Transcript Persistence of Parvovirus B19, genotype 2 in transplant patients Susanne Modrow

Persistence of
Parvovirus B19, genotype 2
in transplant patients
Susanne Modrow
Institut für Medizinische Mikrobiologie
Universität Regensburg
Disease Manifestation in immunocompetent individuals
Frequent
unspecific illness
Erythema infectiosum, fifth disease, slapped cheek disease (Ringelröteln)
transient anemia
transient mono-, oligo-, polyarthritis/arthropathy
Rare
Mono-, oligo-, polyarthritis
Henoch-Schönlein purpura/Papular-purpuric gloves-and-socks-syndrome (PPGSS)
Idiopathic thrombocytopenic purpura
Thrombocytopenia/granulocytopenia/pancytopenia
Virus-associated hemophagocytic syndrome (VAHS)
Acute liver failure/hepatitis
Vasculitis/giant cell arteritis/polyarteritis nodosa/myositis
Myocarditis
Glomerulonephitis
Chronic fatigue syndrome/meningitis/encephalitis
Gullian-Barré-syndrome
Cerebellar ataxia
Patients with special problems
Patients with increased
red blood cell turnover
severe anemia
Pregnant women
spontaneous abortion
aplastic crisis
Hydrops fetalis
intrauterine death
Immuodeficient patients chronic anemia
pure red cell aplasia
chronic thrombocytopenia
chronic granulocytopenia
chronic pancytopenia
chronic arthritis
myocarditis/pericarditis/acute heart failure
acute liver failure/hepatitis
meningitis/encephalitis
IVIG-treatment of a kidney transplant recipient
• Parvovirus B19-infection (genotype 2) was diagnosed in association
with severe anemia 2 months after transplantation
• Source of infection is unknown, the patient obtained several erythrocyte
concentrates
• During a period of 26 months three periods of severe anemia were
observed in combination with high viremia (> 4x1011 geq/ml)
• Repeated IVIG-treatment was associated with the reduction of virus
load to 100-1000 geq/ml and with resolvement of anemia
• Virus elimination from peripheral blood could not be achieved
• Today, > 50 months after transplantation, the patient displays low level
viremia without symptoms
• Recurrent high viremia may occur in persistenly infected patients
• Virus load has to be monitored in order to avoid severe symptoms by
early IVIG treatment
14
Transfusion
of red cells
Reticulocytes (%),
Haemoglobin (g/dl)
12
10
8
6
4
2
0
1E+17
1E+16
IgM
1E+15
1E+14
IgG
IVIG
1E+13
2d á 20g5d á 40g
1E+12
1E+11
5d á 40g
PCR
Parvovirus B19 cop/ml
1E+10
ELISA IgM / IgG:
negative
positive
1E+09
1E+08
PCR/qualitatve:
negative
positive
1E+07
1E+06
1E+05
1E+04
1E+03
1E+02
0
month post Tx
3
6
9
12
18
21
24
27
30
Phylogenetic analysis of parvovirus B19 genotypes 1-3
Parvovirus B19 – Genotypes 1 to 3:
Amino Acid Differences in the VP1-unique region
1
gt 1:
gt 2:
gt 3:
<- Epitope ->
50
MSKKSGKWWESDDKFAKAVYQQFVEFYEKVTGTDLELIQILKDHYNISLD
MSKESGKWWESDDKFAKDVYKQFVEFYKKVTGTDLELIQILKDHYNISLD
MSKTTNKWWESSDKFAQDVYKQFVQFYEKATGTDLELIQILKDHYNISLD
51
gt 1:
gt 2:
gt 3:
100
HPLENPSSLFDLVARIKNNLKNSPDLYSHHFQSHGQLSDHPHALSSSSSH
NPLENPSSLFDLVARIKSNLKDSPDLYSHHFQSHGQLSDHPHALSPSSSH
NPLENPSSLFDLVARIKSNLKNSPDLYSHHFQSHGQLSDHPHALSSSNSS
101
-----PLA2-------------- 150
gt 1:
AEPRGENAVLSSEDLHKPGQVSVQLPGTNYVGPGNELQAGPPQSAVDSAA
gt 2:
TEPRGENAVLSSEDLHKPGQVSIQLPGTNYVGPGNELQAGPPQSAVDSAA
gt 3:
AEPRGENAVLSSEDLHKPGQVSIQLPGTNYVGPGNELQAGPPQNAVDSAA
151--*---*----*-----*----200
gt 1:
RIHDFRYSQLAKLGINPYTHWTVADEELLKNIKNETGFQAQVVKDYFTLK
gt 2:
RIHDFRYSQLAKLGINPYTHWTVADEELLKNIKNETGFQAQAVKDYFTLK
gt 3:
RIHDFRYSQLAKLGINPYTHWTVADEELLKNIKNETGFQAQAVKDYFTLK
201
227
gt 1:
GAAAPVAHFQGSLPEVPAYNASEKYPS
gt 2:
GAAAPVAHFQGSLPEVPAYNASEKYPS
gt 3:
GAAAPVAHFQGSLPEVPAYNASEKYPS
Comparison of IgG reactivity using VP1-unique
region of genotypes 1 - 3 as antigens in ELISA
3
2,5
reactivity
2
VP1-ur/gt1
VP1-ur/gt2
1,5
VP1-ur/gt3
1
0,5
0
Sera B19/gt1
Sera B19/gt2
Sera B19-negativ
Comparison of IgG avidity using VP1-unique region of
genotypes 1 - 3 as antigens in ELISA
50
45
40
avidity index
35
30
VP-ur/gt1
25
VP-ur/gt2
VP-ur/gt3
20
15
10
5
0
sera B19/gt1
sera B19/gt2
Co-workers
Today in Regensburg:
Yesterday in Regensburg:
Dr. Antje Knöll
Dr. Annelie Plentz
Dipl.-Biol. Juha Lindner
Dipl.-Biol. Claudia Müller
Dr. Ulla Raab
Dr. Andrea Hemauer
Dr. Andreas Gigler
Dr. Simone Dorsch
Dipl.Biol. Markus Möbs
Dipl.-Bio. Regina Rabl
....... And outside in the rest of the world ...
PD Dr. Hartwig Lehmann, Pädiatrie, Universität Gießen
Prof. Dr. Philipp von Landenberg, Universität Mainz
Prof. Dr. Klaus Hedman, Institut für Virologie, Universität Helsinki
Dr. Bärbel Kaufmann, Purdue University, West Lafayette
Dr. Sean Doyle, National University of Ireland, Dublin