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Biomedical subjects

M Peeters

Publications and source records attributed to M Peeters.

At least 163 records · Page 9Linked to original sources

Demographic factors associated with HTLV-1 infection in a Gabonese community.

An epidemiological study of human T-lymphotropic virus type 1 (HTLV-1) and syphilis has been carried out in a multiethnic community of seven neighbouring villages located in eastern Gabon on 1240 subjects over 5 years old (82.7% of the population in this age range). Antibodies to HTLV-1 (anti-HTLV-1) were detected by ELISA with confirmation by Western Blot and antibodies to syphilis by Venereal Diseases Research Laboratory assay with confirmation by the Treponema pallidum haemaglutination assay. The prevalence rate of anti-HTLV-1 was 8.5% and increased from 3.7% in the 5-14 years age group to 23.8% in the over 60 years age group. Logistic regression showed that the positivity for anti-HTLV-1 was associated with age, ethnic group and sex (higher prevalence in females). The seroprevalence rate of syphilis was 8.2%. Seropositivity for syphilis and HTLV-1 were related but age was a confounding variable in this relationship. This study showing a highly heterogeneous distribution of HTLV-1 in a geographically limited area suggests the role of environmental and behavioural factors in HTLV-1 transmission.

Adolescent↗

Molecular phylogeny of part of the env gene of HIV-1 strains isolated in Côte d'Ivoire.

OBJECTIVES: To examine the genetic variation of HIV-1 isolates in Abidjan, Côte d'Ivoire, and to determine the extent to which phylogenetic trees based on sequence information of part of the env gene containing the principal neutralizing domain are representative for documenting genetic variability. DESIGN: Phylogenetic comparison of 13 HIV-1 strains isolated from patients in Abidjan with previously documented HIV-1 strains of different geographic origin. METHODS: To sequence a 900 base-pair fragment of the env gene containing V3, V4, V5 and the beginning of gp41 of three to four clones per isolate. Phylogenetic tree analysis was performed with the software package TREECON. RESULTS: Eleven HIV-1 isolates of Abidjan were classified as genotype A, while two were classed as genotypes B and D. Intra-genotype A distances at the nucleotide level were a maximum of 14.1%. Inter-genotype distances between genotype A and genotypes B, C, and D varied from 16.0 to 22.6%. Phylogenetic trees, based on sequence data of a 300 base-pair fragment containing the V3 loop, showed significant differences in tree topology and statistical confidence with phylogenetic trees based on sequence data of the 900 base-pair env fragment. CONCLUSIONS: Genotype A Côte d'Ivoire HIV-1 strains, which comprise 11 out of 13 isolates, predominate in Abidjan, which may indicate a local burst of particular variants. Phylogenetic trees should be interpreted with caution when based on a more limited number of nucleotides, such as the V3 region.

Base Sequence↗

Cross-neutralizing antibodies to HIV-1ANT70 and HIV-1IIIB in sera of African and Belgian HIV-1-infected individuals.

OBJECTIVES: To determine the neutralizing antibody patterns to HIV-1ANT70 (ANT70) and HIV-1IIIB (IIIB) in human sera obtained from HIV-1-infected individuals from different African countries and Belgium. Second, to correlate the presence of neutralizing antibodies in sera and their ability to bind to synthetic peptides derived from eight different HIV-1 V3 loop sequences. DESIGN AND METHODS: Forty sera from Belgium and 88 obtained from seven countries in Africa were tested for their ability to neutralize ANT70 (one of the most genetically divergent HIV-1 isolates documented), and IIIB. Sera found to cross-neutralize both viruses were further challenged with four HIV-1 field isolates. All sera were tested on a panel of V3 loop peptides obtained from different HIV-1 genotypes. RESULTS: Four patterns of sera were identified, including 33 (26%) sera not neutralizing any of the isolates, seven (5%) sera neutralizing only ANT70, 45 (35%) sera neutralizing only IIIB, and 43 (34%) sera cross-neutralizing both isolates. Sera capable of cross-neutralizing both ANT70 and IIIB consistently neutralized other field isolates tested, with a remarkable similarity in neutralizing antibody titre. A significantly higher number of sera cross-neutralizing both ANT70 and IIIB compared with sera lacking neutralizing antibodies, reacted simultaneously in enzyme-linked immunosorbent assays (ELISA) with three or more V3 loop peptides belonging to HIV-1 strains of different genotypes. However, none of the sera cross-neutralizing ANT70 and IIIB were reactive in ELISA with the ANT70 V3 loop peptide. CONCLUSION: These results suggest that despite pronounced genomic variation of the HIV-1ANT70 isolate, there are strongly conserved neutralizing epitopes situated outside the V3 loop that are shared by other HIV-1 isolates. These findings suggest that genetic variation might be surmountable in the design of a polyvalent HIV vaccine, if neutralizing antibodies are found to be correlates of protection in HIV infection.

Acquired Immunodeficiency Syndrome↗

Antibodies to V3 loop peptides derived from chimpanzee lentiviruses and the divergent HIV-1ANT-70 isolate in human sera from different geographic regions.

OBJECTIVE: To study the spread of antibodies to V3 loop peptides of two chimpanzee lentiviruses and the divergent HIV-1ANT-70 isolate (group O) in human sera from different geographic regions, and to compare this with reactions to peptides from known North American (subtype B) and Zaïrean (subtype D) strains. METHODS: A total 2495 HIV-1-antibody-positive sera from nine countries were tested by enzyme-linked immunosorbent assay for antibodies to the V3 loop of 10 HIV/SIV isolates (including MN, SF2, HXB2, RF, MAL, ELI, Z6 and ANT-70 for HIV-1, and cpz-gab and cpz-ant for SIV). RESULTS: In each country, the highest prevalences were observed against the MN peptide (58.8-91.7%). Seroreactivity to other peptides from subtype B were generally lower. Prevalences of antibodies to V3 peptides derived from Zaïrean strains belonging to subtype D were generally lower than to subtype B. Relative high prevalences of sera reactive with the SIVcpz-gab V3 peptide were observed. The lowest rates were seen in Brazil (4.2%) and Belgium (25.7%). Among the African countries, the prevalence rates varied between 30.1 and 67.6%. Prevalence to the V3 loop derived from the SIVcpz-ant strains was much lower. Prevalence of sera reactive to the ANT-70 V3 loop peptide was very low, and the highest rates were observed in Cameroon (10.2%), Niger (6%) and Gabon (4.6%). Only the sera reactive to the ANT-70 V3 loop peptide from Cameroon and Gabon were confirmed on a specific HIVANT-70 Western blot (i.e., presence of antibodies to the envelope protein gp 120). CONCLUSIONS: The extent to which different V3 peptide reactivity patterns reflect the circulation of different HIV-1 strains in a particular population is not yet clear. However, V3 peptide serology using the very specific V3 peptide of the HIVANT-70 is a good indicator of the very aberrant group O in a particular population.

Amino Acid Sequence↗

Quantification of human immunodeficiency virus in plasma by RNA PCR, viral culture, and p24 antigen detection.

A semiquantitative PCR technique for detecting human immunodeficiency virus type 1 (HIV-1) RNA in plasma was compared with quantitative viral culture and p24 antigen detection in plasma. Ninety-three samples from 20 symptomatic, 10 asymptomatic, and 10 seronegative individuals were tested. For most of the seropositive patients, consecutives samples were examined. Viral RNA was extracted from plasma by the method described by Boom et al. (R. Boom, C.J. A. Sol, M. M. M. Salimans, C.L. Jansen, P. M. E. Wertheim-van Dillen, and J. van der Noordaa, J. Clin. Microbiol. 28:495-503, 1990). The RNA PCR was the most sensitive method (100 and 74% sensitivity for symptomatic and asymptomatic patients, respectively) and produced less divergent results with the consecutive samples from individual patients compared with the other techniques. All samples positive by viral culture or p24 antigen assay were also positive in the RNA PCR. For each of the three assays, the number of positive results obtained correlated with the disease stage. The estimated mean number of HIV-1 RNA copies was significantly higher in symptomatic patients (22,750 copies per ml) than in asymptomatic patients (1,820 copies per ml). It was also higher in samples positive for viral culture than in culture-negative samples. No close correlation was found between the amount of HIV-1 RNA and the amount of p24 antigen or the titer of infectious virus in plasma or between this titer and the level of p24 antigen. The plasma RNA PCR may be a useful additional marker of disease progression and may be valuable for monitoring the effects of antiviral therapy.

Acquired Immunodeficiency Syndrome↗

Test conditions greatly influence permeation of water soluble molecules through the intestinal mucosa: need for standardisation.

Permeability tests are widely used to investigate the pathogenesis of various gastrointestinal diseases including coeliac disease, infectious diarrhoea, and inflammatory bowel disease. In Crohn's disease they are used as activity parameters by some investigators. Lack of standardisation, however, makes it very difficult to compare data reported in different studies. The aim of this study was to gather permeation data in well controlled test conditions to standardise the methods. Nine healthy volunteers each received five consecutive permeability tests by mouth using polyethylene glycol-400 (PEG-400) and 51Cr-EDTA as probe molecules. The probes were dissolved in water, a glucose solution, a starch solution, a hyperosmolar lactulose-mannitol solution, and a liquid meal. A significantly decreased permeation for both probes was found when given with the hyperosmolar solution. The 51Cr-EDTA permeation was also decreased with water. The permeability index, 51Cr-EDTA/PEG-400, corrected for influencing factors, confirmed that the lactulose-mannitol solution and plain water yield lower values of macro-molecule permeation than starch, glucose or liquid meal. Hyperosmolarity was clearly accompanied by a decrease in permeability probably caused by reversed solvent drag. Interindividual variability of probe permeation and permeability index is very low with a standard liquid meal. It is proposed that for permeability studies a standard liquid meal is always used.

Adult↗

Non-Hodgkin lymphoma in Gabon and its relation to HTLV-I.

A case-control study was performed in Libreville, Gabon, to determine whether a relationship can be established between the relatively high proportion of non-Hodgkin lymphoma (NHL) among all cancer cases and the high seroprevalence rate of HTLV-I observed, and to discover whether cases of adult T-leukemia/lymphoma (ATLL) related to HTLV-I exist in Gabon. From November 1987 to April 1989, a total of 32 patients with NHL were recruited; 6 were infants with Burkitt's lymphoma and 26 were adults with NHL. Each patient was matched with 2 asymptomatic controls for age, sex and ethnic group. HTLV-I serology was done by ELISA and Western blot. Comparison of the groups was done by chi-square analysis. None of the 6 infants with Burkitt's lymphoma and none of their controls had antibodies to HTLV-I. Of the 26 patients with NHL, 7 (26.9%) had HTLV-I antibodies. Among the 52 controls, the HTLV-I rate was 13.4% (n = 7). There was no difference between cases and controls (Fisher's exact test, p = 0.16). Among the 26 NHL, 4 cases fitted the criteria of ATLL and were HTLV-I-positive; 3 others who were positive for HTLV-I were a woman with lymphoblastic gastric NHL and 2 old men with an unclassified lymphoma. From the results of this limited series it is not possible to state that there is an association between NHL and HTLV-I infection. Nevertheless, cases of ATLL related to HTLV-I are reported from this area. Based on the HTLV-I seroprevalence rates reported in Gabon, the estimated incidence rate of ATL among seropositive people in Gabon appears much lower than in Japan. Different explanations can be proposed, but under-diagnosis of ATLL is probably one of the main factors.

Adolescent↗

Isolation of a repeated sequence from the genome of Bordetella parapertussis with characteristics of an insertion sequence element.

A repeated DNA sequence in the genome of Bordetella parapertussis was identified by means of heteroduplex formation and S1 nuclease treatment. Cloning and sequencing of the repeated sequence, revealed that it comprised 1306 basepairs, contained inverted repeats at its termini, and two large open reading frames. This insertion sequence element was designated IS1001, and was found in about 20 copies in 10 B. parapertussis strains analyzed. Identical hybridization patterns were observed in B. parapertussis when IS1001 was used as a probe. B. pertussis strains did not hybridize to IS1001.

Amino Acid Sequence↗

Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes.

OBJECTIVE: To determine the extent of genetic variation among internationally collected HIV-1 isolates, to analyse phylogenetic relationships and the geographic distribution of different variants. DESIGN: Phylogenetic comparison of 70 HIV-1 isolates collected in 15 countries on four continents. METHODS: To sequence the complete gag genome of HIV-1 isolates, build multiple sequence alignments and construct phylogenetic trees using distance matrix methods and maximum parsimony algorithms. RESULTS: Phylogenetic tree analysis identified seven distinct genotypes. The seven genotypes were evident by both distance matrix methods and maximum parsimony analysis, and were strongly supported by bootstrap resampling of the data. The intra-genotypic gag distances averaged 7%, whereas the inter-genotypic distances averaged 14%. The geographic distribution of variants was complex. Some genotypes have apparently migrated to several continents and many areas harbor a mixture of genotypes. Related variants may cluster in certain areas, particularly isolates from a single city collected over a short time. CONCLUSIONS: The genetic variation among HIV-1 isolates is more extensive than previously appreciated. At least seven distinct HIV-1 genotypes can be identified. Diversification, migration and establishment of local, temporal 'blooms' of particular variants may all occur concomitantly.

Africa↗

Metabolism of thiamine triphosphate in rat brain: correlation with chloride permeability.

Our results show that a net synthesis of thiamine triphosphate (TTP) can be demonstrated in vitro using rat brain extracts. The total homogenate was preincubated with thiamine or its diphosphate derivative (TDP), centrifuged, and washed twice. With TDP (1 mM) as substrate, a 10-fold increase in TTP content was observed in this fraction (nuclear fraction, membrane vesicles). A smaller, but significant, increase was observed in the P2 fraction (mitochondrial/synaptosomal fraction). In view of the low TTP content of our fractions, it was carefully assessed that authentic TTP was being formed. Incorporation of radioactivity from [beta-32P]TDP and [gamma-32P]ATP in TTP suggests that these two compounds are its precursors. Furthermore, TTP synthesis was inhibited by ADP and relatively low concentrations of Zn2+. These results suggest that TTP synthesis is catalyzed by an ATP:TDP transphosphorylase rather than by the cytoplasmic adenylate kinase that may be present in the vesicles. After osmotic lysis of the vesicles at alkaline pH, TTP was recovered in protein-bound form. Concomitantly, a soluble thiamine triphosphatase, with alkaline pH optimum, was also released from the vesicles. No net synthesis could be obtained in the cytosolic fraction or in detergent-solubilized systems. Like TTP synthesis, chloride permeability of the vesicles was increased when the homogenate had been incubated with thiamine and particularly with TDP. Our results suggest a regulatory role of TTP on chloride permeability, but the target remains to be characterized.

Animals↗

Characterization of IS1001, an insertion sequence element of Bordetella parapertussis.

By analysis of repetitive DNA in Bordetella parapertussis, an insertion sequence element, designated IS1001, was identified. Sequence analysis revealed that IS1001 comprised 1,306 bp and contained inverted repeats at its termini. Furthermore, several open reading frames that may code for transposition functions were identified. The largest open reading frame coded for a protein comprising 406 amino acid residues and showed homology to TnpA, which is encoded by an insertion sequence element (IS1096) found in Mycobacterium smegmatis. Examination of flanking sequences revealed that insertion of IS1001 occurs preferentially in stretches of T's or A's and results in a duplication of target sequences of 6 to 8 bases. IS1001 was found in about 20 copies in 10 B. parapertussis strains analyzed. No restriction fragment length polymorphism was observed in B. parapertussis when IS1001 was used as a probe. An insertion sequence element similar or identical to IS1001 was found in B. bronchiseptica strains isolated from pigs and a rabbit. In these strains, about five copies of the IS1001-like element were present at different positions in the bacterial chromosome. Neither B. pertussis nor B. bronchiseptica strains isolated from humans and dogs contained an IS1001-like element. Therefore, IS1001 may be used as a specific probe for the detection of B. parapertussis in human clinical samples.

Amino Acid Sequence↗

Polymerase chain reaction assay for pertussis: simultaneous detection and discrimination of Bordetella pertussis and Bordetella parapertussis.

A polymerase chain reaction (PCR) assay which allows the simultaneous detection and discrimination of the two causative agents of pertussis, Bordetella pertussis and Bordetella parapertussis, was developed. Primer pairs were based on insertion sequence elements IS481 and IS1001. IS481 is specific for B. pertussis and is present in about 80 copies per cell, while IS1001 is specific for B. parapertussis and is found in 20 copies per cell. An internal control was included in the PCR assay to monitor the performance of the PCR and to identify possible inhibitory components in clinical samples. Discrimination of amplified DNA derived from the internal control, B. pertussis, or B. parapertussis was accomplished by differential spacing of the primers. The sensitivity of the combined PCR method was found to be very high and allowed the detection of one cell of either pathogen. The usefulness of the method was investigated by using a limited number of clinical samples derived from patients with serologically proven pertussis.

Base Sequence↗

Blood transfusion as a major risk factor for HTLV-I infection among hospitalized children in Gabon (Equatorial Africa).

To study the risk factors for HTLV-I infection of African infants living in a high seroprevalence area, a survey was conducted among hospitalized children and their mothers in Franceville, southern Gabon. A total of 610 children (6 months to 14 years old) from 555 families and 434 mothers participated in the study. HTLV-I seroprevalence was 7.1% in the mothers and 2.8% in the children. No increase by age was observed in the children. Significantly more children with sickle cell anemia (11 of 57, or 19.2%) were infected than others (1%) (Fisher's exact test p < 0.001). Of the 13 seropositive infants (C+) whose mothers were tested, six (43%) had a seropositive mother (M+) [p < 0.001, prevalence ratio (PR) 10.12, 95% CI 3.40-30.35, attributable risk (AR) 0.55]. Risk factors for nonmaternally acquired HTLV-I infection were previous blood transfusion (Fisher's exact test p < 0.001, PR 15.74, CI 5.20-47.60, AR 0.71) and hospital admission. In a hospitalized pediatric population in Gabon mother-to-child transmission and blood transfusion (because of sickle cell disease) were equally implicated in HTLV-I infection. Control of HTLV-I infection in children in Africa requires prevention of both vertical and transfusion-associated transmission, which may be exceedingly difficult in developing countries.

Adolescent↗

Virological and polymerase chain reaction studies of HIV-1/HIV-2 dual infection in Côte d'Ivoire.

Dual serological reactivity to the human immunodeficiency virus (HIV) types 1 and 2 is common in Côte d'Ivoire. To assess whether dual infection is the reason for dual seropositivity we sought HIV-1 and HIV-2 proviral DNA in primary uncultured peripheral blood mononuclear cells from selected seropositive patients in Côte d'Ivoire with the polymerase chain reaction (PCR). PCR on primary lymphocytes in 36 dually seropositive samples revealed the presence of both HIV-1 and HIV-2 proviral DNA in 12 cases and the presence of HIV-1 only in 24 cases. In 18 of these 36 samples a virus was isolated and identified by PCR. HIV-1 was isolated from the 9 specimens with only HIV-1 proviral DNA in the primary lymphocytes. Among dually PCR-positive samples, 2 viral isolates reacted with both HIV-1 and HIV-2 primers; and only HIV-2 (n = 1) or HIV-1 (n = 6) strains were isolated from the other samples. The findings show that surveys based on serology may overestimate the prevalence of mixed infections in areas where both HIV-1 and HIV-2 occur.

Biomarkers↗