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1.
Acta Anaesthesiol Scand ; 54(4): 426-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20096022

ABSTRACT

BACKGROUND: Direct puncture by a needle is a risk factor for nerve damage. This investigation used scanning electron microscopy (SEM) to attempt to visualize the damage caused by different needles. METHOD: A 15 cm section of the tibial nerve was removed from the ankle of a patient undergoing below-the-knee amputation. The nerve specimen was punctured perpendicular to the fibers once by each of four needles: an insulated 22 G short-beveled (30 degrees), a 25 G long-beveled Quincke spinal needle, an 18 G Tuohy, and a 25 G Whitacre pencil point. The distal and proximal ends on either side of the needles were marked and the nerve was sectioned into 0.5 cm pieces. Each sample was preserved and then prepared for SEM. The needle tract was observed for evidence of mechanical damage at magnifications between x 47 and x 102 using SEM. RESULTS: The epineurium, perineurium, fascicles, endoneurium, and vessels were identified in each sample. In both the short-beveled and the Whitacre samples, all fascicles along with the surrounding perineurium were intact. In both the Tuohy and the Quincke samples, obvious transection of fascicles and disruption of the perineurium were observed. CONCLUSIONS: This investigation suggests that both the Tuohy and the Quincke needles may be more likely to cause trauma to the tibial nerve than either the short-beveled or the Whitacre needles.


Subject(s)
Needles/adverse effects , Nerve Block/adverse effects , Tibial Nerve/injuries , Tibial Nerve/pathology , Amputation, Surgical , Humans , Leg/surgery , Microscopy, Electron, Scanning , Pilot Projects
2.
Virology ; 388(1): 137-46, 2009 May 25.
Article in English | MEDLINE | ID: mdl-19368950

ABSTRACT

Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness. Constructs recapitulating in vivo SL9-CTL escape variants showed markedly little effect on replication and fitness, as did non-natural conservative mutations targeting immunologically relevant positions of the epitope. Although certain residues of the epitope were constrained by viral requirements, our research reveals that there are multiple SL9 variants that are well tolerated virologically but fail to arise in vivo. In light of this data, assumptions regarding the balance of immune and viral selective pressures on this immunodominant epitope sequence need to be reassessed.


Subject(s)
CD8-Positive T-Lymphocytes/physiology , Genetic Variation , HIV Antigens/genetics , HIV-1/genetics , Immunodominant Epitopes/physiology , Biological Evolution , Cell Line , Gene Expression Regulation, Viral/physiology , HIV-1/immunology , Humans
3.
J Infect Dis ; 184(10): 1268-78, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11679915

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1)-specific CD4(+) T cell response was investigated in 33 untreated HIV-1-infected individuals, using highly sensitive ELISPOT assays and intracellular flow cytometry. The median frequencies of interferon (IFN)-gamma-producing HIV-1 gag-specific CD4(+) T cells did not correlate significantly with control of viral replication or progression. HIV-1 gag-specific interleukin (IL)-4-producing cells were rarely detected. Circulating frequencies of CD4(+) T cells constitutively producing IL-10, however, were significantly higher in individuals with progression or active replication. In 17 of 30 HIV-1-infected individuals, gag antigen was observed to induce IL-10 production from CD4(+) T cells. In 2 individuals, early treatment of acute HIV-1 infection "rescued" low to undetectable gag-specific IFN-gamma-producing CD4(+) T cell responses and dramatically down-regulated constitutive IL-10 production from circulating CD4(+) T cells. The detection of HIV-1-specific IL-10-inducing CD4(+) T cells in HIV-1-infected individuals suggests that HIV-1 may directly subvert specific immune responses by IL-10 induction.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , Interferon-gamma/analysis , Interleukin-10/analysis , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Cohort Studies , Disease Progression , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Products, gag/immunology , HIV Infections/drug therapy , HIV Infections/virology , Humans , Viral Load
4.
Immunol Lett ; 79(1-2): 3-13, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11595284

ABSTRACT

A clearer understanding of HIV-1 specific immune responses in highly-exposed, persistently seronegative (HEPS) subjects is important in developing models of HIV-1 protective immunity. HIV-1 specific cytotoxic T-lymphocytes (CTL) have been described in a cohort of HEPS Kenyan sex workers, and recent work has further elucidated these responses. CTL specific for HIV-1 Env were found in the blood of over half the sex workers meeting criteria for HIV resistance, and in some women recognized unmapped epitopes. The proportion of women with Env-specific CTL increased with the duration of uninfected HIV exposure, suggesting that these responses were acquired over time. CD8+ lymphocyte responses directed against predefined HIV-1 CTL epitopes from various HIV-1 genes were found in the blood and genital tract of >50% resistant sex workers, at a ten-fold lower frequency than in infected subjects. The epitope specificity of CD8+ responses differs between HEPS and HIV infected women, and in HEPS the maintenance of responses appears to be dependent on persistent HIV exposure. Several HIV-1 'resistant' sex workers have become HIV infected over the past 6 years, possibly related to waning of pre-existing HIV-specific CTL, and infection has often been associated with a switch in the epitope specificity of CD8+ responses. These findings suggest that vaccine-induced protective HIV immunity is a realistic goal, but that vaccine strategies of boosting or persistent antigen may be necessary for long-lived protection.


Subject(s)
HIV Seronegativity/immunology , HIV-1/immunology , Sex Work , T-Lymphocytes, Cytotoxic/immunology , Adult , Amino Acid Sequence , Cohort Studies , Epitopes/genetics , Female , Gene Products, env/genetics , Gene Products, env/immunology , Genes, env , HIV Seropositivity/immunology , HIV-1/genetics , Humans , Kenya , Molecular Sequence Data , Time Factors
5.
Immunol Lett ; 79(1-2): 151-7, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11595302

ABSTRACT

T cell responses against HIV-1 have been identified in a number of exposed uninfected populations. We hypothesized that the ability to mount an effective T cell response is partly determined by the human leucocyte antigens (HLA) phenotype of the individual. We examined whether certain HLA supertypes were associated with differential HIV-1 susceptibility in sexually exposed adults and in the setting of mother to child HIV-1 transmission. By multivariate analysis, decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related class I HLA alleles (A2/6802 supertype) in sexually exposed adults (Hazard ratio=0.42, 95% confidence intervals (CI): 0.22-0.81, P=0.009) and perinatally exposed infants (Odds ratio=0.12, 95% CI: 0.03-0.54, P=0.006). The alleles in this HLA supertype are known in some cases, to present the same peptide epitopes (termed 'supertopes'), for T cell recognition. The identification of HIV-1 supertopes, which are associated with protection from HIV-1 infection, has important implications for the application of epitope-based HIV-l vaccines in a variety of racial groups.


Subject(s)
AIDS Vaccines/immunology , HIV Infections/immunology , HIV Infections/prevention & control , HIV-1/immunology , HLA Antigens , Adult , Alleles , Cohort Studies , Female , HIV Infections/genetics , HIV Infections/transmission , HLA Antigens/genetics , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Kenya , Multivariate Analysis , Pregnancy , Risk Factors , Sex Work , T-Lymphocytes/immunology
6.
J Clin Invest ; 107(10): 1303-10, 2001 May.
Article in English | MEDLINE | ID: mdl-11375420

ABSTRACT

HIV-1-specific cytotoxic T-lymphocyte (CTL) responses have been detected at a low frequency in many HIV-1-exposed, persistently seronegative (HEPS) subjects. However, it is unclear how CTLs could protect against HIV acquisition in HEPS subjects, when high levels of circulating CTL fail to prevent disease progression in most seropositive subjects. To address this issue we studied CD8(+) lymphocyte responses to a panel of HIV-1 CTL epitopes in 91 HEPS and 87 HIV-1-infected Nairobi sex workers. HIV-specific responses in seropositive women focused strongly on epitopes rarely or never recognized in HEPS subjects, who targeted epitopes that were subdominant or unrecognized in infected women. These differences in epitope specificity were restricted by only those HLA class I alleles that are associated with a reduced risk of HIV-1 infection in this cohort. Late seroconversion in HEPS donors was associated with a switch in epitope specificity and/or immunodominance to those epitopes preferentially recognized by HIV-1-infected women. The likelihood of detecting HIV-1-specific responses in HEPS women increased with the duration of viral exposure, suggesting that HIV-1-specific CD8(+) responses are acquired over time. The association between differential recognition of distinct CTL epitopes and protection from HIV-1 infection may have significant implications for vaccine design.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Epitopes/immunology , HIV Infections/immunology , HIV Seronegativity/immunology , HIV-1/immunology , Cohort Studies , Female , Genes, MHC Class I , HIV Seropositivity , Histocompatibility Antigens Class I , Humans , Immunodominant Epitopes , Kenya , Oligopeptides/immunology , Risk Factors , Sex Work , T-Lymphocytes, Cytotoxic/immunology
7.
AIDS ; 15(5): 635-9, 2001 Mar 30.
Article in English | MEDLINE | ID: mdl-11317002

ABSTRACT

BACKGROUND: Vitamin A is involved in normal immune function and the maintenance of mucosal integrity through complex effects on cellular differentiation. OBJECTIVE: We sought to determine whether serum vitamin A levels were associated with altered susceptibility to primary infection with HIV-1 in men with high-risk sexual behaviour and genital ulcers who presented for treatment at an STD clinic in Nairobi, Kenya. METHODS: HIV-1 seronegative men were prospectively followed. Vitamin A levels at study entry were compared among 38 men who HIV-1 seroconverted versus 94 controls who remained HIV seronegative. RESULTS: Vitamin A deficiency (retinol less than 20 microg/dl) was very common and was present in 50% of HIV-1 seroconverters versus 76% of persistent seronegatives. Seroconversion was independently associated with a retinol level greater than 20 microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04). Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23-0.93, P = 0.03). CONCLUSION: Vitamin A deficiency was not associated with an increased risk of HIV-1 infection among men with concurrent STD. A decreased risk of HIV-1 seroconversion was independently associated with lower retinol levels. The effects of vitamin A on macrophage and lymphoid cell differentiation may paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable individuals, such as men with genital ulcers. Lack of circumcision and chancroid are confirmed as important co-factors for heterosexual HIV-1 transmission. The role of vitamin A in heterosexual HIV-1 transmission requires further study.


Subject(s)
Genital Diseases, Male/complications , HIV Seropositivity/physiopathology , HIV-1 , Ulcer/complications , Vitamin A Deficiency , Adult , Case-Control Studies , Chancroid/complications , HIV Seropositivity/blood , HIV Seropositivity/complications , Humans , Kenya , Male , Multivariate Analysis , Prospective Studies , Risk Factors , Syphilis/complications , Vitamin A/blood
8.
Immunogenetics ; 53(1): 10-4, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11261925

ABSTRACT

As part of the ongoing study of natural HIV-1 resistance in the women of the Nairobi Sex Workers' study, we have examined a resistance-associated HLA class I allele at the molecular level. Typing by polymerase chain reaction using sequence-specific primers determined that this molecule is closely related to HLA-A*0214, one of a family of HLA-A2 supertype alleles which correlate with HIV-1 resistance in this population. Direct nucleotide sequencing shows that this molecule differs from A*0214, having a silent nucleotide substitution. We therefore propose to designate it HLA-A*02142. We have determined the peptide-binding motif of HLA-A*0214/02142 by peptide elution and bulk Edman degradative sequencing. The resulting motif, X-[Q,V]-X-X-X-K-X-X-[V,L], includes lysine as an anchor at position 6. The data complement available information on the peptide-binding characteristics of this molecule, and will be of use in identifying antigenic peptides from HIV-1 and other pathogens.


Subject(s)
HIV Infections/immunology , HIV Seronegativity/immunology , HIV-1/immunology , HLA-A2 Antigen/genetics , Sex Work , Amino Acid Sequence , Binding Sites/genetics , Cohort Studies , Female , HLA-DR Antigens , Humans , Kenya , Molecular Sequence Data , Mutation
9.
J Virol ; 75(6): 3028-33, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11222730

ABSTRACT

A vigorous expansion of antigen-specific CD8(+) T cells lacking apparent effector function was observed in a rhesus macaque acutely infected with the simian immunodeficiency virus (SIV) strain SIVmac239. Antigen-specific CD8(+) T cells were identified using antigenic-peptide class I major histocompatibility complex tetramers. As many as 8.3% of CD8(+) cells recognized the Mamu-A*01-associated SIV epitope Gag(181-189) (CTPYDINQM); however, these cells demonstrated no effector function when presented with peptide-incubated targets, as measured by intracellular cytokine staining for gamma interferon (IFN-gamma), interleukin-2 (IL-2) production, or direct cellular lysis. Similar results were observed with three other SIV peptide antigens. Nonresponsiveness did not correlate with apoptosis of the CD8(+) cells, nor were cells from this macaque impaired in their ability to present peptide antigens. Associated with the nonresponsive state was a lack of IL-2 production and decreased IL-2 receptor expression. Exogenous IL-2 treatment for 1 week in the absence of antigenic stimulation restored antigen-specific responses and the quantitative correlation between tetramer recognition and antigen-responsive IFN-gamma secretion. This case report suggests a regulatory mechanism that may impede the effector function of antigen-specific T cells during acute infection with SIV or human immunodeficiency virus in some cases. This mechanism may participate in the failure of the immune system to limit infection.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Interleukin-2/immunology , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Antigen Presentation , Apoptosis , Immunophenotyping , Interferon-gamma/metabolism , Interleukin-2/metabolism , Macaca mulatta , Receptors, Interleukin-2/metabolism , Simian Acquired Immunodeficiency Syndrome/virology
10.
J Clin Invest ; 107(3): 341-9, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11160158

ABSTRACT

Resistance to HIV infection in a small group of Kenyan sex workers is associated with CD8+-lymphocyte responses to HIV cytotoxic T-lymphocyte (CTL) epitopes. Eleven prostitutes meeting criteria for HIV resistance seroconverted between 1996 and 1999. The occurrence and specificity of preexisting HIV-1 epitope-specific responses were examined using the IFN-gamma enzyme-linked immunospot assay, and any epitopes recognized were cloned and sequenced from the infecting viral isolate. Immunologic and behavioral variables were compared between late seroconverters and persistently uninfected sex worker controls. HIV-1 CTL epitope responses were present in four of six cases, 5-18 months before seroconversion, and their presence was confirmed by bulk CTL culture. A possible viral escape mutation was found in one of six epitopes. The key epidemiologic correlate of late seroconversion was a reduction in sex work over the preceding year. In persistently uninfected controls, a break from sex work was associated with a loss of HIV-specific CD8+ responses. Late seroconversion may occur in HIV-1-resistant sex workers despite preceding HIV-specific CD8+ responses. Seroconversion generally occurs in the absence of detectable CTL escape mutations and may relate to the waning of HIV-specific CD8+ responses due to reduced antigenic exposure.


Subject(s)
HIV Seropositivity/epidemiology , HIV-1/genetics , Sex Work , Adult , Amino Acid Sequence , CD8-Positive T-Lymphocytes , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Epitopes/chemistry , Female , HIV Antigens/chemistry , HIV Infections/immunology , HIV Infections/transmission , HIV Seronegativity , HIV-1/chemistry , Humans , Interferon-gamma/immunology , Kenya/epidemiology , Lymphocyte Count , Risk-Taking , Sexual Behavior , Time Factors
11.
J Infect Dis ; 183(3): 503-6, 2001 Feb 01.
Article in English | MEDLINE | ID: mdl-11133384

ABSTRACT

Certain HLAs may, in part, account for differences in human immunodeficiency virus type 1 (HIV-1) susceptibility by presenting conserved immunogenic epitopes for T cell recognition. The HLA supertype A2/6802 is associated with decreased susceptibility to HIV-1 among sex workers. The alleles in this supertype present the same HIV-1 peptide epitopes for T cell recognition in some cases. This study sought to determine whether the HLA A2/6802 supertype influenced HIV-1 transmission in a prospective cohort of HIV-1-infected mothers and children in Kenya. Decreased perinatal HIV-1 infection risk was strongly associated with possession of a functional cluster of related HLA alleles, called the A2/6802 supertype (odds ratio, 0.12; 95% confidence interval, 0.03-0.54; P=.006). This effect was independent of the protective effect of maternal-child HLA discordance. These data provide further evidence that HLA supertypes are associated with differential susceptibility to HIV-1 transmission.


Subject(s)
Genes, MHC Class I , HIV Infections/transmission , HIV-1 , HLA-A2 Antigen/genetics , Infectious Disease Transmission, Vertical , Adult , Alleles , Cohort Studies , Female , Genetic Predisposition to Disease , Histocompatibility Testing , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Complications, Infectious/virology , Prospective Studies
12.
Environ Res ; 84(2): 133-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11068926

ABSTRACT

Total mercury and methylmercury concentrations were measured in brain, kidney, liver, and fur from several mink and otter collected in south-central Ontario. There was a large range in concentrations of both total and methylmercury. The percentage of the total mercury present as methylmercury varied among the various tissues; however, the percentage mercury found as the methyl form was relatively constant within a given tissue for all tissues in mink but highly variable in otter. For both species the highest percentage of methylmercury was found in the brain, whereas the lowest percentage was found in the kidneys for the otter and in the fur for the mink. Comparison of mercury concentrations in otter reveals that animals with higher body fat have higher mercury concentrations. Measurements of mercury in fur can be used as a general indicator of internal tissue concentrations.


Subject(s)
Environmental Monitoring , Methylmercury Compounds/analysis , Mink , Otters , Water Pollutants, Chemical/analysis , Animals , Animals, Wild , Brain Chemistry , Hair/chemistry , Kidney/chemistry , Liver/chemistry , Ontario
13.
J Infect Dis ; 182(1): 123-32, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10882589

ABSTRACT

Correlates of resistance to infection by human immunodeficiency virus type 1 (HIV-1) are important for defining potential therapeutic interventions and for prophylactic vaccination. In this study, 11 couples discordant in their HIV-1 infection status were prospectively evaluated for the presence of protective factors. Behavioral characteristics of all subjects entailed a high risk of transmission. Cytotoxic T lymphocyte (CTL) responses against viruses isolated from the infected partner, and against laboratory virus isolates, were detected in 5 (45%) of 11 HIV-negative partners, including a CCR5Delta32-homozygous and a heterozygous subject. No CTL responses were observed in 6 control unexposed subjects. Marked variation in lymphocyte susceptibility to viral infection was noted. Resistance attributable to major histocompatibility complex discordance or anti-major histocompatibility complex antibodies was not identified. These results suggest that a combination of factors, including cellular immunity, viral characteristics, and coreceptor integrity, may be involved in the persistent nontransmission of HIV.


Subject(s)
HIV Infections/transmission , HIV-1/immunology , Receptors, CCR5/genetics , T-Lymphocytes, Cytotoxic/immunology , Adult , Antibodies , B-Lymphocytes/immunology , CD4 Antigens/genetics , CD4 Antigens/immunology , Female , Genotype , HIV Infections/genetics , HIV Infections/metabolism , HIV-1/isolation & purification , HIV-1/physiology , Histocompatibility Antigens/analysis , Histocompatibility Antigens/classification , Histocompatibility Antigens/immunology , Humans , Male , Middle Aged , Prospective Studies , Receptors, CCR5/immunology , T-Lymphocytes, Cytotoxic/physiology , Transfection
14.
Vaccine ; 18(27): 3152-65, 2000 Jul 15.
Article in English | MEDLINE | ID: mdl-10856795

ABSTRACT

In simian immunodeficiency virus (SIV) models, immunization of macaques with uninfected human cells or human major histocompatibility complex (MHC) proteins can induce xenogeneic immune responses which can protect the animals from subsequent SIV challenges. These studies suggest that the induction of anti-MHC immune responses can be a viable vaccine strategy against human immunodeficiency virus type 1 (HIV-1). We have previously shown in mouse studies that DNA immunization with class I and class II MHC-encoding plasmids can elicit both xenogeneic and allogeneic antibody responses against conformationally intact MHC molecules (Vaccine 17 (1999) 2479-92). Here we take these observations one step closer to human applications and report that intradermal needle immunizations of non-human primates with plasmid DNA encoding human MHC alleles can safely elicit xenogeneic anti-MHC antibody responses. Moreover, injecting macaques with DNA encoding a specific macaque allogeneic MHC induced anti-allogeneic MHC antibodies production. These studies show that DNA immunization with MHC-encoding vectors can indeed be used to induce specific anti-human xenogeneic, as well as anti-macaque allogeneic MHC immunity in non-human primates. This strategy could thus be used to mobilize anti-MHC antibody response which may be useful as part of an anti-HIV-1 vaccination approach.


Subject(s)
HLA-A2 Antigen/immunology , HLA-DR Antigens/immunology , Isoantibodies/biosynthesis , Vaccines, DNA/immunology , AIDS Vaccines/immunology , Amino Acid Sequence , Animals , Cloning, Molecular , Female , Flow Cytometry , HIV-1/immunology , HLA-DR Serological Subtypes , Immunization , Macaca mulatta , Molecular Sequence Data
15.
J Infect Dis ; 181(5): 1581-9, 2000 May.
Article in English | MEDLINE | ID: mdl-10823757

ABSTRACT

Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.


Subject(s)
Acquired Immunodeficiency Syndrome/genetics , HIV Infections/genetics , Major Histocompatibility Complex , Polymorphism, Genetic , Sex Work , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/immunology , Adult , Cohort Studies , Confidence Intervals , Disease Susceptibility/immunology , Female , HIV Infections/epidemiology , HIV Infections/immunology , HIV Seronegativity/immunology , HIV Seropositivity/genetics , HIV Seropositivity/immunology , HIV-1 , HLA Antigens/genetics , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Immunity, Innate/immunology , Kenya/epidemiology , Longitudinal Studies , Time Factors
16.
J Immunol ; 164(3): 1602-11, 2000 Feb 01.
Article in English | MEDLINE | ID: mdl-10640781

ABSTRACT

Understanding how individuals with a high degree of HIV exposure avoid persistent infection is paramount to HIV vaccine design. Evidence suggests that mucosal immunity, particularly virus-specific CTL, could be critically important in protection against sexually acquired HIV infection. Therefore, we have looked for the presence of HIV-specific CD8+ T cells in cervical mononuclear cells from a subgroup of highly HIV-exposed but persistently seronegative female sex workers in Nairobi. An enzyme-linked immunospot assay was used to measure IFN-gamma release in response to known class I HLA-restricted CTL epitope peptides using effector cells from the blood and cervix of HIV-1-resistant and -infected sex workers and from lower-risk uninfected controls. Eleven of 16 resistant sex workers had HIV-specific CD8+ T cells in the cervix, and a similar number had detectable responses in blood. Where both blood and cervical responses were detected in the same individual, the specificity of the responses was similar. Neither cervical nor blood responses were detected in lower-risk control donors. HIV-specific CD8+ T cell frequencies in the cervix of HIV-resistant sex workers were slightly higher than in blood, while in HIV-infected donor cervical response frequencies were markedly lower than blood, so that there was relative enrichment of cervical responses in HIV-resistant compared with HIV-infected donors. HIV-specific CD8+ T cell responses in the absence of detectable HIV infection in the genital mucosa of HIV-1-resistant sex workers may be playing an important part in protective immunity against heterosexual HIV-1 transmission.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cervix Uteri/immunology , Epitopes, T-Lymphocyte/analysis , HIV Infections/immunology , HIV-1/immunology , Sex Work , CD8-Positive T-Lymphocytes/metabolism , Cervix Uteri/chemistry , Enzyme-Linked Immunosorbent Assay , Epitopes, T-Lymphocyte/blood , Female , Histocompatibility Testing , Humans , Immunity, Innate , Immunophenotyping , Interferon-gamma/metabolism , Kenya , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Depletion , Mucous Membrane/chemistry , Mucous Membrane/immunology , Peptide Fragments/immunology , Risk Factors
17.
Int J STD AIDS ; 11(12): 804-11, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11138916

ABSTRACT

Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections (STIs) and HIV-1 in a cohort of Nairobi female sex workers (FSWs). A questionnaire was administered and a medical examination was performed. HIV-negative women were randomly assigned to either one gram azithromycin or placebo monthly. Mean age of the 318 women was 32 years, mean duration of sex work 7 years and mean number of clients was 4 per day. High-risk behaviour was frequent: 14% practised anal intercourse, 23% sex during menses, and 3% used intravenous drugs. While 20% reported condom use with all clients, 37% never use condoms. However, STI prevalence was relatively low: HIV-1 27%, bacterial vaginosis 46%, Trichomonas vaginalis 13%, Neisseria gonorrhoeae 8%, Chlamydia trachomatis 7%, syphilis 6% and cervical intraepithelial neoplasia (CIN) 3%. It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes, including a proposed trial of HIV prevention through STI chemoprophylaxis.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , HIV Infections/prevention & control , HIV-1 , Sex Work , Sexually Transmitted Diseases/prevention & control , Adolescent , Adult , Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Cohort Studies , Drug Administration Schedule , Female , HIV Infections/microbiology , Humans , Incidence , Kenya/epidemiology , Middle Aged , Prevalence , Risk-Taking , Sexual Behavior , Sexually Transmitted Diseases/epidemiology , Vaginosis, Bacterial/epidemiology
18.
Can J Infect Dis ; 11(5): 259-63, 2000 Sep.
Article in English | MEDLINE | ID: mdl-18159299

ABSTRACT

OBJECTIVE: To evaluate whether resistance to HIV-1 infection in a subset of highly exposed sex workers correlates with resistance at the cellular level. DESIGN: In vitro evaluation of susceptibility to infection by Kenyan HIV-1 isolates and cellular production of potential mediators of resistance. SETTING: Samples were collected in a primary care clinic in Nairobi. PATIENTS: Thirteen individuals from a cohort of sex workers with a similar risk of acquiring HIV infection and six unexposed controls. INTERVENTIONS: Subjects were provided with appropriate primary care and counselling on the prevention of sexually transmitted diseases. RESULTS: No inherent cellular resistance to infection was identified. CD8⁺ cells from a subset of subjects strongly inhibited viral replication. CONCLUSIONS: Lack of infection in this cohort was not attributable to factors inherent to CD4⁺ cells. Resistance to HIV infection is likely to be multifactorial, and products of CD8⁺ cells and unique features of mucosal sites probably contribute to this state.

19.
J Infect Dis ; 180(6): 1886-93, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10558945

ABSTRACT

A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Chancroid/drug therapy , Ciprofloxacin/therapeutic use , Erythromycin/therapeutic use , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Infective Agents/administration & dosage , Chancroid/microbiology , Chancroid/virology , Ciprofloxacin/administration & dosage , Double-Blind Method , Erythromycin/administration & dosage , Female , HIV Infections/complications , HIV-1 , Haemophilus ducreyi/genetics , Haemophilus ducreyi/isolation & purification , Herpes Genitalis/virology , Humans , Kenya , Male , Middle Aged , Polymerase Chain Reaction , Simplexvirus/genetics , Simplexvirus/isolation & purification , Syphilis/complications , Syphilis/microbiology , Treatment Outcome , Treponema pallidum/genetics , Treponema pallidum/isolation & purification
20.
J Infect Dis ; 180(5): 1686-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10515833

ABSTRACT

Although nosocomial transmission of human respiratory syncytial virus (HRSV) and its effect on morbidity and mortality among immunocompromised adults are well recognized, few studies have applied molecular techniques to differentiate nosocomial from community-acquired infections. Between January and April 1997, an outbreak of HRSV occurred among adult patients in a leukemia/lymphoma ward. Among 45 hospitalized patients undergoing bronchoscopy for investigation of acute respiratory illness, 8 were identified with HRSV infection. One infected patient developed symptoms before admission and was thought to be the index case. However, subsequent sequencing of 7 HRSV isolates identified 2 distinct genotypes, GA5 (1 case) and GB3 (6 cases). The 6 GB3 isolates could be further differentiated into 2 strains with identical nucleotide sequences that differed from each other and from 14 community HRSV isolates. Instead of a single nosocomial outbreak of HRSV, multiple introductions of HRSV likely occurred with distinct lines of nosocomial transmission.


Subject(s)
Cross Infection , Disease Outbreaks , Respiratory Syncytial Virus Infections/transmission , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/classification , Adult , Aged , Bronchoalveolar Lavage Fluid/virology , Cancer Care Facilities , Cross Infection/epidemiology , Cross Infection/transmission , Cross Infection/virology , DNA, Viral/analysis , Female , Hematologic Neoplasms , Hospital Units , Humans , Male , Middle Aged , Molecular Sequence Data , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Viruses/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction
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