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H C Whittle

Publications and source records attributed to H C Whittle.

At least 19 recordsLinked to original sources
PubMed2001

HIV-2 does not protect against HIV-1 infection in a rural community in Guinea-Bissau.

OBJECTIVE: To examine the putative protective effect of HIV-2 infection against subsequent HIV-1 infection. DESIGN: Retrospective analysis of data from two cross-sectional surveys in the same community. METHODS: Two surveys between 1989 and 1998 in a rural area in northwestern Guinea-Bissau provided data from residents aged 15-59 years. HIV testing was done in the first survey. In the second survey, tests were made for both HIV and syphilis, and data on sociodemographic factors and sexual behaviour, including commercial sex work, were gathered. Qualitative polymerase chain reaction amplification of HIV-1 and HIV-2 viral DNA was performed on serologically dually reactive samples. RESULTS: Of the 2276 eligible adult villagers initially tested, 60% (1360) provided a second sample. Of 110 HIV-2-infected subjects, 17 became additionally infected with HIV-1 [incidence rate (IR), 26.3/1000 person-years observation]. Of the 1250 HIV-seronegative subjects, 24 became infected with HIV-1 (IR, 2.8/1000 person-years observation). The incidence rate ratio (IRR), comparing the incidence rate in HIV-2-infected people with the rate in HIV-seronegative subjects, was > 1 in all three "risk groups": men, female commercial sex workers, and other women. The overall estimate of the IRR, adjusted for age group and risk group, was 3.24 (confidence interval, 1.5-7.1). CONCLUSIONS: There was no protective effect of HIV-2 in this population. HIV-2 cannot be regarded as a vaccine, but, instead, may be a risk factor for HIV-1 infection.

Adolescent↗
PubMed2001

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.

BCG Vaccine↗
PubMed2001

Measles antibody responses after early two dose trials in Guinea-Bissau with Edmonston-Zagreb and Schwarz standard-titre measles vaccine: better antibody increase from booster dose of the Edmonston-Zagreb vaccine.

In Guinea-Bissau, children were randomised at 6 months of age to receive either two doses of standard-titre measles vaccine at 6 and 9 months of age or an inactivated polio vaccine at 6 months and standard-titre measles vaccine at 9 months of age. During the first 5 months, children received Edmonston-Zagreb (EZ) vaccine and during the following 11 months, the Schwarz (SW) vaccine. Five percent of the mothers, 74% of children at 6 months of age, and 92% of unvaccinated children at 9 months of age had unprotective levels (<125 mIU/ml) of measles antibodies. Among children receiving EZ vaccine, 1% were unprotected at 18 months of age after either two (3/240) or one (3/211) doses of vaccine, the geometric mean measles antibody titre (GMT) being approximately 1550 mIU/ml in both groups. Among those receiving SW vaccine 9% (34/365) and 3% (9/310) were unprotected at 18 months of age in the two-dose and the one-dose groups (RR = 3.21 (95% confidence interval (CI) 1.56-6.58)), respectively. The GMT was higher after one dose of SW vaccine at 9 months of age (2491 mIU/ml) than after two doses of SW vaccine (1125 mIU) (P < 0.001). In the EZ vaccine group, there was no significant difference in antibody level for children vaccinated in the presence of high or low levels of maternal antibodies, whereas there was a marked difference in the SW group. The second EZ vaccine induced a significant antibody increase between 9 months of age (1191 mIU) and 18 months of age (1602 mIU, P=0.011), whereas antibody levels tended to decline from 9 months (1243 mIU) to 18 months of age (998 mIU, P = 0.124) after the second dose of SW vaccine. Conclusively, after two doses of EZ measles vaccine more children were protected at 18 months of age than after two doses of SW. One dose of SW provided the highest antibody response, but a higher proportion of unprotected than one or two doses of EZ. The EZ vaccine was less sensitive to maternal antibodies, and able to increase the antibody response by revaccination, while the second SW vaccine resulted in an unchanged or lower antibody response.

Age Factors↗
PubMed2001

Failure to detect HLA-A*6802-restricted CD8+ T cells specific for Chlamydia trachomatis antigens in subjects from trachoma-endemic communities.

The role of HLA-A*6802-restricted CD8+ T cells in chlamydial disease was investigated in human ocular infections. Peptides with predicted binding motifs for HLA-A*6802 were synthesized using sequences based on chlamydial antigens, major outer membrane protein (MOMP), macrophage infectivity potentiator (MIP) and heat shock protein (hsp70). Peptides were pooled according to Chlamydia trachomatis protein type and serovar, and were tested in 51Cr-release cytotoxic T lymphocyte (CTL) and enzyme-linked immunospot (ELISPOT) assays, using peripheral blood mononuclear cells (PBMC) isolated from subjects living in trachoma-endemic communities in The Gambia. Significant CTL activity or interferon-gamma release was not detected in any of the subjects, suggesting either that HLA-A*6802 CD8+ T cells may not be important in ocular infections or that the peptides chosen did not represent epitopes.

Adolescent↗
PubMed2001

Peripheral gangrene complicating Salmonella typhi septicaemia in a Gambian infant.

A 1-year-old malnourished boy, who presented with Salmonella typhi septicaemia with a 4-day history of febrile illness, dehydration and severe anaemia, developed bilateral dry gangrene of the hands and feet. Although he improved appreciably, he suffered auto-amputation of the distal phalanges of the left foot after 3 weeks of illness. A high index of suspicion and prompt treatment is highly critical in the treatment of septicaemia in young children.

Foot↗
PubMed2000

Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Adolescent↗
PubMed2000

Maternal HIV-1 and HIV-2 infection and child survival in The Gambia.

OBJECTIVE: To compare the survival of children born to HIV-1 or HIV-2 seropositive mothers with that of children born to HIV-seronegative mothers and to evaluate risk factors for mortality. DESIGN: Physician-blinded prospective study. METHODS: One hundred and one HIV-1-seropositive, 243 HIV-2-seropositive pregnant women, and 468 HIV-seronegative women (control group) matched by age, parity, and health centre, were followed up in a study of mother-to-child transmission of HIV. Mothers and children were seen at 2 and 6 months of age and subsequently followed at 3-monthly intervals up to 18 months of age. HIV infection in children was diagnosed by polymerase chain reaction at 2, 9 or 18 months and by antibody assays at 18 months. RESULTS: Fifteen per cent of children born to HIV-1-infected mothers died compared with 7% of children born to HIV-2-infected mothers [hazard ratio, 2.3; 95% confidence interval (CI), 1.1-4.7; P = 0.02], and 6% of HIV-seronegative mothers (hazard ratio, 2.6; 95% CI, 1.4-5.0; P = 0.003). Six of the 17 children known to be HIV-1 infected died compared with none among the eight HIV-2-infected children (P = 0.13). High proviral load in the babies, high antenatal maternal RNA plasma viral load, and maternal death increased child mortality significantly. CONCLUSIONS: More children born to HIV-1-infected mothers died in comparison with those born to HIV-2-infected mothers or to mothers from the control group. This effect was due to excess death in HIV-1-infected infants which was associated with a high viral load in the affected mother and child.

Female↗
PubMed2000

Prior BCG vaccination improves survival of Gambian patients treated for pulmonary tuberculosis.

The protection provided by BCG against pulmonary tuberculosis ranges from nil to over 90%. While BCG protects against the more serious forms of tuberculosis, it is not known whether or not it protects patients with pulmonary tuberculosis from death. In a study designed to look at the effects of immunotherapy with M. vaccae as an adjunct to chemotherapy in 285 adult Gambian patients treated for proven pulmonary tuberculosis, we examined the association between the presence or absence of a BCG scar and mortality. The data showed that subjects who had a BCG scar were significantly younger than those who did not, and were less likely to have nutritional oedema. During the course of treatment, none of the 85 patients who had a BCG scar died compared to 35 of 200 patients (17.5%) who did not (P < 0.001). In these Gambian patients with pulmonary tuberculosis, prior vaccination with BCG may have provided substantial protection against death. However, there is the possibility that this finding is the result of confounding by other factors or has arisen from bias. Researchers with similar data need to investigate this question as this association, if true, could have major implications for BCG vaccination.

Adolescent↗
PubMed2000

Cytotoxic T-lymphocyte epitopes for HLA-B53 and other HLA types in the malaria vaccine candidate liver-stage antigen 3.

The development of an effective preerythrocytic vaccine against Plasmodium falciparum malaria is likely to require inclusion of components from several preerythrocytic antigens. The association of HLA-B53 with resistance to severe malaria in West Africa provided evidence that HLA class I-restricted CD8(+) T-cell responses play a role in protective immunity in African children, supporting data from rodent models of malaria. Previously, a single epitope from liver-stage-specific antigen 1 (LSA-1) has been shown to be recognized by HLA-B53-specific cytotoxic T lymphocytes (CTL), but HLA-B53 epitopes were not found in four other antigens. In this study we measured CTL responses to peptides from the recently sequenced antigen liver-stage antigen 3 (LSA-3) and identified in it a new epitope restricted by HLA-B53. Several CTL epitopes restricted by other class I types were also identified within LSA-3 in studies in The Gambia and Tanzania. CTL were also identified to an additional P. falciparum antigen, exported protein 1 (Exp-1), the homologue of which is a protective antigen in a rodent model of malaria. These findings emphasize the diversity of P. falciparum antigens recognized by CD8(+) T cells in humans and support the inclusion of components from several antigens in new CTL-inducing vaccines against malaria.

Amino Acid Sequence↗
PubMed1999

Hepatitis B vaccination in infancy in The Gambia: protection against carriage at 9 years of age.

To estimate the efficacy in The Gambia (West Africa) of infant hepatitis B vaccination against infection and carriage with the virus at the age of 9 years. The HBV status of 9-year old children vaccinated in infancy was compared to that of unvaccinated children of the same age. Eight percent of the vaccinated children had been infected by HBV compared to 50% of the unvaccinated control group; HBV carrier status was 0.6 and 10% respectively, resulting in a vaccine efficacy of 83% against infection and of 95% against chronic carriage. The results show that infant vaccination provides a high level of protection at the age of nine years against both HBV infection and chronic carrier status and no booster dose of vaccine is required in the first decade. These findings support the WHO recommendation for the introduction of HBV vaccination into the Expanded Programme on Immunization in Africa.

Carrier State↗
PubMed1999

Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa.

BACKGROUND: Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children. METHODS: Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound. FINDINGS: Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months. INTERPRETATION: Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

Adolescent↗
PubMed1999

What level of hepatitis B antibody is protective?

This study assessed the level of vaccine-induced hepatitis B surface antibody that is protective against hepatitis B infection and carriage in The Gambia. Sera from 700 of a cohort of 1041 children vaccinated against hepatitis B in infancy were serially tested for markers of hepatitis B until age 7 years. No absolute level of protection against infection was found, but all children who attained a peak antibody response to vaccination of >=10 IU/L were protected against carriage of hepatitis B surface antigen. Two-thirds of 45 infected children experienced brief infection (determined by loss of core antibody). This transient infection was likely related to surface antibody level. The data support the use of the peak antibody response as the best indicator of protection against carriage and suggest that most infections after vaccination are short-lived.

Antibody Affinity↗
PubMed1999

Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene.

The active metabolite of vitamin D, 1,25 dihydroxyvitamin D3, is an important immunoregulatory hormone [1]. Its effects are exerted by interaction with the vitamin D receptor, which is present on human monocytes and activated T and B lymphocytes. Variation in the vitamin D receptor gene was typed in 2015 subjects from large case-control studies of three major infectious diseases: tuberculosis, malaria, and hepatitis B virus. Homozygotes for a polymorphism at codon 352 (genotype tt) were significantly underrepresented among those with tuberculosis (chi2=6.22, 1 df, P=. 01) and persistent hepatitis B infection (chi2=6.25, 1 df, P=.01) but not in subjects with clinical malaria compared with the other genotypes. Therefore, this genetic variant, which predisposes to low bone mineral density in many populations, may confer resistance to certain infectious diseases.

Adolescent↗
PubMed1999

Antigen-specific expansion of cytotoxic T lymphocytes in acute measles virus infection.

Skewing of the T-cell receptor repertoire of CD8(+) T cells has been shown in some persistent infections with viruses, such as human immunodeficiency virus, simian immunodeficiency virus, and Epstein-Barr virus. We have demonstrated that similar distortions also occur in nonpersistent measles virus infection. In addition, two of four children immunized with live, attenuated measles virus showed larger and more persistent CD8(+) T-cell expansions than their naturally infected counterparts. The expanded lymphocyte populations were monoclonal or oligoclonal and lysed target cells infected with recombinant vaccinia virus expressing measles virus protein. These results demonstrate that the expansions of CD8(+) T lymphocytes are antigen driven.

Acute Disease↗
PubMed1999

Hepatitis B virus DNA in relation to duration of hepatitis B surface antigen carriage.

This study determined the prevalence and concentration of hepatitis B virus (HBV) DNA in chronic carriers of hepatitis B surface antigen (HBsAg) in The Gambia, West Africa. Ninety-nine young child carriers aged three to four years, 115 older child carriers aged five to 14 years, 71 adult carriers and 105 infected children who were not carriers were included. Detection of HBV DNA was performed by dot blot hybridisation using a radioactive phosphorus (32P) method and by non-radioactive enhanced chemiluminescence (ECL). Chromoscan-3 equipment was used to quantify DNA, and ECL and the 32P method were compared. Sensitivity and specificity of ECL were 95.8% and 100% respectively, with a detection limit of 0.3 pg/microL (0.3 x 10(5) genomic copies) compared to 0.15 pg/microL (0.15 x 10(5) genomic copies) for the 32P-labelled probe. The prevalence of HBV DNA was 74% (74/99) in young carriers, 30% (35/115) in older child carriers and 12.6% (9/71) in adult carriers. The geometric mean (GM) values for HBV DNA were significantly different between age groups (P = 0.031) and HBV DNA, which declined significantly with age (r = 0.16, P < 0.001 for log32P values), ranged from 1.48 pg/microL in young carriers to 0.29 pg/microL in adults over 24 years. The GM value of HBV DNA was related to duration of carriage. Higher values were found in young carriers known to be HBsAg-positive for less than three years compared with adult carriers of at least 20 years' duration. The GM (95% confidence limit [CL]) values were 1.48 pg/microL (1.42, 1.53) and 0.29 pg/microL (0.25, 0.33) respectively. The level of HBV DNA in hepatitis B envelope antigen (HBeAg)-positive carriers was higher than in HBeAg-negative carriers, the GM (95% CL) being 1.23 pg/microL (1.19, 1.27) and 0.34 pg/microL (0.25, 0.42) respectively.

Adolescent↗
PubMed1998

Ex vivo analysis of cytotoxic T lymphocytes to measles antigens during infection and after vaccination in Gambian children.

The study of cytotoxic T cell responses to measles antigens during infection and after vaccination may provide insight into the immunopathology of the infection. It will also provide a knowledge of the immunity conferred by wild or attenuated virus, which will help in the design of new vaccines. Direct cytotoxic T cell responses, which did not require in vitro restimulation, were measured from peripheral blood by a standard 51Cr-release assay in 35 patients with acute measles, using HLA class I matched allogeneic B cells as targets. 77% showed specific responses to measles fusion protein, 69% to the hemagglutinin, and 50% to the nucleoprotein. These responses, which were related to severity of disease and history of previous vaccination, had waned by 14-24 wk after measles when memory responses to the same antigens could be elicited by restimulation in 71% of the 13 patients tested. A similar pattern followed vaccination: direct cytotoxic responses to fusion and hemagglutinin proteins were shown in 70% of the 20 children tested while 50% responded to the nucleoprotein. These responses, which were mediated by both CD8(+) and CD4(+) cells, faded over 6 wk when memory responses could be restimulated. Thus, a vigorous cytotoxic T lymphocyte response to fusion, hemagglutinin, and nucleoproteins is important in both natural and vaccine-induced immunity to measles.

Adolescent↗
PubMed1998

Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans.

BACKGROUND: Genetic factors may affect the susceptibility to tuberculosis, but no specific genes governing susceptibility have been identified. In mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage protein 1 (Nramp1), but the role of the human homologue of this gene, NRAMP1, in tuberculosis is unknown. We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa. METHODS: Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded. RESULTS: Four NRAMP1 polymorphisms were each significantly associated with tuberculosis. Subjects who were heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07; 95 percent confidence interval, 1.86 to 9.12; chi-square= 14.58; P<0.001). CONCLUSIONS: Genetic variation in NRAMP1 affects susceptibility to tuberculosis in West Africans.

Adult↗