"Numbering based on GenBank accession no. AF162273 (isolate HV). aa, amino acids.

"Numbering based on GenBank accession no. AF162273 (isolate HV). aa, amino acids.

signals the decline of infectivity. The infectious period starts 7 days before onset of rash. Clusters of acute primary infection occur in spring and early summer, with regional epidemics recurring every 4-5 years.[5]

The prevalence of B19-specific IgG antibodies increases with age to about 80% in the elderly. The annual seroconversion rate among susceptible women of child-bearing age is estimated to be 1.5%, increasing about 10fold during epidemics.[6] The prevalence of B19 DNA in blood donors varies between 1:200 and 1:35,000.[5] Current virucidal procedures applied to blood products fail to prevent the transmission of B19 virus. However, B19 loads of <104 0 genomes per milliliter of blood are regarded as unlikely to be contagious.[7]

Molecular Epidemiology

B19 viruses exhibit a remarkably high degree of sequence conservation, with a <2% variation between temporally and geographically widely separated isolates. However, the VP1u fragment has been reported to vary by up to 8% in chronically infected patients.[8] This might reflect evasion of neutralization as one mechanism of persistence because VP1u is predominantly involved in the formation of neutralization-relevant epitopes.

Recently, several genetically distinct B19-like parvovirus isolates were obtained from patients in France. Servant et al.[9] have proposed distinguishing between three genotypes [a classical B19-like (genotype 1), aLali-like genotype (genotype 2), and a V9-like genotype (genotype 3)], which are equidistantly related to each other (differences of up to 14.2% across the whole genome) and were shown to cocirculate. Although the clinical spectrum of the newly discovered genotypes appears to resemble that of the B19 lineage, explicit differences in the p6 promoter region (up to 25.2%) point toward distinct cell tropisms. The high ratio of synonymous vs. nonsynonymous mutations characterizing these genotypes indicates ancient separation and long-term evolution of these viruses.[9]

CLINICAL ASPECTS Immunocompetent Hosts

Infection in immunocompetent hosts is asymptomatic in about 25% of cases. During childhood, the clinical hallmark of acute B19 infection is an exanthematous malar rash (''slapped cheeks''), also referred to as erythema infectiosum or fifth disease (to be distinguished from measles, rubella, scarlet fever, and varicella). In persons with normal hematopoiesis, parvovirus B19 induces a clinically unapparent self-limited transient anemia and reticulocytopenia.[10] Apoptotic death of nonpermissive megakaryocytes due to overexpression of NS1 protein[11] occasionally leads to thrombocytopenia, especially in children.

Symmetrical peripheral arthropathies affect about 60% and 30% of acutely infected adult females and males, respectively. In the majority of cases, clinical symptoms usually resolve within 4 weeks because of a classical Th1 response, which aids in clearing B19 virus through VP2-specific IgM and high-affinity neutralizing VP1-specific

IgG antibodies.[5] However, in some cases, B19 DNA can be detected in plasma—albeit only by the most sensitive amplification techniques—for months and even years after symptoms have receded.

Immunity following uncomplicated recovery is believed to ensure life-long protection. Whether B19 infection plays a causal, putatively HLA-restricted role in chronic joint diseases and various other vasculitic and neurological disorders is still being debated.[12] In individuals with elevated red blood cell turnover rates (e.g., sickle cell anemia, congenital erythrocyte membrane defects, and enzymopathies), parvovirus B19 infection may lead to a transient aplastic crisis (TAC) that can prove fatal if not treated promptly.[5,10]

Infection During Pregnancy

About 30-50% of women of child-bearing age are susceptible to B19 infection. The annual seroconversion rate in susceptible women of child-bearing age is estimated to be 1.5%. The risk of infection is highest in women with infected children in the household.[6,13]

The risk of fetal loss appears to be highest (9-15%) in mothers infected during the first 20 weeks of gestation. The highest risk of fetal loss coincides with the period of highest fetal hepatic hematopoietic activity in the second trimester.[13-15]

The risk of hydrops fetalis developing 2-6 weeks after primary maternal infection varies between 0% and 3%. About two thirds of all cases shows remission either spontaneously or after intrauterine transfusion of blood containing B19-neutralizing antibodies.[13,16] The presence of virions in the nuclei of cardiac myocytes suggests that, in addition to B19 fetal anemia, direct cardiac involvement plays a role in the pathogenesis of B19-

induced hydrops fetalis.[12]

Cardiac Manifestations

Cardiac myocytes are fully B19-permissive only in the fetus. However, B19 DNA has also been detected in P-antigen-bearing endothelial cells and myocytes of the heart in patients with myocarditis or dilated cardiomyop-athy who otherwise have no signs of viremic B19 infection.[17-19]

Infection in Immunodeficient Patients

Life-threatening pure red cell aplasia (PRCA) is observed in patients who are unable to mount appropriate titers of neutralizing antibodies against B19 because of severe congenital or acquired immunodeficiencies. In most cases, a chronic persisting course, which demands therapeutic intervention, develops.[10] Recent findings indicate an increased risk of kidney and heart allograft rejection in transplant patients with nonacute, low-level parvovirus B19 DNA (< 1000 genomes per milliliter of blood), which is potentiated by simultaneous infection with the human cytomegalovirus.

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Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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