Search PubMed⌕ Search

Biomedical subjects

H Whittle

Publications and source records attributed to H Whittle.

At least 37 records · Page 2Linked to original sources
PubMed2000

Absence of specific mucosal antibody responses in HIV-exposed uninfected sex workers from the Gambia.

OBJECTIVES: Specific antibodies to HIV envelope that inactivate virus at the mucosal surfaces involved in sexual contact are of interest for the design of a vaccine against HIV-1. It has been suggested that, in frequently HIV-exposed but uninfected individuals, HIV-specific mucosal antibody responses may exist and play a role in resistance against HIV. This study investigated HIV-1 envelope specific mucosal antibody responses in HIV-resistant sex workers in west Africa. METHODS: A group of 26 exposed uninfected female commercial sex workers from the Gambia, who have had repeated exposures to HIV-1 and HIV-2 were studied. We assessed the presence of vaginal IgA and IgG in vaginal swabs against a range of HIV-1 and HIV-2 envelope presentations and performed HIV-1 neutralization assays. RESULTS: No significant vaginal IgA or IgG responses against HIV-1 or HIV-2 were detected, and none of the vaginal secretions tested displayed any HIV-1 neutralizing activity. CONCLUSION: Vaginal antibody responses against HIV were not found in Gambian sex workers who resist HIV infection. Resistance against HIV infection can therefore occur in the absence of specific antibodies against HIV at the genital mucosa. A protective role for HIV-envelope specific IgA in resistance against HIV-1 infection in exposed uninfected individuals as reported in the literature is uncertain.

Antibody Formation↗
PubMed2000

Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia.

Aflatoxins together with chronic hepatitis B virus (HBV) infection contribute to the high incidence of hepatocellular carcinoma in developing countries. An understanding of the mechanism of interaction between these factors would provide a strong rationale for developing effective prevention strategies. In this study in The Gambia we examined the effect of environmental (place of residence and timing of sample collection) and host factors (age, sex, HBV status and interindividual variations in carcinogen metabolising enzymes) in determining blood aflatoxin-albumin adduct levels in 357 individuals of whom 181 were chronic HBV carriers. Samples were analysed for aflatoxin-albumin adducts, HBV status and genotypes of glutathione S-transferase (GST) M1, GSTT1, GSTP1 and epoxide hydrolase (EPXH). Urine samples were analysed for 6beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P450 (CYP) 3A4 activity. Adduct levels were significantly higher in subjects resident in rural [geometric mean adduct level 34.9 pg aflatoxin B1-lysine equivalent (28.5-42.8; 95%CI)/mg albumin] than in periurban areas [22.2 pg (14.9-33.4)/mg] and were approximately twice as high in the dry season [mid-February to March; 83.2 pg (53.3-130.8)/mg] than the wet [July to August; 34.9 pg (28.5-42.8)/mg]. In contrast, HBV status, CYP3A4 phenotype, GSTT1, GSTP1 and EPXH genotypes were not associated with aflatoxin-albumin adduct level. However, mean adduct levels were significantly higher in non-HBV infected subjects with GSTM1 null genotype. The main factors which affect aflatoxin-albumin adduct levels in this population are environmental, notably place of residence and timing of sample collection. This study further emphasises the priority to reduce aflatoxin exposure in these communities by primary prevention measures.

Adolescent↗
PubMed2000

Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa.

OBJECTIVE: To examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death. DESIGN: Retrospective analysis of HIV-2 cohort subjects. METHODS: Fifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used. RESULTS: The mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10 RNA copies/ml [95% confidence interval (CI), 0.81-2.7; P = 0.0006; r = 0.46; n = 52] and 1.76 CD4% faster for every increase in log10 DNA copies/10(5) PBMC (95% CI 0.46-3.1; P = 0.01; r = 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P = 0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10 increase in RNA load (95% CI, 1.3-3.5; P = 0.0023) but only by 1.09 for each log10 increase in DNA load (95% CI, 0.64-1.87; P = 0.8). CONCLUSION: This longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.

Adolescent↗
PubMed2000

Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV.

OBJECTIVES: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia. DESIGN: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia. METHODS: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age. RESULTS: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses. CONCLUSION: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.

CD4 Lymphocyte Count↗
PubMed2000

Hepatitis B infection and aflatoxin biomarker levels in Gambian children.

OBJECTIVES: To examine the relationship between hepatitis B virus (HBV) infection and biomarkers of aflatoxin exposure in West African children. METHODS: Sera from 444 children aged 3-4 years who were selected to be representative of their communities were analysed for aflatoxin-albumin (AF-alb) adducts and markers of hepatitis B infection. RESULTS: There was large interindividual variation in adduct levels (range: 2.2 to 459 pg AF-lysine eq./mg albumin). Adduct level was strongly correlated with season, with an approximately twofold higher mean level in the dry season than the wet. Geometric mean adduct levels in uninfected children, chronic carriers and acutely infected children were 31.6 (n = 404), 44.9 (n = 34) and 96.9 (n = 6) pg/mg, respectively. The relationship of AF-alb level to ethnicity, month of sampling and HBV status was examined in a multiple regression model. Month of obtaining the blood sample (P = 0.0001) and HBV status (P = 0.0023) each made a highly significant contribution to the model; the high AF-alb levels were particularly associated with acute infection. Elevated serum transaminase levels were significantly (P < 0.002) associated with HBV status, with acutely infected children having the highest levels. Ethnicity was not significantly associated with AF-alb adduct levels in the model (P = 0.09). CONCLUSIONS: HBV infection and month of sampling both significantly influence AF-alb adduct levels. The effect of seasonality on adducts was also observed in a previous study of 347 Gambian adults, although there was no correlation between adduct level and HBV status in that population. This difference between children and adults may reflect a more severe effect of HBV infection, particularly acute infection, in childhood on hepatic AF metabolism.

Aflatoxins↗
PubMed2000

A longitudinal study of in vitro IFNgamma production and cytotoxic T cell responses of tuberculosis patients in the gambia.

SETTING: This study was carried out at the MRC Laboratories, The Gambia. OBJECTIVES: To characterize the antigen-specific IFNgamma production and cytotoxic T cell (CTL) responses of patients during active tuberculosis, treatment, and following recovery. DESIGN: PBMC were isolated from 37 patients with tuberculosis and incubated with either PPD, live M. bovis BCG, or no antigen and IFNgamma production measured after 7 days. CTL activity against these antigens was determined using autologous antigen-pulsed monocyte-derived macrophages as target cells. A subset of these patients (7-18 depending on antigen and assey used) were tested 2 months into drug treatment and 3 months after discharge. A group of blood bank donors (n= 21) were also tested to evaluate IFNgamma responses in endemic controls; a subset (n= 16) were also tested for CTL activity. RESULTS: The ability to produce IFNgamma in response to mycobacterial antigens correlated with the Mantoux skin test status of the patient. IFNgamma production to live M. bovis BCG was diminished at diagnosis but returned after 2 months of drug treatment, and was sustained after completion of drug therapy. The CTL responses to both PPD and live M. bovis BCG were reduced during the period of drug treatment compared to those at diagnosis, but returned to the original levels after recovery. CONCLUSIONS: Drug treatment induced marked alterations in the immune responses of tuberculosis patients with induction of IFNgamma production in response to stimulation with live M. bovis BCG. This may indicate activation of both CD4 and CD8 T cells.

Adolescent↗
PubMed2000

Sex-associated differences in the antibody-dependent cellular cytotoxicity antibody response to measles vaccines.

In some countries, excessive non-measles-related mortality has been observed among female recipients of high-titer measles vaccines. We determined if differences in the immune response to measles vaccines underlie the excessive female mortality by measuring the measles virus (MV)-specific antibody-dependent cellular cytotoxicity (ADCC) antibody response in 65 3-year-old Gambian children immunized with Edmonston-Zagreb medium-titer (EZ) or Schwarz standard vaccines during infancy. Among the 20 females and 22 males with undetectable anti-MV antibodies at the time of immunization, females had significantly lower ADCC than males (median cytotoxicities of 1/100 serum dilutions = 8.4 and 12%, respectively; P = 0.04). This sex-associated difference was present only among the six female and seven male recipients of EZ vaccine (median cytotoxicities = 5.1 and 19.0%, respectively; P = 0.02). There were no significant sex-associated differences in neutralizing antibody activity. Decreased ADCC antibody activity may contribute to the lower survival rate observed in females receiving high-titer measles vaccination.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2000

A clinical evaluation of 3M no sting barrier film.

The maintenance of healthy skin depends on factors such as moisture, the nutritional status of the patient, and mechanical forces. A barrier film can be a valuable adjunct in the prevention and treatment of injury to skin. One hospital evaluated barrier film, a new alcohol-free film-forming liquid skin protectant, in its geriatric and spinal cord rehabilitation units. A total of 33 patients were enrolled in the study. The purpose of the evaluation was to determine if barrier film reduced redness, assisted in the adhesion of dressing and condom catheters, prevented or reduced maceration, prevented or reduced skin stripping, and/or had any adverse effects on patients. Redness was reduced in 96% of patients who were at risk. Maceration was prevented in 94% of subjects, and skin stripping was prevented in 100% of patients. Dressing adhesion improved significantly in 90% of subjects. For all subjects, regardless of method of application, barrier film was easy to apply. No patient experienced any adverse effects during the study. On the basis of this clinical trial, we found barrier film to be an effective liquid skin sealant and protectant.

Adult↗
PubMed1999

Vaccines for smallpox.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed1999

Role of schools in the transmission of measles in rural Senegal: implications for measles control in developing countries.

Patterns of measles transmission at school and at home were studied in 1995 in a rural area of Senegal with a high level of vaccination coverage. Among 209 case children with a median age of 8 years, there were no deaths, although the case fatality ratio has previously been 6-7% in this area. Forty percent of the case children had been vaccinated against measles; the proportion of vaccinated children was higher among secondary cases (47%) than among index cases (33%) (prevalence ratio = 1.36, 95% confidence interval (CI) 1.04-1.76). Vaccinated index cases may have been less infectious than unvaccinated index cases, since they produced fewer clinical cases among exposed children (relative risk = 0.55, 95% CI 0.29-1.04). The secondary attack rate was lower in the schools than in the homes (relative risk = 0.31, 95% CI 0.20-0.49). The school outbreaks were protracted, with 4-5 generations of cases being seen in the two larger schools. Vaccine efficacy was found to be 57% (95% CI -23 to 85) in the schools and 74% (95% CI 62-82) in the residential compounds. Measles infection resulted in a mean of 3.8 days of absenteeism per case, though this did not appear to have an impact on the children's grades. Among the index cases, 56% of children were probably infected by neighbors in the community, and 7% were probably infected at health centers, 13% outside the community, and 24% in one of the three schools which had outbreaks during the epidemic. However, most of the school-related cases occurred at the beginning and therefore contributed to the general propagation of the epidemic. To prevent school outbreaks, it may be necessary to require vaccination prior to school entry and to revaccinate children in individual schools upon detection of cases of measles. Multidose measles vaccination schedules will be necessary to control measles in developing countries.

Absenteeism↗
PubMed1999

Respiratory illness after severe respiratory syncytial virus disease in infancy in The Gambia.

OBJECTIVE: To determine the frequency of later respiratory tract morbidity after respiratory syncytial virus (RSV) disease in infancy. DESIGN: Cohort study with passive, clinic-based surveillance. SETTING: Outpatient department in The Gambia. SUBJECTS: One hundred five children admitted to the hospital with severe RSV disease (case cohort), 105 control children matched for age not admitted to the hospital during the previous RSV season (control cohort 1), and 102 control children born after the RSV season (control cohort 2). MAIN OUTCOME MEASURES: Frequencies of pneumonia, wheezing, and hospital admission with acute lower respiratory tract infection. RESULTS: Pneumonia was more common in case children than in both control groups (adjusted incidence rate ratio [IRR, 95% CI]: 3.80 [2.73, 6. 10]), as was wheezing (IRR 7.33 [3.10,17.54]), pneumonia or wheezing (IRR 3.96 [2.60, 6.04]), and admission with pneumonia or wheezing (IRR 3.40 [1.87, 6.15]). The incidence rate per 100 child-years for pneumonia in the dry season for 12-month-old children was 27 for case patients, 8.1 for control cohort 1, and 6.51 for control cohort 2. By 3 years of age, the rates had fallen to low levels in all groups. CONCLUSIONS: Pneumonia and wheezing are significantly more common in children after RSV-associated lower respiratory tract disease than in control subjects, but the incidence declines rapidly with increasing age.

Acute Disease↗
PubMed1999

Broadly cross-reactive HIV-specific cytotoxic T-lymphocytes in highly-exposed persistently seronegative donors.

HIV-specific cytotoxic T-lymphocytes (CTL) are believed to play a key part in the control of virus levels throughout HIV infection. An important goal of a potential prophylactic vaccine against HIV is therefore to elicit a strong CTL response which is broadly cross-reactive against a diverse range of HIV strains. We have detected HIV-specific CTL in two groups of highly-exposed but persistently seronegative female sex workers in Africa which show extensive cross-reactivity between different viral sequences. In a small group of women exposed to both HIV-1 and HIV-2 in Gambia, studied over 4 years, we have repeatedly detected HLA-B35-restricted CTL which exhibit cross-reactivity between the HIV-1 and HIV-2 sequences of the CTL epitopes. In women with particularly intense exposure to what are likely to be multiple clades of HIV-1 in Nairobi Kenya, we have detected CTL directed towards epitopes conserved between HIV-1 clades. In neither group is there any evidence that variation in CCR5 sequence or expression is responsible for their apparent resistance to HIV infection. However, in seropositive donors from Oxford infected with African strains of HIV-1, we have defined CTL responses which are specific for particular clades and have mapped some unique A clade CTL epitopes, together with others to highly-conserved regions of the virus. Further information about the extent of cross-reactive CTL immunity will be important for future vaccine design and evaluation.

Amino Acid Sequence↗
PubMed1999

Molecular epidemiology of respiratory syncytial virus in The Gambia.

Respiratory syncytial virus (RSV) infection in The Gambia occurs seasonally in association with the rainy season. This study examined the genetic variability of RSV isolates from four consecutive epidemics from 1993-6. Each epidemic was made up of a number of variants which were replaced in subsequent epidemics. Analysis of attachment (G) protein gene sequences showed that isolates were closely related to those observed in the rest of the world. However, many isolates from 1993 and 1994 were unlike other isolates observed in the developed world during this period and were more similar to isolates from 1984 in Europe. In addition, the most commonly observed genotype in the UK in the 1990s was not detected in The Gambia during this period.

Amino Acid Sequence↗
PubMed1999

The duration of human ocular Chlamydia trachomatis infection is age dependent.

We studied the relationship between age and prevalence, duration and incidence of clinical and laboratory evidence of ocular Chlamydia trachomatis infection in a cohort of Gambian subjects examined bi-weekly for 6 months. The duration of disease and infection, estimated by stratified survival analysis, proportional hazards regression and Weibull modelling, was markedly age-dependent. The estimated median duration of disease was 13.2 weeks in 0-4-year-old subjects and 1.7 weeks in those age 15 and over. Adjustment for multiple infections, and for missing observations did not alter this trend. The cumulative incidence rate of disease was reduced threefold with age. More rapid disease resolution is the main source of reduction in prevalence of active trachoma and ocular C. trachomatis infection with age; disease incidence was reduced to a lesser extent. This age-dependent resolution may be effected by adaptive cellular immune mechanisms. Mechanisms responsible for natural immunity should receive appropriate emphasis in vaccine design.

Adolescent↗