Perceptions of the usefulness of external support to immunization coverage in Chad: an analysis of the GAVI-Alliance cash-based support

Introduction: Chad is one of the countries supported by the GAVI-Alliance that remains with unsatisfactory vaccination coverage. This paper tries to  understand the main barriers to better coverage. Methods: These barriers were categorised as up or downstream against the health system building blocks as proposed by WHO and compared with barriers and activities identified by the country in its health system's strengthening grant proposal as approved by the GAVI Alliance in 2007. Data were collected using a modified Delphi system and by analysis of grant and annual report documents. Results: Most of the activities anticipated under the GAVI health system's strengthening proposal are activities targeting downstream barriers (the neglect of upstream issues is of major importance in a decentralised state like Chad) and aligned with, not complementary to, immunization services strengthening activities. Further, both set of cash grants are blind to important recommendations such as the need to address barriers at the level of leadership and governance and at the level of the financing system and also about initiatives to promote community demand of vaccination services. Conclusion: In Chad slow vaccination progress is aggravated by several contextual barriers: the size of the country, the low population density, the nomadic nature of a significant part of its peoples, the recent civil war, associated with civil unrest and political instability and its geographical localization. In this situation it would be important to sustain downstream operations (the major focus of the ISS grant) while taking a long term view of the needs of the health system. The GAVI effectively supports downstream operations, but neglects the long term view.Key words: Africa, Chad, global health initiatives, immunization, vaccination coverag

Maternal Latent Mycobacterium tuberculosis Does Not Affect the Infant Immune Response Following BCG at Birth: An Observational Longitudinal Study in Uganda

Background: BCG has low efficacy in tropical countries. We hypothesized that maternal latent Mycobacterium tuberculosis (M.tb) infection (LTBI) results in fetal tolerance to mycobacterial antigens and impaired responses to BCG immunization. Methods: We enrolled 132 LTBI-positive and 150 LTBI-negative mothers and their babies in Entebbe, Uganda. Infants were BCG-immunized at birth. Cord blood and samples at weeks 1, 4, 6, 10, 14, 24, and 52 were analyzed for cytokine/chemokine responses to M.tb antigens by Luminex 17-plex assay in 6-day whole blood cultures and antibody responses by ELISA. Of the 17 Luminex analytes, seven (IL-2, IL-5, IL-10, IL-13, IL-17A, TNF, and IFN-γ) were included in the main analysis as they were considered most likely to represent T cell responses. Immune sensitization was defined as a detectable cord blood cytokine response to PPD for any of the seven cytokines. Patterns of cytokine and antibody responses were compared between infants of mothers with and without LTBI using linear mixed models adjusting for confounders. Results: Most infants (73%) were sensitized in utero to M.tb antigens, with no overall difference seen between infants born to mothers with or without LTBI. Patterns of post-BCG cytokine and antibody responses to mycobacterial antigens were similar between the two infant groups. Conclusions: Our data do not support the hypothesis that maternal LTBI results in an impaired response to BCG immunization, in Ugandan infants. BCG vaccination at or shortly after birth is likely to be beneficial to all infants, irrespective of maternal LTBI status.UK Medical Research Council; DELTAS Africa Initiative SSACAB; DELTAS Initiative MUIIplus; Commonwealth Scholarships Commission; MRC/UVRI and LSHTM Uganda Research Unit; EU Horizon 2020 programme; MRC London Intercollegiate Doctoral Training Partnership; MRC; UK Medical Research Council (MRC); UK Department for International Development (DFID)

Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology

Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology. © 2013 Mohan et al

COVID-19, systemic crisis, and possible implications for the wild meat trade in sub-Saharan Africa

Wild animals play an integral and complex role in the economies and ecologies of many countries across the globe, including those of West and Central Africa, the focus of this policy perspective. The trade in wild meat, and its role in diets, have been brought into focus as a consequence of discussions over the origins of COVID-19. As a result, there have been calls for the closure of China’s “wet markets”; greater scrutiny of the wildlife trade in general; and a spotlight has been placed on the potential risks posed by growing human populations and shrinking natural habitats for animal to human transmission of zoonotic diseases. However, to date there has been little attention given to what the consequences of the COVID-19 economic shock may be for the wildlife trade; the people who rely on it for their livelihoods; and the wildlife that is exploited. In this policy perspective, we argue that the links between the COVID-19 pandemic, rural livelihoods and wildlife are likely to be more complex, more nuanced, and more far-reaching, than is represented in the literature to date. We develop a causal model that tracks the likely implications for the wild meat trade of the systemic crisis triggered by COVID-19. We focus on the resulting economic shockwave, as manifested in the collapse in global demand for commodities such as oil, and international tourism services, and what this may mean for local African economies and livelihoods. We trace the shockwave through to the consequences for the use of, and demand for, wild meats as households respond to these changes. We suggest that understanding and predicting the complex dynamics of wild meat use requires increased collaboration between environmental and resource economics and the ecological and conservation sciences

Prevalence of Swine Gastrointestinal Parasites in Nyagatare District, Rwanda

While pig farming has been growing rapidly in Rwanda, its potential contribution to the prevalence of zoonotic infections is not well known. Pig production is usually affected by gastrointestinal parasites, some of which are zoonotic and can threaten human health. The knowledge about the status of such infections is essential for policy decisions and interventions. We aimed to investigate the prevalence of swine gastrointestinal parasites in Nyagatare district, Rwanda. A cross-sectional study involved collecting 104 faecal samples from apparently healthy pigs. The floatation technique was used to identify the parasites and frequency distribution analysis, and Pearson chi-square tests of association were conducted for this study data. Overall, the prevalence of swine gastrointestinal parasites was 84.6%, and the predominant species were Strongyle-type helminths representing 70.2%, followed by coccidia (55.8%), Strongyloides ransomi (39.4%), and Ascaris suum (10.6%). Of all parasitized pigs (n=88), 84.1% developed coinfections involving 2, 3, or 4 different parasite species. The results showed a statistically significant correlation between the location of pigs and parasitic infections and that some prevalent parasites are zoonotic. Interventions among pig farmers in Nyagatare should aim to improve awareness and to provide information on the negative impacts of swine gastrointestinal parasites on pig production and human health