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Biomedical subjects

H Whittle

Publications and source records attributed to H Whittle.

At least 19 recordsLinked to original sources
PubMed1996

A community-based study of human immunodeficiency virus type 2 provirus load in rural village in West Africa.

A community-based study of provirus load in human immunodeficiency virus (HIV) type 2-infected subjects was done in a rural village in Guinea-Bissau. HIV-2 provirus load varied considerably, with a geometric mean of 124.3 (95% confidence interval, 86.0-179.6) copies/10(5) CD4 cells, which is a level similar to that found in HIV-1 infection. Neither malaria parasitemia, active syphilis, or human T cell leukemia virus coinfection significantly influenced provirus load, nor did age. Eleven of 104 HIV-2-infected subjects had died after 3 years of follow-up; 9 of those who died had a high provirus load of > or = 100 copies/10(5) CD4 cells and a relatively low CD4 cell percentage of < 29%.

Adult↗
PubMed1995

Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries.

OBJECTIVE: To examine whether the reduction in mortality after standard titre measles immunisation in developing countries can be explained simply by the prevention of acute measles and its long term consequences. DESIGN: An analysis of all studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries. STUDIES: 10 cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. MAIN OUTCOME MEASURES: Protective efficacy of standard titre measles immunisation against all cause mortality. Extent to which difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. RESULTS: Protective efficacy against death after measles immunisation ranged from 30% to 86%. Efficacy was highest in the studies with short follow up and when children were immunised in infancy (range 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality. CONCLUSION: These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.

Bangladesh↗
PubMed1995

HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load.

OBJECTIVES: To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activities in HIV-2-infected individuals and to relate these to HIV-2 proviral load. METHODS: Peripheral blood mononuclear cells were collected from 16 HIV-2-seropositive and four HIV-1/2 dually seropositive subjects. CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard 51Cr-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein. Proviral load was quantified by polymerase chain reaction (PCR) which used HIV-2 long terminal repeat primers and an external standard control made by an HIV-2CBL-22 chronically infected C8166 cell line. A biotinylated primer was used to capture the 35S dATP-incorporated secondary PCR product in a quantitative radiometric assay. RESULTS: After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, respectively, whereas a CTL response was noted against Nef protein in five (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multiple HIV proteins were simultaneously recognized. The sum of specific lysis (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio, or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r = -0.625, P = 0.003 and r = -0.674, P = 0.001, respectively). CONCLUSION: HIV-2-specific CTL to multiple gene products was demonstrated in most HIV-2-infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis that CTL are important in the control of HIV-2 replication.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Asymptomatic carriage of Haemophilus ducreyi confirmed by the polymerase chain reaction.

OBJECTIVE: To investigate asymptomatic carriage of Haemophilus ducreyi by using polymerase chain reaction (PCR) on samples from women at high risk of infection. SUBJECTS: 213 commercial sex workers (CSWs) recruited in The Gambia, West Africa. METHODS: Genital samples (cervical, vaginal and ulcer) were tested for the presence of H ducreyi by PCR with the technique of "one tube nested primer". RESULTS: 12 CSWs were PCR positive for H ducreyi; 8 of these women had genital ulcers on examination. CONCLUSION: Using a simplified PCR technique for detecting H ducreyi we have shown that 2% of CSWs were carrying the organism without clinical symptoms or signs. This has important implications for sexually transmitted disease control programmes in areas with a high prevalence of chancroid.

Base Sequence↗
PubMed1994

Trials of Edmonston-Zagreb measles vaccine in Guinea-Bissau: serological responses following vaccination with Edmonston-Zagreb strain at 4-8 months versus vaccination with Schwarz strain at 9-12 months of age.

In two trials of measles vaccination in Guinea-Bissau, children were randomized to receive either the Edmonston-Zagreb (EZ) virus at age 4-8 months or, as a control group, a standard dose (5000 p.f.u.) of the Schwarz (SW) virus at 9-12 months. In the first trial a medium dose of EZ virus (40,000 p.f.u.) was used and in the later trial a high dose (150,000 p.f.u.). Pre- and postvaccination blood samples were analysed with a haemagglutination inhibition (HAI) test and an enzyme-linked immunosorbent assay (ELISA). For the ELISA the blood samples were collected on filter paper. Of 362 prevaccination specimens, 18 and 55%, respectively, were positive in the ELISA and HAI tests. At 18-20 months, the children who had received the EZ vaccine had a seropositivity of 91% by the ELISA method and one of 89% by the HAI method. The equivalent values for the SW group of children were 100 and 96% respectively. Antibody levels in the EZ group, as measured by either method, were significantly lower than the levels in the SW group. The serological results of the present study suggest that lowering the age at measles vaccination to below 9 months is feasible. However, further studies are needed to determine which virus strain, dosage and age at vaccination will prove to be optimal in countries where severe measles is common before the age of 9 months.

Antibodies, Viral↗
PubMed1994

Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in Guinea-Bissau: five-year follow-up.

A trial of protective efficacy which compared medium-titre Edmonston-Zagreb (EZ) measles vaccine (10(4.6) p.f.u.) from the age of 4 months with the standard Schwarz (SW) measles vaccine given from the age of 9 months was started in an urban community in Guinea-Bissau in 1985. Because trials of high-titre measles vaccine have found increased mortality among female recipients, we examined whether EZ medium-titre vaccine was associated with any long-term impact on mortality, suppression of T-cells, or growth. The mortality rate ratio over 5 years of follow-up was 1.12 for EZ children compared with children in the standard group (P = 0.63). Seventy-five percent of the children still residing in the area at 5 years of age took part in an immunological and anthropometric examination. There was no difference in T-cell subsets between the two groups. There was no difference in mid-upper-arm circumference, but EZ children were significantly shorter than the children in the standard group. In conclusion, medium-titre EZ was not associated with reduced survival or persistent immunosuppression.

Age Factors↗
PubMed1994

Twin children in The Gambia: evidence for genetic regulation of physical characteristics in the presence of sub-optimal nutrition.

It has been demonstrated that physical growth characteristics are subject to genetic regulation. However, in developing countries, environmental factors such as food availability and frequent infections are associated with growth faltering which is particularly marked in infancy. We have conducted anthropometric measurements of a cohort of twin children aged less than 14 years living in a rural area of The Gambia to ascertain the extent to which genetic factors influence physical growth in the presence of a sub-optimal diet. Almost 25% of the children were more than 2SD below the median of the reference population in terms of their height-for-age Z score, indicating a marked level of undernutrition. Nevertheless, the within-pair variances were significantly less for monozygous than for dizygous twin pairs for the following variables: height, head circumference and body mass index (p < 0.01); weight (p < 0.02) and mid upper arm circumference (p < 0.1), indicating that there is a strong genetic influence on growth regulation despite the sub-optimal nutrition.

Adolescent↗
PubMed1994

HIV type 2 proviral load measured by quantitative polymerase chain reaction correlates with CD4+ lymphopenia in HIV type 2-infected individuals.

The efficiency of detection of 2 sets of primer pairs from putatively conserved regions of the human immunodeficiency virus type 2 (HIV-2) genome were assessed in 86 seropositive individuals from The Gambia by nested polymerase chain reaction (PCR). HIV-2 long terminal repeat (LTR) target sequences were detected in DNA extracted from peripheral blood mononuclear cells (PBMCs) in 84 of 86 (97%) individuals whereas HIV-2 integrase (pol) gene sequences were detected in 39 of 41 (95%) individuals. The use of LTR target sequences and recombinant Pfu DNA polymerase, rather than Taq polymerase, in a modified secondary amplification reaction mediated the incorporation of 35S-labeled nucleotides in a quantitative radiometric assay. This sensitive assay was used to quantify HIV-2 proviral DNA in clinical samples and compared well with estimations by limiting end-point dilution of target molecules. A linear response between counts and the number of copies amplified from serial dilutions of pROD10 plasmid DNA (3-2000 copies) yielded a standard curve to allow extrapolation to clinical data. Increased levels of HIV-2 proviral DNA, expressed as copies per 10(5) CD4-positive lymphocytes, were associated with declining CD4 count in 63 adult patients (Spearman rank correlation, r = -0.71, n = 63, p < 0.001) and with the occurrence of HIV-related clinical disease. Kruskall-Wallis analysis of variance analysis showed the mean proviral copy number (log10) to be significantly different between groups (p < 0.001) where CD4 counts were grouped as < 200/mm3 (3.4 +/- 1.05 copies), 200-500/mm3 (2.84 +/- 0.93 copies), and > 500/mm3 (1.88 +/- 0.43 copies).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The effects of HIV-2 infection in a rural area of Guinea-Bissau.

OBJECTIVE: To investigate the clinical and immunologic effects, and pattern of mortality associated with HIV-2 infection. SETTING: A rural community in Guinea-Bissau. METHODS: Serologic screening of 2774 subjects aged > 14 years followed by studies of the prevalence of clinical and immunologic abnormalities among 133 subjects with HIV-2 infection and 160 seronegative controls, and surveillance of mortality among all subjects who were screened during a mean of 2 years of follow-up. RESULTS: Generalized lymphadenopathy was the only clinical abnormality significantly associated with HIV-2 infection. Infection was associated with lower CD4 counts and higher beta 2-microglobulin and neopterin levels. During follow-up, 5.5% of infected subjects died compared with 1.8% of the seronegatives (rate ratio adjusted for age and sex, 3.5; 95% confidence interval ((CI), 1.8-6.7). Proportional hazard regression analysis showed that the rate ratio varied with age (P = 0.003) and there was some evidence that the excess of mortality in infected subjects was, in absolute terms, least in the oldest subjects (trend test; P = 0.08). CONCLUSIONS: The findings support previous suggestions that HIV-2 is less pathogenic than HIV-1; the data also suggest that mortality associated with infection may be lower in older subjects.

Adolescent↗
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↗
PubMed1994

Long term impact of high titer Edmonston-Zagreb measles vaccine on T lymphocyte subsets.

Several trials of high titer measles vaccine (> 10(4.7) plaque-forming unit) have found female recipients of Edmonston-Zagreb (EZ) vaccine to have lower survival than female recipients of standard measles vaccine. Two trials with medium and high titer EZ vaccine from the age of 4 months were conducted in Guinea-Bissau. To test for possible long term impact on the immune system, an investigation of T cell subsets was conducted among all children still residing in the community at 3 to 5 years of age. No differences were found between recipients of medium titer vaccine and controls. In the second trial, however, recipients of high titer had lower CD4:CD8 ratios than controls and had significantly higher CD8 percentages and lower CD4:CD8 ratios than recipients of medium titer EZ. When analyzed by sex, differences were found only among the girls. However, these differences were small and seemed unlikely to explain the reduced survival which has been associated with high titer EZ measles vaccination. In the 2 years after the investigation of T cell subsets, there was no increased mortality for recipients of EZ vaccine. Hence it is unlikely that high titer vaccine has an persistent adverse effect on survival after 3 years of age.

CD4-CD8 Ratio↗