RESUMEN
Despite high exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), the predictors for seropositivity in the context of husbandry practices for camels in Eastern Africa are not well understood. We conducted a cross-sectional survey to describe the camel herd profile and determine the factors associated with MERS-CoV seropositivity in Northern Kenya. We enrolled 29 camel-owning households and administered questionnaires to collect herd and household data. Serum samples collected from 493 randomly selected camels were tested for anti-MERS-CoV antibodies using a microneutralisation assay, and regression analysis used to correlate herd and household characteristics with camel seropositivity. Households reared camels (median = 23 camels and IQR 16-56), and at least one other livestock species in two distinct herds; a home herd kept near homesteads, and a range/fora herd that resided far from the homestead. The overall MERS-CoV IgG seropositivity was 76.3%, with no statistically significant difference between home and fora herds. Significant predictors for seropositivity (P ⩽ 0.05) included camels 6-10 years old (aOR 2.3, 95% CI 1.0-5.2), herds with ⩾25 camels (aOR 2.0, 95% CI 1.2-3.4) and camels from Gabra community (aOR 2.3, 95% CI 1.2-4.2). These results suggest high levels of virus transmission among camels, with potential for human infection.
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Crianza de Animales Domésticos/métodos , Camelus , Infecciones por Coronavirus/epidemiología , Coronavirus del Síndrome Respiratorio de Oriente Medio , Zoonosis/epidemiología , Adulto , Factores de Edad , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/transmisión , Estudios Transversales , Escolaridad , Composición Familiar , Femenino , Humanos , Kenia/epidemiología , Masculino , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Análisis de Regresión , Estudios Seroepidemiológicos , Factores Socioeconómicos , Encuestas y Cuestionarios , Migrantes , Zoonosis/transmisiónRESUMEN
SETTING: A third of the world's population has latent tuberculous infection (LTBI). Current TB diagnostics used in developing countries are ineffective and are unable to distinguish LTBI from active TB. Identifying biomarkers that could aid in the early detection of TB and in distinguishing TB states could be a major breakthrough in global TB control. OBJECTIVE: To identify potential immune biomarkers to distinguish active TB from LTBI. DESIGN: A cross-sectional study was conducted among 19 active TB patients, 8 TB-negative individuals (controls) and 16 LTBI non-human immunodeficiency virus infected individuals in Nairobi, Kenya. Excess supernatants from the QuantiFERON®-TB Gold In-Tube test were used to measure immune analytes using a Th17-focused Milliplex® assay. RESULTS: Overall antigen-specific responses were higher in the LTBI group than in active TB patients and controls. Interleukin (IL) 17F, macrophage inflammatory protein 3 alpha (MIP-3α), IL-13, IL-17A, IL-5, interferon-gamma (IFN-γ), IL-9, IL-1ß and IL-2 were significantly differentially produced by individuals with LTBI and active TB patients. Receiver operator curve analysis revealed good discriminative abilities of these analytes. Co-expression analysis highlighted uniquely co-expressed cytokine pairs between TB groups. CONCLUSION: These findings suggest that IL-17F, MIP-3α, IL-13, IL-17A, IL-5, IL-9, IL-1ß and IL-2, in addition to IFN-γ, could identify and uniquely discriminate between TB states.
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Citocinas/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Adulto , Antígenos Bacterianos/inmunología , Biomarcadores/metabolismo , Estudios Transversales , Femenino , Humanos , Kenia , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In May 2011 in Turkana County, north-western Kenya, tissue samples were collected from goats suspected of having died of peste des petits ruminant (PPR) disease, an acute viral disease of small ruminants. The samples were processed and tested by reverse transcriptase PCR for the presence of PPR viral RNA. The positive samples were sequenced and identified as belonging to peste des petits ruminants virus (PPRV) lineage III. Full-genome analysis of one of the positive samples revealed that the virus causing disease in Kenya in 2011 was 95.7% identical to the full genome of a virus isolated in Uganda in 2012 and that a segment of the viral fusion gene was 100% identical to that of a virus circulating in Tanzania in 2013. These data strongly indicate transboundary movement of lineage III viruses between Eastern Africa countries and have significant implications for surveillance and control of this important disease as it moves southwards in Africa.
Asunto(s)
Genoma Viral , Virus de la Peste de los Pequeños Rumiantes/genética , Animales , Cabras , Kenia , Filogenia , ARN Viral/aislamiento & purificaciónRESUMEN
A better understanding of the cellular targets of HIV infection in the female genital tract may inform HIV prevention efforts. Proposed correlates of cellular susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly correlated between these two compartments. Cervix-derived CD4(+) T cells expressing CD69, α(4)ß(7), or α(4)ß(1) were preferential HIV targets; this enhanced susceptibility was strongly correlated with increased CCR5 expression in α(4)ß(7)(+) and CD69(+) CD4(+) T cells, and to a lesser extent in α(4)ß(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins was not observed, integrin inhibitors had no effect on virus entry, and pseudotypes with an env that preferentially binds α(4)ß(7) still demonstrated enhanced entry into α(4)ß(1)(+) cells. In summary, a rapid and sensitive HIV entry assay demonstrated enhanced susceptibility of activated endocervical CD4(+) T cells, and those expressing α(4)ß(7) or α(4)ß(1). This may relate to increased CCR5 expression by these cell subsets, but did not appear to be due to direct interaction of α(4)ß(7) or α(4)ß(1) with HIV envelope.
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Linfocitos T CD4-Positivos/virología , Cuello del Útero/virología , Integrina alfa4beta1/inmunología , Integrinas/inmunología , Receptores CCR5/inmunología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , Adulto , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/inmunología , Linfocitos T CD4-Positivos/inmunología , Cuello del Útero/inmunología , Femenino , Regulación de la Expresión Génica , VIH-1/genética , VIH-1/inmunología , Interacciones Huésped-Patógeno , Humanos , Inmunidad Mucosa , Integrina alfa4beta1/genética , Integrinas/genética , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Persona de Mediana Edad , Especificidad de Órganos , Cultivo Primario de Células , Receptores CCR5/genética , Receptores Virales/genética , Receptores Virales/inmunología , Transducción de Señal , Internalización del Virus , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
OBJECTIVE: To determine HIV high risk groups among adults visiting Kenyatta National Hospital Voluntary Counselling and Testing Centre by use of Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS). DESIGN: A cross-sectional study of adults. SETTING: Kenyatta National Hospital Voluntary and Counselling Centre. RESULTS: Of the 6,415 adults screened for antibodies to HIV at Kenyatta National Hospital VCT Centre between July 2002 and February 2003, 728 tested positive in the two HIV screening tests used at the center, indicating a prevalence of 11%. Of these seropositive cases, 355 consented to participate in the study. Using STARHS, 34 (9.6%) of the plasma samples were classified as being from individuals with recent infection (within 170 days), giving an annual estimated HIV-1 incidence in this population of 1.3 infections per 100 person-years with a 95% CI of 0.872-1.728%. Young adults had a higher rate of new infection than older adults. Young females were infected much earlier in life, with a peak age of new infections of 26 years, versus 31 years for young males. CONCLUSION: This study confirms our hypothesis that STARHS or Detuned assay can be used to determine HIV incidence in this population. The HIV high risk groups as identified by this study are young women between ages 16 to 26 years old and men between ages 45 to 55 years of age.
Asunto(s)
Anticuerpos Anti-VIH/sangre , Seropositividad para VIH/sangre , Seropositividad para VIH/epidemiología , VIH-1/inmunología , Adolescente , Adulto , Algoritmos , Instituciones de Atención Ambulatoria , Intervalos de Confianza , Estudios Transversales , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Seropositividad para VIH/diagnóstico , Humanos , Incidencia , Kenia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
Contrary to early expectations, recent studies have shown near-perfect adherence to HIV antiretrovirals in sub-Saharan Africa We conducted qualitative interviews with patients purchasing low-cost, generic antiretroviral therapy to better understand the social dynamics underlying these findings. We found that concerns for family well-being motivate adherence, yet, the financial sacrifices necessary to secure therapy may paradoxically undermine family welfare. We suggest that missed doses may be more due to a failure to access medication rather than a failure to adhere to medications, and that structural rather than behavioral interventions may be most useful to insure optimal treatment response.
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Antirretrovirales/uso terapéutico , Actitud Frente a la Salud , Medicamentos Genéricos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Conductas Relacionadas con la Salud , Cooperación del Paciente , Adulto , Áreas de Influencia de Salud , Costo de Enfermedad , Quimioterapia Combinada , Femenino , Infecciones por VIH/epidemiología , Humanos , Estudios Longitudinales , Masculino , Uganda/epidemiologíaRESUMEN
Our objective was to determine the level of adherence and reasons for non-adherence to antiretroviral therapy (ART) among HIV-positive (HIV+) people on ART in a resource-limited setting. Patients receiving ART were recruited into the cross-sectional study from three treatment centres in Kampala, Uganda. The number of missed doses over the last three days was assessed by structured patient interviews and dichotomized at +/-95% adherence. Reasons for non-adherence were assessed with both structured patient interviews and unstructured qualitative interviews. Independent predictors of non-adherence were assessed with multivariate logistic regression. In all, 304 HIV-infected persons on ART were enrolled into the study. Factors associated with non-adherence were marital status (odds ratio (OR) = 2.93, 95% confidence interval (CI) 1.32-6.50) and low monthly income <50 US$ [OR = 2.77, 95% CI 1.64-4.67]. We concluded that levels of self-reported adherence in patients receiving ART in Kampala are comparable to levels in resource-rich settings with inability to purchase and secure a stable supply as a major barrier to adherence.
Asunto(s)
Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cooperación del Paciente , Inhibidores de la Transcriptasa Inversa/economía , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Anciano , Estudios Transversales , Quimioterapia Combinada , Femenino , Humanos , Entrevistas como Asunto , Modelos Logísticos , Masculino , Persona de Mediana Edad , UgandaRESUMEN
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.
Asunto(s)
Seronegatividad para VIH/inmunología , VIH-1/inmunología , Trabajo Sexual , Linfocitos T Citotóxicos/inmunología , Adulto , Secuencia de Aminoácidos , Estudios de Cohortes , Epítopos/genética , Femenino , Productos del Gen env/genética , Productos del Gen env/inmunología , Genes env , Seropositividad para VIH/inmunología , VIH-1/genética , Humanos , Kenia , Datos de Secuencia Molecular , Factores de TiempoRESUMEN
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.
Asunto(s)
Vacunas contra el SIDA/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Antígenos HLA , Adulto , Alelos , Estudios de Cohortes , Femenino , Infecciones por VIH/genética , Infecciones por VIH/transmisión , Antígenos HLA/genética , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Kenia , Análisis Multivariante , Embarazo , Factores de Riesgo , Trabajo Sexual , Linfocitos T/inmunologíaRESUMEN
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.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Epítopos/inmunología , Infecciones por VIH/inmunología , Seronegatividad para VIH/inmunología , VIH-1/inmunología , Estudios de Cohortes , Femenino , Genes MHC Clase I , Seropositividad para VIH , Antígenos de Histocompatibilidad Clase I , Humanos , Epítopos Inmunodominantes , Kenia , Oligopéptidos/inmunología , Factores de Riesgo , Trabajo Sexual , Linfocitos T Citotóxicos/inmunologíaRESUMEN
The goal of the present study was to determine whether there were HIV-1 specific cellular immune responses among a subgroup of women within a cohort of Nairobi prostitutes (n = 1800) who, despite their intense sexual exposure to HIV-1, are epidemiologically resistant to HIV-1 infection. Of the 80 women defined to be resistant, 24 were recruited for immunological evaluation. The HIV-1-specific T-helper responses were determined by IL-2 production following stimulation with HIV-1 envelope peptides and soluble gp120. Cytotoxic T lymphocyte responses were determined by lysis of autologous EBV-transformed B cell lines infected with control vaccinia virus or recombinant vaccinia viruses containing the HIV-1 structural genes env, gag and pol. Resistant women had significantly increased HIV-1 specific T-helper responses, as determined by in vitro IL-2 production to HIV-1 envelope peptides and soluble glycoprotein 120, compared with low-risk seronegative and HIV-1-infected controls (P < or = 0.01, Student's t-test). Seven of the 17 (41%) resistant women showed IL-2 stimulation indices > or = 2.0. HIV-1-specific CTL responses were detected among 15/22 (68.2%) resistant women compared with 0/12 low-risk controls (Chi-squared test, P < 0.001). In the two resistant individuals tested, the CTL activity was mediated by CD8+ effectors. Many HIV-1-resistant women show evidence of HIV-1-specific T-helper and cytotoxic responses. These data support the suggestion that HIV-1-specific T-cell responses contribute to protection against HIV-1 infection.
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Seronegatividad para VIH/inmunología , VIH-1/inmunología , Inmunidad Celular , Trabajo Sexual , Adulto , Antígenos CD4/inmunología , Pruebas Inmunológicas de Citotoxicidad , Femenino , Antígenos VIH/inmunología , Humanos , Interleucina-2/biosíntesis , Leucocitos Mononucleares/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
BACKGROUND: Imported malaria is quite common in the United States. Increasing antimalarial drug resistance and changes in travel patterns may have important implications for the prevention, clinical presentation, and management of this disease. METHODS: Medical records were reviewed for 121 patients with microscopically confirmed malaria diagnosed at 2 university-affiliated hospitals in San Francisco, Calif, between 1988 and 1997. RESULTS: Among 57 travelers from the United States, only 13 (23%) had been compliant with an appropriate chemoprophylactic regimen. No patients developed falciparum malaria after consistent chemoprophylactic therapy with mefloquine hydrochloride. However, 12 (19%) of US residents with imported malaria developed Plasmodium vivax or Plasmodium ovale infections despite an appropriate chemoprophylactic regimen, generally with a late onset suggestive of relapsing disease. Clinical presentations were similar between foreign residents and American travelers and between patients with falciparum and nonfalciparum infections; 98% of patients had a history of fever. Sixteen percent of patients had received previous evaluations during which the diagnosis of malaria was not considered. In 9% of patients, there were errors in treatment. Only 1 patient developed severe malaria. CONCLUSIONS: Our results suggest that a standard chemoprophylactic regimen is highly effective in preventing falciparum malaria, but that many American travelers do not receive it. Also, relapsing P vivax or P ovale infection despite appropriate chemoprophylactic therapy was not uncommon among our cases. The presentation of imported malaria is nonspecific, highlighting the need to consider the diagnosis in any febrile patient who has been in a malaria-endemic area. Although errors in diagnosis and treatment were quite common in our study population, patient outcomes were good once the appropriate therapy was initiated.
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Malaria , Malaria/terapia , Adolescente , Adulto , Antimaláricos/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/prevención & control , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Estudios Retrospectivos , Viaje , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/genética , Infecciones por VIH/genética , Complejo Mayor de Histocompatibilidad , Polimorfismo Genético , Trabajo Sexual , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adulto , Estudios de Cohortes , Intervalos de Confianza , Susceptibilidad a Enfermedades/inmunología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Seronegatividad para VIH/inmunología , Seropositividad para VIH/genética , Seropositividad para VIH/inmunología , VIH-1 , Antígenos HLA/genética , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Humanos , Inmunidad Innata/inmunología , Kenia/epidemiología , Estudios Longitudinales , Factores de TiempoRESUMEN
HIV-specific cytotoxic T-lymphocytes (CTL) are believed to play a key part in the control of virus levels throughout HIV infection. An important goal of a potential prophylactic vaccine against HIV is therefore to elicit a strong CTL response which is broadly cross-reactive against a diverse range of HIV strains. We have detected HIV-specific CTL in two groups of highly-exposed but persistently seronegative female sex workers in Africa which show extensive cross-reactivity between different viral sequences. In a small group of women exposed to both HIV-1 and HIV-2 in Gambia, studied over 4 years, we have repeatedly detected HLA-B35-restricted CTL which exhibit cross-reactivity between the HIV-1 and HIV-2 sequences of the CTL epitopes. In women with particularly intense exposure to what are likely to be multiple clades of HIV-1 in Nairobi Kenya, we have detected CTL directed towards epitopes conserved between HIV-1 clades. In neither group is there any evidence that variation in CCR5 sequence or expression is responsible for their apparent resistance to HIV infection. However, in seropositive donors from Oxford infected with African strains of HIV-1, we have defined CTL responses which are specific for particular clades and have mapped some unique A clade CTL epitopes, together with others to highly-conserved regions of the virus. Further information about the extent of cross-reactive CTL immunity will be important for future vaccine design and evaluation.
Asunto(s)
Donantes de Sangre , VIH-1/inmunología , VIH-2/inmunología , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Reacciones Cruzadas , Mapeo Epitopo , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Femenino , Gambia , Proteína p24 del Núcleo del VIH/inmunología , Antígeno HLA-B35/inmunología , Humanos , Datos de Secuencia Molecular , Polimorfismo Genético , Receptores CCR5/genética , Trabajo Sexual , Linfocitos T Citotóxicos/virologíaRESUMEN
A small group of women (n = 80) within the Nairobi-based Pumwani Sex Workers Cohort demonstrates epidemiologic resistance to HIV-1 infection. Chemokine receptor polymorphisms and beta-chemokine overproduction have been among the mechanisms suggested to be responsible for resistance to HIV-1 infection. This study attempts to determine if any of those mechanisms are protecting the HIV-1-resistant women. Genetic analysis of CCR5 and CCR3 from the resistant women demonstrated no polymorphisms associated with resistance. Expression levels of CCR5 among the resistant women were shown to be equivalent to that found in low-risk seronegative (negative) controls, while CXCR4 expression was greater among some of the resistant women. In vitro infection experiments showed that phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from resistant women were as susceptible to infection to T cell- and macrophage-tropic North American and Kenyan HIV-1 isolates as were the PBMCs from negative controls. No significant difference in circulating plasma levels of MIP-1alpha and MIP-1beta were found between the resistant women and negative or HIV-1-infected controls. In vitro cultures of media and PHA-stimulated PBMCs indicated that the resistant women produced significantly less MIP-1alpha and MIP-1beta than did negative controls and no significant difference in RANTES levels were observed. In contrast to studies in Caucasian cohorts, these data indicate that CCR5 polymorphisms, altered CCR5 and CXCR4 expression levels, cellular resistance to in vitro HIV-1 infection, and increased levels of beta-chemokine production do not account for the resistance to HIV-1 infection observed among the women of the Pumwani Sex Workers Cohort.
Asunto(s)
Quimiocina CCL5/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Proteínas Inflamatorias de Macrófagos/inmunología , Membrana Celular/metabolismo , Quimiocina CCL3 , Quimiocina CCL4 , Femenino , Infecciones por VIH/epidemiología , Humanos , Inmunidad Innata , Kenia/epidemiología , Receptores CCR3 , Receptores CCR5/biosíntesis , Receptores CCR5/genética , Receptores CXCR4/biosíntesis , Receptores de Quimiocina/biosíntesis , Receptores de Quimiocina/genética , Trabajo Sexual , Células U937RESUMEN
Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.
Asunto(s)
Epítopos de Linfocito T/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Estudios de Cohortes , Secuencia Conservada , Epítopos de Linfocito T/química , Femenino , Productos del Gen gag/inmunología , Proteasa del VIH/inmunología , Transcriptasa Inversa del VIH/inmunología , Antígenos HLA-A/inmunología , Antígenos HLA-B/inmunología , Antígeno HLA-B18 , Humanos , Inmunidad Innata , Kenia , Péptidos , Análisis de Secuencia , Trabajo Sexual , Linfocitos T Citotóxicos/virologíaRESUMEN
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.