Biomedical subjects

M Mendy

Publications and source records attributed to M Mendy.

At least 19 recordsLinked to original sources

PubMed2001

Prevalence of HBV core promoter/precore/core mutations in Gambian chronic carriers.

One hundred forty-two precore/core sequences were obtained from Gambian chronic hepatitis B virus (HBV) carriers and the predominant variants defined. The two point mutations, from A to T and G to A at nt positions 1762 and 1764 in the basic core promoter region, were found in only 7/99 (7%) of the samples where this region was sequenced. These mutations were found in both HBeAg-positive and -negative patients. The precore stop-codon mutation at nt position 1896 was found in 14/51 (27%) of HBeAg-negative samples, which is a lower prevalence rate in comparison with other parts of the world with high carrier rates. In HBeAg-positive patients the core amino acid sequences were conserved, but after seroconversion to anti-HBe significantly more changes were apparent. Several of the amino acid substitutions found have been described previously been in wild-type viruses of other genotypes.

Amino Acid Sequence↗

PubMed2001

Transmission of hepatitis B virus infection in Gambian families revealed by phylogenetic analysis.

BACKGROUND/AIMS: Transmission of hepatitis B virus (HBV) in Africa occurs horizontally, with most people becoming infected between the ages of 1 and 5 years. The index cases in such events have been assumed to come from within the family unit or from sources outside the immediate family, such as other families or inhabitants of the same compound or village. Here, we define these routes of transmission by phylogenetic tree analysis of sequences from the entire pre-core/core region of the virus, in Gambian chronic carriers. METHODS: Amplification by polymerase chain reaction of serum extracted HBV-DNA was followed by direct sequencing of the target region. Following editing and alignment of these sequences, phylogenetic tree analysis was performed using the neighbour-joining and maximum-likelihood methods. RESULTS: Despite the overall conserved nature of the sequences of the pre-core/core region from 142 chronic carriers, distinct clusters were easily defined at the family and village level, but not on a wider geographical separation. CONCLUSIONS: Phylogenetic tree analysis of sequences obtained from family members provided strong evidence of intrafamilial transmission of HBV in at least two-thirds of the families studied from Gambia.

Cluster Analysis↗

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

Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia.

BACKGROUND: A selective mutation, an arginine-to-serine substitution in codon 249, of the p53 gene has been identified as a "hotspot" mutation in hepatocellular carcinoma (HCC). This mutation occurs in populations that are exposed to aflatoxins and have a high prevalence of hepatitis B virus carriers. We evaluated whether this mutation could be detected in cell-free DNA isolated from the plasma of subjects from The Gambia to detect this mutation that is strongly associated with HCC. METHODS: Fifty-three patients with HCC, 13 patients with cirrhosis, and 53 control subjects were prospectively recruited from The Gambia. Sixty patients, of non-African origin, with various liver pathologies were also selected from France. DNA was extracted and purified from 200-microL aliquots of plasma. The Ser-249 p53 mutation was detected by restriction endonuclease digestion of polymerase chain reaction products from exon 7 and was confirmed by direct sequencing of the amplified DNA. RESULTS: The Ser-249 p53 mutation was detected in plasma DNA from 19 (36%) of the 53 patients with HCC, two (15%) of the 13 patients with cirrhosis, and three (6%) of the 53 control subjects. This mutation was not detected in any plasma DNA from the European patients. The adjusted odds ratio for having the mutation was 16.4 (95% confidence interval = 3.0-90.5) for patients with HCC compared with the control subjects. CONCLUSION: The Ser-249 p53 mutation in plasma DNA is strongly associated with HCC in Gambian patients. This mutation was also detected at a much lower prevalence in plasma DNA from Gambian patients with cirrhosis and in Gambian control subjects, findings that may lead to the earlier detection of HCC. Use of the Ser-249 p53 mutation should facilitate further molecular epidemiologic studies on the development of HCC.

Adult↗

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↗

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

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

Aflatoxin exposure and DNA damage in the comet assay in individuals from the Gambia, West Africa.

The single cell gel electrophoresis assay (Comet assay) was used to measure DNA damage in peripheral lymphocytes from a group of individuals from The Gambia in order to determine whether such damage could be associated with increased exposure to aflatoxin in this population. Responses obtained were correlated to responses previously obtained [1] in a cross-sectional study in the same individuals of various cytogenetic alterations [chromosomal aberrations, micronuclei (crest positive and negative staining), and sister chromatid exchanges], and aflatoxin-albumin adducts. Analysis of variance methods were used to assess the effects of smoking, GSTM1 genotype, sex, age, and smoking status. A comparison was also made between The Gambian individuals and a group of healthy, non-smoking volunteers in the United Kingdom where aflatoxin exposure would be expected to be low. From the earlier study [1], it was determined that the levels of the sister chromatid exchanges and micronuclei were higher in The Gambian group than in a European group where aflatoxin exposure was lower, but that there were no correlations between the adduct levels and the cytogenetic abnormalities at the individual level. In the present study, DNA damage as measured in the Comet assay was not significantly higher than in the healthy United Kingdom volunteers. In addition, there were no associations between cytogenetic damage, GSTM1 genotype, age, sex, lifestyle factors (smoking and aflatoxin exposure), and Comet response at the individual level. Comet response was higher in females than males in The Gambia if one outlier was excluded from analysis and not taking into account other sources of variability. It would appear that DNA damage as measured in the Comet assay in peripheral blood lymphocytes is not a sensitive genotoxic marker of aflatoxin exposure in this population.

Adolescent↗

PubMed1995

The ligase chain reaction distinguishes hepatitis B virus S-gene variants.

A novel method for the identification of hepatitis B virus (HBV) variants was developed. The ligase chain reaction (LCR) distinguished the sequences of two isolates from the Gambia showing a change at nucleotide 421 within the region coding for the surface protein a antigenic determinant. One sequence was derived from a child previously immunized with HBV vaccine, while the other, reported here for the first time, was from a chronic carrier. Nucleotide variations within the target sequence at, or up to 3 bases from the point of ligation inhibited the reaction. The LCR recognised variations in as little as 0.9 fmol DNA and will permit the rapid detection of HBV variants in molecular epidemiological studies.

Base Sequence↗

PubMed1995

Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages.

In 1984, all non-immune children under the age of 5 years in the Gambian villages of Keneba and Manduar were vaccinated against hepatitis B virus (HBV). All children born in these villages since 1984 have been vaccinated in infancy. Despite a rapid fall in antibody concentrations, vaccine efficacy against HBV infection and chronic carriage of HBsAg has increased with time. Overall, vaccine efficacies in 1993 against HBV infection and chronic HBsAg carriage were 94.7% (95% Cl 93.0-96.0) and 95.3% (91.0-97.5), respectively. Breakthrough infections in vaccinated children largely originate from chronic HBsAg carriers. Thus, we tested 261 chronic carriers for HBV DNA and e antigen. The prevalence of these markers of infectivity, and the amount of HBV DNA, decreased greatly with age. Detailed studies of breakthrough infections over two 4-year periods revealed that in the second period there were fewer than half the expected numbers of infections. Our findings suggest that in Keneba and Manduar long-term vaccination is progressively decreasing HBV transmission by chronic carriers, since their infectivity diminishes with time.

Adolescent↗

PubMed1994

Do bedbugs transmit hepatitis B?

An intervention study was done over two years in seven Gambian villages to determine the contribution of bedbugs to hepatitis B transmission. In addition, fortnightly questionnaires were completed for each child to assess other possible routes of transmission. The intervention, insecticide spraying of the child's dwelling, was highly effective in reducing exposure to bedbugs but there was no effect on hepatitis B infection. No other risk factor for transmission was identified despite a consistent village-to-village variation in the rate of childhood infection. The major mode of transmission of hepatitis B in childhood remains unknown.

Animals↗

PubMed1994

Breakthrough infections and identification of a viral variant in Gambian children immunized with hepatitis B vaccine.

Hepatitis B (HB) breakthrough infections, identified by the presence of HB core (c) antibody, were found in 32 of 358 Gambian children vaccinated with plasma-derived HB vaccine. Over 2 years, 15 of these children lost their HBc antibodies. These children had significantly higher HB surface antibody levels before infection than those who retained HBc antibodies. One child, who responded well to the vaccine, had HB viral DNA detected in the presence of HBs antibodies. The S gene sequence of this DNA showed nucleotide changes that resulted in an amino acid substitution at residue 141 (lysine to glutamic acid) of the surface antigen. This finding suggests the child was infected with a variant virus that was not neutralized by antibodies resulting from HB vaccination.

Child↗

PubMed1994

A novel hepatitis B virus variant in the sera of immunized children.

A novel hepatitis B virus (HBV) variant was detected in the sera of two children in The Gambia, West Africa. The children had been immunized with plasma-derived vaccine and had developed antibody titres of 1448 international units x 10(-3) (mIU)/ml and 133 mIU/ml respectively against the hepatitis B surface antigen (HBsAg). Despite the protective levels of antibodies, HBV DNA was subsequently detected in both children. The complete surface (S) protein gene sequence demonstrated that this HBV isolate was closely related to the ayw4 subtype. However, five nucleotide changes were identified and two of these were unique to the Gambian isolate. One of these changes was within the region of the S gene coding for the immunodominant a determinant of the S protein. A unique nucleotide change from adenosine to guanosine at nucleotide 421 was found, resulting in an amino acid substitution at residue 141 from lysine to glutamic acid. Previous studies have shown that amino acids 141 to 146 are critical for binding to the protective anti-HBsAg antibodies. The presence of a variant HBV in these children suggests the emergence of a novel strain of HBV which can evade immune recognition. This has potential implications for HBV diagnosis and prophylaxis.

Amino Acid Sequence↗

PubMed1993

Efficacy of hepatitis B vaccine in the Gambian expanded programme on immunisation.

Because of the high prevalence of hepatitis B virus (HBV) infection in The Gambia, HBV vaccination has been incorporated into the national expanded programme on immunisation. We have assessed the efficacy of the vaccine against HBV infection and chronic carriage by examining 720 3-4-year-old children who had received the vaccine in infancy and 816 who had not received it. The vaccine was 84% (95% CI 78-89%) effective against infection and 94% (84-98%) effective against chronic carriage. Vaccinated infants of mothers positive for hepatitis B surface and e antigens were at greater risk of breakthrough infection and chronic carriage than infants of uninfected mothers. The high vaccine efficacy against the HBV carrier state, the main risk factor for the development of chronic liver disease and liver cancer, offers hope that the prevalence of these diseases may be reduced in the future.

Carrier State↗

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↗

PubMed1991

Vaccination against hepatitis B and protection against chronic viral carriage in The Gambia.

358 children in the Gambian villages of Keneba and Manduar, where hepatitis B virus (HBV) infection is endemic, were vaccinated with plasma-derived vaccine against HBV according to one of four regimens and followed for up to 4 years. Two regimens by which vaccine was injected intradermally into children between 0 and 4 years old led to peak geometric mean (95% CI) concentrations of antibody against HBV surface antigen of 270 (202-358) and 555 (418-748) mlU/ml. The third regimen--intramuscular vaccination of children aged between 0 and 4 years--gave geometric mean peak antibody concentrations of 926 (765-1122) mlU/ml. A fourth regimen was intramuscular vaccination of children between 1 and 9 months old, which gave geometric mean antibody concentrations of 5431 (3903-75,456) mlU/ml. Despite these widely divergent responses and a 89% decay in antibody over the first 2 years, vaccination against HBV was 97% effective in preventing chronic infection. Vaccination was less effective in preventing uncomplicated infection: 5.3% of 264 vaccinees in Keneba and 19.1% of 94 vaccinees in Manduar tested positive for antibody to HBV core antigen. These "breakthrough infections" did not differ in frequency between regimens, and were associated with low initial antibody responses and chronic maternal carriage of HBV.

Adolescent↗

PubMed1991

HIV-2-induced immunosuppression among asymptomatic West African prostitutes: evidence that HIV-2 is pathogenic, but less so than HIV-1.

Two hundred and forty-one prostitutes working in The Gambia were tested for retroviral infections and their immune system evaluated. Sixty-three were seropositive for HIV-2 only, five for HIV-1 only and six for both HIV-1 and HIV-2 (26.1, 2.1 and 2.5%, respectively). When compared to seronegative individuals, the 63 women infected with HIV-2 clearly had an abnormal immune system, with significantly lower CD4+ and higher CD8+ lymphocyte counts and percentages, lower CD4+:CD8+ ratios, lower CD25+ (activated) lymphocyte counts, and lower lymphocyte proliferation responses after stimulation with phytohaemagglutinin, purified protein derivative (PPD), Candida or pokeweed mitogen, and higher levels of neopterin and beta 2-microglobulin. However, when the HIV-2-seropositive prostitutes were compared with the five women infected with HIV-1, the former were less abnormal, with significantly higher CD4+ percentages and CD4+:CD8+ ratios and lower CD8+ percentages and counts. Immunological anomalies were seen in five women known to have been infected with HIV-2 for less than 17 months. Coinfection with HTLV-1 resulted in more severe immunological alterations than infection with HIV-2 alone.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Risk factors for transmission of hepatitis B virus to Gambian children.

Risk factors for hepatitis B virus transmission were examined in 973 Gambian children aged 6 months to 5 years. 33% had evidence of infection with hepatitis B virus and a third of these were carriers. A significant association was found between infection and tropical ulcer scars, and between e antigenaemia and the presence of bedbugs in each child's bed. There was no association between infection and traditional scarring, circumcision, or injections. Skin disease and arthropods are the two most likely modes of transmission of hepatitis B virus between children in West Africa.

Acute Disease↗