Community case management of pneumonia: at a tipping point?

Pneumonia is the leading cause of child mortality globally. Community case management (CCM) of pneumonia by community health workers is a feasible, effective strategy to complement facility-based management for areas that lack access to facilities. We surveyed experts in the 57 African and Asian countries with the highest levels and rates of childhood mortality to assess current policies, implementation and plans regarding CCM of pneumonia. About one-third (20/54) of countries reported policies supporting CCM for pneumonia, and another third (18/54) reported no policy against the strategy. Half (27/54) the countries reported some implementation of CCM for pneumonia, but often on a small scale. A few countries sustain a large-scale programme. Programmes, community health workers and policy parameters varied greatly among implementing countries. About half (12/26)of non-implementing countries are planning to move ahead with the strategy. Momentum is gathering for CCM for pneumonia as a strategy to address the pneumonia treatment gap and help achieve Millennium Development Goal 4. Challenges remain to: (1) introduce this strategy into policy and implement it in high pneumonia burden countries; (2) increase coverage of this strategy in countries currently implementing it; and (3) better define and monitor implementation at the country level

Community case management of pneumonia: at a tipping point?

Pneumonia is the leading cause of child mortality globally. Community case management (CCM) of pneumonia by community health workers is a feasible, effective strategy to complement facility-based management for areas that lack access to facilities. We surveyed experts in the 57 African and Asian countries with the highest levels and rates of childhood mortality to assess current policies, implementation and plans regarding CCM of pneumonia. About one-third (20/54) of countries reported policies supporting CCM for pneumonia, and another third (18/54) reported no policy against the strategy. Half (27/54) the countries reported some implementation of CCM for pneumonia, but often on a small scale. A few countries sustain a large-scale programme. Programmes, community health workers and policy parameters varied greatly among implementing countries. About half (12/26)of non-implementing countries are planning to move ahead with the strategy. Momentum is gathering for CCM for pneumonia as a strategy to address the pneumonia treatment gap and help achieve Millennium Development Goal 4. Challenges remain to: (1) introduce this strategy into policy and implement it in high pneumonia burden countries; (2) increase coverage of this strategy in countries currently implementing it; and (3) better define and monitor implementation at the country level

Improving CLL Vγ9Vδ2-T-cell fitness for cellular therapy by ex vivo activation and ibrutinib

The efficacy of autologous (αβ) T-cell-based treatment strategies in chronic lymphocytic leukemia (CLL) has been modest. The Vγ9Vδ2-T cell subset consists of cytotoxic T lymphocytes with potent antilymphoma activity via a major histocompatibility complex-independent mechanism. We studied whether Vγ9Vδ2-T cells can be exploited as autologous effector lymphocytes in CLL. Healthy control Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells. However, CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and degranulation, despite an increased frequency of the effector-type subset. Consequently, cytotoxicity against malignant B cells was hampered. A comparable dysfunctional phenotype was observed in healthy Vγ9Vδ2-T cells after coculture with CLL cells, indicating a leukemia-induced mechanism. Gene-expression profiling implicated alterations in synapse formation as a conceivable contributor to compromised Vγ9Vδ2-T-cell function in CLL patients. Dysfunction of Vγ9Vδ2-T cells was fully reversible upon activation with autologous monocyte-derived dendritic cells (moDCs). moDC activation resulted in efficient expansion and predominantly yielded Vγ9Vδ2-T cells with a memory phenotype. Furthermore, ibrutinib treatment promoted an antitumor T helper 1 (TH1) phenotype in Vγ9Vδ2-T cells, and we demonstrated binding of ibrutinib to IL-2-inducible kinase (ITK) in Vγ9Vδ2-T cells. Taken together, CLL-mediated dysfunction of autologous Vγ9Vδ2-T cells is fully reversible, resulting in potent cytotoxicity toward CLL cells. Our data support the potential use of Vγ9Vδ2-T cells as effector T cells in CLL immunotherapy and favor further exploration of combining Vγ9Vδ2-T-cell-based therapy with ibrutinib