Clinical and laboratory findings in patients with persistent parvovirus 19 infection

Parvovirus B19 (B19) is the etiological agent of the common childhood disease, erythema infectiosum (EI), also named fifth disease. About 50% of humans are infected during childhood, but the virus is also transmitted to adults and about 80 % of the elderly are seropositive. Apart from asymptomatic infection, which is common, the clinical presentations in EI are usually slight catarrhal symptoms and fever followed by rash, typically intense on cheeks and later distributed on the extensor parts of legs and arms. For infected adults, the rash is less common, whereas the frequency of arthropathy, which may last for months or years, is about 50%. The main replicative sites of the virus are erythropoetic cells, and anaemia is a well-known manifestation of the infection, especially in immunocompromised patients. Pregnant women,when infected, are at risk of spontaneous abortion, hydrops fetalis and, later in pregnancy, intrauterine fetal death. B19 has also been associated with rheumatologic diseases, hepatitis, myocarditis and neurological manifestations.

In 1993, we used PCR-technique and found B19 DNA in the bone marrow (BM) of a patient with chronic fatigue, anaemia and leukopenia. Since then, we have followed her and other patients with chronic symptoms of fatigue, arthralgia and fever and found that some of them have persistent B19 DNA in BM for years after primary infection. The prevalence of B19 DNA in BM in the general population was not previously Imown To get a hint of the frequency, we tested the BM of 100 patients with haematological disorders, from whom BM samples were available, and in 4% B 19 DNA PCR was positive. In the studied group, 59% were B 19 IgG-positive and we concluded that B19 DNA in BM is not a general finding in seropositive individuals.

Arthropathy is a common manifestation of B 19 infection in adults and sometimes even meets the official criteria for rheumatoid arthritis. Consequently, the frequency of B 19 DNA in BM of rheumatic patients is of interest. We studied a group of 50 patients with various rheumatological diseases. B19 DNA was found in 13 of 50 patients (26%), a significantly higher level than in our previous study.

Immunocompromised patients are susceptible to B19 infection, but our hypothesis is that individuals, who are otherwise immunocompetent, may have a selective immune deficiency with respect to B19 causing the virus to persist and evoke symptoms of chronic immunological stimulation. To confirm this hypothesis, we have studied patients with persistent B19 DNA in BM with regard to general immunological parameters such as HLA-type, lymphocyte subpopulations and cytokine profiles. We also investigated the specific CD8 T-cell response to B19 antigens with an ELISpot assay for detecting IFNã production. Although the patients with persistent B 19 DNA in BM had no general, uniform immunological aberration, their B19 specific cellular immune responses diverged from those of controls supporting our hypothesis of a selective immune deficiency

List of scientific papers

I. Lundqvist A, Tolfvenstam T, Bostic J, Soderlund M, Broliden K (1999). Clinical and laboratory findings in immunocompetent patients with persistent parvovirus B19 DNA in bone marrow. Scand J Infect Dis. 31(1): 11-6.
https://pubmed.ncbi.nlm.nih.gov/10381211

II. Lundqvist A, Tolfvenstam T, Brytting M, Stolt CM, Hedman K, Broliden K (1999). Prevalence of parvovirus B19 DNA in bone marrow of patients with haematological disorders. Scand J Infect Dis. 31(2): 119-22.
https://pubmed.ncbi.nlm.nih.gov/10447317

III. Lundqvist A, Isa A, Tolfvenstam T, Kvist G, Broliden K (2005). High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients. J Clin Virol. 33(1): 71-4.
https://doi.org/10.1016/j.jcv.2004.11.011

IV. Isa A, Lundqvist A, Lindblom A Tolfvenstam T, Broliden K (2006). Cytokine responses in acute and persistent human Parvovirus B19 infection. Clin Exp Immunol. [Accepted]
https://doi.org/10.1111/j.1365-2249.2006.03286.x

V. Isa A, Norbeck O, Hirbod T, Lundqvist A, Kasprowicz V, Bowness P, Klenerman P, Broliden K, Tolfvenstam T (2006). Aberrant cellular immune responses in humans infected persistently with parvovirus B19. J Med Virol. 78(1): 129-33.
https://doi.org/10.1002/jmv.20514