Vitamin A and D Levels Correlate with Outcomes Following Acute Parvovirus B19 Infection in Children with Sickle Cell Disease

Background: Human parvovirus B19, a common childhood infection that typically causes mild disease in healthy individuals, causes life-threatening anemia due to transient red cell aplasia (aplastic crisis) in individuals with sickle cell disease (SCD). This complication often leads to hospitalization and red blood cell transfusions. Limiting the amount of transfusions is imperative to avoid alloimmunization. Strategies to mitigate complications from parvovirus B19 or reduce disease severity in SCD patients are needed. In this prospective observational study, we aim to describe the relationship between vitamin A and D levels and severity of symptoms during parvovirus B19 infection in pediatric patients with SCD. Methods: Twenty pediatric patients with SCD admitted to St. Jude Children's Research Hospital experiencing aplastic crisis and identified as having an active parvovirus B19 infection were under an IRB approved protocol (NCT02261480) and followed prospectively for 120 days post-infection. Acute parvovirus B19 infection was diagnosed by fever and a positive virus-specific IgM ELISA or PCR. Aplastic crisis was defined by worsened anemia without sufficient compensatory reticulocytosis in the setting of an acute parvovirus B19 infection. Virus-specific antibody responses were measured from sera or nasal washes (NW) by ELISA using parvovirus B19 virus-like particles (VLP) as target antigens. Peak serum antibody titers were defined (among measurements from Days 0, 7, 30, and 120). Total erythrocyte transfusion volumes required during the admission were quantified. Hematologic indices and vitamin A and D levels were obtained on Day 0. Vitamin A (retinol) was measured using UPLC and vitamin D (25[OH]D) was measured using a Roche Elecsys Vitamin D ELISA. Statistical analyses were performed with Spearman's rank correlation coefficient or Mann Whitney tests. We scored significance as p<0.05. Results: Twenty patients with different genotypes of SCD requiring hospital admission due to acute parvovirus B19 infection were sequentially enrolled (15 HbSS, 3 HbSC, 1 HbSD, 1 HbSβeta +thalassemia). Thirty-five percent (7/20) of patients were vitamin D deficient (VDD, defined here as <20 ng/mL) while 89% (17/19, one sample was not measured) of patients were marginally or severely vitamin A deficient (defined here as <20 μg/dL) on Day 0. Correlative analyses between vitamin levels and markers of disease severity are shown in figure 1. Lower vitamin D levels trended with lower hemoglobin (r=0.399, p=0.082) and there was a significant inverse correlation between transfused volume and vitamin D levels (r=-0.626, p=0.003, Figure 1B). There was a significant positive correlation of vitamin A levels on Day 0 with hemoglobin concentration (r=0.549, p=0.015, Figure 1D), and an inverse correlation between vitamin A levels and lactate dehydrogenase (r=-0.505, p=0.027, Figure 1F). Children with replete vitamin D levels exhibited significantly better peak virus-specific serum IgG (p=0.037) and IgA (p=0.011) responses (Figure 2A-B). Additionally, vitamin A, which plays an important role in mucosal immunity, correlated positively with virus-specific IgG (r=0.574, p=0.013) and IgA (r=0.480, p=0.044) in nasal passages on Day 30 (Figure 2C-D). Conclusions: In pediatric patients admitted to the hospital for acute parvovirus B19 infection, low vitamin A and D levels were associated with greater disease severity (greater hemolysis, lower hemoglobin concentration, and greater transfusion volumes). Higher vitamin levels were associated with better virus-specific antibody responses. While cause-effect relationships were not discerned in this study, we hypothesize that poor nutritional status contributed to poor outcomes and that efforts to improve nutrition may reduce the severity of parvovirus B19 disease in patients with SCD. Figure 1 Figure 1. Disclosures Hankins: UpToDate: Consultancy; Vindico Medical Education: Consultancy; Global Blood Therapeutics: Consultancy; Bluebird Bio: Consultancy.

Eculizumab as a Treatment for Hyper-Haemolytic and Aplastic Crisis in Sickle Cell Disease

Background: Patients with sickle cell disease can experience various crises including sequestration crisis, haemolytic crisis and aplastic crisis. Due to alloantibody formation, transfusion alloantibodies can cause a haemolytic crisis. Treatment involves avoiding packed red blood cell transfusions, as well as intravenous immunoglobulin, steroids and eculizumab to decrease the chances of haemolysis. Case description: We report the case of a 42-year-old man who was found to have worsening anaemia after packed red blood cell transfusion with evidence suggestive of haemolytic crisis. Due to reticulocytopenia, aplastic crisis was also suspected and later confirmed via parvovirus IgG and IgM titres. The patient did not improve with steroid and intravenous immunoglobulin therapy and was treated with eculizumab as a salvage therapy. Conclusion: Concurrent hyper-haemolytic crisis and aplastic crisis should be suspected in patients with features of haemolysis and reticulocytopenia. Prompt recognition and treatment with eculizumab are paramount in those who fail steroid and intravenous immunoglobulin treatment.

Human parvovirus B19: a review of clinical and epidemiological aspects in Brazil

Since the first evidence of human parvovirus B19 (B19V) infection in late 80s, several studies have been conducted to clarify the spectrum of clinical diseases in Brazil. B19V infection is prevalent in the general population and has exhibited a cyclical pattern of occurrence every 4–5 years, with the predominance of genotype 1 over 3b. During epidemic periods the wide range of clinical conditions, such as ertythema infectiosum, arthropathy, transient aplastic crisis, nonimmune hydrops fetalis and B19V-hepatitis were diagnosed. However, many infections are likely asymptomatic or have a self-limiting clinical course and are not readly diagnosed. Besides, the similarity of the symptoms of ertythema infectiosum to other rash diseases and the broadly circulation of arboviruses makes differential diagnosis more difficult. In this article, we provide a historical comprehensive overview of the research on parvovirus B19 conducted in Brazil, with a focus on the clinical and epidemiological aspects of the infection.

Parvovirus B19-Infected Tubulointerstitial Nephritis in Hereditary Spherocytosis

Background Human parvovirus B19 (B19V) causes glomerulopathy or microangiopathy, but not tubulopathy. We experienced an 11-year-old girl with spherocytosis who developed acute kidney injury on a primary infection of B19V. She presented with anuria, encephalopathy, thrombocytopenia, and coagulopathy, along with no apparent aplastic crisis. Methods Continuous hemodiafiltration, immunoglobulin, and intensive therapies led to a cure. Results A kidney biopsy resulted in a histopathological diagnosis of tubulointerstitial nephritis without immune deposits. The virus capsid protein was limitedly expressed in the tubular epithelial cells with infiltrating CD8-positive cells. Conclusions Viral and histopathological analyses first demonstrated B19-infected tubulointerstitial nephritis due to the aberrant viremia with hereditary spherocytosis.

Aplastic Crisis Induced by Human Parvovirus B19 Infection in a Previously Healthy Adult Male

Background: Human parvovirus B19 (B19 V) induced aplastic crisis is very rare and in this paper, we describe a healthy adult male suddenly developed acute aplastic crisis induced by B19 V was found to have hereditary spherocytosis (HS).Case presentation: A 31-year-old male presented with fever, general fatigue and dizziness. The complete blood counts showed severe anemia. Folate levels, glucose-6-phosphate dehydrogenase levels, the direct Coombs' test and osmotic fragility tests were all normal. And B19 V infection was proven both by the detection of B19 V DNA using PCR and the presence of B19 V IgM by serology and the patient improved following six units of packed red blood cells and antiviral treatment.Conclusions: This is the first report to describe a case with B19 V, EBV and CMV co-infection diagnosed in a patient with HS in China and DNA test of B19 V is recommended in acute aplastic crisis diseases.