Prevention and treatment of infection in patients with an absent or hypofunctional spleen: A British Society for Haematology guideline.

Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were published by the British Committee for Standards in Haematology in 1996 and updated in 2002 and 2011. With advances in vaccinations and changes in patterns of infection, the guidelines required updating. Key aspects included in this guideline are the identification of patients at risk of infection, patient education and information and immunisation schedules. This guideline does not address the non-infective complications of splenectomy or functional hyposplenism (FH). This replaces previous guidelines and significantly revises the recommendations related to immunisation. Patients at risk include those who have undergone surgical removal of the spleen, including partial splenectomy and splenic embolisation, and those with medical conditions that predispose to FH. Immunisations should include those against Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus) and influenza. Haemophilus influenzae type b (Hib) is part of the infant immunisation schedule and is no longer required for older hyposplenic patients. Treatment of suspected or proven infections should be based on local protocols and consider relevant anti-microbial resistance patterns. The education of patients and their medical practitioners is essential, particularly in relation to the risk of serious infection and its prevention. Further research is required to establish the effectiveness of vaccinations in hyposplenic patients; infective episodes should be regularly audited. There is no single group ideally placed to conduct audits into complications arising from hyposplenism, highlighting a need for a national registry, as has proved very successful in Australia or alternatively, the establishment of appropriate multidisciplinary networks.

Elixhauser comorbidity method in predicting death of Spanish inpatients with asplenia and pneumococcal pneumonia.

BACKGROUND: Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP. METHODS: Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM). RESULTS: 97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97-0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997-2021. CONCLUSIONS: Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality.

Immunological Efficacy of Pneumococcal Vaccination Including the 13-Valent Pneumococcal Conjugate Vaccine in Adult Patients With Sickle Cell Disease: Results of the Randomized DREVAC Controlled Trial.

BACKGROUND: Patients with sickle cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD. METHODS: This was a randomized open-labeled phase 2 study of the immunogenicity of PCV13 at week 0, followed by PPSV23 at week 4, compared with PPSV23 alone at week 4 in adult patients with SCD. The proportion of responders (4-fold increase in serotype-specific immunoglobulin [Ig] G antibodies) to ≥10 shared serotypes was assessed at week 8. Secondary end points were (1) geometric mean titers, (2) responders to 0-1, 2-5, 6-9, or 10-12 serotypes, (3) pneumococcal opsonophagocytic activity, and (4) response durability at weeks 24 and 96. RESULTS: In total, 128 patients were randomized in the PCV13/PPSV23 (n = 63) or PPSV23-alone groups (n = 65). At week 8, 24.56% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary end point (P = .02). These numbers were 36.2% and 8.7% for opsonophagocytic activity responders (P = .002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, or 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At week 96, geometric mean titers were significantly higher in the PCV13/PPSV23 than in the PPSV23-alone group for 5 serotypes (4, 14, 19A, 19F, 23F). CONCLUSIONS: A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415.

Burden of COVID-19 disease and vaccine coverages in Apulian splenectomized patients: A retrospective observational study.

Splenectomy/asplenia is a condition associated with immune-compromission and specific vaccines are recommended for these patients, including the anti-COVID-19 vaccine. Among the high-risk group for which vaccination was prioritized in Italy, the immunocompromised patients after therapies or treatments were included. The Apulian regional archive of hospital discharge forms was used to define the list of splenectomized Apulian inhabitants, considering data from 2015 through 2020. The overall vaccination status of asplenic patients was assessed via data collected from the Regional Immunization Database. The history of SARS-CoV-2 infection and the infectious disease outcomes were extracted from the Italian Institute of Health platform "Integrated surveillance of COVID-19 cases in Italy". 1219 Apulian splenectomized inhabitants were included; the incidence rate of SARS-CoV-2 infection was 15.0 per 100 persons-year with a proportion of re-infection equal to 6.4%; the proportion of hospitalization was 2.9%, with a case-fatality rate of 2.6%. The vaccine coverage (VC) for the anti-COVID-19 vaccine basal routine was 64.2%, for the first booster dose was 15.4%, and for the second booster dose was 0.6%. A multifactorial approach is needed to increase the vaccination uptake in this sub-group population and to increase the awareness of the asplenia-related risks to patients and health personnel.

Efficacy of a novel patient-focused intervention aimed at increasing adherence to guideline-based preventive measures in asplenic patients: the PrePSS trial.

PURPOSE: To determine whether a novel intervention improves the adherence to guideline-based preventive measures in asplenic patients at risk of post-splenectomy sepsis (PSS). METHODS: We used a prospective controlled, two-armed historical control group design to compare a novel, health action process approach (HAPA)-based telephonic intervention involving both patients and their general practitioners to usual care. Eligible patients were identified in cooperation with the insurance provider AOK Baden-Wuerttemberg, Germany. Patients with anatomic asplenia (n = 106) were prospectively enrolled and compared to a historical control group (n = 113). Comparisons were done using a propensity-score-based overlap-weighting model. Adherence to preventive measures was quantified by the study-specific 'Preventing PSS score' (PrePSS score) which includes pneumococcal and meningococcal vaccination status, the availability of a stand-by antibiotic and a medical alert card. RESULTS: At six months after the intervention, we estimated an effect of 3.96 (95% CI 3.68-4.24) points on the PrePSS score scale (range 0-10) with mean PrePSS scores of 3.73 and 7.70 in control and intervention group, respectively. Substantial improvement was seen in all subcategories of the PrePSS score with the highest absolute gains in the availability of stand-by antibiotics. We graded the degree of participation by the general practitioner (no contact, short contact, full intervention) and noted that the observed effect was only marginally influenced by the degree of physician participation. CONCLUSIONS: Patients who had received the intervention exhibited a significantly higher adherence to guideline-based preventive measures compared to the control group. These data suggest that widespread adoption of this pragmatic intervention may improve management of asplenic patients. Health insurance provider-initiated identification of at-risk patients combined with a patient-focused intervention may serve as a blueprint for a wide range of other preventive efforts leading to patient empowerment and ultimately to better adherence to standards of care.

Congenital asplenia study: clinical and laboratory characterisation of adults with congenital asplenia.

Congenital asplenia is a rare disorder commonly associated with other visceral and cardiac congenital anomalies. Isolated congenital asplenia is even less common than syndromic forms. The risk of severe bacterial infections associated with asplenia is the most concerning clinical implication and carries a significant mortality risk. Prophylactic measures against the clinical syndrome known as overwhelming postsplenectomy infections (OPSI) include vaccination, prophylactic and emergency antibiotics and health education including fever management and travel advice. This case series describes fourteen adults with congenital asplenia and polysplenia syndrome, most of whom were diagnosed incidentally as adults, and outlines the nature of their diagnosis, clinical phenotype, family history and key pathology findings.

Surgical management of hearts with isomeric atrial appendages.

BACKGROUND AND AIM: On the basis of previously published accounts, coupled with our own experience, we have assessed the surgical approaches to patients with isomeric atrial appendages. METHODS: We reviewed pertinent published studies on surgical treatment of individuals with isomeric atrial appendages, with the pertinent surgical details provided by most of the manuscripts. RESULTS: Half of patients with right isomerism, and two-thirds of those with left isomerism have bilateral superior caval veins. Azygos extension of the inferior caval vein is reported in three-quarters of those with left isomerism. The coronary sinus is universally absent in right isomerism, along with totally anomalous pulmonary venous connection, and is absent in two-fifths of those with left isomerism. Univentricular atrioventricular connections are expected in up to three-quarters of those with right isomerism. Atrioventricular septal defect is reported in up to four-fifths, more frequently in right isomerism, with such patients typically having discordant ventriculoatrial connections or double outlet right ventricle. Reported mortalities extend to 85% for those with right, and 50% for those with left isomerism. In right isomerism, mortality is up to 54% for systemic-to-pulmonary arterial shunting, up to 75% for univentricular repair, and up to 95% for repair of totally anomalous pulmonary venous connection itself. No more than one-quarter had undergone Fontan completion, with reported mortalities of 21%. CONCLUSION: Early surgical results are satisfactory in patients with left isomerism, but disappointing for those with right. Recent advances in cardiac and liver transplantation may offer improved survival.

RPSA, a candidate gene for isolated congenital asplenia, is required for pre-rRNA processing and spleen formation in Xenopus.

A growing number of tissue-specific inherited disorders are associated with impaired ribosome production, despite the universal requirement for ribosome function. Recently, mutations in RPSA, a protein component of the small ribosomal subunit, were discovered to underlie approximately half of all isolated congenital asplenia cases. However, the mechanisms by which mutations in this ribosome biogenesis factor lead specifically to spleen agenesis remain unknown, in part due to the lack of a suitable animal model for study. Here we reveal that RPSA is required for normal spleen development in the frog, Xenopus tropicalis Depletion of Rpsa in early embryonic development disrupts pre-rRNA processing and ribosome biogenesis, and impairs expression of the key spleen patterning genes nkx2-5, bapx1 and pod1 in the spleen anlage. Importantly, we also show that whereas injection of human RPSA mRNA can rescue both pre-rRNA processing and spleen patterning, injection of human mRNA bearing a common disease-associated mutation cannot. Together, we present the first animal model of RPSA-mediated asplenia and reveal a crucial requirement for RPSA in pre-rRNA processing and molecular patterning during early Xenopus development.

Complications in the adult asplenic patient: A review for the emergency clinician.

BACKGROUND: The spleen performs several important physiologic functions. However, patients can have functional asplenia or have their spleen removed for a number of reasons, which can put them at risk for several dangerous complications. OBJECTIVE: This narrative review provides a focused evaluation of adult asplenic patients and complications in the emergency departing setting. DISCUSSION: The spleen plays integral roles in the immune and reticuloendothelial systems and also modulates the inflammatory and coagulation cascades. Asplenia refers to the anatomic or physiologic loss of splenic function, which may be due to trauma, immunological, hematological, or oncological etiologies. Asplenic patients are at risk for several complications including infection, arterial and venous thrombosis, and pulmonary hypertension. Fever in an asplenic patient and overwhelming post-splenectomy infection (OPSI) are medical emergencies with a high mortality and require rapid evaluation and management with broad-spectrum antibiotics. Asplenic patients are at increased risk of arterial thrombosis, such as coronary artery disease, and venous thrombosis including deep venous thrombosis, pulmonary embolism, and splenic and portal vein thrombosis. Management of venous thrombosis includes anticoagulation. Pulmonary hypertension with associated right ventricular dysfunction may also occur in asplenia. These patients require hemodynamic stabilization with an emphasis on inciting causes and treatment of the pulmonary hypertension. CONCLUSIONS: The spleen is an integral organ involved in several physiologic functions. Asplenia, or absence of spleen function, is associated with severe complications. Knowledge of these complications can improve the care of these patients.

Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons.

Isolated congenital asplenia (ICA) is the only known human developmental defect exclusively affecting a lymphoid organ. In 2013, we showed that private deleterious mutations in the protein-coding region of RPSA, encoding ribosomal protein SA, caused ICA by haploinsufficiency with complete penetrance. We reported seven heterozygous protein-coding mutations in 8 of the 23 kindreds studied, including 6 of the 8 multiplex kindreds. We have since enrolled 33 new kindreds, 5 of which are multiplex. We describe here 11 new heterozygous ICA-causing RPSA protein-coding mutations, and the first two mutations in the 5'-UTR of this gene, which disrupt mRNA splicing. Overall, 40 of the 73 ICA patients (55%) and 23 of the 56 kindreds (41%) carry mutations located in translated or untranslated exons of RPSA. Eleven of the 43 kindreds affected by sporadic disease (26%) carry RPSA mutations, whereas 12 of the 13 multiplex kindreds (92%) carry RPSA mutations. We also report that 6 of 18 (33%) protein-coding mutations and the two (100%) 5'-UTR mutations display incomplete penetrance. Three mutations were identified in two independent kindreds, due to a hotspot or a founder effect. Finally, RPSA ICA-causing mutations were demonstrated to be de novo in 7 of the 23 probands. Mutations in RPSA exons can affect the translated or untranslated regions and can underlie ICA with complete or incomplete penetrance.

Mutations in RPSA and NKX2-3 link development of the spleen and intestinal vasculature.

Idiopathic intestinal varicosis is a developmental disorder defined by dilated and convoluted submucosal veins in the colon or small bowel. A limited number of families with idiopathic intestinal varices has been reported, but the genetic cause has not yet been identified. We performed whole-exome and targeted Sanger sequencing of candidate genes in five intestinal varicosis families. In four families, mutations in the RPSA gene were found, a gene previously linked to congenital asplenia. Individuals in these pedigrees had intestinal varicose veins and angiodysplasia, often in combination with asplenia. In a further four-generation pedigree that only showed intestinal varicosities, the RPSA gene was normal. Instead, a nonsense mutation in the homeobox gene NKX2-3 was detected which cosegregated with the disease in this large family with a LOD (logarithm of the odds) score of 3.3. NKX2-3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice. Our results provide a molecular basis for familial idiopathic intestinal varices. We provide evidence for a relationship between the molecular pathways underlying the development of the spleen and intestinal mucosal vasculature that is conserved between humans and mice. We propose that clinical management of intestinal varices, should include assessment of a functional spleen.

Septic shock caused by Capnocytophaga canis after a cat scratch.

Capnocytophaga canis is an uncommon cause of septic shock. Only three cases have been previously reported in the literature. In this article, we describe the case of a 70-year-old male admitted to the intensive care unit for septic shock of unknown origin. On day 2, one anaerobic bottle out of the two sets taken at admission turned positive with Gram-negative bacilli. The pathogen was identified by 16S rRNA gene as C. canis. The strain was characterized and compared with other clinical isolates of Capnocytophaga spp.

Prevention of post-splenectomy sepsis in patients with asplenia - a study protocol of a controlled trial.

BACKGROUND: Patients with asplenia have a significantly increased lifelong risk of severe invasive infections, particular post-splenectomy sepsis (PSS). Clear preventive measures have been described in the literature, but previous studies found poor implementation of prevention recommendations. Aim of the study is to improve the adherence to guideline-based preventive measures and thereby reduce the incidence of PSS by a novel telephone-delivered intervention that involves both patients and their physicians. METHODS: A prospective controlled, two-armed historical control group design is used to evaluate the new intervention compared to usual care. The intervention for patients includes both educational aspects and, building on the Health Action Process Approach (HAPA), intervention components that promote motivation and planning of preventive measures. For physicians the intervention is primarily information-based. The primary outcome, the adherence to preventative measures, is indicated by a study-specific 'Preventing PSS-score' (PrePSS-score), which is assessed at baseline and at 6-months follow-up. Secondary outcomes include, amongst others, patient self-efficacy and action-planning, asplenia-specific health literacy, general self-management and asplenia-specific self-management. In a process-evaluating part of the study interview-data on patients' and physicians' evaluation of the intervention will be gathered. DISCUSSION: This trial will provide evidence about the effectiveness of the novel prevention intervention for asplenic patients. If demonstrated beneficial, the intervention manual will be made publicly available to enable implementation in practice. The experience gained within this trial may also be valuable for prevention strategies in patients with other diseases. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00015238; Trial registration date 07. December 2018.

Pneumococcal purpura fulminans in asplenic or hyposplenic patients: a French multicenter exposed-unexposed retrospective cohort study.

BACKGROUND: Pneumococcal infections remain the main cause of overwhelming post-splenectomy infections, and purpura fulminans may develop in almost 20% of patients with overwhelming post-splenectomy infection. We aimed at describing the impact of asplenia/hyposplenia on the clinical features and the outcomes of adult patients admitted to the intensive care unit (ICU) for pneumococcal purpura fulminans. METHODS: A 17-year national multicenter retrospective cohort study included adult patients admitted to 55 French ICUs for an infectious purpura fulminans from 2000 to 2016. Patients with pneumococcal purpura fulminans were analyzed according to the absence or presence of asplenia/hyposplenia. RESULTS: Among the 306 patients admitted to the ICU for purpura fulminans, 67 (22%) had a pneumococcal purpura fulminans, of whom 34 (51%) had asplenia (n = 29/34, 85%) or hyposplenia (n = 5/34, 15%) and 33 (49%) had eusplenia. The prevalence of pneumococcal purpura fulminans was seven times higher in asplenic/hyposplenic patients compared to eusplenic patients with purpura fulminans (n = 34/39, 87% vs. n = 33/267, 12%; p < 0.001). The median time interval between the occurrence of asplenia/hyposplenia and ICU admission was 20 [9-32] years. Pneumococcal vaccine coverage was 35% in asplenic/hyposplenic patients. Purpura was more frequently reported before ICU admission in asplenic/hyposplenic patients (n = 25/34, 73% vs. n = 13/33, 39%; p = 0.01). The rate of bacteremia did not differ between asplenic/hyposplenic and eusplenic patients (n = 31/34, 91% vs n = 27/33, 82%; p = 0.261). SAPS II (60 ± 14 vs. 60 ± 18; p = 0.244) and SOFA (13 [1-5] vs. 14 [1-4, 6]; p = 0.48) scores did not differ between asplenic/hyposplenic and eusplenic patients. There were no significant differences between asplenic/hyposplenic and eusplenic patients regarding the rate of limb amputation (n = 9/34, 26% vs. 15/33, 45%; p = 0.11) and hospital mortality (n = 20/34, 59% vs. n = 15/33, 45%; p = 0.27). CONCLUSIONS: Half of pneumococcal purpura fulminans episodes occurred in asplenic or hyposplenic patients. Pneumococcal vaccine coverage was reported in one third of asplenic/hyposplenic patients. Half of pneumococcal purpura fulminans episodes occurred more than 20 years after splenectomy. Outcomes of pneumococcal purpura fulminans did not show significant differences between patients with or without asplenia or hyposplenia, although the small number of patients included limited our power to detect potential differences between groups.

Haemophilus influenzae type b capsular polysaccharide antibody levels in Japanese young patients with hematological malignancies and asplenia.

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 µg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 µg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.

Prevalence and distribution of functional splenic tissue after splenectomy.

BACKGROUND: Individuals splenectomised for trauma have lower infection rates than those splenectomised for other conditions. Residual functional splenic tissue (FST) after splenectomy may provide ongoing immunological protection. AIMS: To quantify the prevalence and volume of residual FST post-splenectomy using standard testing. METHODS: Splenectomised adults were recruited from the Spleen Australia clinical registry. Eligible individuals had been splenectomised at least 1 year prior to their visit and resided in Victoria. Splenic function was identified by evaluating Howell-Jolly bodies and IgM memory B cells. A 99m-Technetium-labelled, heat-denatured erythrocyte scintigraphic scan was performed if splenic function was detected. RESULTS: Initially, 75 splenectomised individuals (all cause) were recruited, with a median of 58 years of age and who were splenectomised a median of 14 years previously. The most common indications for splenectomy were trauma (30.7%) and haematological disease (28.0%). Scintigraphy identified FST in nine individuals (12.0%). Eight had been splenectomised for trauma. In this cohort, 34.8% of individuals splenectomised for trauma had residual FST. To explore our findings further, 45 additional individuals were recruited, predominately individuals splenectomised for trauma. Twenty-five individuals completed assessments by December 2018. An additional 11 individuals had FST, of whom 9 had been splenectomised for trauma. Overall, we identified 20 individuals with residual FST. Volumes ranged from 2.2 to 216.0 cc. We saw individuals with accessory spleens and splenotic nodules and an individual with both. Seventeen individuals had been splenectomised for trauma. CONCLUSIONS: Residual FST is commonly seen in individuals splenectomised for trauma. It can present in varying distributions and of varying volume. The clinical significance is unclear.

The Spectrum of Cardiac Anomalies Associated with Heterotaxy: A Single-Center Study of a Large Series Based on Computed Tomography.

The aim of the study was to identify and correlate the anatomical variants of cardiac structures among patients with heterotaxy. In this retrospective cross-sectional analysis of 13 years duration, 302 patients of congenital heart diseases associated with heterotaxy were studied. All these patients had undergone a meticulous clinical evaluation, echocardiography, and cardiac computed tomography. The mean age of the cohort was 38.4 months, with 180 males and 122 females. The cohort had 184 patients of right isomerism and 118 of left isomerism. More than half of the cohort had abnormal pulmonary veins. Over 75% of the cohort had low pulmonary blood flow. Abnormal relationship of great arteries was seen in nearly 69% of the cohort. Atrio-venticular canal defect was the commonest anatomical variant. Overall, 43% of the cohort had single ventricle physiology, predominantly associated with right isomerism. Heterotaxy forms a difficult anatomical subset to comprehend due to the plethora of possible abnormalities. However, unless the cardiac and visceral anatomy is delineated well, the surgical plan becomes suboptimal and often elusive, leaving tough choices for cardiac surgeon. It is essential to obtain all the possible anatomical information using additional imaging modalities to devise a basis for a comprehensive plan for medical and surgical management. A better understanding of the genetic and molecular factors in the etiology, coupled with the application of state-of-the-art imaging techniques, is likely to add to our knowledge of heterotaxy to bring about improved surgical outcomes and a better quality of life for patients suffering from this complex entity.

Fatal pneumococcal septicemia in a girl with visceral heterotaxy and polysplenia: a case report.

We report an unusual case of a 15-month old previously healthy girl who died of pneumococcal septicemia in the background of visceral heterotaxy with polysplenia. Heterotaxy can also present with asplenia whereas polysplenia cases usually present with functional asplenia. Of particular note, this girl received the 13-valent pneumococcal conjugate vaccine as recommended by the Centers for Disease Control and Prevention in the routine pediatric immunization schedule used in the USA and Canada. Unfortunately, although the strain causing death (serotype 22F) is not contained in Prevnar 13®, it is in the 23-valent pneumococcal polysaccharide vaccine (e.g. Pneumovax 23®), currently suggested only for immunocompromised children age 2 with either functional or anatomic asplenia. This syndrome has the potential of being diagnosed prenatally. The intent of our case report is to raise awareness of the syndrome, highlight that heterotaxy patients with polysplenia are at danger for infections with encapsulated organism, such as pneumococcus, meningococcus, and Haemophilus influenza amongst others due to functional asplenia, recommend the 23-valent pneumococcal polysaccharide vaccine for these children before age two for the outlined reasons, and illustrate that with early diagnosis of the heterotaxy syndrome, and early diagnosis and treatment of septic complications, the morbidity or death of young children with heterotaxy syndrome can likely be reduced or prevented.

Congenital asplenia due to a tlx1 mutation reduces resistance to Aeromonas hydrophila infection in zebrafish.

It is documented that tlx1, an orphan homeobox gene, plays critical roles in the regulation of early spleen developmental in mammalian species. However, there is no direct evidence supporting the functions of tlx1 in non-mammalian species, especially in fish. In this study, we demonstrated that tlx1 is expressed in the splenic primordia as early as 52 hours post-fertilization (hpf) in zebrafish. A tlx1-/- homozygous mutant line was generated via CRISPR/Cas9 to elucidate the roles of tlx1 in spleen development in zebrafish. In the tlx1-/- background, tlx1-/- cells persisted in the splenic primordia until 52 hpf but were no longer detectable after 53 hpf, suggesting perturbation of early spleen development. The zebrafish also exhibited congenital asplenia caused by the tlx1 mutation. Asplenic zebrafish can survive and breed normally under standard laboratory conditions, but the survival rate of animals infected with Aeromonas hydrophila was significantly lower than that of wild-type (WT) zebrafish. In asplenic zebrafish, the mononuclear phagocyte system was partially impaired, as demonstrated by retarded b7r expression and reduced ccr2 expression after injection with an inactivated A. hydrophila vaccine. Furthermore, the expression of MHCII/IgM was significantly reduced in the congenitally asplenic fish compared with that of the WT zebrafish. Taken together, our data suggest that tlx1 is a crucial regulator of spleen development in fish, as it is in mammals. We have also provided a new perspective for studying the role of the spleen during pathogen challenge in fish.

Case report of congenital asplenia presenting with Haemophilus influenzae type a (Hia) sepsis: an emerging pediatric infection in Minnesota.

BACKGROUND: In the pre-vaccine era, invasive disease with Haemophilus influenzae, type b (Hib) commonly presented with osteoarticular involvement. Haemophilus influenzae, type a (Hia) sepsis is a rare but emerging problem in recent years. Here, we report a case of sepsis with concomitant osteoarthritis due to Hia that was the presenting infectious disease manifestation of isolated asplenia in a young child. This unique observation adds to our understanding of sepsis and asplenia in children. CASE PRESENTATION: A five-year-old girl developed acute Hia bacteremia and sepsis. The patient developed arthritis shortly after onset of septic shock. Arthrocentesis was culture-negative, but given the difficulty differentiating between septic and reactive arthritis, prolonged antibiotic administration was provided for presumed osteoarticular infection, and the patient had an uneventful recovery. The finding of Howell-Jolly bodies on blood smear at the time of presentation prompted an evaluation that revealed isolated congenital asplenia. Evaluation for known genetic causes of asplenia was unrevealing. Investigation by the Minnesota Department of Health revealed an emergence of Hia infections over the past 5 years, particularly in children with an American Indian background. CONCLUSIONS: Hia is an important pathogen in the differential diagnosis of invasive bacterial infections in children and shares overlap in clinical presentation and pathogenesis with Hib. Invasive Hia disease can be a presenting manifestation of asplenia in children. Hia is an emerging pathogen in American Indian children.