Parvovirus B19 and ME/CFS

The translation to Italian of this article is available here.

Introduction

Parvovirus B19 is a single-stranded DNA virus with a tropism for precursors of  Homo sapiens’ erythrocytes. It was discovered in 1975 (Cossart YE et al. 1975) and was associated with human disease in 1981 (Pattison JR. et al. 1981). Its genome consists of a linear single-stranded DNA with a length of 5.600 bases that includes the genes for the two capsid proteins VP1 and VP2 and for the non-structural protein NP1 (Trösemeier JH. et al. 2014). Its Linnaean classification is the one reported in the table below. Parvovirus B19 has a diameter of only 25 nm, and this explains its name: parvum is a Latin adjective that means small. In children, the acute infection is associated with erythema infectiosum (also known as Fifth disease). In immunocompetent adults, it can cause acute symmetric polyarthropathy, whereas in the immunocompromised host persistent B19 infection is manifested as pure red cell aplasia and chronic anaemia (Heegaard ED et Brown KE 2002). Parvovirus B19 spreads through respiratory secretions, such as saliva, sputum, or nasal mucus, when an infected person coughs or sneezes [R]. It is known to persist in peripheral white blood cells (Saal JG. et al. 1992). 

Parvovirus B19 and ME/CFS

Prolonged and chronic fatigue has been described during acute and convalescent parvovirus infection (Kerr JR et al. 2001) and it is associated with raised levels of TNF-α and INF-γ. A study followed 39 patients with acute Parvovirus B19 infection for an average of two years and reported that 5 (13%) of them developed CFS. Most of them had positive PCR and/or positive IgG in blood for B19. Deterioration in memory and concentration, post-exertional malaise, and myalgia were present in all of them. The prevalence of anti-VP1/2 IgG was about the same in patients and controls, while anti-NS1 IgG and DNA in serum where more prevalent in patients than in controls (Kerr JR. et al. 2002). In 2009 Fremont and colleagues searched for viral DNA in gut biopsies (from both the gastric antrum and the duodenum) and they found a higher prevalence in patients vs controls. And yet, patients with positive PCR for Parvovirus B19 DNA in biopsies had negative PCR in their blood (Frémont M. et al. 2009). Another study found a higher prevalence of anti-NS1 IgG in patients vs controls, whereas serum DNA, anti-VP1/2 IgG, anti-VP 1 IgM, anti-NS1 IgM were not different between patients and controls. Antibodies to NS1 were associated with arthralgia, among patients (Kerr JR. et al. 2010). Recently, another group confirmed a normal prevalence of anti-VP1/2 IgG in patients with an increase in anti-VP 1 IgM and serum DNA (Rasa S. et al. 2016).

1: biopsies from both the gastric antrum and the duodenum. 2: they used this kit. WBC, white blood cells.

I have found four cases of ME/CFS patients with confirmed active B19 infection (DNA in the blood) successfully treated with intravenous immunoglobulins, with rapid resolution of symptoms and clearance of the infection. In three cases the treatment was as follows: 400mg/kg/day for five days (Kerr JR. et al. 2003). In the remaining patient the posology is not reported (Jacobson SK. et al. 1997).

Discussion

Acute Parvovirus infection can lead to ME/CFS in more than 10% of cases (Kerr JR et al. 2001), (Kerr JR. et al. 2002). This prevalence is in agreement with the percentage of those who develop ME/CFS after Giardia duodenalis (Mørch K et al. 2013), Epstein-Barr virus, Coxiella burnetii, and Ross River virus (Hickie I. et al. 2006) symptomatic and laboratory-confirmed infections (see also this post). This would suggest that different pathogens can trigger a common pathway that ultimately leads to ME/CFS. And yet, markers of active Parvovirus B19 infection are more common among ME/CFS patients than in healthy controls: this is the case of viral DNA in gastric mucosa (Frémont M. et al. 2009) and serum (Rasa S. et al. 2016), and of anti-VP 1 IgM (Rasa S. et al. 2016). Moreover, the synthesis of specific IgGs to NS1 is significantly more prevalent in patients vs controls, and this kind of antibodies has been documented to be more frequent in case of more severe and persistent course of B19 infection (von Poblotzki A. et al. 1995). Four cases of ME/CFS with active B19 infection were successfully treated with IVIG (Jacobson SK. et al. 1997), (Kerr JR. et al. 2003). At the same time, the seroprevalence of B19 with regards to VP 1/2 IgG is the same in patients and controls (Kerr JR. et al. 2002), (Kerr JR. et al. 2010), (Rasa S. et al. 2016) which means that the number of individuals that get the virus in their lifetime is the same in patients and controls.

Conclusion

Seroprevalence of Parvovirus B19 is the same in ME/CFS patients and controls, but active infection is more prevalent in cases versus controls. Moreover, patients are more likely to have IgGs to NS1, a marker of persistent course of B19 infection. IVIGs might be a therapeutic option in ME/CFS patients with active B19 infection.