Hypertension in sub-Saharan Africa: cross-sectional surveys in four rural and urban communities.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of adult mortality in low-income countries but data on the prevalence of cardiovascular risk factors such as hypertension are scarce, especially in sub-Saharan Africa (SSA). This study aims to assess the prevalence of hypertension and determinants of blood pressure in four SSA populations in rural Nigeria and Kenya, and urban Namibia and Tanzania. METHODS AND FINDINGS: We performed four cross-sectional household surveys in Kwara State, Nigeria; Nandi district, Kenya; Dar es Salaam, Tanzania and Greater Windhoek, Namibia, between 2009-2011. Representative population-based samples were drawn in Nigeria and Namibia. The Kenya and Tanzania study populations consisted of specific target groups. Within a final sample size of 5,500 households, 9,857 non-pregnant adults were eligible for analysis on hypertension. Of those, 7,568 respondents ≥ 18 years were included. The primary outcome measure was the prevalence of hypertension in each of the populations under study. The age-standardized prevalence of hypertension was 19.3% (95%CI:17.3-21.3) in rural Nigeria, 21.4% (19.8-23.0) in rural Kenya, 23.7% (21.3-26.2) in urban Tanzania, and 38.0% (35.9-40.1) in urban Namibia. In individuals with hypertension, the proportion of grade 2 (≥ 160/100 mmHg) or grade 3 hypertension (≥ 180/110 mmHg) ranged from 29.2% (Namibia) to 43.3% (Nigeria). Control of hypertension ranged from 2.6% in Kenya to 17.8% in Namibia. Obesity prevalence (BMI ≥ 30) ranged from 6.1% (Nigeria) to 17.4% (Tanzania) and together with age and gender, BMI independently predicted blood pressure level in all study populations. Diabetes prevalence ranged from 2.1% (Namibia) to 3.7% (Tanzania). CONCLUSION: Hypertension was the most frequently observed risk factor for CVD in both urban and rural communities in SSA and will contribute to the growing burden of CVD in SSA. Low levels of control of hypertension are alarming. Strengthening of health care systems in SSA to contain the emerging epidemic of CVD is urgently needed.

Short communication: No detrimental immunological effects of mycophenolate mofetil and HAART in treatment-naive acute and chronic HIV-1-infected patients.

Mycophenolate mofetil has been proposed for HIV-1 therapy because of its guanine-depleting effect, which is expected to interfere with HIV-1 replication directly by hampering reverse transcription and indirectly via inhibition of CD4+ T cell proliferation. However, treatment with mycophenolate mofetil might also compromise lymphocyte reconstitution and HIV-specific immunity. Therefore we longitudinally studied the effects of mycophenolate mofetil in combination with HAART on T cell proliferation, lymphocyte reconstitution, and HIV-specific CD4+ and CD8+ T cell responses in six therapy-naive, acute or chronic HIV-1-infected patients, as compared to eight patients treated with HAART alone. T cell proliferation in whole blood cultures of patients treated with mycophenolate mofetil was inhibited. Strikingly, ex vivo Ki67 expression within T cells was not influenced by treatment with mycophenolate mofetil. In vitro studies showed that Ki67 expression occurs at an early step of the cell cycle and was not inhibited by guanine depletion. When treatment with mycophenolate mofetil was stopped a transient increase in apoptosis and Ki67-expressing T cells was detected. This observation together with near complete inhibition of T cell proliferation in whole blood cultures during treatment with mycophenolate mofetil indicated that T cell proliferation was inhibited in patients treated with mycophenolate mofetil. Still, there was no evidence for detrimental effects of treatment with mycophenolate mofetil in addition to HAART on CD4+ T cell reconstitution or HIV-specific immunity.

Lymphocyte numbers and function in relation to periodontitis and smoking.

BACKGROUND: T and B lymphocytes play important roles in periodontitis. Smoking is considered a risk factor for periodontitis and may exert its negative effects through leukocytes. Taking smoking into consideration, the aim of this study was to analyze numbers of circulating T (CD3+) cells and their CD4+ and CD8+ subpopulations, B (CD19+) cells, and T-cell proliferative capacity in periodontitis. METHODS: Lymphocyte immunophenotyping for T cells, their CD4+ and CD8+ subsets, and B cells was performed on peripheral blood from 76 periodontitis patients and 36 controls. Proliferative capacity of T cells was determined in whole-blood lymphocyte culture assays after mitogenic stimulation. RESULTS: Total T cells, CD4+ and CD8+ subpopulations, and responsiveness to specific T-cell stimuli did not differ between patients and controls; in addition, B cells were not significantly elevated in periodontitis patients. However, more periodontal breakdown in smoking patients was associated with higher numbers of CD3+ T cells, as well as with CD4+ and CD8+ T-cell subsets, and increased T-cell proliferation. Numbers of B cells were not affected by smoking. CONCLUSIONS: The increased numbers of T-cells and elevated T-cell responsiveness in patients who smoke may be one of several explanations why smoking is a risk factor for periodontitis. The mechanism of how T-cell function contributes to increase the severity of periodontal breakdown in smoking periodontitis patients needs to be investigated further.

Spontaneous outgrowth of EBV-transformed B-cells reflects EBV-specific immunity in vivo; a useful tool in the follow-up of EBV-driven immunoproliferative disorders in allograft recipients.

During immunosuppressive medication, Epstein-Barr virus (EBV) infection is associated with a risk of developing posttransplant lymphoproliferative disease (PTLD). The appropriateness of a spontaneous EBV B-cell transformation (SET) assay as a monitor of EBV-specific immunity was evaluated to investigate if it safely allows reducing immunosuppressive medication, thereby decreasing the risk of developing PTLD. PBMC were isolated longitudinally from 20 pediatric renal allograft recipients treated with prednisone and cyclosporine combined with either azathioprine or mycophenolate mofetil. Most significantly, EBV-peptide-specific CD8+ T cells were detectable in the blood of patients with negative SET assays, coinciding with significantly lower EBV loads, whereas these cells were less frequent in the blood of patients with positive SET assays. Reducing the levels of immunosuppression resulted in normalization of the SET assays. Therefore, the SET assay is a reflection of the interaction between viral replication, transformation of B cells, and EBV-specific immunity in vivo and hence a valuable screening test for EBV-driven lymphoproliferative phenomena in allograft recipients.

Persistent immune activation in HIV-1 infection is associated with progression to AIDS.

BACKGROUND: HIV-1 infection is characterized by chronic generalized CD8 and CD4 T cell hyperactivation, the biological effect of which is not understood. OBJECTIVE: To study the relation between chronic immune activation and CD4 T cell depletion in HIV-1 infection. DESIGN: Prospective cohort study among participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who have a known seroconversion date (n = 102). METHODS: CD4 and CD8 T cell activation marker expression was analysed by FACScan before and after seroconversion (1 and 5 years after seroconversion); T cell proliferation and T cell numbers were also measured. Cox proportional hazard analyses were used to study the predictive value of these parameters for progression to AIDS. RESULTS: Preseroconversion low CD4 T cell numbers or elevated levels of CD4 T cell activation were associated with increased risk for development of AIDS after HIV-1 seroconversion. Progression to AIDS was associated with loss of both CD4 and CD8 naive T cells. The predictive value of CD8 T cell activation was confirmed and, in addition, in the course of infection low CD4 T cell counts and increasing proportions of dividing CD4 T cells, dividing CD8 T cells or elevated CD4 T cell activation marker expression became independent predictors of progression to AIDS. CONCLUSIONS: Increased T cell activation has predictive value for HIV-1 disease progression even before seroconversion. These data support the hypothesis that persistent hyperactivation of the immune system may lead to erosion of the naive T cell pool and CD4 T cell depletion.

Depletion of naive CD4 T cells by CXCR4-using HIV-1 variants occurs mainly through increased T-cell death and activation.

OBJECTIVE: Using SCID-Hu mice models and in vitro culture systems, it has been shown that syncytium inducing/CXCR4 using (X4) HIV-1 variants affect thymic function through infection and killing of CXCR4 thymocytes. The effect of X4-emergence on naive, memory and effector T-cell subset kinetics in vivo is, however, not known. DESIGN: Prospective cohort study. METHODS: Analysis of changes in naive, memory and effector CD4 and CD8 T-cell numbers and cell division before and after the emergence of X4 variants. RESULTS: Significantly lower numbers of CD4 T cells in patients with X4 variants (n = 18) compared to patients with non-syncytium inducing/CCR5 using variants (n = 74) were due to increased loss of naive and CD27 memory CD4 T cells. In addition, emergence of X4 variants was associated with a small but significant decline in naive CD8 T-cell numbers and increased proportions of dividing CD4 and CD8 naive, memory and effector T cells. CONCLUSION: Loss of naive T cells may suggest thymic dysfunction, however, such an effect would explain only part of the accelerated naive CD4 T-cell decline because of the longevity of naive T cells. Our data suggest that the accelerated naive CD4 T-cell decline induced by X4 variants is caused mainly by increased death and recruitment to the memory compartment of these cells.

Frequencies of circulating cytolytic, CD45RA+CD27-, CD8+ T lymphocytes depend on infection with CMV.

Viral infections may cause serious disease unless the adaptive immune system is able to clear the viral agents through its effector arms. Recent identification and functional characterization of subpopulations of human CD8(+) T cells has set the stage to study the correlation between the appearance of particular subsets and common viral infections during childhood, i.e., EBV, CMV, varicella-zoster virus (VZV), and the attenuated measles-mumps-rubella (MMR) vaccine strains. In a cohort of 220 healthy children we analyzed lymphocytes and subpopulations of CD4(+) and CD8(+) T cells. The presence of the cytolytic CD45RA(+)CD27(-) subset of CD8(+) T cells correlated with prior CMV infection as defined by seroconversion (p < 0.0001). The number of this CD8(+) T cell subset remained stable during follow-up over 3 years in 40 children. The CD45RA(+)CD27(-) subset of CD8(+) T cells first appeared during acute CMV infection and subsequently stabilized at an individual set-point defined by age and immunocompetence. The functional importance of these cells in CMV surveillance was reflected by their increased numbers in immunosuppressed pediatric kidney transplant patients. Preferential expansion of CD8(+)CD45RA(+)CD27(-) cytolytic T cells seems unique for CMV.

Reconstitution of naive T cells during antiretroviral treatment of HIV-infected adults is dependent on age.

OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45RA and/or CD27 were considered memory type cells. RESULTS: The recovery rates of naive CD4 and CD8 T cells were similar, were negatively correlated with age and were decreasing 5% and 3.6% per year, respectively. In a multivariate regression analysis, only age was significantly correlated with the naive T cell recovery rates. The recovery rate of memory T cells showed no relation to age. The average regeneration rate of naive CD4 T cells during HAART, i.e., 0.34 x 10(6) cells/l per day, is not lower than regeneration rates in HIV-negative adults following cytotoxic chemotherapy or CD4 monoclonal antibody therapy. CONCLUSION: These observations suggest that the thymus contributes considerably to the regeneration of naive T cells in adults on HAART, and that the impact of HIV infection on naive T cell production is small, or rapidly reversible.

Seasonal influences on immunological parameters in HIV-infected homosexual men: searching for the immunomodulating effects of sunlight.

In view of the capacity of ultraviolet radiation (UVR) to induce suppression of various immunological parameters and to enhance the viral replication of HIV, we investigated whether seasonal influences on immunological parameters that are relevant for HIV infection could be identified. As the sunny season is associated with high levels of ambient UVR, a decline of immunological parameters and an increase of the HIV viral load during the summer months might ensue. We analysed the immunological data of the HIV-infected homosexual men who participated in the Amsterdam Cohort Study on HIV infection and AIDS (1984-1996; n = 556). The effect of season on the individual development of various immunological parameters in time was examined by means of a random effects model for repeated measurements. Lower levels in the mean number of CD4+ T cells and the mean CD4+/CD8+ ratio were found during summer and spring, respectively (P = 0.0001/0.0001). For the CD8+ T cells, high mean values were observed both in April and September (P = 0.0001). The highest T-cell reactivity values were found during the summer (P = 0.0001). No effect of season on the viral load was established. The seasonal effect on CD4+ T cells seemed to be more pronounced at a more advanced stage of the HIV infection. It is concluded that the lower CD4+ T-cell counts during summer support the notion that solar UVR may have a suppressive effect on the cellular immunity of HIV-infected persons. However, whether this observation can be attributed to the effect of ambient UVR solely is questionable, as the other immunological parameters follow different seasonal courses and other reports suggest that both internal and environmental factors influence immunological parameters.