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Background: There are significant limitations in Haiti for the diagnosis and management of sickle cell disease (SCD), including the non-availability of universal newborn screening (NBS) and transcranial Doppler (TCD) ultrasound screening, and the lack of diagnostic laboratory resources, oral penicillin and hydroxyurea (HU). Methods: Beginning in September 2019, CSHSCD (R01HL149121), a 5-year NIH-sponsored observational comparative study of children with SCD from Haitian ethnicity in Miami and in Haiti compared to children of African American ethnicity with SCD, was designed to increase access to care in Haiti. The study aims are 1) to compare the incidence of SCD among newborns from Haitian and African American ethnicity in Miami, 2) to establish NBS programs for hemoglobinopathies in Haiti, and 3) to compare cohorts of children in SCD at the study sites. The participating sites are the University of Miami (UM, Miami, Florida), Hôpital Saint Damien (HSD, Tabarre, Haiti), Hôpital de l'Université d'Etat d'Haïti (HUEH, Port-au-Prince, Haiti), Hôpital Universitaire Justinien (HUJ, Cap Haitien, Haiti), and Hôpital Sacré Coeur (HSC, Milot, Haiti). HUJ and HSC use two NBS screening methods (isoelectric focusing and Sickle SCAN rapid test) and HSD and HUEH use isoelectric focusing only. CSHSCD supplies penicillin and HU and trains TCD examiners to implement stroke risk screening. Data are collected in REDCap. Results: During the first 2 years and despite the COVID-19 pandemic, we established NBS sites with a cohesive network of physicians and nurses trained in the care of children with SCD in Haiti. This capacity building will support sustainability of the program. We successfully identified at least 15 new cases of SCD via newborn screening, trained six TCD examiners, and enrolled 130 children with SCD in follow up, providing them with penicillin prophylaxis and hydroxyurea for severe cases according to local protocols . Implementation activities which have helped are close communications between the investigators, monthly Zoom meetings to coordinate efforts with enrollment updates every month, the availability of rapid tests (Sickle SCAN and Gazelle miniature cellulose acetate electrophoresis) for the diagnosis of SCD, especially when there is no laboratory equipment on site. Implementation challenges we have faced are mostly two. The first is the timely completion of DUNS and SAM registration for the two public hospitals, with one site achieving this after 9 months and the other site taking 18 months to complete. The reasons for the delay are the inability for the UM site to direct these efforts, following strict rules, and the Haitian hospital officers' lack of familiarity with website requirements. We were able to achieve these registrations with the assistance of one Haitian study staff who is very acquainted with internet navigation and became familiarized with requirements. Outsourcing materials to Haiti is another major challenge, with either gaps in the delivery of supplies because of multiple steps involved in ordering and shipping or with delays in releasing equipment once it is at the Port-au-Prince customs, resulting in gaps in NBS in one of the sites for 8 weeks. We have minimized these issues by opening a one-year ticket to order materials from the different companies involved. Also, Haiti's lack of infrastructure, available materials and medications, and political instability limit health care delivery. Conclusion: Since its inception, we have achieved major milestones, including capacity building and implementation of NBS, TCD training, and enrollment of children with SCD into the prospective cohorts despite the current COVID-19 pandemic. Material outsourcing challenges have been the major implementation problem we have faced due to systemic factors. We anticipate that these factors will be corrected or minimized as we have learned how to handle them. These problems were expected as part of conducting an international study in a low-resource setting. Acknowledgment: We acknowledge NHLBI for supporting this work. Disclosures Alvarez: Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; GBT: Membership on an entity's Board of Directors or advisory committees. Romano: Genentech: Research Funding; Vycor: Current holder of individual stocks in a privately-held company; NovaVision: Consultancy.

The injection of extracts of leukemic and Hodgkin’s disease tissues of man elicit an antibody reaction in both man and rabbit. This response is similar to that elicited by leukemic mouse tissues when injected into rabbits. The antibody reaction may be demonstrated by the technics of passive cutaneous anaphylaxis, immunodiffusion, microprecipitin and immunofluorescence. Tissue extracts from non-leukemic individuals do not elicit a similar response. Rabbits immune-tolerant to normal human tissues produce antibodies specific to leukemic human antigens. Antibodies develop in those individuals who are exposed for a long time to either human or mouse leukemia. These immunologic studies demonstrate specific antigenic differences between normal and leukemic tissue extracts. It is postulated that the difference between normal and leukemic extracts is the consequence of the presence of viruses or the alterations caused by them.

The present studies are an extension of earlier reports on the antibody response of mice to a leukemogenic virus (S-63). These investigations were designed to show whether a correlation exists between in vivo and in vitro determinations, and whether protective antibodies against the virus could be produced in immune-tolerant animals. Viral neutralization and protection studies in mice were compared with passive cutaneous anaphylaxis (PCA), immunodiffusion, microprecipitin, and immunofluorescent tests using similar antigens and antibodies. As shown in tables 1, 2 and 3, antibody could be demonstrated by both in vivo and in vitro methods, and these studies showed (table 2) that the antibody was protective. The S-63 leukemia virus was isolated in 1963 from a mouse ascites cell leukemia line. That cell line had been carried in the laboratory for over 3 years. The virus has been carried in ICR mice since its isolation. Immunologic studies were carried out to determine the relation between the virus and the originating ascites cell. Studies of antibodies produced in normal rabbits against the S-63 virus were unsatisfactory for purposes of these experiments because of cross reaction with normal mouse tissue. Immune-tolerant animals have yielded valuable information: Antibodies produced in immune-tolerant rabbits injected with the S-63 virus do not cross react against intact ascites cells from which the virus was originally isolated. Conversely, antibodies similarly produced against the ascites cells do not react against the virus antigen. Antibodies produced in immune-tolerant rabbits against ascites cells protect mice against ascites cell-induced leukemia, but not against the disease induced by S-63 virus. Mice challenged with ascites cells and treated with antiascites cell gamma globulin are protected against the disease. The best therapeutic advantage is obtained when treatment is started either at the time of cell inoculation or in the early stages of the disease. Antibodies which protect newborn animals from infection develop in adult ICR mice recovering from S-63 virus leukemia. These antibodies produced by convalescent mice are similar, from the standpoint of protection, to those produced in immune-tolerant rabbits.