HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers

OBJECTIVES: Most HIV-1 transmission is sexual; therefore, immune responses in the genital mucosa may be important in mediating protection against HIV infection. This study examined HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan female sex workers. METHODS: HIV-1-specific immune responses were compared in HIV-1-resistant and HIV-1-infected sex workers, and in lower risk uninfected women. Cervical and vaginal samples from each group were tested for HIV-1-specific IgA and IgG by enzyme immunoassay. Systemic T-helper lymphocyte cell responses to HIV-1 envelope peptide epitopes were assayed using an interleukin 2 bioassay. HIV-1 risk-taking behaviours were assessed using standardized questionnaires. RESULTS: HIV-1-specific IgA was present in the genital tract of 16 out of 21 (76%) HIV-1-resistant sex workers, five out of 19 (26%) infected women, and three out of 28 (11%) lower risk women (P < 0.0001). Among lower risk women, the presence of HIV-1-specific IgA was associated with HIV-1 risk-taking behaviour. Systemic T-helper lymphocyte responses to HIV-1 envelope peptides were present in 11 out of 20 (55%) HIV-1-resistant women, four out of 18 (22%) infected women, and one out of 25 (4%) lower risk women (P < 0.001). T-helper lymphocyte responses did not correlate with the presence or titre of virus-specific mucosal IgA in any study group. CONCLUSIONS: HIV-1-specific IgA is present in the genital tract of most HIV-1-resistant Kenyan sex workers, and of a minority of lower risk uninfected women, where it is associated with risk-taking behaviour. These data suggest a role for mucosal HIV-1-specific IgA responses in HIV-1 resistance, independent of host cellular responses.     

检测HIV-1耐药株的异源双链泳动分析技术的建立及临床应用

目的探讨利用异源双链泳动分析技术(HMA)检测HIV-1耐药株的可行性和临床应用。方法从接受高效抗逆转录病毒治疗(HAART)的HIV-1感染者血浆中抽提RNA,采用套式RT-PCR方法扩增HIV-1的PR和RT基因片段,并对扩增的基因片段进行异源双链泳动分析。结果本方法对血清中HIV-1RNA含量2000copies/ml以上的样本都能有效扩增。在18例参加HAART治疗的HIV感染者中,17例的HMA结果在聚丙烯酰氨凝胶电泳上,没有出现有意义的异源双链泳动带。1例发现有异源双链二聚体,这1例后经序列测定证实,确定有耐药位点的基因变异。结论异源双链泳动分析技术能够及时、间接地反映HIV-1在治疗过程中耐药株的存在。该方法的建立能在临床上为临床医生制定治疗方法提供参考依据。     

Incidence of HIV-1 dual infection and its association with increased viral load set point in a cohort of HIV-1 subtype C-infected female sex workers

This longitudinal study aimed to determine the incidence and pathogenic implications of dual human immunodeficiency virus type 1 (HIV-1) infection in a cohort of female sex workers. Blood samples from 31 recently infected women were screened by use of a heteroduplex mobility assay and sequencing. The median viral load set point was 5404 copies/mL (n=22), which was measured by use of the bDNA assay. Within 3 months of infection, 19% (6/31) of the women were dually infected with 2 distinct HIV-1 subtype C viruses. No evidence of superinfection was detected over the course of 24 months of follow-up, indicating that the risk of dual infection is highest around the time of the initial infection. There was a significant association between dual infection and elevated viral load set point.     

Epidemiology of rheumatic diseases: a cohort of 23,550 patients in rheumatology clinics in Burkina Faso

Clinical Rheumatology - The aim of this work is to study the epidemiological characteristics of rheumatic conditions in a cohort of 23,550 patients followed up in Ouagadougou, Burkina Faso. This...     

Rapid risk household screening by neonatal arm circumference: results from a cohort study in rural Burkina Faso

Neonatal arm circumference (NAC) and other attributes of the newborn and its household were analysed as potential predictors of child death in a cohort of 1367 newborn children representing the majority of births in a rural area of Burkina Faso from 1992 to 1994. During 3872 person years observed 264 children died, resulting in an average mortality rate of 6.8% per year. 90 mm was chosen as the best cut-off to differentiate low NAC associated with high mortality from normal NAC. The hazard ratio of children with low NAC (15.7%) compared to others was 1.7 ( P < 0.001) in Cox regression. Kaplan-Meier curves of cumulative survival showed that this higher risk lasted throughout the first two years of life. Multivariate Cox regression comparing NAC with other variables known or suspected to influence child survival yielded a model including mother's death, twin birth, affiliation to a particular health centre, home delivery and birth during the rainy or harvest season as other significant risk factors beside NAC. Protective factors were mother's participation in antenatal care despite considerable distance to the health centre, medium household size (5–7 members) and household cash crop production. We propose a simple risk score for rapid household screening in rural Burkina Faso and comparable settings elsewhere for identifying households at risk of experiencing child death. As much of the other variables' contribution to the explanation of survival pattern is absorbed by NAC in more parsimonious models, even simpler screening strategies based on NAC make sense. In the study area risk households will be offered periodical home visits by the local nurse promoting immunization, treatment of illness and strengthening the mothers' competence to recognize and manage frequent health problems of their children as part of a 'Shared Care' concept.     

A variant of DC-SIGN gene promoter associated with resistance to HIV-1 in serodiscordant couples in Burkina Faso

ObjectiveTo study the involvement of variations in 4 genes associated with susceptibility and/or protection against HIV-1 in serodiscordant couples in Burkina Faso, namely, genes encoding HLA-B57, interferon regulatory factor 1 (IRF1), dendritic cell-specific ICAM3-grabbing nonintegrin (DC-SIGN) and CCR5 delta 32 (CCR5Δ32).MethodsTwo DC-SIGN and two IRF1 single nucleotide polymorphisms (SNPs) as well as HLA-B57*01 and CCR5Δ32 alleles were genotyped in 51 serodiscordant couples in Burkina Faso. DC-SIGN, IRF1 and HLA-B57*01 genotyping was carried out by real time PCR using TaqMan assays (Applied Biosystems, USA and Sacace Biotechnologies, Italy). CCR5Δ32 deletion was investigated by PCR.ResultsThe two SNPs of DC-SIGN promoter showed a significant genotypic difference in serodiscordant couples. After multivariate analysis, only the association between DC-SIGN rs2287886 and HIV-1 remained significant (P<0.01). No association was found between IRF1 SNPs and HIV-1 infection. CCR5Δ32 wild type allele was found in 100% of serodiscordant couples. A high frequency of HLA-B57*01 allele was found in the HIV-positive (78%) compared with HIV-negative group (51%), however this difference was no longer significant after the correction of the sex confounding effect in the logistic regression model.ConclusionsOur study suggests a protective role of a variation of DC-SIGN promoter and genetic resistance to HIV-1 in serodiscordant couples in Burkina Faso.     

Elevated T cell counts and RANTES expression in the genital mucosa of HIV-1-resistant Kenyan commercial sex workers

The initial site of exposure to human immunodeficiency virus (HIV)-1 during heterosexual transmission occurs in the genital tract. Although the majority of immunological studies have focused on the immune response to HIV-1 at the systemic level, our understanding of tissue-specific immunity is deficient. The goal of the present study was to characterize T cell populations found in the cervix of women shown to be resistant to infection by HIV-1. Levels of both systemic and cervical mucosal lymphocytes were compared between HIV-1-resistant, HIV-1-uninfected, and HIV-1-infected commercial sex workers (CSWs) as well as HIV-1-uninfected non-CSW control subjects at low risk for exposure. The HIV-1-resistant CSWs had increased cervical CD4+ and CD8+ T cell counts, compared with the HIV-1-uninfected CSWs; importantly, these increases were not reflected in the systemic lymphocyte compartment. There was a 2-fold increase in CD4+ T cell counts in the HIV-1-resistant CSWs, compared with both the HIV-1-infected and the HIV-1-uninfected CSWs. Expression of the HIV-1 coreceptors CCR5 and CXCR4 was also determined, and cytokine and beta chemokine levels in the genital mucosa were assessed. The HIV-1-resistant CSWs had a 10-fold increase in RANTES expression, compared with the HIV-1-uninfected CSWs. This is the first study to show elevated levels of beta chemokines and CD4+ T cells in the genital tracts of women who are exposed to HIV-1 and yet are uninfected.     

Genetic diversity and population structure of Mycobacterium tuberculosis in HIV-1-infected compared with uninfected individuals in Burkina Faso

HIV-1 infection and HIV-1-induced immune deficiency may play a role in selecting particular Mycobacterium tuberculosis (MTB) strains (i.e. genotypes). We compared 43 MTB isolates obtained from HIV-1-infected patients with 77 MTB isolates obtained from HIV-1-uninfected patients in Burkina Faso, by means of DNA fingerprinting methods (MIRU-VNTR plus spoligotyping). This study suggests a lack of structure of the MTB population caused by HIV-1 infection and a similar genetic diversity of MTB in HIV-1-infected compared with uninfected individuals.     

Malaria morbidity,treatment-seeking behaviour,and mortality in a cohort of young children in rural Burkina Faso

OBJECTIVE: To describe the pattern of fever-associated morbidity, treatment-seeking behaviour for fever episodes, and cause-specific mortality in young children of a malaria-holoendemic area in rural Burkina Faso. METHODS: In a longitudinal community-based intervention study, 709 representative children aged 6-31 months were followed daily over 6 months (including the main malaria transmission period) through village-based field staff. RESULTS: Of 1848 disease episodes, 1640 (89%) were fever episodes, and of those, 894 (55%) were attributed to malaria (fever + > or =5000 parasites/microl). Eighty-five percent of fever episodes were treated, mainly with chloroquine and paracetamol, 69% of treatments took place in households, 16% in local health centres, 13% in villages, and 1% in hospitals. Treatment-seeking in a health centre or hospital was associated with accessibility and disease severity. Cerebral malaria and malnutrition-associated diarrhoea were the most frequently diagnosed causes of death. While most children with a post-mortem diagnosis of diarrhoea had not received any treatment, children who died of malaria had often received insufficient treatment. In particular, there was a lack of an appropriate second-line treatment at formal health services after chloroquine treatment had failed to resolve symptoms. CONCLUSIONS: These findings call for more effective prevention and treatment of malaria, malnutrition and diarrhoea in rural African communities, as well as for better supervision of existing malaria treatment guidelines in formal health services.     

Determinants and causes of mortality in HIV-infected patients receiving antiretroviral therapy in Burkina Faso: a five-year retrospective cohort study

In this study, we investigated the causes of death and the factors associated with mortality in a cohort of patients receiving highly active antiretroviral therapy (HAART) in Burkina Faso, an African country with limited resources. This retrospective cohort study included patients aged 15 years and older who started HAART for the first time between January 2003 and December 2008 in 14 health districts. We used survival analyses, including the Kaplan-Meier method, to examine potential predictors of death and two Cox proportional hazard models to estimate hazard ratios for death, first from baseline covariates and then from time-dependent covariates. A total of 6641 patients initiated HAART during this period; of these, 5608 were included in the analysis. By the end of the study period, 4310 of those patients were still receiving HAART, 690 had died, 207 had been transferred and 401 were lost to follow-up. The median duration of follow-up was 23.2 months [interquartile range (IQR): 12.4-36.9], and the overall incidence of mortality was 6 per 100 person-years. The clinical stage, CD4 count, body mass index (BMI), haemoglobin level, HAART regimen, gender, age, profession and year of initiation were the primary risk factors associated with death. In the multivariate analysis, BMI, clinical stage, treatment regimen and CD4 count remained significantly associated with death. The most frequent causes of death were wasting syndrome, tuberculosis and anaemia. This result highlights the already advanced stage of immunodeficiency among patients in Burkina Faso when they start HAART. Testing patients for HIV and starting antiretroviral therapy earlier are necessary to further reduce the mortality of patients living with HIV. This study provides a solid evidence base with which future evaluations of HAART in Burkina Faso can be compared.     

HIV-1 Env-specific cytotoxic T-lymphocyte responses in exposed, uninfected Kenyan sex workers: a prospective analysis

The prospective significance of HIV-specific cytotoxic T lymphocyte (CTL) responses in highly exposed, persistently seronegative populations is unknown. In 1996-1997 we screened for CTL responses against HIV clade B Env in 39 recently enrolled Kenyan female sex workers, and followed these women prospectively. Annual HIV incidence was 5.8%. CTL were independently associated with age and recent HIV-1 exposure,but were not prospectively associated with protection in a multivariable model that included HIV-1 exposure and duration of sex work.     

应用枚举法估计乐山市暗娼基数的研究

目的 探索枚举法在暗娼基数估计中的应用，并对四川省乐山市中心城区暗娼基数进行估计。方法 采用枚举法，根据不同街道暗娼的密集程度分层抽样调查，计算各层调查样本的均数、标准差、95％可信区间；推算、汇总，获得目标人群的估计数。结果 以不同街道暗娼密集程度分层计算，估计乐山市中心城区暗娼总数1756人；以高危场所规模分层计算，估计乐山市中心城区暗娼总数1405人。结论 街道暗娼密集程度和高危场所规模都可作为枚举法抽样调查的依据，但在大型城市宜按街道暗娼密集度分层抽样调查。在中、小型城市宜按高危场所规模分层抽样调查，使结果更稳定、可信。     

A medico-social appraisal of commercial sex workers in a metropolitan city from eastern India

This cross-sectional study of 146 commercial sex workers (CSWs) selected by stratified sampling, in a red light area of Kolkata, showed that 25.3% were teenagers and 37.0% were forced into the profession due to poverty. White discharge was present in 42.5% of the CSWs. Only 65.1% had the proper knowledge of the causes of disease, but 49.3% preferred to go to "quacks" for treatment, while 42.5% preferred traditional medicine. Knowledge of the prevention of sexually transmitted infections by condom use was correct in 44.2% of the CSWs, but 17.8% used condoms regularly. One fourth of the CSWs having 5 or more clients per day used condoms regularly.     

Social development of commercial sex workers in India: an essential step in HIV/AIDS prevention

India has the highest number of HIV/AIDS cases in the world. Current HIV/AIDS prevention strategies are based on regular and appropriate condom use. However, most commercial sex workers (CSWs), who form the core/high-risk groups toward whom the prevention strategy is directed, are disempowered and socioeconomically marginalized. This does not allow them to insist on condom use by the client, especially in absence of governmental structural support. This paper discusses HIV/AIDS prevention issues that relate to CSWs in India; issues that play a vital role in initiation, perpetuation, and expansion of economic activity of CSWs; and those factors that influence the HIV/AIDS preventive practices of CSWs. This paper argues that CSWs can be empowered and emancipated; that HIV/AIDS control and prevention efforts in India must recognize that ad hoc promotion of condom use or similar such programs will not be effective to control HIV/AIDS; and that more extensive developmental work aimed at betterment of living conditions of CSWs is required for effective HIV/AIDS prevention.     

Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia

OBJECTIVE: To assess and compare the mortality rates of patients with HIV-1, HIV-2 or both infections (HIV-D) in the same population. DESIGN: Clinic-based cohort study. METHODS: HIV-seropositive patients aged 15 years and older who attended the Medical Research Council clinics in Fajara between May 1986 and September 1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell staging, WHO staging, and CD4 cell counts was performed at baseline. Patients attended clinic every 3 months; if they did not attend, they were visited at home by field workers to ascertain survival status. No patient was on antiretroviral therapy during the study period. RESULTS: Data from 1519 HIV-positive adult patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107 patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost to follow-up. The median follow-up was 12 months (range 0-128). CD4 cell counts were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio for mortality in the CD4 cell count category 500 cells/microl or greater was 0.50 for HIV-2 (95% CI 0.28-0.88) and 1.27 (95% CI 0.51-3.7) for HIV-D. Among those with CD4 cell counts less than 500 cells/microl the mortality rates in HIV-2 and HIV-D were similar to those in HIV-1. DISCUSSION: HIV-2-infected patients with CD4 cell counts of 500 cells/microl and greater had a significantly lower mortality rate than HIV-1-infected patients. HIV-2-infected patients with advanced disease had the same poor prognosis as patients with HIV-1. Dually infected patients had mortality rates similar to HIV-1.     

应用乘数法估计深圳市性工作者和吸毒人群规模

目的 调查估计深圳市性工作者和吸毒人群规模,分析影响评估结果的因素,为制定有针对性的艾滋病防治策略提供科学依据.方法 在6个区中,分别应用乘数法对各区的性工作者和吸毒人群规模进行调查估计.结果 深圳市在2003年、2006年分别有63 706名、110 684名性工作者和21 741名、38 113名吸毒者,两类高危人群中,特区内分别占28.8%、64.6%和52.5%、40.3%.结论 运用乘数法对艾滋病高危人群进行估计实施简易,结果可信,但随时间改变,特区内外的人群规模差距缩小.