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Biomedical subjects

F Plummer

Publications and source records attributed to F Plummer.

At least 19 recordsLinked to original sources
PubMed2001

Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers.

Although HIV-specific cellular immune responses are found in a number of HIV highly-exposed, persistently seronegative (HEPS) cohorts, late seroconversion can occur despite pre-existing cytotoxic T lymphocytes (CTL), suggesting that a protective HIV vaccine may need to induce a broader range of HIV-specific immune responses. Low levels of HIV-specific IgA have been found in the genital tract and plasma of the majority of Nairobi HEPS sex workers and appeared to be independent of HIV-specific cellular responses. IgA purified from genital tract, saliva and plasma of most HEPS sex workers were able to neutralize infection of PBMC by a primary (NSI) clade B HIV isolate, as well as viral isolates from clades A and D, which predominate in Kenya. In addition, these IgA were able to inhibit transcytosis of infective HIV virions across a transwell model of the human mucosal epithelium in an HIV-specific manner. Preliminary work in other HEPS cohorts has suggested the recognition of different gp41 epitopes in HEPS and HIV-infected subjects. Although present at low levels, these IgA demonstrated cross-clade neutralizing activity and were able to inhibit HIV mucosal transcytosis, suggesting an important functional role in protection against HIV infection.

Antibody Specificity↗
PubMed2001

Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi.

BACKGROUND: Reference lymphocyte subset values for African children are lacking. This study documents these values as well as their alterations associated with perinatal and postnatal HIV-1 transmission and with protection from HIV-1 infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative nonpregnant women and their children (controls) and for uninfected, perinatally infected and postnatally infected children born to HIV-1-seropositive mothers in Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and CD8+ lymphocyte counts and percentages were determined and compared at the age ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6 to 10 years of age. RESULTS: Among control children counts differed from published values of other populations. In all age ranges, whereas the absolute values were significantly higher than adult values, the percentages were significantly lower. Children perinatally infected with HIV-1 had clearly distinguishable differences in lymphocyte subset percentages by 3 months of age, when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%) for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%) for control children, P < 0.001; whereas the median CD8+ percentage was 37.0% (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5% (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected and control children disappeared after 1 year of age. CONCLUSIONS: Normal lymphocyte subset values among African children differ from those in other populations. Significant differences are detectable by 3 months of age in CD4+ and CD8+ lymphocyte percentages among perinatally infected infants, which may be useful as an adjunct in diagnosis. Transient differences observed among HIV-1-exposed but uninfected infants could reflect a successful immune response to HIV-1 challenge.

CD4 Lymphocyte Count↗
PubMed2000

Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells.

HIV-1-specific IgA has been described in the genital tract and plasma of HIV-1 highly exposed, persistently seronegative (HEPS) individuals, and IgA from these sites has been shown to neutralize HIV-1. This study examines the ability of IgA isolated from HEPS individuals to inhibit transcytosis across a tight epithelial cell layer. A Transwell system was established to model HIV-1 infection across the human mucosal epithelium. The apical-basolateral transcytosis of primary HIV-1 isolates across this mucosal model was examined in the presence and the absence of IgA isolated from the genital tract, saliva, and plasma of HEPS individuals enrolled in both a sex worker cohort in Nairobi, Kenya, and a discordant couple cohort in Italy. In the absence of IgA, HIV-1 primary isolates were actively transported across the epithelial membrane and were released on the opposite side of the barrier. These transcytosed HIV-1 particles retained their ability to infect human mononuclear cells. However, IgA purified from the mucosa and plasma of HEPS individuals was able to inhibit HIV-1 transcytosis. Inhibition was seen in three of six cervicovaginal fluid samples, five of 10 saliva samples, and three of six plasma samples against at least one of the two primary HIV-1 isolates tested. IgA from low risk, healthy control subjects had no inhibitory effect on HIV-1 transcytosis. The ability of mucosal and plasma IgA to inhibit HIV-1 transcytosis across the mucosal epithelium may represent an important mechanism for protection against the sexual acquisition of HIV-1 infection in HEPS individuals.

Anti-HIV Agents↗
PubMed2000

Human immunodeficiency virus type 1-infected women exhibit reduced interferon-gamma secretion after Chlamydia trachomatis stimulation of peripheral blood lymphocytes.

Epidemiologic, animal, and in vitro models suggest an important role for interferon (IFN)-gamma in the clearance of Chlamydia trachomatis infection. IFN-gamma in the supernatants of in vitro-stimulated peripheral blood mononuclear cells (PBMC) from 22 human immunodeficiency virus type 1 (HIV-1)-infected and 73 uninfected women at high risk for C. trachomatis acute pelvic inflammatory disease (PID) was studied. PBMC were stimulated with C. trachomatis purified major outer membrane protein (MOMP) and whole elementary bodies (EBs) from the 4 predominant serovars (E, F, K, and L2) that circulate in Nairobi. PBMC IFN-gamma secretion after stimulation with C. trachomatis EBs was significantly decreased in HIV-1-infected women. Among HIV-1-infected women, CD4 T cell depletion was associated with lower IFN-gamma secretion from PBMC stimulated with either C. trachomatis MOMP or EB antigen. Decreased antigen-specific IFN-gamma production may enhance the susceptibility of HIV-1-infected women to C. trachomatis PID.

Acute Disease↗
PubMed2000

Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate.

OBJECTIVE: To characterize functional properties of HIV-specific IgA in samples representing both systemic and mucosal compartments of HIV-1 highly exposed persistently seronegative (HEPS) individuals. METHODS: IgA was purified from plasma and mucosal samples from HEPS individuals and tested for the ability to neutralize infection of peripheral blood mononuclear cells (PBMC) by a non-syncytium inducing HIV-1 (clade B) primary isolate. None of these individuals had measurable HIV-1-specific IgG. RESULTS: HIV-1-specific neutralizing activity of the purified IgA from plasma (n = 15), saliva (n = 15) and cervicovaginal fluid (CVF) (n = 14) were found in the majority of samples (73, 73 and 79%, respectively). In contrast, plasma, saliva and CVF samples of low-risk, uninfected HIV-seronegative individuals lacked neutralizing IgA, with the exception of two out of 34 (6%) saliva samples. CONCLUSION: Mucosal and plasma IgA from HEPS individuals can neutralize HIV-1 infection.

Cervix Uteri↗
PubMed1999

Association of Chlamydia trachomatis heat-shock protein 60 antibody and HLA class II DQ alleles.

A total of 113 female commercial sex workers had individual alleles for HLA class II genes determined by using labeled sequence-specific oligonucleotide probes to hybridize to polymerase chain reaction products of amplified DNA. Women also had microimmunofluorescent (MIF) antibody titers to Chlamydia trachomatis elementary bodies and ELISA antibody to recombinant chlamydial heat-shock protein 60 (Chsp60) determined. Women were prospectively followed at monthly intervals over 2 years for incident C. trachomatis infection and acute pelvic inflammatory disease (PID). HLA DQA1*0401 and DQB1*0402 alleles were statistically associated with increased prevalence and amount of antibody to Chsp60 but not MIF antibody. However, these alleles did not alter the risk for chlamydial PID. The potential role that HLA DQ may play in chlamydial disease pathogenesis requires further study.

Antibodies, Bacterial↗
PubMed1998

The role of cytotoxic T-cells in HIV infection.

HIV-specific cytotoxic T lymphocytes (CTL) are believed to play a major role in controlling virus levels through the asymptomatic period of HIV infection. For the rational design of an HIV vaccine, we need to know whether protective immunity can ever develop following HIV exposure in people who remain uninfected. We have detected HIV-specific CTL in 5/6 repeatedly exposed, persistently seronegative female sex-workers in The Gambia. Their CTL, repeatedly detected over two years, recognise epitopes presented by HLA-B35 which are cross-reactive between HIV-1 & HIV-2, suggesting they could have been primed first by HIV-2 exposure and subsequently boosted by exposure to HIV-1. Using previously identified clade B HIV-1 epitope peptides, we have now detected HIV-specific CTL in 6/15 highly exposed and apparently HIV-resistant Kenyan prostitutes, predominantly towards epitopes highly conserved between B and the Kenyan A & D clades of HIV-1. This CTL activity towards conserved virus epitopes may represent protective immunity to HIV generated in response to repeated exposure, and prophylactic HIV vaccines should aim to generate similar CTL responses.

Cells, Cultured↗
PubMed1997

Antibody to chlamydial hsp60 predicts an increased risk for chlamydial pelvic inflammatory disease.

To determine whether serum antibody to Chlamydia trachomatis antigens alters the risk of C. trachomatis pelvic inflammatory disease (PID), 280 female sex workers were prospectively evaluated over a 33-month period for incident C. trachomatis and Neisseria gonorrhoeae cervical infection and for clinical PID. At enrollment, women were tested for antibody to C. trachomatis elementary bodies by an indirect microimmunofluorescence assay and to recombinant chlamydial hsp60 (Chsp60) by an ELISA format. At each follow-up visit, women were tested for cervical chlamydial and gonococcal infection and were identified as having clinical PID if they complained of lower abdominal pain and were found to have uterine and adnexal tenderness on pelvic examination. The data demonstrate that antibody to Chsp60 predicts a 2- to 3-fold increased risk for C. trachomatis PID.

Adolescent↗
PubMed1996

Bacteriuria in a cohort of predominantly HIV-1 seropositive female commercial sex workers in Nairobi, Kenya.

Although significant bacteriuria and urinary tract infection are more common in immunocompetent women than men, studies linking HIV immunosuppression with an increased risk of developing urinary infection have so far only been carried out in men. We therefore examined the relationship between bacteriuria and HIV status and CD4+cell count in a relatively homogeneous cohort of female commercial sex workers (CSW) attending a community clinic in Nairobi. Two hundred and twenty-two women were enrolled, and grouped according to HIV status and CD4 count. Group 1 were HIV seronegative (n = 52); Group 2 were HIV seropositive with CD4 + counts above 500 x 10(6)/l (n = 51); Group 3 were HIV seropositive with CD4 + counts between 201 and 500 x 10(6)/l (n = 67); Group 4 were HIV seropositive with CD4+counts below 200 x 10(6)/l (n = 52). Clinical signs and symptoms were noted and mid-stream specimens of urine obtained for culture and sensitivity. Overall 23% (50/222) had significant bacteriuria. The rates in each group respectively were 25%, 29%, 19% and 23% and there was no significant association between bacteriuria and HIV status; or between bacteriuria and level of immuno-suppression as indicated by CD4 + count. Overall 19% (30/222) of women had symptoms (frequency; dysuria; loin pain; smelly urine) or signs (fever; loin tenderness) compatible with urinary tract infection. However there was no significant association between symptoms or signs of infection and bacteriuria or HIV status. A typical range of pathogens, predominantly Enterobacteriaceae, were isolated and there were high rates of resistance to commonly used antimicrobials as well as 10% resistance to ciprofloxacin. Although high rates of significant bacteriuria can occur in highly sexually-active women, this appears unrelated to HIV infection or the level of HIV-related immunosuppression and is generally asymptomatic or clinically indistinct.

Adolescent↗
PubMed1996

An immunohistochemical analysis of naturally occurring chancroid.

Haemophilus ducreyi is a major cause of genital ulcer disease in many developing countries and is associated with augmented transmission of human immunodeficiency virus (HIV). However, the mechanisms through which H. ducreyi produces ulceration are poorly understood. The characteristics of the host response to H. ducreyi and the pathobiology of its potential contribution to increased HIV susceptibility are not known. Chancroid ulcer biopsies from 8 patients were analyzed histologically and immunohistochemically. All biopsies had perivascular and interstitial mononuclear cell infiltrates that extended deep into the dermis. The infiltrate, which contained macrophages and CD4 and CD8 lymphocytes, was consistent with a delayed hypersensitivity type cell-mediated immune response. The recruitment of CD4 T lymphocytes and macrophages may in part explain the facilitation of HIV transmission in patients with chancroid.

Biopsy↗
PubMed1994

Human immunodeficiency virus infection in long-distance truck drivers in east Africa.

BACKGROUND: A cross-sectional survey was performed to determine the seroprevalence and correlates of human immunodeficiency virus (HIV) infection among long-distance truck drivers in Kenya. METHODS: Truck drivers along the Mombasa-Nairobi highway were enrolled at a roadside research clinic. A standardized interview and serologic evaluation for HIV and syphilis were conducted. RESULTS: We enrolled 970 truck drivers and their assistants of whom 257 (27%) had HIV antibodies. In univariate analysis, HIV infection was correlated with older age, non-Kenyan nationality, Christian religion, longer duration of truck driving, travel outside of Kenya, less frequent visits to wives, and more frequent visits to prostitutes. Uncircumcised status, history of genital ulcer disease or urethritis during the previous 5 years, and a positive Treponema pallidum hemagglutination assay for syphilis were each associated with positive HIV serostatus. Univariate correlates of uncircumcised status included younger age, non-Kenyan nationality, Christian religion, travel outside of Kenya, and less frequent visits to prostitutes. There was a significant association between uncircumcised status and 5-year history of genital ulcer disease or serologic evidence of syphilis, but not with 5-year history of urethritis. In multivariate analysis, HIV infection was independently associated with uncircumcised status (adjusted odds ratio [OR], 4.9; 95% confidence interval [CI], 2.8 to 8.4), history of genital ulcer disease (adjusted OR, 2.4; 95% CI, 1.5 to 4.1), history of urethritis (adjusted OR, 1.8; 95% CI, 1.1 to 2.9), more frequent sex with prostitutes (more than once per month; adjusted OR, 1.7; 95% CI, 1.1 to 2.8), and positive T pallidum hemagglutination assay (adjusted OR, 1.2; 95% CI, 1.0 to 1.4). The attributable risk percentage for the association between HIV and uncircumcised status was 70%, and the population attributable risk was 25%. CONCLUSIONS: Truck drivers in east Africa are at high risk of HIV infection. The strongest correlates of HIV seropositivity were uncircumcised status and history of both ulcerative and nonulcerative sexually transmitted diseases.

Adolescent↗
PubMed1994

Association between cervical inflammation and cervical shedding of human immunodeficiency virus DNA.

A cross-sectional study was conducted among prostitutes in Nairobi, Kenya, to determine the prevalence and correlates of cervical human immunodeficiency virus (HIV) DNA. Ninety-two HIV-seropositive prostitutes were evaluated during 137 clinic visits. Cervical HIV DNA was detected by polymerase chain reaction assay in 36 (39%) women at initial visits and in 40 (44%) women at any visit. There was a significant correlation between cervical HIV and microscopic evidence of cervical inflammation (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1-24.6). Using multivariate analysis to adjust for possible confounding, the adjusted OR for the association between cervical inflammation and cervical HIV DNA was 8.7 (95% CI, 2.0-37.2). Conditions associated with cervical inflammation are associated with the detection of HIV proviral DNA. Whether such conditions lead to increased infectivity remains to be proven.

Adult↗
PubMed1994

Chlamydia trachomatis from individuals in a sexually transmitted disease core group exhibit frequent sequence variation in the major outer membrane protein (omp1) gene.

60 cervical Chlamydia trachomatis infections identified by antigen detection from 51 prostitute women in Nairobi, Kenya were evaluated for sequence polymorphism in the major outer membrane protein (omp1) gene. DNA from clinical specimens was amplified by the polymerase chain reaction and cycle sequenced through variable domains (VD) 1, 2, and 4.37 (63%) samples had variant VD sequences, 19 (32%) samples had prototype VD sequences, and 4 (6%) samples had prototype VD sequences, and 4 (6%) samples contained omp1 sequences from two or more C. trachomatis strains. Among the 37 variant strains, 18 had two or fewer nucleotide substitutions in one or two VDs and represented point mutational drift variants. 19 strains had a larger number of nucleotide changes and displayed mosaic omp1 sequences that may have been generated by omp1 VD recombination. We conclude that the prevalence of C. trachomatis omp1 DNA polymorphism is substantial among prostitute women in Nairobi, Kenya and that this is the likely result of immune selection pressure.

Amino Acid Sequence↗
PubMed1994

Preparation for AIDS vaccine evaluation in Mombasa, Kenya: establishment of seronegative cohorts of commercial sex workers and trucking company employees.

In preparation for human immunodeficiency virus (HIV) prophylactic vaccine trials, prospective cohorts of HIV seronegative female commercial sex workers and male trucking company employees were established in Mombasa, Kenya, with the aims of defining HIV seroincidence and correlates of HIV seroconversion. Female and male cohorts were followed at 1- and 3-month intervals, respectively, with questionnaires, physical examinations, evaluation for sexually transmitted diseases, and HIV serologic testing. Between February and September, 1993, 1,277 women and 748 men were tested for antibodies to HIV-1. Seroprevalence was 55.4% among commercial sex workers and 17.7% among trucking company employees. Three hundred fifty-two HIV-seronegative women and 507 seronegative men were enrolled in the cohort studies. Annualized seroincidence rates of HIV infection were 16.4% (95% CI 8.8-27.0) among commercial sex workers and 6.6% (95% CI 2.5-13.8) among trucking company employees. These cohorts may be valuable resource for evaluating HIV vaccines and other potential preventive interventions.

AIDS Vaccines↗
PubMed1993

Detection of HIV DNA in cervical and vaginal secretions. Prevalence and correlates among women in Nairobi, Kenya.

OBJECTIVE: Factors that influence heterosexual transmission of the human immunodeficiency virus (HIV), including sexually transmitted diseases, contraceptive practices, sexual practices, HIV-related immunosuppression, and presence of cervical ectopy and the penile foreskin, have been identified through cross-sectional and prospective cohort epidemiological studies. To more directly characterize factors that influence infectivity, we conducted a study of HIV shedding from the genital tract in women. DESIGN: Ninety-seven HIV-seropositive women attending a sexually transmitted disease clinic in Nairobi, Kenya, completed a questionnaire and underwent a physical examination and an evaluation for sexually transmitted diseases. Cervical and vaginal secretions were obtained for HIV DNA detection using polymerase chain reaction amplification. RESULTS: Human immunodeficiency virus DNA was detected by polymerase chain reaction in 28 (33%) of 84 cervical samples and 13 (17%) of 77 vaginal samples. The prevalence of HIV was higher in specimens from the endocervix than from the vaginal wall (P = .002), and there was no correlation between presence of virus at the two sites. After adjusting for age, cervical HIV shedding was independently associated with oral contraceptive pill use (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.7 to 77.6), cervical mucopus (OR, 6.2; 95% CI, 0.9 to 41.4; P = .05), cervical ectopy (OR, 5.0; 95% CI, 1.5 to 16.9), and pregnancy (OR, 4.5; 95% CI, 1.2 to 16.3). CONCLUSIONS: Human immunodeficiency virus was detected in one third of cervical samples and one sixth of vaginal samples. The presence of HIV DNA in cervical secretions was significantly associated with oral contraceptive pill use, cervical ectopy, and pregnancy. There was a marginally significant association with cervical mucopus. The identification of factors that increase the infectivity of women suggests potential strategies for reducing heterosexual transmission of HIV.

AIDS Serodiagnosis↗