.41 microgram/ml in group B. In the second study, 66 infants were given PRP-T in the lyophilized form at 2, 3 and 4 months of age. The GMT 1 month after the first dose was 0.09 microgram/ml, after the second 0.74 microgram/ml and after the third 2.32 micrograms/ml. After the third dose, 72% of children had antibody levels greater than 1.0 microgram/ml and 93% greater than 0.15 microgram/ml. No serious side-effects were observed and the rate of adverse reactions was consistent with the concurrent administration of diphtheria-tetanus-pertussis (DPT) vaccine.

Age Factors↗
PubMed1994

HIV-2-infected patients survive longer than HIV-1-infected patients.

OBJECTIVE: To compare survival of patients infected with HIV-1 and HIV-2. DESIGN: Longitudinal follow-up of 175 HIV-1- and 294 HIV-2-infected patients identified in, or referred to a hospital in The Gambia. METHODS: Survival analysis methods were used and the death rate ratios for HIV-2 relative to HIV-1 patients were estimated using proportional hazard regression models that allowed for age, sex and clinical or immunological features. RESULTS: The overall death rate ratio for HIV-2 relative to HIV-1 was 0.67 [95% confidence interval (CI), 0.49-0.91] when adjusted for age, sex and World Health Organization Bangui clinical classification. When allowing for age, sex and three strata of CD4+ count, the rate ratio was 0.64 (95% CI, 0.43-0.94), and for three strata of beta 2-microglobulin levels 0.60 (95% CI, 0.42-0.84). CONCLUSION: Mortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗