IntroductionTracking progress towards Sustainable Development Goal (SDG) 3·6 of reducing traffic deaths and serious injuries poses a measurement challenge in most low-income and middle-income countries (LMICs) due to large discrepancies between reported official statistics and estimates from global health measurement studies. We assess the extent to which national population censuses and health surveys can fill the information gaps.MethodsWe reviewed questionnaires for nationally representative surveys and censuses conducted since 2000 in LMICs. We identified sources that provide estimates of household ownership of vehicles, incidence of traffic deaths and non-fatal injuries, and prevalence of disability.ResultsWe identified 802 data sources from 132 LMICs. Sub-Saharan African countries accounted for 43% of all measurements. The number of measurements since 2000 was high, with 97% of the current global LMIC population having at least one measurement for vehicle ownership, 77% for deaths, 90% for non-fatal injuries and 50% for disability due to traffic injuries. Recent data (since 2010) on traffic injuries were available from far fewer countries (deaths: 21 countries; non-fatal injuries: 62 and disability: 12). However, there were many more countries with recent data on less-specific questions about unintentional or all injuries (deaths: 41 countries, non-fatal: 87, disability: 32).ConclusionTraffic injuries are substantially underreported in official statistics of most LMICs. National surveys and censuses provide a viable alternative information source, but despite a large increase in their use to monitor SDGs, traffic injury measurements have not increased. We show that relatively small modifications and additions to questions in forthcoming surveys can provide countries with a way to benchmark their existing surveillance systems and result in a substantial increase in data for tracking road traffic injuries globally.
Although most current treatments for autoimmunity involve broad immunosuppression, recent efforts have aimed to suppress T cells in an antigen-specific manner to minimize risk of infection. One such effort is through targeting antigen to the apoptotic pathway to increase presentation of the antigen of interest in a tolerogenic context. Erythrocytes present a rational candidate to target because of their high rate of eryptosis, which facilitates continual uptake by antigen-presenting cells in the spleen. Here, we develop an approach that binds antigens to erythrocytes to induce sustained T cell dysfunction. Transcriptomic and phenotypic analyses revealed signatures of self-tolerance and exhaustion, including up-regulation of PD-1, CTLA4, Lag3, and TOX. Antigen-specific T cells were incapable of responding to an adjuvanted antigenic challenge even months after antigen clearance. With this strategy, we prevented pathology in a mouse experimental autoimmune encephalomyelitis model. CD8+ T cell education occurred in the spleen and was dependent on cross-presenting Batf3+ dendritic cells. These results demonstrate that antigens associated with eryptotic erythrocytes induce lasting T cell dysfunction that could be protective in deactivating pathogenic T cells.
IntroductionTimely, accurate and detailed information about traffic injuries are essential for managing national road safety programmes. However, there is considerable under-reporting in official statistics of many low and middle-income countries (LMICs) and large discrepancies between estimates from the Global Burden of Disease (GBD) study and WHO’s Global Health Estimates (GHE). We compared all sources of epidemiological information on traffic injuries in Cambodia to guide efforts to improve traffic injury statistics.MethodsWe estimated the incidence of traffic deaths and injuries and household ownership of motor vehicles in Cambodia from nationally representative surveys and censuses. We compared findings with GDB and GHE estimates.ResultsWe identified seven sources for estimating traffic deaths and three for non-fatal injuries that are not included as data sources in GBD and GHE models. These sources and models suggest a fairly consistent estimate of approximately 3100 deaths annually, about 50% higher than official statistics, likely because most hospital deaths are not recorded. Surveys strongly suggest that the vehicle fleet is dominated by motorcycles, which is not consistent with GBD estimates that suggest similar numbers of motorcyclist and vehicle occupant deaths. Estimates of non-fatal injuries from health surveys were about 7.5 times official statistics and 1.5 times GBD estimates.ConclusionIncluding local epidemiological data sources from LMICs can help reduce uncertainty in estimates from global statistical models and build trust in estimates among local stakeholders. Such analysis should be used as a benchmark to assess and strengthen the completeness of reporting of the national surveillance system.
IntroductionThere is considerable uncertainty in estimates of traffic deaths in many sub-Saharan African countries, with the Global Burden of Disease (GBD) and the Global Status Report on Road Safety (GSRRS) reporting widely differing estimates. As a case study, we reviewed and compared estimates for Tanzania.MethodsWe estimated the incidence of traffic deaths and vehicle ownership in Tanzania from nationally representative surveys. We compared findings with GBD and GSRRS estimates.ResultsTraffic death estimates based on the 2012 census (9382 deaths; 95% CI: 7565 to 11 199) and the 2011–2014 Sample Vital Registration with Verbal Autopsy (8778; 95% CI: 7631 to 9925) were consistent with each other and were about halfway between GBD (5 608; 95% UI: 4506 to 7014) and WHO (16 252; 95% CI: 13 130 to 19 374) estimates and more than twice official statistics (3885 deaths in 2013). Surveys and vehicle registrations data show that motorcycles have increased rapidly since 2007 and now comprise 66% of vehicles. However, these trends are not reflected in GBD estimates of motorcycles in the country, likely resulting in an underestimation of motorcyclist deaths.ConclusionReducing discrepancies between GBD and GSRRS estimates and demonstrating consistency with local epidemiological data will increase the legitimacy of such estimates among national stakeholders. GBD, which is the only project that models the road-user distribution of traffic deaths in all countries, likely severely underestimates motorcycle deaths in countries where there has been a recent increase in motorcycles. Addressing police under-reporting and strengthening surveillance capacity in Tanzania will allow a better understanding of the road safety problem and better targeting of interventions.
BackgroundThere are large discrepancies between official statistics of traffic injuries in African countries and estimates from the Global Burden of Disease (GBD) study and WHO’s Global Status Reports on Road Safety (GSRRS). We sought to assess the magnitude of the discrepancy in Ethiopia, its implications and how it can be addressed.MethodsWe systematically searched for nationally representative epidemiological data sources for road traffic injuries and vehicle ownership in Ethiopia and compared estimates with those from GBD and GSRRS.FindingsGBD and GSRRS estimates vary substantially across revisions and across projects. GSRRS-2018 estimates of deaths (27 326 in 2016) are more than three times GBD-2019 estimates (8718), and these estimates have non-overlapping uncertainty ranges. GSRRS estimates align well with the 2016 Demographic and Health Survey (DHS-2016; 27 838 deaths, 95th CI: 15 938 to 39 738). Official statistics are much lower (5118 deaths in 2018) than all estimates. GBD-2019 estimates of serious non-fatal injuries are consistent with DHS-2016 estimates (106 050 injuries, 95th CI: 81 728 to 130 372) and older estimates from the 2003 World Health Survey. Data from five surveys confirm that vehicle ownership levels in Ethiopia are much lower than in other countries in the region.InterpretationInclusion of data from national health surveys in GBD and GSRRS can help reduce discrepancies in estimates of deaths and support their use in highlighting under-reporting in official statistics and advocating for better prioritisation of road safety in the national policy agenda. GBD methods for estimating serious non-fatal injuries should be strengthened to allow monitoring progress towards Sustainable Development Goal target 3.6.
The current standard of care for autoimmune disease is administration of immunosuppressive agents that require a lifetime of treatment and leave patients susceptible to opportunistic infections. Thus, there is a great need for therapies that induce lasting and antigen-specific tolerance, which would require fewer treatments and allow the immune system to fully respond to pathogens. A promising target for the induction of antigen-specific tolerance is the apoptotic pathway. Antigen-presenting cells create a tolerogenic milieu upon recognition of apoptotic debris, and antigen presentation by APCs to T cells in the absence of inflammatory cues typically leads to anergy and deletion. A large source of endogenous apoptotic cells is erythrocytes, or red blood cells. The purpose of this study is to discover antibody fragments (Fabs) that bind erythrocytes, and use these Fabs to deliver antigen to erythrocytes for processing via the apoptotic pathway and presentation to T cells for tolerance. Phage display on mouse erythrocytes yielded high affinity Fabs that lacked binding to peripheral blood mononuclear cells and induced no hematological changes. Erythrocyte-binding Fabs were recombinantly expressed with the model antigen ovalbumin and administered to mice. Targeting ovalbumin to erythrocytes led to robust abortive proliferation of antigen-specific T cells. Remaining cells appeared phenotypically exhausted, and had reduced capacity to produce inflammatory cytokines upon restimulation. Antigen presentation of erythrocyte-targeted antigen occurred in the spleen, because T cell exhaustion was completely reversed in splenectomized mice. Thus, targeting erythrocytes may induce lasting antigen-specific tolerance.
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