In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is α⁺-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that α⁺-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that α⁺-thalassemia may facilitate so-called “benign”Plasmodium vivaxinfection to act later in life as a “natural vaccine” against severePlasmodium falciparummalaria. Here, in aP. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of α⁺-thalassemia ≥0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a−b−]) on theFY*Aallele. In this study population there were 23 heterozygous and no homozygous individuals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous (FY*A/FY*A^null) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence ofP. vivaxinfection inFY*A/FY*A(83/508 = 0.163) compared withFY*A/FY*A^null(2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47–8.91). Emergence ofFY*A^nullin this population suggests thatP. vivaxis involved in selection of this erythroid polymorphism. This mutation would ultimately compromise α⁺-thalassemia/P. vivax-mediated protection against severeP. falciparummalaria.

We analyzed the deaths in an outpatient human immunodeficiency virus (HIV) care clinic at University Hospitals in Cleveland from January 1995 through

Removal of the spleen had already been established as a routine technique to treat splenic trauma and other diseases affecting the spleen before the anatomy, physiology, and function of the spleen were known in the mid-twentieth century. It is now widely accepted that the splenectomized individual is at increased risk for infection, in particular, overwhelming post-splenectomy infection (OPSI). OPSI is a syndrome of fulminant sepsis occurring in splenectomized (asplenic) or hyposplenic individuals that is associated with high mortality and morbidity. Poorly opsonized bacteria such as encapsulated bacteria, in particular, Streptococcus pneumoniae, are often implicated in sepsis. The spleen is a reticuloendothelial organ that facilitates opsonization and phagocytosis of pathogens, in addition to cellular maintenance. Splenectomy is associated with an impairment in immunoglobulin production, antibody-mediated clearance, and phagocytosis, leading to an increased risk of infection and sepsis. Early identification of the at-risk patient, early blood cultures prior to antibiotic administration, urgent blood smears and fast pathogen-detection tests, and sepsis bundles should be utilized in these patients. Prompt management and aggressive treatment can alter the course of disease in the at-risk splenectomized patient. Overwhelming post-splenectomy infection can be prevented through vaccination, chemoprophylaxis, and patient education. This article evaluates post-splenectomy sepsis by summarizing the anatomy and function of the spleen, physiological changes after splenectomy that predispose the splenectomized patient to infection, and current management and prevention strategies.

Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001) reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.