Risks for adverse pregnancy outcomes and infections in daycare workers: an overview of current epidemiological evidence and implications for primary prevention.

Childcare providers are overwhelmingly women of childbearing age. Occupational risks in this sector include exposure to biological (infectious) or physical (standing, carrying loads) hazards, many of which are associated with adverse pregnancy outcomes such as children with congenital infections, low birth weight or prematurity. Here, the authors examined literature on pregnancy outcomes and infectious hazards related to employment in daycare settings. Overall, 33 original studies (10 reporting pregnancy issues, 23 focusing on infectious risks) published in 1980-2018 were retained following a Medline search. Pregnancy issues in daycare workers have rarely been studied, and inconsistent risks of spontaneous abortion, congenital malformations and fetal growth retardation have been reported. Literature pertaining to infectious risks in daycare settings is extensive. The risk of a primary cytomegalovirus infection during pregnancy was increased for daycare workers caring for >6 children and younger children, changing diapers ≥3 days/week, not wearing gloves when changing diapers, and having employment in daycare for ≤2 years. Personal factors (nulliparity, ethnicity) were also independent risk factors. Parvovirus B19 (B19V) infections appear to be related to employment in daycare, but also to having one's own children and an increased number of siblings. Consequently, the risk of a primary B19V infection during an outbreak is of most concern among younger nulliparous workers caring for large numbers of young infected children. Since the main occupational hazard is viral infection, feasible prevention strategies include improving workers' awareness, serological monitoring during pregnancy, educating on appropriate preventive measures, and ensuring age-appropriate immunization of children and staff in childcare facilities. Int J Occup Med Environ Health. 2020;33(6):733-56.

Congenital infections in Hong Kong: an overview of TORCH.

Congenital infections refer to a group of perinatal infections that may have similar clinical presentations, including rash and ocular findings. TORCH is the acronym that covers these infections (toxoplasmosis, other [syphilis], rubella, cytomegalovirus, herpes simplex virus). There are, however, other important causes of intrauterine/perinatal infections, including enteroviruses, varicella zoster virus, Zika virus, and parvovirus B19. Intrauterine and perinatal infections are significant causes of fetal and neonatal mortality and important contributors to childhood morbidity. A high index of suspicion for congenital infections and awareness of the prominent features of the most common congenital infections can help to facilitate early diagnosis, tailor appropriate diagnostic evaluation, and if appropriate, initiate early treatments. In the absence of maternal laboratory results diagnostic of intrauterine infections, congenital infections should be suspected in newborns with certain clinical features or combinations of clinical features, including hydrops fetalis, microcephaly, seizures, cataract, hearing loss, congenital heart disease, hepatosplenomegaly, jaundice, or rash. Primary prevention of maternal infections during pregnancy is the cornerstone of prevention of congenital infection. Available resources should focus on the promotion of public health.

Advances in the Development of Antiviral Strategies against Parvovirus B19.

Parvovirus B19 (B19V) is a human pathogenic virus, responsible for an ample range of clinical manifestations. Infections are usually mild, self-limiting, and controlled by the development of a specific immune response, but in many cases clinical situations can be more complex and require therapy. Presently available treatments are only supportive, symptomatic, or unspecific, such as administration of intravenous immunoglobulins, and often of limited efficacy. The development of antiviral strategies against B19V should be considered of highest relevance for increasing the available options for more specific and effective therapeutic treatments. This field of research has been explored in recent years, registering some achievements as well as interesting future perspectives. In addition to immunoglobulins, some compounds have been shown to possess inhibitory activity against B19V. Hydroxyurea is an antiproliferative drug used in the treatment of sickle-cell disease that also possesses inhibitory activity against B19V. The nucleotide analogues Cidofovir and its lipid conjugate Brincidofovir are broad-range antivirals mostly active against dsDNA viruses, which showed an antiviral activity also against B19V. Newly synthesized coumarin derivatives offer possibilities for the development of molecules with antiviral activity. Identification of some flavonoid molecules, with direct inhibitory activity against the viral non-structural (NS) protein, indicates a possible line of development for direct antiviral agents. Continuing research in the field, leading to better knowledge of the viral lifecycle and a precise understanding of virus-cell interactions, will offer novel opportunities for developing more efficient, targeted antiviral agents, which can be translated into available therapeutic options.

Saccharomyces cerevisiae-derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease.

Parvovirus B19 infections are typically mild in healthy individuals, but can be life threatening in individuals with sickle cell disease (SCD). A Saccharomyces cerevisiae-derived B19 VLP vaccine, now in pre-clinical development, is immunogenic in wild type mice when administered with the adjuvant MF59. Because SCD alters the immune response, we evaluated the efficacy of this vaccine in a mouse model for SCD. Vaccinated mice with SCD demonstrated similar binding and neutralizing antibody responses to those of heterozygous littermate controls following a prime-boost-boost regimen. Due to the lack of a mouse parvovirus B19 challenge model, we employed a natural mouse pathogen, Sendai virus, to evaluate SCD respiratory tract responses to infection. Normal mucosal and systemic antibody responses were observed in these mice. Results demonstrate that mice with SCD can respond to a VLP vaccine and to a respiratory virus challenge, encouraging rapid development of the B19 vaccine for patients with SCD.

Surto de parvovírus B19 no município de Crissiumal/17ª CRS/ RS, agosto de 2016 / Parvovirus B19 outbreak in the municipality of Crissiumal/17ª CRS/ RS, august 2016

Em 18/08/2016, uma escola infantil notificou à vigilância do município de Crissiumal a ocorrência de vários casos de crianças com febre e exantema. A partir dessa informação, a equipe da vigilância, junto com médico da rede de atenção à saúde, deslocou-se até a escola para realizar avaliação clínica dos casos e fazer a investigação epidemiológica com vistas a confirmar a ocorrência de surto de doença exantemática, identificar a causa e desencadear medidas de controle. (AU)

[Childhood diseases with exanthema]. / Kinderziekten met vlekjes.

- Due to high vaccination coverage, measles and rubella (German measles) are now rarely seen in the Netherlands, which makes recognition of these diseases difficult. - Measles can also occur in people who have been immunized, as a result of vaccination failure. - Swift recognition of measles and rubella is necessary in order to manage them adequately and to prevent spreading of the disease. - Measles, rubella, and erythema infectiosum ('fifth disease') may result in complications during pregnancy. - Measles, rubella, scarlet fever, erythema infectiosum, and roseola ('sixth disease') can be difficult to differentiate. - In the Netherlands, diagnosis of a patient with measles or rubella, or of more than 1 patient with erythema infectiosum within one institution, must be reported to the local health authority within 1 working day. - Exclusion from school or a day-care facility is not required for any if the diseases discussed.

Safety and immunogenicity of a candidate parvovirus B19 vaccine.

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydropsfetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 µg dose of parvovirus B19 recombinant capsid; 2.5 and 25 µg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important.

Occupational hazards for pregnant nurses.

OVERVIEW: Depending on her working environment, specific immunities, and stage of pregnancy, a pregnant nurse may find it difficult to avoid teratogenic and fetotoxic exposures, as well as working conditions that could jeopardize her pregnancy. A clinical review of the occupational hazards faced by pregnant nurses can be useful to the concerned nurse or health care system, as can suggestions on ways to reduce risk and a list of pertinent occupational safety resources.

Detection of IgE anti-parvovirus antibodies in human breast milk.

Breast milk is a complex fluid, rich in nutrients and non-nutritional bioactive components, including antimicrobial factors, immunoglobulins, cytokines, and anti-inflammatory substances. Although IgE is implicated in viral immunity, its role in breast milk in parvovirus B19 immunity has not been studied. Total immunoglobulin levels of IgE, IgG, and IgE anti-parvovirus B19 antibodies were determined by ELISA and Western blot analysis in breast milk and in sera from a mother and her nursing infant (female, 10 mo). For specific IgE protein determination, breast milk was fractionated by chromatography on G-100 Sephadex; 3 peaks were collected and separated by SDS PAGE. The levels of total IgE in breast milk and its fractions were low (<2.4 ng/ml), and those of maternal and infant serum were negligible (18 and 4.3 IU/ml, respectively). Nevertheless, the breast milk and maternal and infant sera contained IgE anti-parvovirus B19 antibodies, even though the infant was never infected with parvovirus B19. Total serum levels of maternal IgG were within the normal range and those of infant IgG were low (473 mg/dl); total IgG in breast milk was not determined. Maternal serum contained some detectable IgG anti-parvovirus antibodies that were not present in infant serum or breast milk. Total maternal and infant serum levels of IgM and IgA were within the normal ranges. The presence of IgE anti-parvovirus B19 antibodies in breast milk suggests that IgE anti-viral antibodies are transmitted in breast milk and may provide protective responses in nursing children.

Management of an obstetric health care provider with acute parvovirus B19 infection.

We report a case of an obstetrician with acute parvovirus B19 infection and the series of exposed pregnant women. Currently, there are no established guidelines regarding management of an obstetric health care provider with acute parvovirus B19 infection. We propose a management scheme of this clinical scenario.

Prevalence and quantitation of parvovirus B19 DNA levels in blood donors with a sensitive polymerase chain reaction screening assay.

BACKGROUND: Blood donor parvovirus B19 DNA prevalence with sensitive nucleic acid test assays has recently been demonstrated to be higher than that found with assays designed to detect high viral titers in the plasma manufacturing sector. STUDY DESIGN AND METHODS: Stored plasma aliquots from 5020 donations collected between 2000 and 2003 at seven US blood centers were tested. Testing was performed with a real-time B19 DNA polymerase chain reaction (PCR; TaqMan, Applied Biosystems) assay with a 50 percent limit of detection (LOD) of 1.6 IU per mL (95% confidence interval [CI], 1.2-2.1 IU/mL) and a 95 percent LOD of 16.5 IU per mL (95% CI, 10.6-33.9 IU/mL). Confirmation and quantitation of B19 DNA was accomplished by retesting of two additional subaliquots. Confirmed-positive specimens were tested for the presence of anti-B19 immunoglobulin M (IgM) and IgG with FDA-licensed assays. RESULTS: B19 DNA prevalence was 0.88 percent (95% CI, 0.64%-1.2%). Among the 23 donations with B19 DNA titers of at least 20 IU per mL, the median DNA concentration was 105 IU per mL with an interquartile range of 42 to 481 IU per mL; the highest value was 1869 IU per mL. All B19 DNA-positive donations were positive for the presence of IgG and 10 (23%) were also positive for the presence of IgM; IgM seropositivity was associated with increasing DNA levels (p = 0.0013). CONCLUSION: Low-level B19 DNA was detected in nearly 1 percent of donations. The 23 percent of DNA-positive donations with both IgM and IgG B19 antibody most likely represent acute resolving infection, whereas those with IgG but no IgM are most consistent with a more chronic and possibly persistent phase of B19 infection.

Molecular mechanism underlying B19 virus inactivation and comparison to other parvoviruses.

BACKGROUND: B19 virus (B19V) is a human pathogen frequently present in blood specimens. Transmission of the virus occurs mainly via the respiratory route, but it has also been shown to occur through the administration of contaminated plasma-derived products. Parvoviridae are highly resistant to physicochemical treatments; however, B19V is more vulnerable than the rest of parvoviruses. The molecular mechanism governing the inactivation of B19V and the reason for its higher vulnerability remain unknown. STUDY DESIGN AND METHODS: After inactivation of B19V by wet heat and low pH, the integrity of the viral capsid was examined by immunoprecipitation with two monoclonal antibodies directed to the N-terminal of VP1 and to a conformational epitope in VP2. The accessibility of the viral DNA was quantitatively analyzed by a hybridization-extension assay and by nuclease treatment. RESULTS: The integrity of the viral particles was maintained during the inactivation procedure; however, the capsids became totally depleted of viral DNA. The DNA-depleted capsids, although not infectious, were able to attach to target cells. Comparison studies with other members of the Parvoviridae family revealed a remarkable instability of B19V DNA in its encapsidated state. CONCLUSION: Inactivation of B19V by heat or low pH is not mediated by capsid disintegration but by the conversion of the infectious virions into DNA-depleted capsids. The high instability of the viral DNA in its encapsidated state is an exclusive feature of B19V, which explains its lower resistance to inactivation treatments.

Blood donor screening for parvovirus B19 in Germany and Austria.

BACKGROUND: Although the main transmission pathway of parvovirus B19 (B19) is typically via the respiratory route, several transfusion-transmitted infections have been reported. To increase blood safety, all blood donations to our blood donor service have been screened by a B19 minipool real-time nucleic acid testing (NAT) since April 2000. Additional customers have been screened since the summer of 2003. STUDY DESIGN AND METHODS: In total, 2.8 million donations from Germany and Austria were screened for B19 by real-time minipool NAT. A subgroup of 50 B19 DNA-positive donors was screened for B19 immunoglobulin G (IgG) and IgM antibodies and B19 DNA over a 6-month period. Results were compared to those of 100 B19 DNA-negative donors. RESULTS: Data accumulated over the past 6 years indicate a high incidence period from May 2004 to January 2006. In total, the incidence was 12.7 and 261.5 per 100,000 donations with high virus loads equal to or above 10(5) and below 10(5) IU per mL, respectively. Median virus concentration in the case group was 4.85 x 10(7) IU per mL at Time Point T0 and was reduced to 4 x 10(2) IU per mL at the time of the next donation (3 months later). Neutralizing antibodies (VP2) were detected in all donations if virus load was reduced to less than 10(5) IU per mL. CONCLUSION: The release of B19 DNA-positive blood products with a concentration of less than 105 IU per mL is thought to be safe due to the high level of neutralizing VP2 antibodies and is currently examined in a donor recipient infectivity study. In contrast, blood products with a high B19 DNA concentration (> or =10(5) IU/mL), some of which did not contain neutralizing antibodies, were discarded to protect at risk individuals.

Inactivation of parvovirus B19 in human platelet concentrates by treatment with amotosalen and ultraviolet A illumination.

BACKGROUND: The human erythrovirus B19 (B19) is a small (18- to 26-nm) nonenveloped virus with a single-stranded DNA genome of 5.6 kb. B19 is clinically significant and is also generally resistant to pathogen inactivation methods. Photochemical treatment (PCT) with amotosalen and ultraviolet A (UVA) inactivates viruses, bacteria, and protozoa in platelets (PLTs) and plasma prepared for transfusion. In this study, the capacity of PCT to inactivate B19 in human PLT concentrates was evaluated. STUDY DESIGN AND METHODS: B19 inactivation was measured by a novel enzyme-linked immunosorbent spot (ELISPOT) erythroid progenitor cell infectivity assay and by inhibition of long-range (up to 4.3 kb) polymerase chain reaction (PCR), under conditions where the whole coding region of the viral genome was amplified. B19-infected plasma was used to test whether incubation of amotosalen with virus before PCT enhanced inactivation compared to immediate PCT. RESULTS: Inactivation of up to 5.8 log of B19 as measured by the infectivity assay, or up to 6 logs as measured by PCR inhibition can be achieved under non-limiting conditions. Inactivation efficacy was found to increase with incubation prior to UVA illumination. Without incubation prior to illumination 2.1 +0.4 log was inactivated as determined by infectivity assay. When measured by PCR inhibition, inactivation varied inversely with amplicon size. When primers that spanned the entire coding region of the B19 genome were used, maximum inhibition of PCR amplification was demonstrated. CONCLUSION: Under defined conditions, PCT with amotosalen combined with UVA light can be used to inactivate B19, a clinically significant virus that can be transmitted through blood transfusion, and heretofore has been demonstrated to be refractory to inactivation.

Evaluation of a new LightCycler reverse transcription-polymerase chain reaction infectivity assay for detection of human parvovirus B19 in dry-heat inactivation studies.

BACKGROUND: Human parvovirus B19 (B19) is a widely distributed infectious agent, which causes a variety of illnesses including erythema infectiosum (fifth disease) especially in children, arthritis, aplastic crisis, and hydrops fetalis. B19 can be transmitted from asymptomatic blood donors to recipients of their blood components. Fifth disease has been reported in patients receiving red blood cells, platelets, solvent/detergent-treated plasma, and clotting factor concentrates. STUDY DESIGN AND METHODS: A new B19-specific Light Cycler (LC) reverse transcription-polymerase chain reaction (RT-PCR) infectivity assay was developed for quantitative analysis of the infectivity of B19 in virus validation studies. The cycling conditions and the primers of the new assay were designed to amplify spliced RNA forms but not precursor RNA or B19 genome. One 50 percent infectious dose, determined on UT7/Epo-S1 cells of low passage, equaled 3.74+/-0.1 log international units of B19 DNA. RESULTS: The efficiency of the dry-heat process (100 degrees C) on inactivation of B19 spiked and lyophilized with fibrinogen, a major component of the clotting factor concentrate and hemostatic dressing products, was investigated by use of B19-specific LC RT-PCR infectivity assay. At 1.3 to 1.7 percent residual moisture of fibrinogen, the infectivity of B19 was reduced dramatically by 3.3 to 5.1 log for 1 and 2 hours of dry-heat treatment, respectively. B19 infectivity was reduced 1.5, 2.8, and 3.8 log for 1, 2, and 3 hours of dry-heat treatment, respectively, at 0.5 to 0.7 percent residual moisture level. CONCLUSION: These findings suggest that level of residual moisture of lyophilized fibrinogen with B19 spike correlated with a different resistance of B19 to dry-heat treatment, and that low moisture may stabilize virus against heat.

Heat sensitivity of human parvovirus B19.

BACKGROUND AND OBJECTIVES: To date there has been no published report on a systematic evaluation of the heat sensitivity of human parvovirus B19 (B19) and the related safety of the plasma-derived fractionated products. In this study, we examined the heat sensitivity of B19 by using the infectivity assay with cultured cells. MATERIALS AND METHODS: The heat sensitivity of B19 was examined by measuring the reduction in viral infectivity titres after heating liquid containing B19 at 60 degrees C. Viral infectivity was assayed by detection of viral antigens or viral mRNA in infected cells. As a control, canine parvovirus (CPV) was also heat-treated. RESULTS: B19 displayed quite different inactivation kinetics to CPV when both were heated in liquid at 60 degrees C. In sharp contrast to the latter, B19 was rapidly inactivated within 1 h when the virus was suspended in 5% or 25% human serum albumin solution, phosphate-buffered saline, or complete medium. However, B19 appeared to be resistant to heat inactivation in liquid containing 60% sucrose. CONCLUSIONS: The heat sensitivity of B19 in liquid was clearly different from that of CPV. Significantly, the efficiency to inactivate B19 and reduce its infectivity following heating in liquid was mainly affected by the composition of the solutions used for virus suspension.