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Parvovirus B19 infection in Hong Kong.

Human parvovirus B19 is a small DNA virus that can cause a number of diseases, notably erythema infectiosum in children, and aplastic crisis in patients with chronic haemolytic disorders. With the availability of serological tests for parvovirus infection, much is known about the prevalence of this virus in the Western population. However, there have not been any data on the epidemiological pattern of parvovirus B19 infection in Hong Kong and its surrounding region. In this report we have studied the sero-prevalence of parvovirus B19 in Hong Kong in 1983 and 1993, and were able to show a low incidence of parvovirus infection in the intervening 10 years, leading to a shift in the prevalence rate of parvovirus infection in the general population. From 1991 to 1996, of 276 patients presenting with illness which might have been caused by B19, only 2.5% were positive for IgM and 19.6% for IgG anti-B19. The prevalence of IgG anti-B19 among patients with thalassaemia major requiring frequent blood transfusion in 1995 was similar to those in the same age group in the general population, substantiating the observation that B19 infection was not common in Hong Kong in recent years.

Adolescent↗

Parvovirus H-1-induced cell death: influence of intracellular NAD consumption on the regulation of necrosis and apoptosis.

The autonomous parvovirus H-1 exerts tumor-suppressive effects in living organisms and has been shown to specifically interfere with the survival of transformed cells in culture. The mechanism(s) by which H-1 virus induces death of transformed cells is not yet well understood. It has recently been reported that H-1 virus induces apoptotic cell death in the human monocytic U937 cell line, as assessed by biochemical and morphological changes of infected cells (Rayet, B., Lopez-Guerrero, J.-A., Rommelaere, J., Dinsart, C., 1998. Induction of programmed cell death by parvovirus H-1 in U937 cells: connection with the TNFalpha signalling pathway. J. Virol. 72, 8893-8903). Here we show that parvovirus H-1 infection induced early biochemical changes pointing to apoptotic events also in the transformed human keratinocyte cell line, HeLa, and the transformed rat fibroblast cell line, P1. Morphologic changes, however, and in particular the early breakdown of plasma membrane integrity, suggested that apoptosis did not go to completion, leading to necrotic cell death as the major result of parvovirus infection of HeLa and P1 cells. Parvovirus infection of these, and to a significantly lesser extent of U937 cells, was accompanied by rapid depletion of intracellular NAD stores. Inhibition of NAD-consuming enzymes interfered with parvovirus-induced NAD depletion and increased the proportion of H-1 virus-infected cells displaying apoptotic features of cell death. In contrast, a similar prevention of NAD depletion through stimulation of NAD production had little influence on the cell death pathway, suggesting that NAD-consuming enzymes may promote necrosis in a direct way rather than through inducing the overall drop of intracellular NAD.

Animals↗

Parvovirus B19 DNA in kidney tissue of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) represents a clinicopathological syndrome with diverse causes. We examined the possibility that some cases of FSGS are associated with parvovirus B19 infection. We studied renal biopsy tissue from 40 patients, including those with idiopathic FSGS, collapsing FSGS, membranous nephropathy, and minimal change disease, as well as normal renal tissue removed at the time of nephrectomy from 4 patients. DNA was extracted from frozen blocks of kidney tissue and amplified using nested polymerase chain reaction. Parvovirus B19 DNA was amplified from 8 of 10 patients with idiopathic FSGS, 9 of 10 patients with collapsing FSGS, 6 of 10 patients with membranous nephropathy, 5 of 10 patients with minimal change disease, and 2 of 4 cancer nephrectomy samples. The prevalence of parvovirus B19 DNA was greater among patients with idiopathic FSGS and collapsing FSGS compared with patients with other diagnoses (P = 0.05). In situ hybridization studies using digoxigenin-labeled DNA probes failed to detect parvovirus B19 nucleic acid in any of the kidney tissue samples. These results suggest that parvovirus B19 DNA is commonly found in the kidneys of patients with a range of renal diagnoses, possibly representing latent DNA from past infection. The failure to localize parvovirus B19 nucleic acid within kidney argues against ongoing, high-level viral replication. Nevertheless, the increased prevalence of B19 DNA in patients with idiopathic FSGS and collapsing FSGS could indicate a pathogenic role for the virus in the cause of FSGS in certain patients.

Biopsy↗

Human parvovirus B19: immunity of Greek females and prenatal investigation of hydrops fetalis.

Sera from 308 healthy Greek females of reproductive age were examined for specific IgG antibodies to human parvovirus B19 by recombinant-Elisa to determine the immunity rates of this part of population to parvovirus B19. Also paired maternal sera and amniotic fluids from nine pregnancies with hydrops fetalis were investigated for specific IgG and IgM antibodies and parvovirus DNA by polymerase chain reaction and southern hybridization analysis. The latter study was conducted to find out the participation of parvovirus B19 infection in hydrops fetalis cases in Greece. The overall prevalence of IgG antibodies in healthy Greek females was at a rate of 57.8% rising with age. One case of hydrops fetalis out of the nine examined, was diagnosed prenatally as parvovirus B19 maternal-fetal infection. It was a twin pregnancy with one fetus hydropic and the other growth retarded. Premature birth of liveborn infants was followed by neonatal death, 48 h after delivery. The contribution of parvovirus B19 in cases of non-immune hydrops fetalis was at 11% in this part of the world.

Adult↗

Dot-blot hybridisation assay for detection of parvovirus B19 infections using synthetic oligonucleotides.

Pools of 10 synthetic oligonucleotides with sequences derived from the genome of parvovirus B19 and of 30 bases in length were made and labelled at the time of synthesis with digoxigenin (DIG) or dinitrophenyl (DNP) at the 5' end. They were used in a dot-blot hybridisation assay to detect parvovirus B19 DNA in sera submitted for routine virological diagnosis where parvovirus infection was suspected. Detection down to 10-100 fg DNA (equivalent to 10(3)-10(4) copies of parvovirus B19 genome) was obtained with both probe cocktails and colorimetric or chemiluminescent detection systems. Of 141 clinical samples examined from 126 patients presenting with rash and/or joint pains, 107 were clearly negative with both probes, 20 were clearly positive and the remaining 14 samples gave discrepant results. Of these 34 samples, 33 contained parvovirus B19 specific IgM. The parvovirus oligonucleotide probe cocktail produced and labelled with either DIG or DNP provided a useful diagnostic reagent for the detection of specific DNA in clinical specimens using a simple and sensitive dot-blot assay.

Adult↗

Parvovirus host range, cell tropism and evolution.

The past few years have seen major advances in our understanding of the controls of evolution, host range and cell tropism of parvoviruses. Notable findings have included the identification of the transferrin receptor TfR as the cell surface receptor for canine parvovirus and feline panleukopenia virus, and also the finding that specific binding to the canine TfR led to the emergence of canine parvovirus as a new pathogen in dogs. The structures of the adeno-associated virus-2 and porcine parvovirus capsids, along with those of the minute virus of mice, have also advanced our understanding of parvovirus biology. Structure-function studies have shown that in several different parvoviruses the threefold spikes or peaks of the capsid control several aspects of cell tropism and host range, and that those are subject to selective pressures leading to viral evolution. The cell and tissue tropisms of different adeno-associated virus serotypes were demonstrated to be due, in part, to specific receptor binding.

Animals↗

Parvovirus B19 outbreak on an adult ward.

In November and December 1992, an outbreak of parvovirus B19 infection occurred among patients and staff on an adult mixed surgical ward at a large hospital in London. Three patients and 15 staff members were serologically confirmed as acute cases. The attack rate among susceptible members of staff was 47%. In those infected, arthralgia (80%) and rash (67%) were the most common symptoms. Of six susceptible in-patients on the ward, three became infected. One of the in-patients who had carcinoma of the mouth was viraemic for more than 10 days with marrow suppression resulting in the postponement of chemotherapy until intravenous immunoglobulin was given and he was no longer viraemic. Control measures taken included closure of the ward to new admissions, transfer of only immune staff to the ward, and restriction of the ward nursing staff to working only on that ward. Although no specific exposure was conclusively identified as a risk factor, there was a suggestion of an increased risk of acquiring parvovirus B19 infection among those staff who did not adopt strict hand washing procedures after each physical contact with a patient (RR = 2.33; P = 0.07). Knowledge of parvovirus B19 among interviewed health care workers was poor: only 42% reported knowing about parvovirus B19 and only 38% could name a patient category at risk of a severe outcome following infection. This is the first report of a nosocomial outbreak affecting an adult ward and of possible transmission of parvovirus B19 infection from staff to in-patients. Hospital control of infection teams should include parvovirus B19 in their outbreak containment plans.

Adult↗

Seroprevalence of parvovirus B19 infection in daycare educators.

This study was undertaken to provide first-time estimates for the seroprevalence of parvovirus B19 infection among daycare educators in Montréal, Canada, and to identify factors associated with seropositivity. A cross-sectional design was used. Directors and educators from 81 daycare centres (DCCs) were surveyed about DCC and personal characteristics respectively, and serum samples from 477 female educators were tested for parvovirus B19 IgG antibodies. The seroprevalence of parvovirus B19 was 70%. Parvovirus B19 seropositivity was significantly associated with age and with working experience in DCCs, but the latter association was restricted to educators aged less than 40 years. In conclusion, working as a daycare educator appears to be associated with increased risk of acquiring parvovirus B19 infection, but this finding will require further investigation. Because of the large proportion of educators susceptible to acquiring parvovirus B19 infection, our findings also highlight the need for preventive measures.

Administrative Personnel↗

The age-specific prevalence of human parvovirus immunity in Victoria, Australia compared with other parts of the world.

The age-specific immunity to human parvovirus infection was estimated in Victoria, Australia using prospectively collected samples from the Royal Children's Hospital, the Royal Women's Hospital and the Australian Red Cross Blood Service and from sera stored at the Victorian Infectious Diseases Reference Laboratory (VIDRL). All testing was performed at VIDRL using a commercial enzyme-linked immunosorbent assay (Biotrin). Of the 824 sera tested, 28% of those drawn from people aged 0-9 years contained protective antibodies to human parvovirus. This rose to 51% in the next decade of life. There was then a slow rise to about 78% immunity over 50 years of age. An analysis of all requests for parvovirus serology at VIDRL from 1992 to 1998 suggested that parvovirus tended to occur in 4-year cycles, with 2 epidemic years followed by 2 endemic years. A review of published reports of parvovirus immunity suggested that parvovirus infection may be more common, with a correspondingly higher proportion of the community immune, in temperate as opposed to tropical countries.

Adolescent↗

Donor-transmitted parvovirus infection in a kidney transplant recipient presenting as pancytopenia and allograft dysfunction.

Parvovirus B19 is a nonenveloped single-stranded DNA virus that commonly causes a benign childhood infection typically manifesting as a "slapped-cheek" rash. In immunodeficient hosts, this infection can cause persistent anemia and occasionally pancytopenia. Recently, direct renal involvement has been reported in renal transplant recipients leading to various forms of glomerulopathy and allograft dysfunction. Most cases are primary infections and are donor transmitted through the transplanted organ. Clinical and virological response to intravenous immunoglobulin (Ig) is usually excellent. We describe a case of donor-transmitted parvovirus infection in a 23-year-old male who received his first cadaver renal transplant. The patient had an uncomplicated postoperative course with immediate graft function. Eight weeks after transplantation, he presented with fever, polyarthralgia, pancytopenia, and allograft dysfunction. Serological studies revealed elevated IgM titers against parvovirus B19. A renal biopsy was performed, which showed no evidence of acute rejection but with moderate degree of tubular damage. Parvovirus B19 viral DNA was detected in the renal tissue via polymerase chain reaction (PCR). The patient received a 10-day course of intravenous Ig (400 mg/kg/day) with excellent response. His blood count normalized and the allograft improved to baseline function. The incidence of parvovirus infection in renal transplant patients is probably underestimated, because patients are not routinely screened for it and anemia and/or pancytopenia in these patients are often ascribed to immunosuppressive drugs. Because this infection is treatable, we conclude that parvovirus B19 infection should be actively considered in transplant patients presenting with pancytopenia and allograft dysfunction.

Adult↗

Prediction of fetal anemia with Doppler measurement of the middle cerebral artery peak systolic velocity in pregnancies complicated by maternal blood group alloimmunization or parvovirus B19 infection.

OBJECTIVES: To confirm the relationship between the middle cerebral artery peak systolic velocity (MCA PSV) and hemoglobin values in fetuses at risk for anemia (due to maternal blood group alloimmunization or parvovirus B19 infection) and to investigate the clinical value of this method in the management of these pregnancies regardless of previous transfusions. SUBJECTS AND METHODS: Forty singleton pregnancies, 30 affected by alloimmunization and 10 by intrauterine parvovirus B19 infection, were referred to our tertiary center between 1998 and 2000. All cases underwent Doppler measurement of the MCA PSV immediately before fetal blood sampling and just before and after intrauterine transfusion. Hemoglobin determination was always performed after diagnostic cordocentesis, before starting and after terminating fetal transfusion. RESULTS: Overall, we performed 165 fetal blood samplings (hemoglobin values) and obtained 165 corresponding MCA PSV values, 140 in pregnancies complicated by red-cell alloimmunization and 25 by parvovirus B19 infection. In order to adjust for the effect of gestational age on the measurements, the data were expressed in multiples of the median (MoM). We found a good correlation between MCA PSV MoM and Hb MoM in both groups (alloimmunization, r2 = 0.6; y = 2.21 - 1.41 x + 0.24 x 2; parvovirus infection, r2 = 0.68; y = 2.09 - 0.58 x - 0.16 x 2). The reduction of post-transfusion MCA PSV values was statistically significant ( P < 0.0001). Using a threshold of 1.29 for MoM PSV, the sensitivity and the specificity of MCA pulsatility indices on pretransfusion values in predicting any degree of fetal anemia (Hb < or = 0.84 MoM) were 73.1% and 81.5% in the alloimmunization group and 100% and 100% in the parvovirus infection group, respectively. CONCLUSION: We can confirm the presence of an inverse correlation between MCA PSV measurements and hemoglobin values in fetuses at risk for anemia due to maternal blood group alloimmunization and fetal parvovirus B19 infection. The MCA PSV is a reliable method for the prediction of anemia not only in fetuses before the first intrauterine transfusion, but also in those which have undergone one or more transfusions, with good sensitivity and specificity in both groups of fetuses at risk.

Anemia↗

Human parvovirus B19 in cord blood of premature infants.

We investigated whether intrauterine parvovirus B19 infection is associated with premature birth by evaluating parvovirus B19 antibodies and DNA in umbilical cord blood from 76 premature infants. We performed enzyme-linked immunoadsorbent (ELISA) and polymerase chain reaction (PCR) assays to detect B19-specific IgM antibodies and parvovirus DNA. No parvovirus DNA was detected in cord blood sera, and no sample was positive for anti-parvovirus B19 IgM antibodies. Parvovirus appears unlikely to lead to premature birth.

Antibodies, Viral↗

An association between fetal parvovirus B19 infection and fetal anomalies: a report of two cases.

The association between fetal parvovirus B19 infection and hydrops was first reported in 1984. The virus has a predilection for the erythroid cell line, which in the fetus may produce anemia. Recent cases of parvovirus infection in other fetal cell lines have raised concern that the infection may induce fetal anomalies in rare cases. We report two pregnancies complicated by parvovirus B19 infection. In each instance the patient had normal second trimester ultrasounds but subsequently developed fetal abnormalities--disruptions of normal structure. One infant has myocardial infarction, splenic calcifications, and mild hydrocephalus. The other had moderate hydrocephalus with central nervous system scarring. There are two possible mechanisms in which parvovirus may induce fetal anomalies. Both direct infection of fetal organs and vascular inflammation have been documented in association with B19 parvovirus. Although fetal abnormalities associated with parvovirus are rare, continued study of this organism may indicate a greater pathologic potential than is now thought.

Adult↗

Role of parvovirus B19 infection in childhood idiopathic thrombocytopenic purpura.

Although parvovirus B19 exhibits a strong tissue-tropism for erythroid progenitor cells leading to anaemia, several case reports indicate that parvovirus B19 infection may also cause the development of thrombocytopenia. Despite recent studies, the frequency and clinical relevance of this association have remained questionable. Consequently, and in view of the paucity of evidence regarding a viral aetiology for idiopathic thrombocytopenic purpura (ITP), we examined the role of parvovirus B19 in 47 children with newly diagnosed ITP. Specific viral DNA indicating a current or recent parvovirus B19 infection was demonstrated in 6 of 47 patients (13%) employing the polymerase chain reaction technique. Our study suggests that children with ITP and associated parvovirus B19 infection are characterized by acute onset of profound thrombocytopenia. Among the parvovirus B19 positive children, duration of disease was brief in three children treated with immunoglobulin but chronic in the remaining three patients given high-dose steroids. Prospective studies are needed to confirm these initial observations. This virus should be considered as a possible aetiologic agent in some children with ITP.

Acute Disease↗

Detection of adeno-associated virus 2 and parvovirus B19 in the human dorsolateral prefrontal cortex.

Although animal parvoviruses have long been recognized as causes of brain pathology in multiple animal models, especially during early development, human parvoviruses are rarely thought of as neurotropic or causes of neuropathology in humans. However, several recent case reports have suggested possible associations of parvovirus B19 (B19) infection with various neurological and neuropsychiatric symptoms. Adeno-associated virus 2 (AAV2) is related to B19 but has thus far not been shown to be associated with any human disease but is of clinical interest because of the recent use of recombinant AAV vectors in human gene therapy, including gene delivery to the brain. To date, there have been no large-scale studies of the propensity of wild-type human parvoviruses to infect the brain. The Stanley Medical Research Institute Brain Collection offered a unique opportunity to study a large sample (n = 104) of dorsolateral prefrontal cortex (DLPC) DNAs isolated from unaffected control, schizophrenic, and bipolar disorder brains for the presence of parvoviral sequences. This is the first investigator-blinded study to document the presence of parvoviral sequences in the DLPC by utilizing highly sensitive nested polymerase chain reaction (nPCR) and DNA sequencing. Of the overall sample, 6.7% to 12.5% were positive for AAV2, and 14.4% to 42.3% were positive for B19 sequences, with no statistical differences among subgroups. This is the first report to demonstrate the presence of human parvoviruses in a large cohort of adult DLPC, which underscores the need to gain a better insight into the basic biology of parvovirus-brain interactions, including mechanisms of infection and persistence.

Adult↗

Nosocomial human parvovirus B19 infection: lack of transmission from a chronically infected patient to hospital staff.

OBJECTIVE: To assess the potential for nosocomial spread of parvovirus B19 from a chronically infected patient. DESIGN: Employees exposed to the index case and control (unexposed) employees were evaluated by baseline and follow up parvovirus B19 serologies and hematologic assessments, and completed baseline and follow up epidemiologic questionnaires. SETTING: A chronically infected patient was hospitalized on a hematology ward in a research referral hospital for 3.5 weeks prior to a diagnosis of parvovirus B19 infection and the institution of isolation precautions. METHODS: Sera were screened for parvovirus B19 DNA (dot blot analysis), and IgG and IgM anti-B19 antibodies (capture immunoassay). Hematologic assessment included CBC, differential, and reticulocyte count. RESULTS: The index case had parvovirus B19 DNA at approximately 10(6) genome copies per ml of serum, elevated IgM and low levels of IgG B19 antibodies. Of the 21 exposed staff, 11 (52%) had IgG B19 antibodies and were immune; of the 8 unexposed staff, 6 (75%) had IgG B19 antibodies. No employees developed IgM B19 antibodies, B19 DNA, hematologic abnormalities, or clinical symptoms. CONCLUSIONS: In contrast to reports of documented nosocomial transmission of B19 parvovirus from patients in transient aplastic crisis, nosocomial transmission did not occur--even in the absence of isolation precautions--presumably from the lower level of B19 viremia in our chronically infected (rather than acutely infected) patient.

Antibodies, Viral↗

Infection due to parvovirus B19 in patients infected with human immunodeficiency virus.

Parvovirus B19 has been described as a cause of chronic anemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). In this study serological assays and the polymerase chain reaction (PCR) were used to establish the prevalence of both prior and active infection due to parvovirus B19 among a general population of 105 HIV-infected individuals (cohort I) and among 22 HIV-infected patients with anemia (cohort II). Eight individuals in cohort I (7.6%) had IgG antibodies to parvovirus B19, while none had B19-specific IgM antibodies. In cohort II, four patients (18.2%) had B19-specific IgG antibodies and none had IgM antibodies. Only one person in cohort I (0.95%) and one person in cohort II (4.5%) had evidence on PCR of persistent infection with parvovirus B19; both of these patients lacked IgG and IgM antibodies to parvovirus. Both individuals with B19 viremia were anemic and had CD4 lymphocyte counts suggesting advanced immunosuppression (< 50/mm3). The observed low prevalences of B19 seropositivity and active B19 infection differ from the rates documented in previous studies and indicate that infection with parvovirus B19 is uncommon in some groups of HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Genetic characterization of feline parvovirus sequences from various carnivores.

Infections with viruses of the feline parvovirus subgroup such as feline panleukopenia virus (FPV), mink enteritis virus (MEV) and canine parvovirus (CPV-2) [together with its new antigenic types (CPV-2a, CPV-2b)] have been reported from several wild carnivore species. To examine the susceptibility of different species to the various parvoviruses and their antigenic types, samples from wild carnivores with acute parvovirus infections were collected. Viral DNA was amplified, and subsequently analysed, from faeces or formalin-fixed small intestines from an orphaned bat-eared fox (Otocyon megalotis), a free-ranging honey badger (Mellivora capensis), six captive cheetahs (Acinonyx jubatus), a captive Siberian tiger (Panthera tigris altaica) and a free-ranging African wild cat (Felis lybica). Parvovirus infection in bat-eared fox and honey badger was demonstrated for the first time. FPV-sequences were detected in tissues of the African wild cat and in faeces of one cheetah and the honey badger, whereas CPV-2b sequences were found in five cheetahs and the bat-eared fox. The Siberian tiger (from a German zoo) was infected with a CPV-type 2a virus. This distribution of feline parvovirus antigenic types in captive large cats suggests an interspecies transmission from domestic dogs. CPV-2 sequences were not detected in any of the specimens and no sequences with features intermediate between FPV and CPV were found in any of the animals examined.

Acinonyx↗