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F A Plummer

Publications and source records attributed to F A Plummer.

At least 19 recordsLinked to original sources
PubMed1996

Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya.

BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. INTERPRETATION: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya.

BACKGROUND: HIV infection is a major risk factor for pneumococcal disease in industrialised countries. Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction. We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease. METHODS: A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992. 587 participants were HIV positive and 132 remained HIV negative. Set protocols were used to investigate common presentations. Cases were identified clinically and radiographically. Streptococcus pneumoniae and other pathogens were diagnosed by culture. FINDINGS: Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17.8, 95% CI 2.5 to 126.5). In seropositive women the incidence rate was 42.5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years. By serotyping, most recurrent events were re-infection. A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11%. Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae. At first presentation the mean CD4 cell count was 302/microL(SD 191) and was 171/microL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 0.29 to 0.66). Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae. INTERPRETATION: Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa.

AIDS-Related Opportunistic Infections↗
PubMed1996

Increased risk of infection with human immunodeficiency virus type 1 among uncircumcised men presenting with genital ulcer disease in Kenya.

The factors responsible for the explosive spread of human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa continue to be identified and debated. One of the most controversial factors has been male circumcision. This cross-sectional study was conducted to measure the association between circumcision status and infection with HIV-1 among men with genital ulcer disease. Eight hundred and ten men participated in the study, of whom 190 (23%) were HIV-1-positive. A logistic regression model adjusted for behavioral and historical showed that HIV-1 positivity was independently associated with being uncircumcised (adjusted odds ratio [OR], 4.8; 95% confidence interval [CI], 3.3-7.2) and with a history of urethral discharge (adjusted OR, 2.0; 95% CI, 1.4-2.8). This association could not be explained by measures of sexual exposure to HIV-1 among this population. Male circumcision should be considered as an intervention strategy for AIDS control.

Adolescent↗
PubMed1996

Primary and secondary syphilis lesions contain mRNA for Th1 cytokines.

Phagocytosis of Treponema pallidum by cytokine-activated macrophages aids bacterial clearance and lesion resolution in early syphilis. To investigate the cytokine profiles of cells infiltrating primary and secondary syphilis lesions, reverse transcription and polymerase chain reaction (RT-PCR) were used to detect cytokine mRNA in 13 lesion biopsies. Both primary and secondary lesions contained mRNA encoding interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-12p40, and IL-10. In contrast to a lesion from a patient with recurrent herpes simplex virus type 2, no message for IL-4 could be detected in any of the syphilis lesions, and 10 of 13 had no mRNA for IL-5 or IL-13. These findings are consistent with a Th1-predominant local cellular response activating macrophages and support the hypothesis that IFN-gamma-activated macrophages are primary effectors in treponeme clearance.

Base Sequence↗
PubMed1996

The epidemiology of Chlamydia trachomatis within a sexually transmitted diseases core group.

Female sex workers in Nairobi were prospectively evaluated for risk factors of incident Chlamydia trachomatis infection. Independent risk factors included cervical ectopy (P=.007), gonococcal infection (P=.002), human immunodeficiency virus (HIV) seropositivity (P=.003), HIV seroconversion (P=.001), and duration of prostitution (P=.002). Eighteen different C. trachomatis outer membrane protein (omp1) genotypes were identified, with the allelic composition of the C. trachomatis population changing significantly over time (P=.005). Seventeen of 19 reinfections > or = 6 months apart were with different C. trachomatis omp1 genotypes. Women with HIV infection had an increased proportion of visits with C. trachomatis infection (P=.001) and an increased risk of reinfection (P=.008). Overall, the data demonstrate significant fluctuations in the genotype composition of the C. trachomatis population and a reduced rate of same-genotype reinfection consistent with the occurrence of strain-specific immunity.

Amino Acid Sequence↗
PubMed1996

Risk factors for Chlamydia trachomatis pelvic inflammatory disease among sex workers in Nairobi, Kenya.

Among 302 female sex workers in Nairobi, Kenya, who were followed for 17.6 +/- 11.1 months, 146 had one or more infections with Chlamydia trachomatis; 102 had uncomplicated cervical infection only, 23 had C. trachomatis pelvic inflammatory disease (PID), and 21 had combined C. trachomatis and Neisseria gonorrhoeae PID. As determined by multivariate logistic regression analysis, risk factors for C. trachomatis PID included repeated C. trachomatis infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.4; P = .0004), antibody to C. trachomatis heat-shock protein 60 (OR, 3.9; CI, 1.04-14.5; P = .04), oral contraceptive use (OR, 0.28; 95% CI, 0.08-0.99; P = .048), and number of episodes of nongonococcal nonchlamydial PID (OR, 1.7; 95% CI, 1.1-2.7; P = .02). Among human immunodeficiency virus (HIV)-seropositive women, a CD4 lymphocyte count of <400/mm3 was an additional independent risk factor for C. trachomatis PID (OR, 21.7; 95% CI, 1.2-383; P = .036); among HLA-typed women, HLA-A31 was independently associated with C. trachomatis PID (OR, 5.6; 95% CI, 1.1-29.4; P = .043). The results suggest an immune-mediated pathogenesis for C. trachomatis PID.

Adult↗
PubMed1996

Focused peer-mediated educational programs among female sex workers to reduce sexually transmitted disease and human immunodeficiency virus transmission in Kenya and Zimbabwe.

Peer-mediated education programs in Kenya and Zimbabwe focusing on female sex workers for the control of human immunodeficiency virus (HIV) infection and other sexually transmitted diseases (STDs) have led to increased condom use and increased adoption of other safer sex practices, as well as declines in STD and HIV incidence among female sex workers. It is likely that similar declines have occurred among their clients and possibly in the general community, although supporting data are limited. These results are encouraging. However, progress in increasing the scale and coverage of intervention programs among female sex workers has been slow. Constraints to expanding program coverage include inadequate political commitment; deficiencies in program planning, management, and human resources; and insufficient funding. The challenges currently are to show that behavioral change can be sustained and to scale up activities from small demonstration projects to district, provincial, and national levels.

Catchment Area, Health↗
PubMed1996

Lesions of primary and secondary syphilis contain activated cytolytic T cells.

This study demonstrates that CD8+ cytotoxic lymphocytes (CTL) are found in both primary and secondary syphilis lesions. CD8+ T cells were detected by immunohistology, and mRNAs for granzyme B and perforin were detected by reverse transcription and PCR, suggesting that CD8+ cytotoxic lymphocytes are activated.

Base Sequence↗
PubMed1996

Genital ulcer disease among STD clinic attenders in Nairobi: association with HIV-1 and circumcision status.

In previous studies, genital ulcers in men have been found to be associated with increased risk of HIV-1 seroconversion. To further explore this association male patients attending a sexually transmitted disease (STD) clinic in Nairobi for either urethritis (controls, n = 276) or a genital ulcer (cases, n = 607) were compared with respect to sexual behaviour, presence of HIV-1 antibody and circumcision status. Patients were followed to study risk factors for incident genital ulcers and HIV-1 seroconversion. At entry, being married was associated with higher prevalence of HIV-1 (OR = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.23). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. It is argued that the association between genital ulcers and HIV-1 infection may be more complex than ulcers simply being a risk factor for HIV-1 infection, and that HIV-1 infection may either increase the risk of acquiring a genital ulcer, or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

Adult↗
PubMed1995

Logistic regression in case-control studies: the effect of using independent as dependent variables.

In case-control studies, cases are sampled separately from controls. In such studies the primary analysis concerns the estimation of the effect of covariables on being a case or a control. To explore causal pathways, further secondary analysis could concern the relationships among the covariables. In this paper the validity of such secondary analysis is addressed. In particular, the use of multiple logistic regression in case-control studies where the dependent variable is not the case/control indicator is explored. It is shown that only under very restrictive conditions will sample regression coefficients correctly estimate their true value. In many situations, it may be valid to regress one covariable on others in the control group, but not in the case group or the combined sample. This principle is illustrated by a study of sexually transmitted disease in Kenya.

Case-Control Studies↗
PubMed1995

Genetic analysis of human DNA recovered from minute amounts of serum or plasma.

A rapid and inexpensive method is described where a small amount of serum or plasma was used as the source of DNA for genetic analysis. Using a silica gel matrix DNA was isolated from 50 microliters of archived serum or plasma. The specimens were collected from 13 individuals at two separate time points 3-6 years apart. The polymorphic region of second exon of the MHC class II gene HLA DQA1 was amplified using the polymerase chain reaction (PCR) to sufficient quantities to permit genetic analysis using allele-specific oligonucleotides (ASO). Allelic typing of each specimen was performed and the reproducibility of the method was demonstrated in that in all 13 cases the two independently isolated specimens produced the identical ASO binding patterns. No qualitative difference was noted in the amplified product generated from plasma or serum. This study demonstrates (a) that minute amounts of serum or plasma are able to provide sufficient quantity and quality of DNA to permit genetic analyses (b) and that the source of serum can be archived for many years.

Alleles↗
PubMed1995

The duration of breastfeeding by HIV-1-infected mothers in developing countries: balancing benefits and risks.

How best to advise mothers infected with human immunodeficiency virus type 1 (HIV-1) in developing countries regarding breastfeeding is an important issue that has generated considerable debate. Previous studies have addressed this problem by means of mathematical models, but without considering the issue of the duration of breastfeeding. A mathematical model was developed to compare the age-specific risks of mother-to-child HIV transmission versus the excess mortality due to not breastfeeding. In this model it is assumed that both the risk of mother-to-child transmission of HIV through breast milk and the relative risk of not breastfeeding do not vary with age. The model indicates that, in HIV-1-seropositive mothers, the decrease in child mortality afforded by breastfeeding may exceed the risk of mother-to-child HIV-1 transmission only during the first 3-7 months of life. Thereafter the risk of HIV-1 transmission probably exceeds the mortality benefit of breastfeeding. Experimental studies of counselling HIV-1-infected mothers to limit their duration of breastfeeding should be considered in the setting of developing countries.

Breast Feeding↗
PubMed1995

Herpes zoster as the initial presentation of human immunodeficiency virus type 1 infection in Kenya.

We conducted a prospective observational study to determine the clinical features, the degree of immunosuppression, and the prevalence of human immunodeficiency virus type 1 (HIV-1) infection associated with herpes zoster in Kenya. The study included 196 HIV-1 positive individuals and 34 HIV-1 negative individuals between the ages of 16 and 50 years who presented to a referral clinic in Nairobi. Comparison of the clinical characteristics in the two groups found that the duration of illness in the HIV-1-positive group was longer (32 vs. 22 days; P < .001) and that the HIV-1-positive group was more likely to have generalized lymphadenopathy (74% vs. 3%; OR: 12.2; 95% CI: 1.6, 91.7), severe pain (69% vs. 39%; OR: 3.6; 95% CI; 1.7, 7.6), bacterial superinfection (15% vs. 6%; OR: 5.7; 95% CI: 1.3, 25.0), and more than one affected dermatome (38% vs. 18%; OR: 2.8; 95% CI: 1.1, 8.0). Dermatomal distribution of the lesions was similar in the two groups, except for cranial lesions, which occurred exclusively in the HIV-1-positive group. The mean CD4 T lymphocyte count at presentation was 333/mm(3) in the HIV-1-positive group and 777/mm(3) in the HIV-1-negative group (P < .001). Herpes zoster is often recognized as the initial HIV-1-related illness in Kenya despite the fact that patients have moderate to severe depression of CD4 cell counts at presentation. Although the clinical features of herpes zoster may be more severe in HIV-1-positive individuals, recovery is generally complete and uncomplicated.

AIDS-Related Opportunistic Infections↗
PubMed1995

Pulsed-field gel electrophoresis for genomic analysis of Neisseria gonorrhoeae.

Pulsed-field gel electrophoresis (PFGE) is a technique for analyzing large DNA fragments. PFGE was compared to auxotyping and Por serovar (A/S) classification to determine its utility in the study of gonococcal infection, subtyping A/S classes, and clone identification. PFGE patterns were stable in vitro after 2 isolates were passaged 50 times, and those from sex partners were indistinguishable with both enzymes. Fourteen proline-requiring IA-6 isolates from Kenya produced 8 NheI and 7 XbaI patterns; these included 6 Tet M-carrying isolates, all producing the same NheI pattern. PFGE patterns of 14 arginine-, hypoxanthine-, and uracil-requiring IA-1,2 isolates, from the US Pacific Northwest and Hawaii in 1993, were less diverse with both enzymes. PFGE analysis represents a potentially useful addition to the current gonococcal classification system.

Contact Tracing↗
PubMed1995

Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection.

From a cohort of female sex workers in Nairobi, Kenya, 163 women were observed to seroconvert to human immunodeficiency virus type 1 (HIV-1) and followed to study progression to HIV-1-related disease. The effect of several covariables on disease progression was studied using a Weibull proportional hazards model. The Weibull survival model was fitted to the observed incubation times. Estimates of the median duration to CDC stage IV-A and IV-C disease were 3.5 and 4.4 years, respectively. Condom use before seroconversion was associated with a reduced risk of CDC stage IV-A disease (relative risk = .64, P < .05). The incubation time of HIV-1-related disease is extremely short in this population.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Human immunodeficiency virus DNA in urethral secretions in men: association with gonococcal urethritis and CD4 cell depletion.

To evaluate the prevalence and correlates of human immunodeficiency virus (HIV)-infected cells in urethral secretions, samples were collected from 106 HIV-seropositive men with and without urethritis. HIV DNA was detected by polymerase chain reaction in 27% of 184 urethral specimens and was associated with CD4 cell depletion (P for trend, .03) and with urethritis (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.2-4.6) or gonorrhea (OR, 2.9; 95% CI, 1.5-5.8). Two multivariate models were constructed that included age, CD4 cell count < 200/mm3, and either urethritis or gonococcal infection. Detection of HIV-infected cells in urethral secretions was independently associated with < 200 CD4 cells/mm3 (OR, 2.2; 95% CI, 0.9-5.2; P = .05) and urethritis (OR, 2.7; 95% CI, 1.3-5.3; P = .003) in the first model and with gonococcal infection (OR, 3.2; 95% CI, 1.6-6.4; P < .001) in the second model. Successful treatment of gonococcal urethritis was associated with a 2-fold reduction in urethral HIV DNA (44% vs. 21%; P = .02). Thus, treatment of gonococcal urethritis may be an effective strategy for reducing HIV transmission.

Adult↗
PubMed1995

Mass antimicrobial treatment in pregnancy. A randomized, placebo-controlled trial in a population with high rates of sexually transmitted diseases.

Sexually transmitted diseases (STDs) are highly prevalent in pregnant women in many developing countries and have been associated with poor obstetric outcomes. Case detection and treatment of STDs in women is problematic and expensive, underscoring the need for other strategies. To explore the potential benefits of routine antimicrobial therapy on pregnancy outcome, we carried out a randomized, double-blind, clinical trial in one of the antenatal clinics in Nairobi, Kenya. Four hundred pregnant women between 28 and 32 weeks' gestation were given a single dose of 250 mg ceftriaxone intramuscularly or a placebo. There was a significant difference between ceftriaxone and placebo-treated women in infant birth weight (3,209 versus 3,056 g, P = .01). In addition, there was a trend toward lower rates of birth weight < 2,500 g (4.0% versus 9.2%, P = .08) and postpartum endometritis (3.8% versus 10.4%, P = .05) in the intervention than in the placebo group. Neisseria gonorrhoeae was isolated from the cervixes of postpartum women in 1.8% of the intervention group as compared to 4.2% of the control group. These data suggest a beneficial effect of antimicrobial prophylaxis on pregnancy outcome. Larger studies should be carried out to examine the public health impact of this intervention.

Adult↗