Black/African individuals often have lower white blood cell (WBC) and absolute neutrophil counts (ANC) associated with a Duffy null red blood cell (RBC) phenotype commonly caused by homozygosity for a −67T>C polymorphism in GATA-1 on chromosome 1, which is responsible for the majority of Fyb negative phenotypes in this population. This leads to absence of expression of the Fyb antigen on red blood cell (RBC) surfaces, though this antigen remains intact on other physiologic surfaces. While this provides relative resistance to some Plasmodium species, it is unclear the complete impact this has on patients with sickle cell disease (SCD). We performed a 1-year retrospective observational study of all patients with SCD (homozygous HbSS or HbS/B0) undergoing chronic RBC exchange at a large, academic pediatric center and two, large adult academic hospitals. We obtained RBC phenotype/genotype, allo-antibody, and complete blood count data. Continuous variables were compared with a Mann–Whitney test and categorical variables were compared using a Fisher's exact test. Our cohort consisted of 99 patients with SCD undergoing chronic RBC exchange. Duffy antigen phenotype was available for 96 patients, and Duffy antigen genotype was available for 19 patients. Amongst genotyped patients, 89% (17/19) had the GATA-1-67T>C polymorphism, while 82.3% (79/96) of patients were Fy(a-b-) by serologic phenotype. There was no significant difference in WBC count, ANC, alloimmunization, or warm autoantibody rates based on Duffy null phenotype (Table 1).
Abstract Bombay phenotype, an exceptionally rare blood type in individuals outside of Southeast Asia, occurs in approximately 1 in 1,000,000 individuals in Europe. This blood phenotype is characterized by the absence of the H antigen on red blood cells (RBCs) and in secretions. As the H antigen is the structure on which the ABO system is built, individuals lacking this antigen are unable to produce A or B antigens and appear as type O on routine ABO phenotyping. H deficiency does not cause ill effect; however, these individuals produce an anti-H alloantibody capable of causing severe acute hemolytic transfusion reactions when exposed to RBCs that express the H antigen. In this case study, we highlight the incidental discovery of a patient with Bombay phenotype in a North American hospital system, expected test results, the immunologic and genetic basis underlying the Bombay and para-Bombay phenotypes, and methods to ensure availability of compatible blood.
To determine whether gender and racial inequities exist among Lasker Award recipients.Observational, cross sectional analysis.Population based study.Recipients of four Lasker Awards from 1946 to 2022.Gender and race (non-white categorized as racialized v white categorized as non-racialized) of all Lasker Award recipients. Personal characteristics of award recipients were categorized by four independent authors using previously established methods and consistency of categorization among authors was analyzed. Women and non-white people were thought to be underrepresented among Lasker Award recipients compared with professional degree recipients overall.Among 397 Lasker Award recipients since 1946, 92.2% (366/397) were men. Most award recipients were identified as white (95.7%, 380/397). One non-white woman was identified as having received a Lasker Award over the course of seven decades. The proportion of women among award recipients in the most recent decade (2013-22) is similar to the first decade of awards (1946-55; 15.6%, 7/45 v 12.9%, 8/62). The median timeframe from terminal degree receipt to Lasker Award conferral for all award recipients is 30 years. The proportion of women who received a Lasker Award between 2019 and 2022 (7.1%) was less than would be expected based on the proportion of life science doctorates awarded to womenin 1989 (30 years previously; 38.1%).The number of women and non-white people in academic medicine and biomedical research continues to increase, yet the proportion of women among Lasker Award recipients has not changed in more than 70 years. Additionally, time from terminal degree receipt to Lasker Award conferral does not appear to fully account for the observed inequities. These findings establish the need for further investigation of possible factors that could hinder women and non-white people from entering the pool of eligible award recipients, potentially limiting the diversification of the science and academic biomedical workforce.
Abstract Introduction/Objective Hand hygiene (HH) decreases healthcare-associated infections (HAI). Available products include alcohol-based gels, foams, wipes, and “gold-standard” hand-washing with soap and water. We tested an investigational device (HyLuxO3; GMI, LLC, patent pending) for antimicrobial effect (AME). HyLuxO3 was engineered to deliver UV-C light energy and high velocity O3 airflow to safely achieve human skin antisepsis within OSHA and EPA regulatory limits. Combined UV and O3 has yet to be evaluated for HH and may demonstrate synergistic AME. Methods HyLuxO3 was tested on LB agar to titrate device variables to ascertain intensities for optimal AME; later testing was performed on VITRO-SKIN (Florida Suncare Testing, Bunnell, FL), a human skin surrogate. ATCC strains of MRSA, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were used to test AME vs. vegetative microbes; Bacillus atrophaeus spores were used as a surrogate for C. difficile. Tested variables included time under device, [O3], airflow velocity, 222 and/or 254 nm UV light, sample distance from UV lamp, and UV beam width. Positive controls were used to calculate log-kill curves for AME. Results Similar results were seen on LB agar and VITRO-SKIN. >7 log-kill and >5 log-kill were acheived vs. vegetative microbes (<30 sec) and spores (60 sec), respectively, under optimized variables. Presence of UV light and sample distance from and time under the device were the most important variables. 254 nm UV had a significantly better AME than 222 nm; combining both UV lamps had a significant synergistic AME. The narrowest UV beam (2 mm) yielded the greatest AME (total energy input kept constant). Adding O3 to UV had a modest but significant synergistic effect; optimal [O3] was 0.3-0.8 ppm. Changing airflow velocity had no significant effect on AME. Conclusion HyLuxO3 is a novel device that achieves >7 log-kill vs. common pathogenic vegetative microbes and >5 log-kill vs. spores using combined UV light and [O3] safe for human skin antisepsis (and surface/fomite decontamination)- and- yields such impressive AME on faster timescales than those required by bleach/other chemical products unsuitable for human skin. Future studies on human hands (using many other microbes) will determine if HyLuxO3 meets regulatory and efficacy requirements for use in and beyond healthcare settings, especially with the specter of emerging respiratory viruses.
Context.— The American Board of Pathology (ABPath) publishes annual performance data for the anatomic pathology (AP) and clinical pathology (CP) board examinations, as well as for ABPath subspecialty examinations. Overall board pass rates for all AP and CP board examinees have increased during the past decade; however, no study has analyzed the board pass rates for pathology subspecialty examinations, and whether these follow the same trend. Objective.— To evaluate ABPath subspecialty examination pass rates to assess the trend in certification. Design.— We analyzed the total number of first-time test takers and board pass rates for 11 pathology subspecialties recognized by the ABPath from 2007 to 2021, acquired from annual reports published by the ABPath. We compared the pass rates in 5-year intervals (2007–2011, 2012–2016, 2017–2021) for each individual specialty. We also analyzed the pass rate of CP subspecialties compared with AP subspecialties. Results.— The overall mean pass rate for ABPath subspecialty examinations during the previous 15 years was 89% (range, 78.9%–100%), with the overall pass rate being significantly higher in 2017–2021 (P = .02). The contemporary overall rate of passing was significantly higher for AP subspecialty examinations (P < .001) and was higher, though not significantly, for CP subspecialties (P = .13). There were significant differences between first-time test takers' mean pass rate (92.1%), repeat test takers' mean pass rate (54.5%), and the overall rate (P < .001). Conclusions.— Contemporary pathology subspecialty board examination pass rates are significantly higher than historic rates, possibly reflecting continuously improving and readily available preparatory materials.
Human monkeypox, a viral zoonotic disease similar to, but clinically less severe than smallpox, was first identified in humans in 1970 in the Democratic Republic of the Congo (DRC).1 Monkeypox presents as a febrile illness with rash, and transmission occurs via direct contact with infected individuals, infected bodily fluids, or indirect contact via fomites. Although no transfusion-transmitted cases have been described,2 viraemia is consistently detected during symptomatic infection and can persist for 2–3 weeks after resolution of a rash in some patients,3 creating a theoretical risk to the blood supply. The kinetics of viraemia during the presymptomatic phase and during asymptomatic infection are not well characterized. Since its discovery, most cases of human monkeypox have occurred in rural regions of Africa, particularly in the DRC and across Central and West Africa. There are two known clades of monkeypox virus — West African and Congo Basin (Central African), which vary by their endemic geography and pathogenicity.4 The Congo Basin clade, currently listed as a Health and Human Services Select Agent in the United States, is associated with higher mortality (up to ~11%), whereas the West African clade has a lower mortality rate (up to ~4%) and is not a Select agent.4 The first outbreak outside of Africa occurred in 2003 in the United States, resulting in over 70 cases.1 In 2022, the largest recorded outbreak of human monkeypox continues to evolve, with 6027 laboratory-confirmed cases as of 4 July 2022 according to the WHO,5 though Our World in Data has reported 11 595 cases as of 14 July 2022.6 Both the 2003 and 2022 outbreaks are attributed to the West African clade, though there is evidence that the strain responsible for the current outbreak continues to evolve into a novel phylogenetic branch.7 Currently, no in vitro screening assay for monkeypox virus in blood donors exists, and regarding monkeypox, the Association for the Advancement of Blood and Biotherapies (AABB) has stated that "evidence does not support the implementation of a donor question or provision of written donor education materials."2 The AABB did offer prescriptive recommendations for centres choosing to defer, with donation allowed after resolution of symptoms with complete separation of scabs or a minimum of 21 days deferral after asymptomatic exposure.2 While many cases of monkeypox infection have been identified in individuals who would likely be deferred from blood donation based on social practices [e.g. men who have sex with men (MSM)], the US Centers for Disease Control (CDC) states that any individual having close contact with a person infected with monkeypox is at risk of acquiring the disease.8 Furthermore, multiple studies have demonstrated that members of the MSM community donate blood despite the self-exclusion questions.9 Therefore, blood donation deferral policies based on self-exclusion questions for social practices cannot be expected to completely eliminate the threat of monkeypox infection to the blood supply. While viraemia does not necessarily equate to transfusion transmissibility, given that current knowledge of viraemia, infectivity, and transmissibility via blood transfusion is limited, there is significant need to investigate the potential for transfusion transmission via focused studies on detection of monkeypox DNA and infectivity in relevant patient and blood donor populations (e.g., donors with multiple sexual partners of recent syphilis seroreactivity). Furthermore, evaluation of the potential for transfusion transmission during presymptomatic or asymptomatic infection, and the development of appropriate animal models to answer these questions are needed, as mounting evidence suggests that asymptomatic monkeypox infection may be theoretically possible.10 As of June 23, 2022, the US CDC's Advisory Committee on Immunization Practices (ACIP) recommends that persons needing pre- or postexposure prophylaxis for monkeypox receive one of two vaccines (ACAM2000 and JYNNEOS) which have previously been licensed for use in the US against smallpox.11 While the ACAM2000 vaccine is administered as a live, replicating Vaccinia virus, the JYNNEOS vaccine is a live, non-replicating Vaccinia virus and is administered through two injections, separated by approximately four weeks.11 As this vaccine strain is non-replicative, it is considered a potentially safer option, and is currently the only US FDA-licensed vaccine for use against monkeypox.12 In contrast, there is currently no vaccine licensed in the United Kingdom or Europe for immunization against monkeypox, though Imvanex, the same vaccine as JYNNEOS, is currently being used off-label to prevent monkeypox in Europe.13 As countries begin to vaccinate high-risk individuals and contacts of possible or confirmed cases, the use of these vaccines is expected to increase, as evidenced by the recent announcement regarding vaccinations in New York City, US and Ottawa, Canada.14, 15 While studies are currently underway to evaluate the efficacy and side effects of the JYNNEOS, and potentially other, monkeypox vaccines, one unknown consequence of this abrupt implementation is the potential impact on the international blood supply. Like the issues that have been encountered with severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infections and vaccination,16 the effects on the blood donation community, particularly regarding blood donation deferrals for monkeypox vaccine recipients, contacts of infected individuals, and infected patients themselves, remain uncertain. Furthermore, the US Food and Drug Administration (FDA) has no deferral period for otherwise healthy blood donors following receipt of the JYNNEOS vaccine.17 Conversely, donors that receive replicating Vaccinia virus vaccines, such as ACAM2000, should be deferred based on 2002 deferral guidance.18 These guidelines are dictated by the nature of the vaccination scab separation and the development of vaccinia symptoms, with additional deferral policies for individuals exposed to vaccine recipients (Table 1). As few donors were receiving smallpox vaccines when this schema was proposed, this algorithm may have been more appropriate, but if replicating Vaccinia virus vaccines see widespread use, the complexity of these guidelines represents a significant barrier to donation. If vaccine date known: If vaccine date unknown but within past three months: The distinct, and potentially confusing, differences between policies for vaccination against, and infection with, a disease that remains obscure to much of the public may cause complications and frustration for blood centre staff and donors, with the potential to further disrupt an already shrinking donor pool. Given the paucity of data, official guidelines are currently unavailable from various organizations across the world regarding deferrals for vaccine recipients. Similarly, deferrals vary for individuals diagnosed with monkeypox. However, deferral policies tend to be available and are generally consistent among various organizations for individuals who come into close contact with a monkeypox case (Table 2). 14 days from the end of symptoms and the disappearance of the vesicular lesion scabs If hospitalization is required — three months We must achieve a fine balance between ensuring both the safety and availability of blood, with primary risk factors to the safety of blood products including: (1) lack of or too lenient donor deferral criteria; (2) confusing donor deferral criteria leading to misinterpretation and/or inaccurate implementation; and (3) preventing disease transmission during the donation process. We must ensure that overly conservative deferral policies that unnecessarily deny otherwise eligible and willing donors are not implemented to prevent exacerbating the persistent blood shortages, while maintaining the safety of blood donors, blood centre staff, and transfusion recipients. While the monkeypox outbreak continues to unfold worldwide and public health officials and researchers attempt to understand the transmission dynamics of the virus, countries have begun to implement vaccination campaigns to bring the outbreak under control. Though live non-replicating vaccines are currently preferred and should not result in deferrals, utilization of replicating Vaccinia immunizations represents an area of concern if their use is necessitated. As policies are being developed and modified in real time, the international blood donation community must actively engage with experts and stakeholders to ensure deferral policies are clear and readily available to maintain an adequate and safe blood supply. Jeremy W. Jacobs performed the research, wrote the first draft of the manuscript, and approved the final version; Laura Filkins revised the manuscript and approved the final version; Garrett S. Booth supervised the research, revised the manuscript, and approved the final version; Brian D. Adkins supervised the research, revised the manuscript, and approved the final version. No funding was received for this research. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Institutional review board approval was not required as all data are publicly available and no human or animal research was performed. No patients were involved in this research, therefore informed consent is not applicable.
Autoimmune haemolytic anaemia (AIHA) is an uncommon haematologic condition characterized by the development of autoantibodies directed against red blood cell (RBC) antigens. The annual incidence of AIHA is estimated at 1–3 cases per 100 000 persons.1 AIHA can be divided into warm antibody-mediated AIHA (wAIHA), cold antibody-mediated AIHA (cAIHA), mixed AIHA, and drug-induced.2 wAIHA accounts for approximately 70% of all cases of immune-mediated haemolysis, while cAIHA accounts for approximately 15%–25% of cases.2 Specific infectious agents have been associated with both wAIHA (e.g., HIV, Epstein–Barr virus [EBV], hepatitis C virus, cytomegalovirus, SARS-CoV-2) and cAIHA (e.g., Mycoplasma pneumoniae, EBV, SARS-CoV-2).2, 3 Notably, Babesia microti, one of the most common causes of human babesiosis, has been implicated in several cases of wAIHA recently.4-6 Babesia microti, an intraerythrocytic protozoan, replicates asexually and then exits via cell membrane disruption and subsequent cell lysis to invade other RBCs.7 This results in haemolysis, though development of clinically evident anaemia is dependent upon a variety of factors including parasite load and underlying immune competence. In the absence of an immune-mediated component of RBC destruction, antimicrobial therapy is often sufficient to eliminate the Babesia and resolve the haemolysis.8 However, in select cases of babesiosis where autoimmune-mediated RBC destruction contributes to haemolysis, adjuvant immunosuppressive therapy may be required.4 Herein, we review all reported cases of babesiosis-associated AIHA to characterize the clinical and laboratory features, therapeutic strategies and outcomes. We also describe a novel case of cAIHA precipitated by Babesia microti infection, which, to our knowledge, has not previously been reported. We reviewed PubMed and EMBASE from inception to 12 January 2023 to identify all known reported cases of AIHA associated with human babesiosis. We analysed patient demographics, laboratory findings, treatment regimens and patient outcomes. We specifically assessed the immunohaematologic results and AIHA classification (i.e., warm, cold, mixed). We identified 20 reported cases (12 males, 8 females) of babesiosis-associated AIHA (Table 1).4-6, 9-15 While AIHA was attributed to babesiosis in all patients, six had a history of conditions associated with a predisposition to development of AIHA (haematologic malignancy n = 3, allogeneic haematopoietic stem cell transplantation n = 1, systemic lupus erythematosus n = 1, wAIHA in remission n = 1) and six were treated with quinine, a known cause of AIHA.16 Among 17 patients with age reported, the median age at diagnosis was 55 years (interquartile range [IQR]: 43–65 years). Spleen presence/absence was reported in 17 patients, 100% of whom were asplenic. The peak parasite load was reported in 15 patients, ranging from <1% to 11.8%. All 20 patients were diagnosed with babesiosis-associated wAIHA — 10 patients had a direct antiglobulin test (DAT) positive for both IgG and C3, nine positive for IgG, and one had a negative DAT but the presence of a warm autoantibody with anti-Jka specificity in the eluate. Notably, none of the patients reportedly underwent assessment for cold agglutinins. The timing to AIHA diagnosis varied, ranging from concurrent with active Babesia infection (n = 7), to up to four weeks post infection (n = 2). However, while prior authors have suggested that babesiosis-induced AIHA occurs 2–4 weeks post infection,4 this is difficult to corroborate due to the variability in timing of laboratory testing. Nine patients reportedly received at least one RBC transfusion, with four patients receiving at least one RBC and/or plasma exchange. The most common antimicrobial regimen consisted of azithromycin and atovaquone, and nine patients reportedly received immunosuppressive therapy in addition to antimicrobial agents. One patient died secondary to multiorgan failure. Considering these findings in which babesiosis has been documented to potentiate development of AIHA, and all known reported cases have specifically been classified as wAIHA, we thought it important to describe a recent patient with presumptive cAIHA associated with Babesia microti infection. A 63-year-old female with history significant for metastatic ovarian cancer treated with bilateral salpingo-oophorectomy, hysterectomy, splenectomy, radiation, and chemotherapy 18 years prior was admitted to an outside hospital with fever, chills, anaemia (haemoglobin 8.9 g/dL; reference: 11.7–15.5 g/dL), and a history of tick-bite one month prior. Infection with Babesia microti was confirmed, with an estimated parasite load of 2.9%. Atovaquone and azithromycin were initiated, and she was discharged. Three days later, repeat evaluation revealed decreased parasitemia to 1.6% but worsening anaemia with a haemoglobin of 6.6 g/dL. Two units of RBCs were administered, and she was transferred to our institution for consideration of RBC exchange. Repeat Babesia quantitation at the outside hospital following the RBC transfusion prior to transfer resulted with 0.3% parasitaemia. On presentation to our facility, her Babesia smear was negative and RBC exchange was deferred. At our institution, haemolysis as evidenced by abnormal chemical studies (lactate dehydrogenase 1441 U/L [reference: 122–241 U/L], haptoglobin <10 mg/dL [reference: 30–200 mg/dL], total bilirubin 2.1 mg/dL [reference: <1.2 mg/dL]) continued with intermittent borderline-detectable parasitaemia (<1%) and down-trending haemoglobin necessitating another single RBC transfusion (Figure 1). ABO type and antibody detection test revealed blood type A RhD-positive with a negative indirect antiglobulin test via gel column agglutination technology, excluding the presence of an IgG-class alloantibody. Testing at the immediate spin/room temperature phase was not originally performed. DAT via standard tube testing was positive using anti-IgG, -C3d polyspecific and anti-C3 monospecific reagents, but negative using anti-IgG monospecific reagents. The patient remained anaemic with ongoing haemolysis, but her clinical condition stabilized, and she was discharged two days later. Azithromycin, atovaquone, and folic acid were continued with weekly outpatient monitoring. Five days after the first DAT, repeat testing again revealed the presence of C3, but not IgG, bound to her RBCs. Cold agglutinin titres were performed at 4°C using type O RhD-positive donor RBCs via standard tube methods without potentiating agents, which resulted at 1:256, while the titre was <1:32 a week prior. Thermal amplitude testing was deferred, as immunosuppressive therapy was not planned at the time of writing due to a generally improving clinical picture. These results represent, to our knowledge, the first case of babesiosis-associated cAIHA, specifically secondary cold agglutinin syndrome (CAS). While we acknowledge that our review was limited to only reported cases of acquired, post-infectious AIHA, the findings from these publications universally have shown wAIHA. Although no prior cases reported cold agglutinin titres, response to steroids and the immunohaematologic findings generally support the diagnosis of wAIHA in these cases. In contrast, CAS does not typically respond to steroids, though CAS secondary to infectious agents such as Mycoplasma pneumoniae and EBV typically resolves following infection resolution, as appears to have been occurring in our case of babesiosis. Additionally, given that splenectomy is often considered a second-line therapy for wAIHA,17 it is notable that all patients with babesiosis-associated AIHA for whom spleen presence has been reported have been asplenic. One possible explanation for the pathophysiologic mechanism of AIHA secondary to babesiosis involves deposition of immune complexes on the surface of RBCs in the setting of systemic infection and inflammation.4 In the absence of splenic clearance, these complexes may result in erythrocyte destruction and/or facilitate complement binding. While IgG-mediated phagocytosis of RBCs primarily occurs in the spleen, complement-mediated phagocytosis occurs predominantly via C3b-opsonized erythrocytes by Kupfer cells in the liver.18 A second possibility relates to the development of antibodies to Babesia antigens that cross-react with RBC antigens.4 Without splenic removal of infected RBCs, IgM and/or IgG autoantibodies may precipitate RBC destruction. While the underlying pathogenesis of babesiosis-associated AIHA remains to be definitively elucidated, these findings suggest that asplenia is a risk factor, and the pathologic mechanism of RBC clearance likely differs from typical AIHA. In summary, transfusion medicine specialists, haematologists, and infectious disease physicians should be cognizant of the possibility that babesiosis may be capable of precipitating AIHA, particularly in asplenic patients, and that the form of immune-mediated clearance is not limited to wAIHA. In patients with haemolysis that appears out of proportion to the parasitaemia, assessment with DAT and elution studies may be informative. Importantly, if the DAT is positive for C3 and negative for IgG, further analysis of cold agglutinins may be warranted, particularly since treatment (if needed) for this entity generally differs as compared with warm autoantibody disease. Jeremy W. Jacobs collected the data, analysed the data, wrote the first draft, and approved the final version. Thomas C. Binns and Elizabeth Abels revised the manuscript. Christopher A. Tormey provided supervision, revised the manuscript, and approved the final version. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors report no conflicts of interest related to this research.
Clinical practice guidelines (CPGs) have significantly influenced medical practice worldwide. Nevertheless, the authorship of CPGs produced by several medical societies has not been representative of the field and population they address, as women and individuals from racial and ethnic minority groups have been underrepresented as authors. We hypothesized that women and individuals from minoritized racial and ethnic groups would also be underrepresented as authors of CPGs produced by the American Academy of Pediatrics (AAP).
