Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo

Activation of Th1 lymphocytes, IFN-gamma production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL-4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)-3] and Th2 (IgE, solubleCD30, and CCL22/macrophage-derived chemokine) activity were measured in 414 HIV-negative tuberculosis patients from The Gambia and Guinée and in 414 healthy household and community controls. Measurements were repeated during treatment to assess the effect of therapy on Th1/Th2 ratio. At diagnosis, sLAG-3 levels were lower in patients than in community controls (p<0.0001), but were higher in household controls exposed to contact with patients than in community controls (p<0.0001). In comparison with community controls, patients had consistently higher levels of IgE, sCD30, and CCL22 (p<0.0001), whereas household controls had lower levels of indicators of Th2 activity (p<0.0001). After treatment, cured patients had higher levels of Th1 (p<0.0001) and lower levels of Th2 (p<0.0001) activity than patients who were not successfully treated or interrupted therapy. In Africa, tuberculosis is associated with low Th1 and high Th2 activity in vivo, whereas close exposure to tuberculosis is associated with a high Th1/Th2 ratio. Patients with favorable outcome after treatment exhibit a higher Th1/Th2 ratio compared to patients with poor clinical outcome.     

Point Seroprevalence Survey of Ehrlichia ruminantium Infection in Small Ruminants in The Gambia

Using the MAP1-B enzyme-linked immunosorbent assay, we tested 1,318 serum samples collected from sheep and goats at 28 sites in the five divisions of The Gambia to determine the Ehrlichia ruminantium seroprevalence rates and to assess the risk for heartwater. About half (51.6%) of 639 sheep were positive, with seroprevalence rates per site varying between 6.9% and 100%. The highest seroprevalence was detected in the western part of the country (88.1% in the Western Division and 62.1% in the Lower River Division). Sheep in the two easterly divisions (Central River and Upper River divisions) showed the lowest seroprevalence of 29.3% and 32.4%, respectively, while those in the North Bank Division showed an intermediate prevalence of 40.6%. In goats, less than one-third (30.3%) of 679 animals tested were positive. The highest seroprevalence was detected in goats in the North Bank Division (59%) and Western Division (44.1%). Goats in the Lower River Division showed an intermediate level of 21.9%, whereas the lowest rates were found in the eastern part of the country (4.8% in the Central River Division and 2.3% in the Upper River Division). At nearly all sites, seroprevalence rates were higher in sheep than in goats. The results show a gradient of increasing heartwater risk for susceptible small ruminants from the east to the west of The Gambia. These findings need to be taken into consideration when future livestock-upgrading programs are implemented.     

Human CD8(+) T cells specific for Mycobacterium tuberculosis secreted antigens in tuberculosis patients and healthy BCG-vaccinated controls in The Gambia

Intracellular flow cytometry analysis of perforin production by CD8(+) T cells showed levels were greatly reduced in tuberculosis (TB) patients compared to healthy controls. Reduced cytotoxic-T-lymphocyte activity was also obtained with CD8(+) T cells from TB patients compared to healthy controls in The Gambia. A change in antigen recognition was noted between the two groups of donors: in addition to recognition of Ag85A and Ag85B, as seen in healthy donors, a prominent ESAT-6 response was found in TB patients.     

Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study

Vitamin D receptor (VDR) gene polymorphisms have been implicated in susceptibility to tuberculosis (TB), but reports have been inconsistent. We genotyped the VDR single-nucleotide polymorphisms (SNPs) FokI, BsmI, ApaI, and TaqI in 1139 case patients and control subjects and 382 families from The Gambia, Guinea, and Guinea-Bissau. The transmission-disequilibrium test on family data showed a significant global association of TB with SNP combinations FokI-BsmI-ApaI-TaqI and FokI-ApaI that were driven by the increased transmission to affected offspring of the FokI F and ApaI A alleles in combination. The ApaI A allele was also transmitted to affected offspring significantly more often than expected. Case-control analysis showed no statistically significant association between TB and VDR variants. BsmI, ApaI, and TaqI showed strong linkage disequilibrium. The significance of the family-based associations found between TB and FokI-BsmI-ApaI-TaqI and the FA haplotype supports a role for VDR haplotypes, rather than individual genotypes, in susceptibility to TB.     

Leapfrog diagnostics: Demonstration of a broad spectrum pathogen identification platform in a resource-limited setting

Background

Purpose of the study was to test a theoretical model to assess and develop policies for the promotion of physical activity among older people as part of an international intervention study.

Methods

248 semi-standardized interviews with policy-makers were conducted in 15 European nations. The questionnaire assessed policy-makers' perceptions of organizational goals, resources, obligations, as well as organizational, political and public opportunities in the area of physical activity promotion among older people. In order to develop policies, workshops with policy-makers were conducted. Workshop outputs and outcomes were assessed for four nations nine months after the workshops.

Results

Policy assessment: Results of the policy assessment were diverse across nations and policy sectors. For example, organizational goals regarding actions for physical activity promotion were perceived as being most favorably by the sports sector. Organizational obligations for the development of such policies were perceived as being most favorably by the health sector. Policy development: The workshops resulted in different outputs: a national intersectoral action plan (United Kingdom), a national alliance (Sweden), an integrated policy (the Netherlands), and a continuing dialogue (Germany).

Conclusions

Theory-driven policy assessment and policy-maker workshops might be an important means of scientific engagement in policy development for health promotion.