Although dogma predicts that under normal circumstances, potentially offensive autoreactive cells are silenced by mechanisms of immune tolerance, islet antigen–reactive B lymphocytes are known to play a crucial role in the development of autoimmunity in type 1 diabetes (T1D). Thus, participation of these cells in T1D may reflect escape from silencing mechanisms. Consistent with this concept, we found that in healthy subjects, high-affinity insulin-binding B cells occur exclusively in the anergic naive IgD+, IgM− B-cell (BND) compartment. Antigen receptors expressed by these cells are polyreactive and have N-region additions, Vh usage, and charged complementarity-determining region 3 consistent with autoreactivity. Consistent with a potential early role in autoimmunity, these high-affinity insulin-binding B cells are absent from the anergic compartment of some first-degree relatives and all prediabetic and new-onset (<1 year) T1D patients tested, but return to normal levels in individuals diabetic for >1 year. Interestingly, these changes were correlated by transient loss of the entire BND compartment. These findings suggest that environmental events such as infection or injury may, by disrupting B-cell anergy, dispose individuals toward autoimmunity, the precise nature of which is specified by genetic risk factors, such as HLA alleles.

Background: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness.

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In late September 2020, the incidence of confirmed COVID-19* in North Dakota began increasing rapidly, from approximately 300 new cases per day to approximately 2,260 cases on November 13, 2020 (1). On October 20, the North Dakota Department of Health reported that contact tracing notification efforts were delayed. Because of the delay, COVID-19 patients were asked to notify their own contacts about potential exposure and encourage them to seek testing for SARS-CoV-2, the virus that causes COVID-19 (2). The Spirit Lake sovereign nation in east central North Dakota is home to approximately 7,500 members of the Spirit Lake Tribe. In response to increasing incidence of COVID-19 on the Spirit Lake Reservation, CDC assisted the Spirit Lake Tribe in building a tribally managed program for comprehensive COVID-19 case investigations, case notification, contact tracing, contact testing, and contact management to ensure timely implementation of these critical epidemic control measures.Through the Spirit Lake Tribe case investigation and contact tracing program, the tribe's COVID-19 Incident Command System staff members conducted case investigations and contact tracing, provided COVID-19 education, followed up with patients regularly by telephone, and monitored daily symptoms of close contacts. Members of the Spirit Lake community served as contact tracers. Symptom monitoring was facilitated through CDC's Text Illness Monitoring system (version TIM 2 ), using a free, two-way text-messaging platform to query enrolled contacts about daily COVID-19 symptoms. The system also alerted Spirit Lake Tribal Health authorities when participants reported symptoms or did not to respond (3). This report describes case investigation and contact tracing for the Spirit Lake Tribe during September 29, 2020 (when the case and contact tracing launched) through November 20, 2020 (when the CDC field response ended) and lessons learned from program implementation. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. †

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