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Biomedical subjects

H Whittle

Publications and source records attributed to H Whittle.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1994

The etiology of pneumonia in malnourished and well-nourished Gambian children.

During a 2-year period 159 malnourished children ages 3 months to 5 years with radiologic evidence of pneumonia were investigated to determine the cause of their pneumonia. In addition 119 malnourished children without pneumonia, 119 well-nourished children with pneumonia and 52 well-nourished children without pneumonia were studied as controls. Percutaneous lung aspiration was performed on 35 malnourished and 59 well-nourished children with pneumonia. Bacteria were isolated from the blood, lung or pleural fluid of 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia and from the blood of 5 (4%) malnourished children without pneumonia. Streptococcus pneumoniae and Haemophilus influenzae, which were the two organisms isolated most frequently in both groups of children with pneumonia, were found in 17 (11%) malnourished and 39 (33%) well-nourished children with pneumonia. Mycobacterium tuberculosis was detected in 5 malnourished children with pneumonia. A potentially pathogenic virus was identified in 35% of malnourished children with pneumonia and 40% of well-nourished children with pneumonia, and from 25% of children without pneumonia. The viruses identified most frequently were adenovirus and respiratory syncytial virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoviridae↗
PubMed1994

Human antibody responses to Pfs 230, a sexual stage-specific surface antigen of Plasmodium falciparum: non-responsiveness is a stable phenotype but does not appear to be genetically regulated.

The 230 kD gamete surface protein of the malaria parasite Plasmodium falciparum (Pfs 230) is a target of transmission blocking antibodies. Anti-Pfs 230 antibodies are induced following natural infection with malaria but are not found in all P. falciparum-exposed individuals. In this study we have shown that approximately 40% of malaria-exposed Gambians do not make antibodies to the native Pfs 230 molecule. This phenotype is remarkably stable over time and does not appear to be related to age, malaria exposure or major histocompatibility complex genotype. Comparison of antibody responses in twins indicates that the anti-Pfs 230 response is not strictly genetically controlled, but a high degree of concordance within both dizygous and monozygous twin pairs suggests that factors associated with exposure to malaria in childhood may be important in determining the subsequent immune response.

Adolescent↗
PubMed1994

Sex-specific differences in mortality after high-titre measles immunization in rural Senegal.

Administration of high-titre measles vaccine (Edmonston-Zagreb (EZ) at > 10(5) plaque-forming units (PFU) per dose) before the age of 9 months has been recommended in areas with high measles mortality before the routine age of immunization after 9 months. The study compares the long-term survival after high-titre measles immunization at 5 months of age with that following routine immunization with standard-titre vaccine at 10 months of age. At 5 months of age the high-titre group received Edmonston-Zagreb (EZ-HT, 5 months) or Schwarz (SW-HT, 5 months) at titres > 10(5) PFU per dose, while the standard-titre group received placebo at 5 months of age and < 10(4) PFU per dose of Schwarz vaccine at 10 months (SW-std, 10 months). All the children were followed up to at least 36 months of age. The mortality ratio (MR) for infants in the EZ-HT, 5 months and SW-HT, 5 months groups was 1.32 (P = 0.089) and 1.45 (P = 0.092), respectively, which did not differ significantly from that of recipients of the SW-std, 10 months. The higher MR among recipients of the high-titre vaccines was due to the significantly lower survival among females compared with the females who received SW-std vaccine (EZ-HT, 5 months MR = 1.76, P = 0.013; SW-HT, 5 months MR = 2.14, P = 0.017). For children aged 5-10 months the high-titre measles vaccine did not increase mortality relative to unvaccinated children who had received placebo.

Bias↗
PubMed1994

Epstein-Barr virus-carrying B cells are large, surface IgM, IgD-bearing cells in normal individuals and acute malaria patients.

In this study the presence of Epstein-Barr virus (EBV) carrying B lymphocytes in different B-cell subpopulations from peripheral blood was determined by spontaneous outgrowth which gives rise to lymphoblastoid cell lines. In healthy seropositive adults, the EBV-carrying B cell was predominantly within the IgM- and IgD-positive but not the IgG-positive subpopulations. Furthermore, these B lymphocytes were in the low-density (large cell) Percoll fraction. The IgM- and IgD-positive B cell phenotype suggests the EBV-carrying B cells to be circulating virgin B cells recently released from the bone marrow. These B cells have an estimated life span of only 6-8 weeks suggesting that long-term EBV persistence in the body may be the result of infection of a more primitive B-cell type. Similar experiments were carried out in children with acute malaria from the Gambia, West Africa, where Burkitt lymphoma (BL) is endemic in order to determine whether a population of EBV-carrying B cells could be identified which had a similar phenotype to the BL cell. The EBV-carrying B cells in this patient group were also found in the IgM-positive, IgG-negative B-cell subpopulation. The majority of these cells were found in the low-density (large cell) Percoll fraction although in some patients a proportion was derived from the high-density (small cell) fraction. This cellular phenotype is not representative of a BL cell.

Acute Disease↗
PubMed1993

Divergent mortality for male and female recipients of low-titer and high-titer measles vaccines in rural Senegal.

The female/male mortality ratio among unimmunized children and children vaccinated with standard or high-titer measles vaccines was examined for all children born in the period 1985-1991 in a rural area of Senegal. The female/male mortality ratio from 9 months to 5 years of age for unvaccinated children was 0.94 (95% confidence interval (CI) 0.75-1.19), significantly different from the ratio of 0.64 (95% CI 0.48-0.85) for recipients of the Schwarz standard measles vaccine (p = 0.040). In the 4-year period, where high-titer measles vaccines were used in the study area, the female/male mortality ratio was 1.33 (95% CI 1.00-1.78) for recipients of high-titer Edmonston-Zagreb or Schwarz vaccines compared with 0.67 (95% CI 0.42-1.07) for recipients of the Schwarz standard vaccine (p = 0.013). Hence, the Schwarz standard and high-titer measles vaccines have divergent sex-specific effects on mortality throughout childhood. Further studies of the underlying mechanisms are needed.

Cause of Death↗
PubMed1993

Competitive EIA for anti-HIV-2 detection in The Gambia: use as a screening assay and to identify possible dual infections.

The performance of a competitive EIA for the detection of HIV-2-specific antibody utilising a viral lysate antigen was assessed over a 3 year period in The Gambia, West Africa, and compared with a commercially available assay, ELAVIA-2, using three panels of sera. An immunodominant region of the transmembrane glycoprotein of an HIV-2 isolate (ANT 53) was also cloned and expressed in E. coli as a beta-galactosidase fusion protein and the resulting recombinant protein substituted in place of the existing viral lysate antigen. Competitive EIAs were found to be both a specific and sensitive means of reliably determining the HIV-2 status of an individual with a high predictive value, particularly when a strategy of concordant positive results in the two EIAs was used. When either anti-HIV-2 competitive EIAs were used in conjunction with a competitive EIA for anti-HIV-1 detection it was possible in the vast majority of cases to identify the virus-type infecting an individual and speciate HIV-1 and HIV-2 infections. A few sera which showed similar regression profiles when diluted over a serial tenfold dilution steps were identified as possible dual infections.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate.

In an urban area of Guinea-Bissau, 384 children were enrolled in a randomized trial comparing morbidity and mortality rates after receiving high-titer Edmonston-Zagreb (EZ) measles vaccine administered from 4 months of age, with a control group receiving inactivated poliomyelitis vaccine at 4 months of age and the standard Schwarz vaccine from 9 months of age. Children were followed to the age of at least 3 years. The mortality ratio of the EZ vaccinees compared with control subjects was 1.79 (range, 1.06 to 3.02; p = 0.027) if children were excluded at the time of migration; if deaths after migration were included, the mortality ratio was 1.53 (range, 0.94 to 2.49; p = 0.087). Girls in the EZ group had significantly higher mortality rates than girls in the control group (mortality ratio = 1.95; range, 1.07 to 3.56; p = 0.027); there was no difference for the boys (mortality ratio = 0.98; range, 0.41 to 2.30). Adjustment for background factors in a Cox regression model did not modify these estimates. Furthermore, female recipients of EZ vaccine had more days with diarrhea (relative risk = 1.35; range, 1.17 to 1.56; p = 0.00003) and were more likely than control subjects to visit a health center in the month after vaccination (relative risk = 1.86; range, 1.05 to 3.31; p = 0.027); those who consulted were more likely to die subsequently (mortality ratio = 2.31; range, 0.99 to 5.41; p = 0.054). These observations were unplanned and require confirmation in larger studies.

Cause of Death↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

The Gambia Hepatitis Intervention Study: follow-up of a cohort of children vaccinated against hepatitis B.

Hepatitis B vaccine has been introduced into The Gambia's national Expanded Programme on Immunization, with the aim of evaluating the impact on chronic liver diseases and in particular on hepatocellular carcinoma. As part of the project, a cohort of 1000 children was recruited to assess the long-term protection induced by the vaccine. The first 3 years of follow-up are described. By the age of 3 years, 95% of the children had protective antibody levels; 4 (0.6%) are known to be carriers in contrast to the 90-140 that would be expected in the absence of vaccination. The protective effectiveness of vaccine in preventing chronic carriage in the first 3 years of life is thus estimated as 95%. Since the risk of becoming a carrier is highest in those infected early in life, these results are encouraging.

Antigens, Viral↗
PubMed1992

Association between HIV-2 infection and genital ulcer diseases among male sexually transmitted disease patients in The Gambia.

OBJECTIVE: To investigate whether genital ulcer diseases are cofactors which enhance the transmission of HIV-2 in West Africa. DESIGN: A cross-sectional study of 435 men presenting with a sexually transmitted disease (STD). SETTING: The outpatient clinic of the Medical Research Council Laboratories, a primary care facility in Fajara, a suburb of Banjul, the capital city of The Gambia (West Africa). PATIENTS, PARTICIPANTS: Six hundred and twenty-four men presenting with a genital complaint, of whom 443 had an STD. Eight of the men with an STD were excluded from further analysis because they were HIV-1-infected (five patients) or had indeterminate Western blot patterns (three patients). The remaining 21 HIV-2-infected and 414 seronegative men constituted our study-group. MAIN OUTCOME MEASURES: Participants were questioned about previous STD and behavioural and demographic characteristics. A physical examination was performed and serum collected for measurement of antibodies against Haemophilus ducreyi and Treponema pallidum. RESULTS: HIV-2-infected men were more likely than HIV-seronegative participants to have previously had a genital ulcer [odds ratio (OR), 3.00; 95% confidence interval (Cl), 1.18-7.60] and to have antibodies against T. pallidum (OR, 5.95; 95% Cl, 2.10-16.91), or H. ducreyi (OR, 4.59; 95% Cl, 1.71-12.33). Circumcised patients with residual foreskin were more likely to be HIV-2 infected than patients with complete circumcision. HIV-2-seropositive patients were six times more likely to have generalized lymphadenopathy than their seronegative counterparts. CONCLUSIONS: Our data suggest that genital ulcerative diseases, such as syphilis and chancroid, are probably cofactors that increase the transmission of HIV-2 in West Africa, and that HIV-2 infection frequently results in generalized lymphadenopathy.

Adolescent↗
PubMed1992

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

OBJECTIVES: To determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. METHODS: All patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were log(e) serum neopterin level, CD4 cell count and log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11) and 13 (9-20) months, respectively. These survival times do not differ significantly. CONCLUSIONS: The Karnofsky score and measurements of serum neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization.

Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.

Animals↗
PubMed1992

HIV-1 and HIV-2 seroprevalence rates in mother-child pairs living in The Gambia (west Africa).

A seroepidemiological study was conducted, during 1988 and 1989, of mother-child pairs living in The Gambia (West Africa) in order to determine the distribution of the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2). Specimens were obtained from 931 children (age range, 14-17, months) and 923 mothers (age range, 14-17 years) using village-based cluster samples; the children are participating in The Gambia Hepatitis Intervention Study (GHIS), a large-scale HBV vaccination program. Large numbers of indeterminate Western blot patterns were observed among the mothers, mainly for HIV-1 antibodies; HIV-1 infected subjects were not found, whereas an HIV-2 seroprevalence rate of 0.75% was observed. The children born to the seven HIV-2 positive women were seronegative for HIV-2 antibodies, and none of the children showed HIV-2 or HIV-1 seropositively.

Adolescent↗