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Background: In the Investigation of the Management of Pericarditis (IMPI) randomized control, 2x2 factorial trial, Mycobacterium indicus pranii (MIP) immunotherapy, adjunctive corticosteroids or MIP combined with corticosteroids was compared to standard tuberculosis (TB) therapy for tuberculous pericarditis (TBP). While MIP and/or the combination of MIP and corticosteroids had no impact on all-cause mortality or pericarditis related outcomes, corticosteroids reduced the incidence of constrictive pericarditis at 12 months. Data suggests that both adjunctive therapies modulate the immune and inflammatory responses to pulmonary TB. Whether they affect systemic antigen-specific T cell responses, key immune mediators of Mycobacterium tuberculosis control, in patients with TBP is unknown. Methods: Participants with definite or probable TBP were randomly assigned to receive five injections of MIP or placebo at 2-week intervals and either 6 weeks of oral prednisolone or placebo. Frequencies of CD4 and CD8 T cells expressing IFN-γ, IL-2 or TNF in response to MIP or purified protein derivative stimulation were measured by intracellular cytokine staining and flow cytometry up to 24 weeks post treatment. Results: Immunotherapy with MIP did not significantly modulate frequencies of Th1 CD4 and CD8 T cells compared to placebo. Adjunctive prednisolone also did not change mycobacteria-specific CD4 or CD8 T cell responses. By contrast, combinatorial therapy with MIP and prednisolone was associated with a modest increase in frequencies of multifunctional and single cytokine-expressing CD4 T cell responses at 6 and 24 weeks post treatment. Conclusions: Consistent with the lack of a significant clinical effect in the IMPI trial, MIP immunotherapy did not significantly modulate mycobacteria-specific T cell responses. Despite the positive effect of prednisolone on hospitalizations and constrictive pericarditis in the IMPI trial, prednisolone did not significantly reduce pro-inflammatory T cell responses in this sub-study. The modest improvement of mycobacteria-specific T cell upon combinatorial therapy with MIP and prednisolone requires further investigation.

Background: There is exponential growth in the interest and implementation of genomics research in Africa. This growth has been facilitated by the Human Hereditary and Health in Africa (H3Africa) initiative, which aims to promote a contemporary research approach to the study of genomics and environmental determinants of common diseases in African populations. Objective: The purpose of this article is to describe important challenges affecting genomics research implementation in Africa. Methods: The observations, challenges and recommendations presented in this article were obtained through discussions by African scientists at teleconferences and face-to-face meetings, seminars at consortium conferences and in-depth individual discussions. Results: Challenges affecting genomics research implementation in Africa, which are related to limited resources include ill-equipped facilities, poor accessibility to research centers, lack of expertise and an enabling environment for research activities in local hospitals. Challenges related to the research study include delayed funding, extensive procedures and interventions requiring multiple visits, delays setting up research teams and insufficient staff training, language barriers and an underappreciation of cultural norms. While many African countries are struggling to initiate genomics projects, others have set up genomics research facilities that meet international standards. Conclusions: The lessons learned in implementing successful genomics projects in Africa are recommended as strategies to overcome these challenges. These recommendations may guide the development and application of new research programs in low-resource settings.

Bioluminescent bays and lagoons are unique natural environments and popular tourist attractions. However, the bioluminescence in many of these water bodies has declined, principally due to anthropogenic activities. In the Caribbean, the bioluminescence in these bays and lagoons is mostly produced by the dinoflagellate Pyrodinium bahamense var. bahamense. Laguna Grande is one of the three year-round bioluminescent water bodies in Puerto Rico that are known to remain but P. bahamense var. bahamense density fluctuations have not been studied. In this study we describe water quality parameters and density fluctuations of the most common dinoflagellates in Laguna Grande, P. bahamense var. bahamense and Ceratium furca, over a three-year period. For this, three sampling stations were established in Laguna Grande from which water samples were collected in triplicate and analyzed for temperature, phosphates, nitrates, salinity, water transparency, fluorescence, and dinoflagellate densities, at the water surface and at 2m depth, from May 2003 to May 2006. The results showed a density fluctuation pattern for P. bahamense var. bahamense, where higher densities were observed mainly from April to September, and lower densities from October to February. Density fluctuations of C. furca were more erratic and a repetitive pattern was not observed. Densities of P. bahamense var. bahamense ranged from 0.48 to 90 978 cells/L and densities of C. furca ranged from 0 to 11 200 cells/L. The mean population density throughout the sampling period was significantly higher in P. bahamense var. bahamense (mean=18 958.5 cells/L) than in C. furca (mean=2 601.9 cells/L). Population densities of P. bahamense var. bahamense were negatively correlated with C. furca densities during the first year of sampling; however, they were positively correlated during the third year. Non-significant differences between surface and 2m depth samples were observed for temperature, phosphates, nitrates, salinity, fluorescence, and densities of P. bahamense var. bahamense and C. furca, suggesting a vertically mixed water column. Water transparency was positively correlated with salinity and negatively correlated with fluorescence. Fluorescence was negatively correlated with salinity. The mean population densities of P. bahamense var. bahamense and C. furca observed in this study were within the range of previous reports in other bioluminescent water bodies in Puerto Rico and Florida, USA. In order to conserve the continuous P. bahamense var. bahamense populations in Laguna Grande, as well as its bioluminescence, it is recommended to maintain the existing water flow levels in the 1.5km long inlet/outlet channel; to maintain unpolluted water quality parameters within the bay, the hydrographical basin and adjacent waters, and to preserve mangrove communities within the basin and adjacent areas. Results of this study may help to develop management plans aiming to conserve P. bahamense, its bioluminescence and the lagoon attraction.