Parvovirus

Category: Illness or disabilities

Type

Involuntary

Introduction and description

Parvovirus is the common name applied to all the viruses in the Parvoviridae taxonomic family. The Parvoviridae are a family of small, rugged, genetically-compact DNA viruses.  There are currently over 75 species in the family, divided among 13 genera and two subfamilies:

Subfamily Densovirinae - infects invertebrates.  To date, very few viruses from the Densovirinae have been studied and sequenced, so the taxonomy may poorly reflect the true diversity of this subfamily.  The genera are

•  Ambidensovirus - Genus includes 11 recognized species that infect insects from multiple orders, crayfish (crustacea) or sea stars (echinoderms)
• Brevidensovirus - Genus includes 2 recognized species that infect insects from the order Diptera
• Hepandensovirus - Genus includes a single species, infecting decapod shrimp
• Iteradensovirus - Genus includes 5 recognized species that infect insects from the order Lepidoptera
• Penstyldensovirus - Genus includes a single species, infecting decapod shrimp

Subfamily: Parvovirinae  - infect vertebrates .  Currently, viruses that infect humans are recognized in 5 genera: Bocaparvovirus (human bocavirus 1–4, HboV1–4), Dependoparvovirus (adeno-associated virus 1–5, AAV1–5), Erythroparvovirus (parvovirus B19, B19V), Protoparvovirus (bufavirus 1–3, BuV1–3; cutavirus, CuV) and Tetraparvovirus (human parvovirus 4 G1–3, PARV4 G1–3).

• Amdoparvovirus - Genus includes 4 recognized species, infecting mink, fox, racoon dogs and skunk
• Aveparvovirus - Genus includes a single species, infecting turkeys and chickens
• Bocaparvovirus - Genus includes 21 recognized species, infecting mammals from multiple orders, including primates
• Chapparvovirus - Proposed additional genera include Chapparvovirus. Consideration of the taxon awaits further investigation and ultimately a decision by the ICTV
• Copiparvovirus - Genus includes 2 recognized species, infecting pigs and cows
• Dependoparvovirus - Genus includes 7 recognized species, infecting mammals, birds or reptiles
• Erythroparvovirus - Genus includes 6 recognized species, infecting mammals, specifically primates, chipmunk or cows
• Protoparvovirus - Genus includes 11 recognized species, infecting mammals from multiple orders, including canines and primates
• Tetraparvovirus - Genus includes 6 recognized species, infecting primates, bats, pigs, cows and sheep

Canine parvovirus, for example, causes a virulent and contagious disease in dogs. In cats, a parvovirus causes feline distemper.  Because the viruses require actively dividing cells to replicate, the type of tissue infected varies with the age of the animal.

Parvoviruses are among the smallest viruses (hence the name, from Latin parvus meaning small) and are 18–28 nm in diameter.  Perhaps due to their extremely small size, parvoviruses were only recently discovered, for example:

•  Dependoparvoviruses, the first parvoviruses to be discovered, were first isolated in the 1960s. Dependoviruses require helper viruses (e.g. herpesviruses) to replicate
• Parvovirus B19, also known as erythroparvovirus 1, or erythrovirus B19, in the genus Erythroparvovirus, was the first known parvovirus to infect humans.  It was discovered in London by Australian virologist Yvonne Cossart in 1974. The virus is named for the patient code of one of the blood bank samples involved in the discovery.

Parvoviruses are believed to be very old, despite being discovered only relatively recently.  The most recent common ancestor of the extant strains of B19, for example, has been dated to about 12,600 years ago. Three genotypes - 1,2 and 3 - are recognised. A recombination between types 1 and 3 gave rise to genotype 2 between 5,000 and 6,800 years ago.

Symptoms

HboV1–4 - human bocavirus 1–4

Human bocavirus 1 [HBoV1] is an agent of acute respiratory infection frequent in children and appears to cause severe wheezing that can be mistaken for asthma. It can also cause inflammatory diseases of the middle ear, and pneumonia in infants in the absence of epidemiological risk factors and comorbidities.

Three new members of the genus Bocavirus, human bocavirus 2 (HBoV2), human bocavirus 3 (HBoV3), and human bocavirus 4 (HBoV4), were discovered relatively recently. HBoV2-4 occur mainly in the gastrointestinal tract but rarely in the respiratory tract, research into these viruses is ongoing

AAV1–5 - adeno-associated virus 1–5

Adeno-associated virus (AAV) infects humans and some other primate species. It belongs to the genus Dependoparvovirus. The virus is a small (20 nm) replication-defective, non-enveloped virus.

AAV is believed not to cause disease, but Dependoviruses require helper viruses (e.g. herpesviruses) to replicate and they may confer some more virulent properties to their symbiotic viral partners. The virus itself appears to cause a very mild immune response.  AAV vectors integrate into the host cell genome.  Despite an apparent lack of understanding of the effect of interaction between viruses, wild-type AAV has attracted considerable interest from gene therapy researchers and has even proceeded to trials.  Needless to say this has caused some concern amongst those whose research goal is in finding the cause of the diseases being targeted, simply because the cause of the disease may be the very virus helped by AAV. 

BuV1–3  - bufavirus 1–3, and cutavirus, CuV

Research into Bufavirus is very recent.  In one study in 2016, for example, results indicated that BuV infections might be widespread in Asia. The BuV-specific humoral immune responses appeared to be strong and long-lasting, pointing to systemic infection in humans.  Bufavirus was only discovered in 2012 using metagenomics testing.  One known symptom is diarrhoea.

Cutavirus is a new human protoparvovirus related to human bufavirus and preliminarily named cutavirus.

PARV4 G1–3 - human parvovirus 4 G1–3

Parvovirus 4 (PARV4) was first discovered in 2005, in a hepatitis B virus-infected injecting drug user (IDU). To date, the best evidence about PARV4 transmission is parenteral roots which comes from IDU individuals. It seems that the prevalence of the virus in the normal population is very low. [PMID:  29910855]

Human parvovirus 4 (PARV4) has also been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users, as well as HCV infected and HBV infected subjects.  No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. [PMID:  22235298]

B19V - parvovirus B19,  [which causes Fifth disease]

B19 virus is most known for causing disease in the paediatric population; however, it can also affect adults.  Any age may be affected, although it is most common in children aged six to ten years.  

It is the classic cause of the childhood rash called fifth disease or erythema infectiosum,  The associated bright red rash of the cheeks gives it the nickname "slapped cheek syndrome".  Fifth disease, however, is only one of several expressions of Parvovirus B19.

In temperate climates the infection usually occurs in spring. The virus is spread by respiratory droplets; blood-borne transmission, however, has been reported.  Most persons with parvovirus B19 infection are asymptomatic or have mild, nonspecific, cold-like symptoms.

Infected patients with normal immune systems are contagious before becoming symptomatic. The incubation period is 4–21 days, with the average being 16 to 17 days. Symptoms last about a week.  The following symptoms are characteristic:

• The disease commences with high fever and malaise, when the virus is most abundant in the bloodstream. There may be headache, nausea and diarrhoea.
• As the fever breaks, a red rash forms on the cheeks, with relative pallor around the mouth ("slapped cheek rash"), sparing the nasolabial folds, forehead, and mouth.  Patients are usually no longer infectious once the characteristic rash of this disease has appeared.
•  "Lace-like, (reticular)" red rash on trunk or extremities then follows the facial rash.. This lacy, itchy full-body rash can last up to 3 weeks.  There is exacerbation of the rash by sunlight, heat, and stress.   In adults the rash is often absent
• Arthralgias and arthritis are commonly reported in association with parvovirus B19 infection in adults. Typically joint symptoms last 1–3 weeks, but in 10–20% of those affected, it may last weeks to months.  Arthropathy, which tends to be symmetrical and involve multiple joints, is more common among middle-aged women
• Most patients have a decrease of erythropoiesis (production of red blood cells) during parvovirus 19 infection
• Teenagers or young adults may develop the so-called "Papular Purpuric Gloves and Socks Syndrome".
  …We present four children with unusual exanthems associated with parvovirus infection: a purpuric periflexural pattern, a purpuric vasculitic pattern, and a combination of the two.  PMID:  30230024

The illness is self-limiting, and most healthy people recover with lasting immunity to reinfection.  Individuals with B19 IgG antibodies are generally considered immune to recurrent infection. About half of adults are B19-immune due to a past infection.

Risks during pregnancy

Parvovirus infection in pregnant women is associated with hydrops fetalis.  This is due to a combination of haemolysis of the red blood cells, as well as the virus directly negatively affecting the red blood cell precursors in the bone marrow.  Parvovirus infects the fetal liver, the main site of erythrocyte production during early development, and can induce severe anaemia and perhaps myocarditis, both of which may lead to congestive heart failure (“hydrops fetalis”).

Parvovirus can also result in miscarriage or stillbirth. There is a 5%–9% risk of fetal loss among infected pregnant women; the risk appears to be greatest in the second trimester.  The risk of transplacental infection among women who are infected during pregnancy is about 30%.

Other complications

Certain populations are vulnerable to complications from the interrupted erythropoiesis that arises with infection. These populations include people with hematologic disorders that cause an increased rate of erythrocyte destruction, such as hereditary spherocytosis and sickle cell disease

People who have a high demand for erythrocyte production are at risk of experiencing severe anaemia or a transient aplastic crisis. In addition, people who are unable to generate an adequate antibody response, such as people with HIV infection, are at risk of persistent parvovirus infection.

Cause

Not enough is known about HboV1–4, AAV1–5, BuV1–3; CuV) and PARV4 G1–3 to reliably provide more detail, however, Parvovirus B19 (B19V) has been studied for some time and many new and interesting facts are beginning to emerge about this virus that may affect our understanding of the others in this group.

The role of helper viruses

Parvovirus B19 is a small non-enveloped DNA virus. It is a human pathogen that preferentially replicates in erythroid progenitor cells.  Erythroid progenitor cells are self-renewing stem cells that give rise to only one type of cell, namely, the erythrocytes (red blood cells). 

B19V is thus an autonomous parvovirus, representing a majority of the Parvoviridae family members that can replicate by themselves in host cells.  In other words B19 has no need of helper viruses to replicate.  This is in contrast to AAV that requires coinfection of a helper virus, such as adenovirus, for replication. 

But, recent research has shown that the genome of human parvovirus B19 virus can replicate in non-permissive cells with the help of adenovirus genes and produces infectious virus.  In other words it has expanded its range of infection by using a helper virus.

B19V, research has discovered, finds its way and persists in many other non-erythroid tissues.  B19V capsid RNA or proteins have been reported in bone marrow, colon, heart, liver, lymphoid, synovial, testicular, and thyroid tissues and more are being found. [PMID: 24998884]

The role of latency

So B19 is a virus capable of latency, which can establish a latent infection in numerous organs.  It occurs world-wide, kicks the immune system into life with a vengeance, and the body is able to remember the infection.  Even if one doesn’t catch this virus when young, it seems that most adults eventually catch it anyway.  The symptoms are generally relatively mild when young and may even be asymptomatic.  This virus is extremely difficult to detect - Parvovirus B19 measures only 23–26 nm in diameter and ranks among the smallest DNA viruses. 

In battle or symbiosis?

One of the other interesting and possibly important things about B19, is that it appears in some cases to act with other viruses, besides the adenovirus mentioned above.  It is almost impossible to work out whether the virus is actually in battle with the other virus and the symptoms are simply a by-product of the battle, or whether the two viruses act in concert to produce a more severe outcome.  Allies or enemies?  Or both?  In the section on the Coxsackievirus, we saw that the human body is a battleground of competing pathogens – bacteria with bacteriophages, viruses, fungi, and parasites, all using the body as a resource to stay alive.  In some cases they deliberately kill the body in order to spread to other bodies, enabling themselves to be released from their prison body.  It is relatively early days for research in this area but the signs are all there that B19 is a major pathogenic player:

and

But it might have made the outcome more severe. 

Cancer?

B19V uses the cellular DNA replication machinery for viral DNA replication.  STAT5 in cells controls cell growth and division, or cell proliferation.  It regulates programmed cell death, or apoptosis, as well as cell differentiation and inflammation.  There appears to be some indication that B19 is able to control STAT5 in order to replicate.  This may indicate that B19 has some role in the development of cancer [PMID:  29922597].  Please note however that this is a very tentative hypothesis, based on very recent research that has not been fully explored. 

The role of Immunosuppression and immunosuppressants

You may be at risk for serious complications from B19 infection if you have a weakened immune system caused by, for example, stress - including grief, fear, depression, anxiety and so on -  or HIV infection.  Hypoxia stresses the body too and has been shown to boost productive B19V infection through enhancement of erythropoietin receptor signaling

So people with atherosclerosis or endothelial dysfunction, smokers, those with lung disease, or those who suffer from sleep apnea [all of which result in hypoxia] may also suffer an outburst of B19 infection.

But far more dangerous appears to be the role of Immunosuppressants – sometimes simply known as ‘steroids’.  Immunosuppressants suppress the immune system and are increasingly being implicated in a large number of illnesses which are complications of simpler infections.

Immunosuppressants are often given to those with so-called Auto-immune diseases.  Under the entirely mistaken belief that the body attacks itself using its immune system, immunosuppressants are used to suppress the ‘attack’.  But the body is normally attacking pathogens - often difficult to detect because they are small or not being looked for.  Smoke particles, nanoparticles and very small viruses, for example, go undetected.

Dexamethasone is an anti-inflammatory and immunosuppressant.  Ironically it is on the World Health Organization's List of Essential Medicines. It is available in most areas of the world and is inexpensive and thus frequently prescribed and it is implicated in causing viral encephalitis complications

Given that illness and disease is caused by either pathogens such as viruses, bacteria, fungi or parasites; or toxins like heavy metals or pesticides, herbicides and insecticides;  radiation, and nutritional deprivation; it seems extremely unwise to suppress the immune system – giving the cause of the illness the chance to wreak more havoc completely unopposed by the body’s only defence.  Admittedly it gives the patient the impression that since the symptoms have disappeared they must be getting better, however, this is not at all helpful - they will clearly eventually become a great deal worse and may well die…. From cancer, from heart disease etc etc. 

It might be worth knowing that according to eHealthme, which collects the ADRs submitted by doctors to the FDA and SEDA, the most common side-effect for the immunosuppressant Rituxan [the trade name for rituximab ] is death.

Destruction of the Blood brain barrier

A range of toxic substances cause the destruction of the blood brain barrier – everything from aluminium, lead, cadmium, mercury and nanoparticles, to those vaccines which have an aluminium adjuvant:

Diagnosis, Prevention and Treatment

At the moment, there are no treatments that directly target Parvovirus B19 virus or any of the other viruses described here.

Diagnosis

These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results.[ PMID: 27806994]

Metagenomic testing is also possible in some countries.

Prevention

There is no need to keep infected children away from school, since in most people this illness is mild and self-limiting, and most children are no longer infective by the time the rash appears and the diagnosis is made. Frequent hand washing can reduce the spread of respiratory droplets. The US Centers for Disease Control and Prevention says that it “does not recommend that pregnant women be routinely excluded from a workplace where an outbreak is occurring. The decision to stay away is a personal decision made after the woman's discussions with her family, doctor and employer”.

It is worth noting that B19 can be acquired via blood transfusion

and

Treatment

Most healthy infected people do not need to consult a physician.. There is no specific therapy, warmth, sleep, rest, adequate fluid intake, are all advised.

References and further reading

• Emerg Infect Dis. 2012 Feb;18(2):264-71. doi: 10.3201/eid1802.111293.  Association of human bocavirus 1 infection with respiratory disease in childhood follow-up study, Finland.  Meriluoto M1, Hedman L, Tanner L, Simell V, Mäkinen M, Simell S, Mykkänen J, Korpelainen J, Ruuskanen O, Ilonen J, Knip M, Simell O, Hedman K, Söderlund-Venermo M.
• J Infect Dis. 2011 Nov;204(9):1403-12. doi: 10.1093/infdis/jir525. Epub 2011 Sep 15.  Seroepidemiology of human bocaviruses 1-4.  Kantola K1, Hedman L, Arthur J, Alibeto A, Delwart E, Jartti T, Ruuskanen O, Hedman K, Söderlund-Venermo M.
• Virus Res. 2014 Sep 22;190:8-16. doi: 10.1016/j.virusres.2014.06.017. Epub 2014 Jul 3.  Persistent parvovirus B19 infection in non-erythroid tissues: possible role in the inflammatory and disease process. - Adamson-Small LA1, Ignatovich IV2, Laemmerhirt MG3, Hobbs JA4.
• Vet Clin North Am Small Anim Pract. 2010 Nov;40(6):1041-53. doi: 10.1016/j.cvsm.2010.07.007.  Canine parvovirus. - Goddard A1, Leisewitz AL.  PMID:  20933134
• CMAJ. 2005 Mar 15; 172(6): 743. doi:  10.1503/cmaj.045293 PMCID: PMC552884 PMID: 15767606  Public Health  Parvovirus B19 infection: fifth disease and more - Erica Weir
• Young NS, Brown KE. Parvovirus B19. N Engl J Med 2004;350:586-97
• Parvovirus B19 infection and pregnancy. Atlanta: US Centers of Disease Control and Prevention.
• Acta Virol. 2014;58(3):199-213.  Human parvovirus B19: a review.  Rogo LD, Mokhtari-Azad T, Kabir MH, Rezaei F.
• Pediatr Dermatol. 2018 Sep 19. doi: 10.1111/pde.13623. [Epub ahead of print]  Unusual skin manifestations associated with parvovirus B19 primary infection in children.  Ferrari B1, Díaz MS1, López M1, Larralde M1,2.
• Am Fam Physician. 2007 Feb 1;75(3):373-6.  Clinical presentations of parvovirus B19 infection.  Servey JT1, Reamy BV, Hodge J.
• Arch Virol. 2014 May;159(5):1239-47. doi: 10.1007/s00705-013-1914-1. Epub 2013 Nov 9.  The family Parvoviridae.  Cotmore SF1, Agbandje-McKenna M, Chiorini JA, Mukha DV, Pintel DJ, Qiu J, Soderlund-Venermo M, Tattersall P, Tijssen P, Gatherer D, Davison AJ.
• Autoimmun Rev. 2003 Jun;2(4):218-23.  Parvovirus B19 infection and autoimmune disease.  Lehmann HW1, von Landenberg P, Modrow S.
• J Med Virol. 2011 Apr;83(4):710-6. doi: 10.1002/jmv.22008.  Prevalence and association of human parvovirus B19V with hepatitis B and C viruses in Nigeria.  Opaleye OO1, Fagbami AH, Lalremruata A, Kun JF.
• Mühlemann B, Margaryan A, Damgaard PB, Allentoft ME, Vinner L, Hansen AJ, Weber A, Bazaliiskii VI, Molak M, Arneborg J, Bogdanowicz W, Falys C, Sablin M, Smrčka V, Sten S, Tashbaeva K, Lynnerup N, Sikora M, Smith DJ, Fouchier RAM, Drosten C, Sjögren KG, Kristiansen K, Willerslev E, Jones TC (2018) Ancient human parvovirus B19 in Eurasia reveals its long-term association with humans. Proc Natl Acad Sci U S A
• Neurology. 2001 Oct 9;57(7):1336-7.  Status epilepticus due to human parvovirus B19 encephalitis in an immunocompetent adult.  Skaff PT1, Labiner DM.  Department of Neurology, University of Arizona College of Medicine, Tucson 85724-5023, USA.
• Front Cell Infect Microbiol. 2018 Jun 5;8:166. doi: 10.3389/fcimb.2018.00166. eCollection 2018. Recent Advances in Replication and Infection of Human Parvovirus B19.  Ganaie SS1, Qiu J1.
• J Child Neurol. 2008 Sep;23(9):1078-80. doi: 10.1177/0883073808315420. Epub 2008 May 16.  Severe ataxia as a complication of human parvovirus B19 acute encephalitis in a child.  Greco F1, Barbagallo ML, Chiodo DC, Guglielmino R, Sorge G.
• J Virol. 2018 Feb 12;92(5). pii: e01881-17. doi: 10.1128/JVI.01881-17. Print 2018 Mar 1.  Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.  Zou W1, Wang Z1, Xiong M2, Chen AY1, Xu P1, Ganaie SS1, Badawi Y3, Kleiboeker S4, Nishimune H3, Ye SQ2, Qiu J5.
• Clin Microbiol Rev. 2017 Jan;30(1):43-113.  Human Parvoviruses.  Qiu J1, Söderlund-Venermo M2, Young NS3.
• CMAJ. 2013 Oct 15;185(15):1342-4. doi: 10.1503/cmaj.121565. Epub 2013 Aug 26.  Parvovirus infection mimicking systemic lupus erythematosus.  Cooray M, Manolakos JJ, Wright DS, Haider S, Patel A. PMID:  23979870
• Nihon Naika Gakkai Zasshi. 2013 Mar 10;102(3):708-9.  [Case report: a case of lupus-like presentation associated with human parvovirus B19 infection].  [Article in Japanese]  Majima S1, Ota T, Omoto A, Fukuda W. PMID: 23777162
• Pediatr Infect Dis J. 2006 Oct;25(10):898-901.  Acute human parvovirus B-19 infection in hospitalized children: A serologic and molecular survey.  Miron D1, Luder A, Horovitz Y, Izkovitz A, Shizgreen I, Ben David E, Ohnona FS, Schlesinger Y.
• Klepfish, A.; Rachmilevitch, E.; Schattner, A. (2006). "Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment". European Journal of Internal Medicine. 17 (7): 505–507. doi:10.1016/j.ejim.2006.05.002. PMID 17098597

Related observations

Hallucination

• Neuroimmunology of bipolar affective disorder 027589
• Neurological aspects of human parvovirus B19 infection: a systematic review 027588
• Parvovirus B19 seroprevalence in a group of schizophrenic patients 027585
• Polymicrogyria and Congenital Parvovirus B19 Infection 027595

Other observations

• Frequency and significance of parvovirus B19 infection in patients with rheumatoid arthritis 027594
• Human parvovirus B19 in Iranian pregnant women: a serologic survey 027587
• Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome 027596
• Parvovirus B19 infection of brain: possible role of gender in determining mental illness and autoimmune thyroid disorders 027591
• The role of parvovirus in the etiology of somatic pathology 027592
• Wells' syndrome associated with parvovirus in a 5-year old boy 027593