Search PubMed⌕ Search

Biomedical subjects

J Todd

Publications and source records attributed to J Todd.

At least 109 records · Page 6Linked to original sources

Stabilities of quantitative plasma culture for human immunodeficiency virus, RNA, and p24 antigen from samples collected in VACUTAINER CPT and standard VACUTAINER tubes.

We evaluated the stability of human immunodeficiency virus (HIV) load markers from blood samples collected in VACUTAINER CPT or standard VACUTAINER brand tubes using sodium heparin or sodium citrate as anticoagulants. Quantitative plasma culture and p24 antigen concentrations were determined, and HIV RNA levels in plasma were measured by both reverse transcription-PCR-enzyme-linked immunosorbent assay (RT-PCR-ELISA) and branched DNA methods. All tubes were stored at room temperature for analysis at 2, 24, 48, and 72 h after the blood samples were drawn. No difference was seen between tube types with respect to the HIV titer in plasma or the positivity rate for all samples that demonstrated a fall in titer over time. Unbound p24 antigen levels in plasma decreased during the initial 48-h period in both tube types. Immune complex-dissociated p24 antigen levels decreased in CPT tubes but not in standard VACUTAINER tubes. The HIV RNA copy number in plasma measured by RT-PCR-ELISA was stable in most subjects and was significantly higher in CPT tubes than in standard VACUTAINER tubes at 24 and 72 h after the blood samples were drawn. The branched DNA probe assay detected a significant decline in HIV RNA equivalent in plasma over 72 h in both collection tubes, the decline being more dramatic in the standard VACUTAINER tube than the CPT tube. Overall, interday variability suggests that samples collected for a particular assay should be processed at the same time after blood is drawn and that a particular tube type be used throughout a given study.

Anticoagulants↗

Malaria chemoprophylaxis, infection of the placenta and birth weight in Gambian primigravidae.

A randomized, double blind, placebo-controlled community based trial of Maloprim (pyrimethamine 12.5 mg+dapsone 100 mg) administered to primigravid pregnant women by Traditional Birth Attendants was carried out in a rural area of The Gambia, West Africa. Placental histology showed less malaria infection in women who received chemoprophylaxis than in those who received placebo. The birth weight of children born to women who received chemoprophylaxis was increased by an average of 153 g. Within the treatment groups, there were no significant differences in the birthweights of babies born to women who had histological evidence of malaria infection of the placenta compared to those who had no malaria infection. This study confirms the beneficial effect of malaria prophylaxis for primigravid pregnant women but questions the mechanism by which malaria affects foetal development.

Acute Disease↗

Cryptosporidium infection in Gambian children less than 5 years of age.

Cryptosporidium infection was studied in Gambian children less than 5 years of age over a 12-month period. Children who presented with diarrhoea at the Medical Research Council (MRC) clinic were selected randomly for detection of Cryptosporidium. They were compared with control children who presented with reasons other than diarrhoea. Cross-sectional surveys were conducted also to assess the community prevalence of Cryptosporidium. Cryptosporidium was found in 53 (9%) of 600 children with diarrhoea. In contrast Cryptosporidium was found in only 17 (3%) of 600 control children (chi 2 = 18.6, 1 df, P < 0.001). All 53 children with Cryptosporidium and diarrhoea were less than 2 years of age. In the community surveys, 11 (4%) of 250 children were Cryptosporidium positive. Cryptosporidium infection showed a well defined seasonal peak in association with the rains and a high relative humidity.

Age Factors↗

Active site-blocked factor Xa prevents thrombus formation in the coronary vasculature in parallel with inhibition of extravascular coagulation in a canine thrombosis model.

Factor Xa is a central procoagulant enzyme, linking the intrinsic and extrinsic activation mechanisms to the final common pathway of coagulation. To assess its contribution to pathologic thrombosis, studies were performed in a canine coronary thrombosis model. Thrombus formation was initiated by the application of electric current via a needle electrode placed in the lumen of the left circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycinyl-arginyl-factor Xa (Xai), a competitive inhibitor of factor Xa assembly into the prothrombinase complex, Factor X, or heparin. Animals infused with saline or factor X (300 micrograms/kg) developed total occlusion of the vessel due to a fibrin/platelet thrombus in 70 +/- 11 minutes (36 of 36 animals) and 74 +/- 13 minutes (8 of 8 animals), respectively. In contrast, infusion of Xai prevented thrombus formation completely at a dose of 300 micrograms/kg (8 of 8 animals). As the dose of Xai was decreased, its antithrombotic effect was diminished, with a patency rate of only 2 of 6 animals at a dose of 90 micrograms/kg. Xai at 300 micrograms/kg prevented the accumulation of 125I-fibrinogen/fibrin at the site of the coronary thrombus by approximately 63% and decreased deposition of 111In-labeled platelets by approximately 57%. Hemostatic parameters of animals infused with Xai demonstrated prolongation of the PT and dose-dependent increased extravascular bleeding tendency. These data indicate that factor Xa has a comparably important role in thrombus formation and extravascular hemostasis, and contrast with previous results in this same animal model in which IXai selectively prevented clotting in the coronary vasculature.

Amino Acid Sequence↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 4. Perceptions of the causes of malaria and of its treatment and prevention in the study area.

Perceptions of the causes of malaria, its treatment and prevention were studied among 996 adults, selected randomly from 73 villages and hamlets in a rural area of The Gambia. Structured questionnaires and other interview techniques were used for data collection. Malaria has no specific name in the study area; it is referred to commonly as Fula kajewo (Fula fever). Only 28% of the respondents knew that mosquitoes transmitted malaria. However, most people believed correctly that August to October was the main malaria season. Eighty-six per cent of the subjects were bed net users. The majority of nets were produced locally, usually white in colour and made of sheeting fabrics. Usage of nets was correlated with ethnic group, age and polygamy but not with education, income, occupation or ownership of certain items which indicate high social status. Analysis of expenditure on mosquito coils indicated that non-users of nets spent 43% more on coils than did users. Bed nets have been used for a long time in the study area; 98% of users saw their parents using them during their childhood.

Adult↗

Identification and characterization of tox21A: a mite cDNA encoding a paralytic neurotoxin related to TxP-I.

A cDNA library established from polyadenylated RNA isolated from the predatory mite Pyemotes tritici was screened for cDNAs homologous to tox34, a cDNA encoding an insect-selective paralytic neurotoxin known as TxP-I. Most of the cDNA inserts of homologous clones were shorter or of equal length to tox34 but a few were longer. Further investigation into the nature of these longer clones led to the identification, sequencing and expression of a distinct cDNA referred to as tox21A. This cDNA is predicted to encode a polypeptide which shares approximately 83% amino acid identity with TxP-I. Larvae infected with a recombinant baculovirus expressing tox21A are paralyzed during infection in a manner similar to larvae infected with tox34-expressing recombinants. The tox21A cDNA may represent a duplicated and diverged copy of the TxP-I gene.

Amino Acid Sequence↗

Entomological risk factors for severe malaria in a peri-urban area of The Gambia.

A study was undertaken of possible entomological risk factors for severe malaria in a peri-urban area of The Gambia. Households of children who had experienced a severe or a mild attack of malaria and of matched controls were visited and their characteristics recorded. Mosquitoes were then collected in the bedrooms of study subjects using both insecticide spray catches and light traps. Mud-walled buildings and bedrooms without ceilings were found more frequently in the households of children who had experienced malaria than in those of controls. Only one difference, which may have arisen by chance, was found between the households of severe and of mild malaria cases; animals were recorded significantly more frequently in the compounds of the severe cases. Mosquito catches reported on two occasions 2 weeks apart showed good reproducibility, indicating that measurements made at the time that a child presented with malaria were likely to reflect those that would have been present at the time that the child was infected. Anopheles gambiae s.l. was found on average more frequently in the bedrooms of children who had experienced malaria than in those of the controls but no difference was found in mosquito numbers between bedrooms of severe or mild cases of malaria. The human blood index and sporozoite rate were similar in mosquitoes caught in households of malaria cases and in those of controls. No evidence was found to support the hypothesis that the level of exposure to malaria-infected mosquitoes is a risk factor for the development of severe malaria.

Animals↗

Persistence of antibody at 18 months following vaccination of young Gambian infants with PRP-OMPC Haemophilus influenzae type b conjugate vaccine.

The rate of decline in anti-PRP antibody levels was measured in two groups of Gambian children who had been given PRP-OMPC at 1 and 3 months or 2 and 4 months of age. In the younger group (n = 70), the geometric mean titre fell from 1.32 micrograms/ml at 4 months to 0.44 micrograms/ml at 18 months. In the older group (n = 54), the geometric mean titre fell from 1.18 micrograms/ml at 5 months to 0.46 micrograms/ml at 18 months. The proportion of vaccinated children with antibody levels over 1.0 microgram/ml fell from 54% 1 month after the second dose of vaccine to 27% at the age of 18 months, while the proportion with levels over 0.15 micrograms/ml fell from 82% to 60%, with no significant differences observed between the vaccination groups. For those children who did not show evidence of environmental boosting, the half-life of anti-PRP antibody was about 100 days. This did not differ between the groups. These findings suggest that to provide lasting immunity PRP-OMPC should be given with a late booster dose at 12-15 months, as is the current practice in the USA. The need for a late booster dose may limit the value of this vaccine in developing countries where vaccination of children is difficult after the 1st year of life.

Antibodies, Bacterial↗

The effects of post-test counselling on condom use among prostitutes in The Gambia.

OBJECTIVES: To determine the effect of counselling on condom use by prostitutes. DESIGN: Cohort study. SETTING: Field-based study in The Gambia. PARTICIPANTS: Thirty-one (12 HIV-positive and 19 HIV-negative) prostitutes. INTERVENTIONS: Post-test HIV counselling. MAIN OUTCOME MEASURES: Levels of condom use. RESULTS: Overall, counselling had no effect on condom use. CONCLUSIONS: Scarce resources should be directed towards providing condoms in bars rather than counselling.

Cohort Studies↗

Determinants of condom use in 24,000 prostitute/client contacts in The Gambia.

OBJECTIVE: To determine the factors that influence condom use among prostitutes and their clients in The Gambia. DESIGN: A cohort of 181 prostitutes working in seven bars and several rural markets in The Gambia were monitored daily for 14 months. A sample of 747 clients of these prostitutes was also questioned. MAIN OUTCOME MEASURE: Proportion of sexual contacts for which a condom was used. RESULTS: Data on 24,181 sexual contacts reported by the prostitutes indicated condom use varied according to type of partner (from 84% with clients to only 4% with regular partners). Condom use with clients varied according to location (from 91% in high-class bars to 59% in rural markets), decreased from 91% with the first client of the evening to 37% with the tenth client, and from 75% with clients paying higher charges (> D19) to 52% with those paying lower charges (< D20). Condom use was not related to the socio-demographic characteristics of the prostitutes. Clients reported lower condom use than prostitutes. Clients aged 20-24 years were least likely to use condoms, while white collar workers, traders, and those paying higher charges, were more likely to use condoms. CONCLUSIONS: The level of condom use in this cohort of prostitutes was high but not consistent. Condom use was determined more by the type of establishment and the characteristics of clients, than by any fixed tendency among the prostitutes. Thus, education campaigns should be directed as much to clients as to prostitutes. In The Gambia, 'lower-class' bars and those in rural areas where prostitutes work should be a priority target.

Adolescent↗

The epidemiology of HIV infection in a rural area of Guinea-Bissau.

OBJECTIVES: To determine the prevalence of HIV infection and its relationship to age, sex and other factors. DESIGN AND SETTING: Cross-sectional survey of a rural community in Guinea-Bissau. METHODS: Questionnaire-administration and screening of sera from subjects aged > or = 15 years. RESULTS: Of the 2770 subjects tested, 220 (7.9%) were HIV-2-seropositive, four (0.1%) were HIV-1-seropositive and 10 (0.4%) were dually reactive. Overall prevalence of HIV-2 was 9.3% in women, peaking at 17.2% in the 35-44 age group, and 6.6% in men, peaking at 19.1% in the 45-54 age group. The mean age of the four subjects with HIV-1 infection was 24 years, which was significantly lower than those with HIV-2 infection. HIV-2 infection was more prevalent among women who were widowed or divorced, women whose husbands were living away from the study area, and women who had lived in the capital, Bissau. The majority of subjects with an infected spouse remained uninfected and none of the women aged < 25 years whose husbands were infected were seropositive. The prevalence varied significantly between settlements within the study area. CONCLUSIONS: The pattern of HIV-2 infection in this rural community has similarities to that found in urban Bissau, and prevalence in both areas peaks in older subjects than in HIV-1 foci. The findings support previous suggestions that HIV-2 is not a recent introduction to Guinea-Bissau, and that it is less pathogenic and less readily transmitted than HIV-1.

Adolescent↗

Safety and immunogenicity of Haemophilus influenzae type B-Neisseria meningitidis group B outer membrane protein complex conjugate vaccine mixed in the syringe with diphtheria-tetanus-pertussis vaccine in young Gambian infants.

To ensure compliance and to reduce costs it is important, especially in less developed countries, that programs of child immunization should require as few clinic attendances and as few injections as possible. Therefore we have investigated whether a Haemophilus influenzae type b conjugate vaccine could be given safely and effectively with diphtheria-tetanus-pertussis vaccine (DTP). One hundred twenty-six Gambian infants were given both polyribosylribitol phosphate (PRP)-outer membrane protein complex (PedvaxHIB) and DTP on the same day at 8, 12 and 16 weeks of age; 60 were given the vaccines mixed in the syringe and 66 were given the vaccines separately. To minimize the injection volume the dose of PRP-OMPC used in both groups was 7.5 micrograms, which is half the usual dose. There were no significant differences in anti-PRP antibody titers between the groups after 1, 2 or 3 doses. The geometric mean titers of antibody for the two groups combined were 0.29 micrograms/ml 1 month after the first dose, 1.03 micrograms/ml after the second dose and 1.11 micrograms/ml after the third dose. Concentrations of antibodies to diphtheria, tetanus and pertussis 1 month after the third dose were not significantly different between the two groups. Systemic side effects were reported with equal frequency in the two groups and were similar to those reported elsewhere for DTP. Tenderness at the injection site was more common where the combined injection (0.75 ml) had been given than where DTP alone (0.5 ml) had been given. The main drawback to the use of these 2 vaccines together is the complexity of the mixing procedure used in this clinical trial.

Antibodies, Bacterial↗

Immunological responses of Gambians in relation to clinical stage of HIV-2 disease.

This study describes a broad spectrum of cellular and antibody-mediated immune responses found in 28 asymptomatic and 37 symptomatic Gambian patients with HIV-2 infection. It shows that these responses vary according to the stage of infection as described by three clinical staging systems. The first system was a local one based on the signs used for the WHO Bangui clinical definition of AIDS, the second, suggested by WHO, was based on a performance scale, and the third was that used by the Centre for Disease Control. Asymptomatic patients had significantly lower mean CD4 counts, lymphoproliferative and interferon-gamma (IFN-gamma) responses and lower IgG and IgM antibody responses to keyhole limpet haemocyanin (KLH) than controls. These measurements and the size of the skin test reaction to purified protein derivative (PPD) or Candida antigen declined significantly according to the stage of infection. Mean values of the serological markers beta 2-microglobulin and neopterin and antibody titres to Epstein-Barr virus capsid antigen (EBVCA) rose significantly according to severity of disease. The Gambian or WHO clinical staging systems, which are easy and cheap to apply, may serve as an alternative to sophisticated and expensive immunological measurements when trying to stage disease and predict prognosis.

Adult↗

Safety, stability, and efficacy of noncapsulated mutants of Actinobacillus pleuropneumoniae for use in live vaccines.

Clonal, noniridescent mutants of Actinobacillus pleuropneumoniae serotypes 1 and 5 were isolated following chemical mutagenesis with ethyl methanesulfonate. The absence of any detectable capsule was confirmed by inhibition radioimmunoassay. There were no differences between the parent and mutant strains in lipopolysaccharide or protein electrophoretic profiles or in hemolytic activity. There was no detectable reversion to the encapsulated phenotype in vitro after passage in mice or pigs or in microporous capsules that were implanted subcutaneously in pigs for 6 weeks. The mutants were able to survive for more than 1 week in pigs following subcutaneous inoculation, which resulted in a strong immune response to whole cells and Apx toxins I and II. Intratracheal challenge of pigs with the serotype 5 mutant at a dose 1 log greater than the 50% lethal dose for the parent resulted in no clinical disease or lesions except in one pig that had slight pneumonia and pleuritis. Twenty-four hours after challenge, A. pleuropneumoniae could not be recovered from the respiratory tracts of any of the challenged pigs except for the one infected pig; this isolate remained noncapsulated. Immunization of pigs with one or both serotypes of noncapsulated mutants protected all pigs against clinical disease following intratracheal challenge with the virulent homologous or heterologous serotype. Nonimmunized control pigs and pigs immunized with a commercial bacterin died or had to be euthanized within 24 h of challenge. Thus, live noncapsulated mutants of A. pleuropneumoniae may provide safe and cost-effective protection against swine pleuropneumonia. These observations support the possibility that noncapsulated mutants of other encapsulated, toxin-producing bacteria may also prove to be efficacious live-vaccine candidates.

Actinobacillus Infections↗

Strains of Mycobacterium terrae complex which react with DNA probes for M. tuberculosis complex.

Following a recent report that two isolates of Mycobacterium terrae complex had given positive reactions with M. tuberculosis complex DNA probes, a joint study was undertaken to determine the extent of these findings in the clinical culture collection holdings of two state health laboratories. A total of 117 M. terrae complex strains (identified by standard biochemical methods) were subjected to M. tuberculosis complex probe testing with the two then-available kits (from Syngene, Inc., and Gen-Probe, Inc.). In addition to the two original isolates first reported, two further M. terrae complex isolates were found to react with the M. tuberculosis complex probes. Two modifications of the Accuprobe (Gen-Probe, Inc.) test method were evaluated. Extension of the selection time to 8 min was the most convenient modification and rendered the M. terrae complex isolates negative when tested with the Accuprobe M. tuberculosis complex probe. However, the effects of increased selection time on the overall sensitivity of the M. tuberculosis complex probe require further study.

DNA Probes↗

The effects of hemoglobin genotype and ABO blood group on the formation of rosettes by Plasmodium falciparum-infected red blood cells.

The mechanisms by which the hemoglobin genotype AS protect against severe malaria are not fully understood. We have investigated the possibility that protection might be achieved through an inability of red blood cells (RBC) with the AS genotype to form rosettes with RBC infected by Plasmodium falciparum. No evidence was obtained to support this hypothesis because RBC with the AS genotype formed rosettes with wild isolates of P. falciparum as readily as RBC with the AA genotype. However, the previous finding that parasitized RBC form rosettes more readily with RBC belonging to group A or B than with RBC belonging to group O was confirmed even in fresh clinical isolates.

ABO Blood-Group System↗

Serotype specificity of immunological assays for the capsular polymer of Actinobacillus pleuropneumoniae serotypes 1 and 9.

The cross-reactivity of the purified polysaccharides of Actinobacillus pleuropneumoniae serotypes 1 and 9 were examined using a variety of highly sensitive assays, such as radioimmunoassay, latex agglutination, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. In addition, conventional immunodiffusion was included for comparison. Latex agglutination, utilizing affinity-purified IgG to capsule, was also used to serotype whole cells. Agglutination or precipitation tests (radioimmunoassay, latex agglutination, and immunodiffusion) indicated no cross-reactivity between the capsules of serotypes 1 and 9, and no cross-reactivity between whole cells by latex agglutination. Assays that required binding of the capsule to a solid support (ELISA and immunoblotting) did demonstrate cross-reactions between serotypes 1 and 9 capsules, although reactions with the heterologous serotype were weaker than with the homologous serotype. The cross-reactivity could not be attributed solely to nonspecific factors because similar cross-reactivity did not occur with serotype 5 or 7 capsules by any assay. Reactivity of antisera with homologous or heterologous capsule was reduced, but not completely eliminated, by adsorption with washed, live bacteria of the heterologous serotype. Thus, the assay, as well as the antigen or specificity of the antibody reagent used, may influence the results of A. pleuropneumoniae serotyping or serological tests.

Actinobacillus pleuropneumoniae↗