Ebola Virus IgG Seroprevalence in Southern Mali

Mali had 2 reported introductions of Ebola virus (EBOV) during the 2013–2016 West Africa epidemic. Previously, no evidence for EBOV circulation was reported in Mali. We performed an EBOV serosurvey study in southern Mali. We found low seroprevalence in the population, indicating local exposure to EBOV or closely related ebola viruses.     

Acquired hypoprothrombinemia due to non-neutralizing antibodies to prothrombin: mechanism and management

A patient developed bleeding due to an acute acquired specific prothrombin deficiency. Unlike previously described patients, this patient had no evidence of an associated lupus anticoagulant. Prothrombin activity and antigen were decreased concordantly and the patient's plasma did not neutralize the activity of added prothrombin or interfere with its measurement by electroimmunoassay. Nevertheless, immunoelectrophoresis and experiments using 125I-prothrombin revealed a prothrombin-binding antibody. The residual prothrombin in the patient's plasma was in the form of a prothrombin-antibody complex. Administration of adrenal corticosteroids was associated with a rise in prothrombin activity and cessation of bleeding, but circulating prothrombin was still bound to the antibody. This suggests that non- neutralizing antibodies to prothrombin cause plasma prothrombin deficiency because of a rapid clearance of prothrombin-antibody complexes, which is slowed by adrenal corticosteroids. The antibody had a relatively low affinity for prothrombin (Kd 5 to 8 X 10(-7)) and was transient. It is possible, therefore, that the antibody arose not to prothrombin itself, but to an antigen sharing an epitope with prothrombin.     

Identification of the amino acid mutations associated with human erythrocyte spectrin alpha II domain polymorphisms

Four distinct spectrin alpha II domain polymorphisms are known to occur in several nonwhite populations. Type 1 is essentially the only form found in whites and is also the most common form in nonwhites. In contrast to most other spectrin mutations that are single-base substitutions, two of the alpha II domain polymorphisms, types 2 and 3, are particularly unusual because they appear to involve 4-Kd insertions relative to type 1. We have identified the mutations responsible for these polymorphisms using biochemical approaches and a computer database of spectrin-domain peptides separated by two-dimensional gels. The type 3 mutation is characterized by an apparent 4-Kd increase in alpha II domain peptides with no change in pI. This apparent molecular weight increase is a sodium dodecyl sulfate (SDS) gel artifact resulting from an Arg-->His mutation at residue 22 of the domain. The type 4 polymorphism shows a basic charge shift with no apparent change in molecular weight on gels. This charge shift results from a mutation of Thr-->Arg at position 174 of the domain. This mutation appears to be linked to a "silent" mutation at position 130 from an Ile-->Val. Support for possible linkage was obtained from analysis of three unrelated donors with the type 2 polymorphism. The type 2 polymorphism shows both the charge shift characteristic of the type 4 mutation and the apparent size shift that defines the type 3 polymorphism. Analysis of type 2 peptides confirmed that the two mutations described above for type 4 as well as the mutation at residue 22 observed in type 3 occur simultaneously in type 2. The observation that the type 2 polymorphism is a composite of the type 3 and 4 mutations is especially surprising because the type 2 polymorphism occurs far more frequently than either the type 3 or 4 forms. The basis for apparent linkage between the mutations at residues 130 and 174, which are encoded by different exons, is also not clear. Identification of the mutations described here permits design of genetic screening analyses that can be applied to larger populations to evaluate this potential linkage.     

Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission

Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five- year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.