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Biomedical subjects

H Whittle

Publications and source records attributed to H Whittle.

At least 145 records · Page 8Linked to original sources

Human-human hybridomas secreting monoclonal antibodies to the Mr 195,000 Plasmodium falciparum blood stage antigen.

Using the human lymphoblastoid cell line, GM 4672, and PBL of Gambian adults immune to Plasmodium falciparum (Pf) malaria, we have produced human-human hybridomas and selected those that produce mAb against Pf antigens. The fusion frequency, using PWM-stimulated donor lymphocytes was between 6.8 X 10(-5) and 1.5 X 10(-6). Using immune fluorescence, immune precipitation, and Pf in vitro growth inhibition, we cloned four hybridomas that reacted with the Pf Mr 195,000 schizont/merozoite protein. The differences in proteins immune precipitated and in growth inhibition indicate that, during development of protective immunity against Pf malaria, a spectrum of antibodies is produced reacting with different epitopes on the same antigen. Only a portion of these antibodies exhibits biological activity, suggesting that the recognition of certain epitopes is required for the development of a protective immune response.

Animals↗

Nursing management of pressure ulcers using a hydrogel dressing protocol: four case studies.

People with spinal cord injury (SCI) are at risk for developing pressure ulcers throughout their lives. Pressure ulcers can lead to significant morbidity, prolonged hospitalization, and diminished quality of life. Rehabilitation nurses play a vital role in preventing and treating pressure ulcers in these clients. In this article, the authors describe four case studies of clients with SCI who have pressure ulcers and discuss the implementation and outcome of a nursing management protocol based on the use of hydrogel dressings. These dressings have been found to promote wound healing, protect against contamination and infection, and reduce pain. They also are usually acceptable to the client and are cost-effective. Hydrogel dressings should be considered as one component of an individualized plan of care for the development of pressure ulcers.

Adult↗

Cost-effectiveness of hepatitis B vaccine in The Gambia.

Hepatitis B vaccine has been progressively introduced into the Gambian programme of immunization since 1986. Other African countries are considering introduction but require evidence of cost-effectiveness to justify such a decision. The cost of the Expanded Programme on Immunization in The Gambia, which includes hepatitis B vaccine, was calculated for 1988. Estimates of the effects of this programme on the incidence of liver cancer were made, based on the national cancer registry and a case control study of primary liver cancer and hepatitis B, regarding hepatitis B vaccine costs as incremental. This gave an estimate of the cost of averting a death from liver cancer in the range US$150-200 (assuming a vaccine cost of US$1 per dose). This indicates that universal hepatitis B immunization is comparable, in terms of cost-effectiveness, to other health interventions in less developed countries.

Adolescent↗

Protective efficacy of high-titre measles vaccines administered from the age of five months: a community study in rural Senegal.

Using data on incidence and secondary attack rates, we examined the protective efficacy of high-titre Edmonston-Zagreb (EZ) and Schwarz (SW-HT) measles vaccines administered at 5 months. Control children were assigned to placebo at age 5 months and standard Schwarz (SW-std) measles vaccine at 9-10 months of age. A large proportion of measles cases was verified serologically. Though high-titre vaccines seemed to be protective before 10 months of age, a significant reduction in disease could not be demonstrated due to low incidence of measles. After 10 months of age, SW-std given at 10 months gave a vaccine efficacy of 100% and induced better protection than SW-HT (P = 0.030) and EZ-HT (P = 0.128) administered at 5 months. In studies of secondary attack rates in the compound, vaccine efficacy was 91% (75%-97%) for EZ-HT, 85% (40%-96%) for SW-HT, and 100% for SW-std. Attack rates were correlated with intensity of exposure (P = 0.0006), being much higher for children exposed in the same hut than for those living in the same compound but in a different household (relative risk = 3.36 [1.32-8.57]). The attack rate was significantly lower among vaccinated than unvaccinated children with no detectable measles antibody (relative risk = 0.41 [0.18-0.93]). In rural areas with a high coverage in the surrounding community, a single dose at 9-10 months may provide sufficient protection. Since high-titre vaccines have been associated with higher mortality than SW-std, further improvements in measles control before 9 months may require two-dose strategies with standard vaccines.

Age Factors↗

A community study of T lymphocyte subsets and malaria parasitaemia.

In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical malaria). Compared with children with no parasitaemia or asymptomatic parasitaemia, children with acute malaria had lymphopenia and significantly lower total CD4 and CD8 cell counts, but there was no significant difference in white blood cell count percentages of CD4 and CD8 cells, or the CD4/CD8 ratio. Children with parasitaemia but without fever had a significantly lower percentage of CD4 cells than children without parasites (P = 0.031), but did not differ in any other haematological index. Controlling for other factors, the CD4 cell percentage was inversely correlated with the density of malaria parasites (P = 0.024), whereas there was no association with CD8 cell percentage or the CD4/CD8 ratio. Asymptomatic parasitaemia may be an important confounder in general community studies of T cell subsets in the tropics.

CD4-CD8 Ratio↗

Measles, polio and tetanus toxoid antibody levels in Gambian children aged 3 to 4 years following routine vaccination.

A nation-wide cross-sectional survey of 816 children 3-4 years old was carried out in The Gambia between September 1990 and July 1991 to assess the seroprevalence of antibodies against 3 diseases included in the expanded programme on immunization: measles, poliomyelitis and tetanus. Among 689 children whose records were available, 94.5% were fully immunized. Measles vaccine was administered to 97% of the children and 91% of these had detectable antibodies at the time of the survey. Antibodies against type 1 and type 3 polioviruses, after up to 6 doses of oral polio vaccine, were present in 88.1% and 89.3% of the children respectively. Ninety-seven percent of the children who had received 4 doses of diphtheria-pertussis-tetanus vaccine (DPT) and 91% of those who received 3 doses had detectable tetanus toxoid antibodies at the age of 3-4 years. This study shows that serological responses to EPI vaccines given in infancy persist at very satisfactory levels throughout early childhood.

Administration, Oral↗

A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal.

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

Cohort Studies↗

Kaposi's sarcoma in the Gambia, West Africa is less frequent in human immunodeficiency virus type 2 than in human immunodeficiency virus type 1 infection despite a high prevalence of human herpesvirus 8.

OBJECTIVES: To investigate the distribution of Kaposi's sarcoma (KS) cases in patients with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) infection in the Gambia; to document the prevalence of human herpesvirus 8 (HHV-8) infection in various population groups in the Gambia. STUDY DESIGN/METHODS: A retrospective analysis of KS cases in hospital records at the Medical Research Council (MRC) hospital was performed, along with a cross-sectional survey of HHV-8 prevalence in hospital-based and community-based study population with polymerase chain reaction (PCR) and serologic assays. RESULTS: After adjusting for gender and CD% at the first visit, HIV-1-positive patients were 12.4 times more likely to have KS than were HIV-2-positive patients. The prevalence of antibodies to HHV-8 and the HHV-8 genome was high in both HIV-1-positive and HIV-2-positive patients without KS. The prevalence of antibodies was also high in pregnant women who were HIV-1-positive, HIV-2-positive, or HIV-negative (73%, 83%, and 79%, respectively). CONCLUSIONS: HHV-8 infection is widespread in the Gambia. In addition to immunosuppression and HHV-8 infection, other cofactors specifically related to HIV-1 rather than HIV-2 appear to be involved in the development of KS.

AIDS-Related Opportunistic Infections↗

Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection.

OBJECTIVES: To elucidate why the virulence of HIV-1 and HIV-2 infections differ in West African populations. STUDY DESIGN/METHOD: Peripheral blood plasma virion RNA and cellular proviral DNA levels were measured in a cross-section of 59 HIV-1 and 49 HIV-2 singly infected individuals representing all stages of infection in The Gambia, West Africa. Novel reverse transcriptase polymerase chain reaction (RT-PCR) assays specific and sensitive for virus quantification of non-clade B HIV-1 and HIV-2 infections were used. RESULTS: HIV-1 and HIV-2 proviral and plasma RNA levels were inversely correlated with CD4+ count for both infections with cellular proviral load similar at each stage of infection. Critically, up to three-fourths of HIV-2-infected individuals with high CD4 percentages (> 28%) had undetectable (< 500 copies/mL) levels of peripheral blood HIV-2 RNA in contrast to HIV-1-infected individuals who had readily detectable plasma virus at all stages of infection (P < .0001). Plasma RNA levels were similar in the intermediate and end stages of infection, indicating similar replication potential for both viruses. In the cross-section of HIV-1- and HIV-2-infected patients studied, the data indicate a wider dynamic range of HIV-2 RNA in vivo compared with HIV-1. DISCUSSION: Low levels of HIV-2 replication and virion expression characterize individuals with high CD4+ lymphocyte counts, suggesting that a very different dynamic equilibrium exists between virus and host for HIV-2 compared with HIV-1. By analogy with HIV-1, our data implicate a considerably lower turnover of HIV-2 virion RNA in vivo with a markedly reduced production of infectious genomes in individuals during the subclinical phase of infection. CONCLUSION: The lower levels of virion expression of HIV-2 infections in vivo are compatible with observed differences in the natural history of HIV-1 and HIV-2 infections, relating to overall differences in the pathogenesis and disease progression of the two infections.

Acquired Immunodeficiency Syndrome↗

Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa.

Hepatocellular carcinoma is one of the major human cancers, causing at least 250,000 deaths each year. Two of the major risk factors for this disease are aflatoxin exposure and hepatitis B virus. This study was undertaken to explore the relationship between dietary exposure to aflatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people who were either hepatitis B virus surface antigen-positive or -negative. The diets of 20 individuals, 10 males and 10 females, with ages ranging from 15 to 56 years, were monitored for 1 week, and aflatoxin intake levels were determined for each day. Starting on the fourth day, total 24-h urines were consecutively obtained for 4 days. The subjects were generally paired for hepatitis B virus status. Preparative monoclonal antibody affinity chromatography/high-performance liquid chromatography and competitive enzyme-linked immunosorbent assays were carried out on each of the urine samples, and the relationship between aflatoxin intake values and the excretion of (a) total aflatoxin metabolites and (b) aflatoxin-N7-guanine (AFB-N7-guanine) was determined. The average intake of total aflatoxins was 12.0 micrograms for the entire study group during the 1-week collection period. However, there was considerable day-to-day variation in exposures, from a low of zero to a high of 29.6 micrograms total aflatoxins/day. Initial efforts to characterize total aflatoxin metabolites in the urine samples were made by competitive enzyme-linked immunosorbent assay. The correlation coefficient for the analysis was 0.65, with P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗