Molecular characterization of the envelope transmembrane glycoprotein of 13 new human immunodeficiency virus type 1 group O strains from six different African countries.
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Publications and source records attributed to S Mboup.
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A longitudinal cohort study was conducted to define the prevalence and temporal pattern of antibody response to the HIV-2 virion-associated proteins p26gag and Vpx. One hundred and forty-one asymptomatic HIV-2-infected women were enrolled, and followed for up to 11 years. Eighty-one percent of the subjects had antibodies to p26, and 51% to Vpx; response to these two antigens was not correlated. The response to both proteins was determined early in infection, and remained stable over time. The absence of antibodies to p26 was a highly significant predictor of CDC category IV HIV-related disease (p < 0.01) in both univariate and multivariate analysis. Antibody response to Vpx alone was not associated with disease progression. However, those individuals lacking anti-p26 antibodies, and with anti-Vpx antibodies, were six times more likely to be classified as CDC category IV by the end of the study (p < 0.01). This represents the first identification of virus-specific serological markers for HIV-2-related disease progression.
Human immunodeficiency virus type 1 (HIV-1) group O strains have been described as highly divergent, compared with the vast majority of the viruses involved in the worldwide AIDS pandemic, classified in group M. To gain new insights into the diversity and genetic characteristics of group O, we have sequenced the accessory gene region (from vif to vpu) of 14 isolates. Analyses of the deduced amino acid sequences for Vif, Vpr, the first exon of Tat, and Vpu indicate that most of the functional domains of these proteins, as described for group M viruses, are highly conserved and retained among all the group O strains we have characterized. The only difference concerns the Vif phosphorylation sites, which are absent in all of the group O isolates we have sequenced; in contrast, they are well conserved in nearly all of the group M isolates, in which they play critical roles in the regulation of viral replication and infectivity. As already observed for group M isolates, the Vpu protein is also highly diverse among group O strains. Phylogenetic analyses of these sequences indicate that HIV-1 group O can be separated into four different clusters, containing most of the strains we have characterized (except one, which clusters outside of the analyzed viruses). Taking into account the criteria used for clades in group M, we were not able to define group O clades definitively.
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OBJECTIVE: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile. METHODS: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization. RESULTS: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (Pvalue = 0.04). CONCLUSION: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.
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OBJECTIVE: To study the validity and performance of a number of rapid indicators for the diagnosis of sexually transmitted infections (STIs) in female prostitutes in Dakar, Senegal; characteristics of these indicators were rapidly obtainable, easy to perform, accurate, useful at district level, and reasonable cost. METHODS: An STI prevalence study in female prostitutes (n = 374) seen at the STD clinic in Dakar, Senegal was done; a history, clinical examination, simple laboratory tests, and "gold standard" microbiological tests were performed. For a number of sociodemographic data, actual or past symptoms of STI, clinical signs, and rapid laboratory tests, validity variables, performance characteristics, and likelihood ratios for detection of gonococcal or chlamydial cervical infection were determined. RESULTS: Cervical infection (chlamydial or gonococcal) was present in 24.9% of prostitutes; 46% had trichomoniasis and 29.4% had syphilis. Young age, abnormal vaginal discharge, endocervical mucopus, a positive leucocyte esterase test on urine, and 10 or more leucocytes in Gram stained smears of vaginal, cervical, or urine samples were significantly associated with cervical STI. Some of the rapid indicators had high sensitivity, others high specificity but none had acceptable overall validity. None of the indicators had at the same time a sensitivity above 50% and a positive predictive value above twice the background prevalence of cervical infection. 10 or more leucocytes in the cervical smear had a likelihood ratio of 1.83 increasing pretest probability of 24.9% to post-test probability of 38%, the best result obtained by any of the rapid indicators. CONCLUSIONS: Rapid indicators of cervical STIs are insufficiently valid, which largely restricts their usefulness to high STI prevalence situations for instance, in prostitute populations and in STD patient management.
OBJECTIVE: To determine to what extent HIV-1 group O strains are present in different African countries. MATERIALS AND METHODS: A total of 14,682 samples of sera from a range of patients from 12 different African countries were tested. All the sera were tested with an enzyme-linked immunosorbent assay (ELISA) using a combination of V3 peptides from ANT-70 and MVP-5180. Samples reactive in ELISA were retested in a line immunoassay (LIA-O). Samples reactive in ELISA were also retested with an in-house Western blot to determine the presence of antibodies to gp120 of HIV-1 ANT-70. Polymerase chain reaction was performed on HIV-1 group O and group O indeterminate sera. RESULTS: Of all the sera samples tested, only 19 sera had antibodies to group O V3 peptides exclusively and 46 were indeterminate for group O infection in LIA-O. The highest prevalence of HIV-1 group O infection among HIV-positive sera was observed in Cameroon (2.1%) and neighbouring countries, 1.1% in Nigeria and 0.9% in Gabon. The lowest rates were seen in west Africa: 0.07% in Senegal, 0.14% in Togo, 0.16% in Chad and 0.3% in Niger. Group O sera were observed in almost all the population categories tested. The ANT-70 V3 peptide in LIA-O was reactive with all of the sera considered to be HIV-1 group O antibody positive by LIA, versus 78.9% for the MVP-5180 peptide. Thirteen out of 19 group O samples of sera were tested in PCR. Eight samples were identified as group O by specific group O pol and/or V3 primers; in the remaining five samples no HIV RNA could be detected. Of the indeterminate sera samples, two were identified as group O. CONCLUSION: In eight of the 12 countries tested, antibodies to group O viruses were identified. Numbers of HIV-1 group O viruses are low. Their presence is not restricted to Cameroon and neighbouring countries but can also be found in west and south-east Africa.
A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly during two visits after vaccination. Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days, in children under 15 years of age, was made by weekly home visits. Examining physicians, blind to vaccination status, took samples for culture and serologic testing. Pertussis was defined as 21 or more days of cough confirmed by culture, serology, or contact with a culture-confirmed person. Beginning 28 days after the third vaccine dose, the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group (RRac/wc) was 1.54 (95% CI, 1.23-1.93). In children younger than 18 months of age, RRac/wc was 1.16 (95% CI, 0.77-1.73) and 1.76 (95% CI, 1.33-2.33) in children older than 18 months, which suggests a shorter duration of protection with the acellular vaccine (P = 0.090). Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine: 31% (95% CI, 7-49) versus 55% against the protocol case definition, and 85% (95% CI, 66-93) versus 96% for the more severe WHO case definition. Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP, this difference was less prominent before 18 months of age, the customary age for a fourth dose. The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose.
Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine. Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine. The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine. An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic. In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus. Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs. We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.
This cross-sectional study was carried out among male outpatients with symptoms of STDs at the STD reference centre at the Institute of Social Hygiene (IHS), Dakar, Senegal, from March 1989 through May 1991. This study was used to determine the prevalence of STDs and HIV among male patients attending an STD clinic and to identify their socio-demographic characteristics and risk factors. A total of 975 patients were enrolled in the study. The most common syndromes were urethritis (76%) and genital ulcers (22%). Considering single infections, the major STD agents were Neisseria gonorrheae (N.gonorrheae, 30%), Chlamydia trachomatis (C.trachomatis, 15%), Treponema pallidum (T.pallidum, 12%), and Haemophilus ducreyi (H.ducreyi, 7%). HIV prevalence was 2.6 percent (25/975). After multivariate analysis, the risk factors associated with HIV infection were a history of sex with prostitutes (odds ratio [OR] = 8.6, 95% confidence interval [CI] = 2.0-37.8), unprotected sexual contact (OR = 5.6, 95% CI = 1.2-25.0), a history of urethritis (OR = 3.4, 95% CI = 1.3-8.9), current STDs due to H.ducreyi or T.pallidum (OR = 6.1, 95% CI = 2-18.8), and mixed STD infection (OR = 5.3, 95% CI = 1.3-21.8). HIV prevalence was quite low in this population compared to similar studies of STD patients from other sub-Saharan African countries. Neisseria gonorrheae and Chlamydia trachomatis were the leading causes of STDs. A history of risky sexual behaviour, previous STDs, current genital ulcers, and mixed STD infections were associated with HIV infection. Further studies are necessary to determine changes in the relationship of STDs and HIV infection in this population.
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Sequences of the HIV-2 envelope C2-C3 region were obtained after direct PCR amplification of proviral DNA from the brain and peripheral blood mononuclear cells of an HIV-2-infected AIDS patient. Tissue-specific sequences confirmed previous observations that HIV-2 is indeed present in the central nervous system of infected individuals. Distinct but related quasi-species were present in these two different tissues of the same individual. Residues at position 18 and 19 of the V3 loop and overall charge of the loop suggest that the brain virus was NSI/macrophage tropic; whereas the sequences from the two blood samples were indicative of a SI/T-cell tropic virus. This is the first description of these two genotypes in the same HIV-2-infected individual. Analysis of more samples from different compartments would help to better understand tissue-specific factors in quasi-species evolution in vivo.
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OBJECTIVE: To determine the effect of HIV-1 and HIV-2 infection on the prevalence of cervical human papillomavirus (HPV) and squamous intraepithelial lesions (SIL) in a population of high-risk women in Senegal. DESIGN AND PARTICIPANTS: Cross-sectional study among 759 female commercial sex workers, including 68 with HIV-1, 58 with HIV-2, 14 with HIV-1 and 2, and 619 without HIV infection. RESULTS: Overall, HPV was detected in 43% of women by polymerase chain reaction (PCR), and in 7% by Southern transfer hybridization, with 7.4% of all women having SIL. The mean CD4 count was 820, 1205, and 727 x 10(6)/l for those with HIV-1, HIV-2, and dual HIV-1 and 2 infections, respectively, and 1447 x 10(6)/l for those without HIV infection. Both HIV-1 and HIV-2 were associated with HPV, as detected by PCR [HIV-1 odds ratio (OR), 2.9; 95% confidence interval (Cl), 1.7-4.9; HIV-2 OR, 1.7; 95% Cl, 1.0-2.9]. HIV-2 was also associated with cervical SIL, and although the association between HIV-1 and SIL did not attain statistical significance, a trend was apparent (HIV-1 OR, 1.8; 95% Cl, 0.7-4.7; HIV-2 OR, 2.9; 95% Cl, 1.2-7.2). CONCLUSIONS: Despite less immunosuppression with HIV-2, both HIV-1 and HIV-2 were associated with detection of HPV. HIV-2 was also associated with SIL. Further studies are needed to examine the risks of high-grade SIL and invasive cervical cancer with HIV-1 versus HIV-2 infection.
The epidemiologic and sociodemographic characteristics of human deficiency virus (HIV) infection vary from one country to another. The objective of this study was to determine the prevalence of HIV infection in pregnant women in Dakar and associated factors. Systematic anonymous screening was performed in pregnant women admitted to the maternity ward. Women whose seropositivity was confirmed by Western blot retroviral serology were included. One woman out of four was assigned by simple random selection to the case control group. Over a 24 month period, 12,498 women were tested. 104 were seropositive (44 HIV1, 58HIV2, and 2 HIV1-HIV2 giving a prevalence of 0.8%. Factors associated with HIV1 and HIV2 were different: mean age 21.7 years for HIV1 versus 30.6 for HIV 2 (p = 0.05); origin in Guinea-Bissau for HIV2 (p = 0.001); mean number of pregnancies 2.6 for HIV1 versus 5.9 for HIV2 (p = 0.001); mean parity 1.5 for HIV1 versus 4.5 for HIV2 (p < 0.01); vitality of the conception product in 85.1% for HIV2 versus 67.5% for HIV1 (p = 0.0001). These data confirm the low prevalence of HIV infection in pregnant women, with a predominance for HIV2. The factors identified in associated with virus type suggest a different mode of transmission and/or reduced virulence or HIV2 compared with HIV1. Knowledge of these factors helps orient management strategies, especially in pregnant women.
A study on nosocomial infections was conducted in the Laboratory of Bacteriology-Virology of Aristide Le Dantec's Hospital, in collaboration with the Gynecology Obstetrics clinic located both in the same Dakar's hospital, during May 1995. The aim of the study was to define the phenotypical characteristics of various bacterial strains isolated from the atmosphere health care staff's hands, medical equipment (material, antiseptics) and patients (hospitalized pregnant and newborns in day Nursery). A total of 133 strains were collected and the most frequent isolates were Staphylococcus aureus (27 strains) and Klebsiella pneumoniae (10 strains) encountered mainly in the atmosphere. Otherwise, Escherichia coli (11 strains) and Enterococcus faecalis (11 strains) were more present in hospitalized patients. Results obtained after antimicrobial agents susceptibility (Antibiotics and Heavy metal salts) by Antibiogramm and Minimal inhibitory concentrations (MIC) and also data from biotyping of Klebsiella strains have allowed us to say there's a probable contamination of hospitalized patients by the bacteria from the atmosphere but manuportage too.
Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.