Roseola Research Articles

CD134 is a cellular receptor specific for human herpesvirus-6B entry

Human herpesvirus-6B (HHV-6B) is a T lymphotropic β-herpesvirus that is clearly distinct from human herpesvirus-6A (HHV-6A) according to molecular biological features. The International Committee on Taxonomy of Viruses recently classified HHV-6B as a separate species. The primary HHV-6B infection causes exanthem subitum and is sometimes associated with severe encephalopathy. More than 90% of the general population is infected with HHV-6B during childhood, and the virus remains throughout life as a latent infection. HHV-6B reactivation causes encephalitis in immunosuppressed patients. The cellular receptor for HHV-6A entry was identified as human CD46, but the receptor for HHV-6B has not been clear. Here we found that CD134, a member of the TNF receptor superfamily, functions as a specific entry receptor for HHV-6B. A T-cell line that is normally nonpermissive for HHV-6B infection became highly susceptible to infection when CD134 was overexpressed. CD134 was down-regulated in HHV-6B-infected T cells. Soluble CD134 interacted with the HHV-6B glycoprotein complex that serves as a viral ligand for cellular receptor, which inhibited HHV-6B but not HHV-6A infection in target cells. The identification of CD134 as an HHV-6B specific entry receptor provides important insight into understanding HHV-6B entry and its pathogenesis.

Mapping the telomere integrated genome of human herpesvirus 6A and 6B

Human herpesvirus 6B (HHV-6B) is the causative agent of roseola infantum. HHV-6A and 6B can reactivate in immunosuppressed individuals and are linked with severe inflammatory response, organ rejection and central nervous system diseases. About 0.85% of the US and UK population carries an integrated HHV-6 genome in all nucleated cells through germline transmission. We have previously reported that the HHV-6A genome integrated in telomeres of patients suffering from neurological dysfunction and also in telomeres of tissue culture cells. We now report that HHV-6B also integrates in telomeres during latency. Detailed mapping of the integrated viral genomes demonstrates that a single HHV-6 genome integrates and telomere repeats join the left end of the integrated viral genome. When HEK-293 cells carrying integrated HHV-6A were exposed to the histone deacetylase inhibitor Trichostatin A, circularization and/or formation of concatamers were detected and this assay could be used to distinguish between lytic replication and latency.

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Differentiating roseola infantum with pyuria from urinary tract infection

The aim of this study was to identify factors for differentiating roseola infantum from urinary tract infection (UTI) and to describe a cohort of infants diagnosed with roseola infantum and sterile pyuria. The medical records of infants diagnosed with roseola infantum or UTI were examined. Multivariate analysis was performed to identify factors associated with UTI. Demographic and clinical variables were compared between infants who had roseola infantum with or without sterile pyuria. There were 301 infants included: 158 in the roseola group (21, 13.3% with sterile pyuria) and 143 in the UTI group. The relative risk of UTI over roseola infantum: increased with leukocytosis (white blood cell [WBC] count >10,000/mm(3), odds ratio [OR] = 85.62) and pyuria (OR = 18.97); decreased with age (OR = 0.90); increased in boys (OR = 2.48); increased with WBC count 4000-10,000/mm(3) (OR = 4.24); and decreased with duration of fever (OR = 0.84). There was a significantly higher proportion of girls in the roseola pyuria group (81.0%) compared with the no pyuria group (44.5%, P = 0.002). A significantly higher proportion of infants in the roseola pyuria group (76.2%) received antibiotics than infants in the no pyuria group (38.0%, P = 0.002). Leukocytosis is the strongest predictor of UTI over roseola infantum. Sterile pyuria may occur in infants with roseola infantum.

Efficacy of Dextromethorphan and Cyclosporine A for Acute Encephalopathy

Acute encephalopathy with biphasic seizures and late reduced diffusion was recently established clinicoradiologically as an encephalopathy syndrome. The outcome of this encephalopathy is characterized by a low mortality rate and high incidence of neurologic sequelae. Although the exact pathogenesis of this encephalopathy is uncertain, excitotoxic injury with delayed neuronal death is proposed. On the basis of this hypothesis, we tried a combination therapy of N-methyl-D-aspartate receptor antagonist, dextromethorphan, and apoptosis inhibitor, cyclosporine A, in four patients with acute encephalopathy with biphasic seizures and late reduced diffusion. All patients recovered except for hyperactivity in one patient. Furthermore, an additional four patients with near-miss encephalopathy, who showed mild disturbance of consciousness at 24 hours after prolonged febrile seizures associated with exanthem subitum, recovered without secondary seizures by the early administration of dextromethorphan. The combination regimen of dextromethorphan and cyclosporine A could be effective for the treatment and prevention of acute encephalopathy with biphasic seizures and late reduced diffusion.

Animal models for human herpesvirus 6 infection

Human herpesvirus (HHV)-6A and HHV-6B are two enveloped DNA viruses of β-herpesvirus family, infecting over 90% of the population and associated with several diseases, including exanthema subitum (for HHV-6B), multiple sclerosis and encephalitis, particularly in immunosuppressed patients. Animal models are highly important to better understand the pathogenesis of viral infections. Naturally developed neutralizing antibodies to HHV-6 or a related virus were found in different species of monkeys, suggesting their susceptibility to HHV-6 infection. Both HHV-6 DNA and infectious virus were detected in experimentally infected Cynomolgus and African green monkeys, although most animals remained clinically asymptomatic. Furthermore, HHV-6A infection was shown to accelerate the progression of AIDS (acquired immunodeficiency syndrome) in macaques and to lead to the development of neurological symptoms in the marmoset model. Humanized SCID (severe combined immunodeficiency) mice efficiently replicated HHV-6 and were also susceptible to coinfection with HHV-6 and HIV-1 (human immunodeficiency virus 1). As CD46 was identified as a receptor for HHV-6, transgenic mice expressing human CD46 may present a potentially interesting model for study certain aspects of HHV-6 infection and neuroinflammation.

Catastrophic Kawasaki disease unresponsive to IVIG in a 3-month-old infant: a diagnostic and therapeutic challenge

The present report describes the severe evolution of Kawasaki disease in a three-month-old infant. The ailment was initially atypical in its presentation, with the patient exhibiting only persistent fever in association with a progressive lethargy and maculopapular rash on the face, trunk and limbs erroneously diagnosed as roseola infantum. On the 10th day of the condition, mainly due to the unexplained persistence of fever, the infant was admitted to a local hospital. The typical features of KD appeared only on the 14th day of illness with the relapse of the maculopapular rash in association with non-purulent conjunctivitis; dry, reddish and fissured lips; tongue with reddish and hypertrophic papillae; erythema and edema of the palms and soles. During the following days, the ailment rapidly evolved to a catastrophic clinical picture characterized by generalized vasculitis, splenic infarction, pulmonary thrombosis, giant right and left coronary aneurysms, dilatation of common and internal iliac arteries and progressive ischemia of the distal third of the feet resulting in necrotic lesions of both halluces. Appropriate therapy was initiated, but repeated administration of intravenous immunoglobulin G (IVIG) followed by three days of administration of methylprednisolone did not abate the intense inflammatory activity. The remission of inflammation and regression of vascular lesions were only achieved during the following five weeks after the introduction of methotrexate associated with etanercept. The report of this case aims to draw attention to severe forms of KD that exhibit an unfavorable evolution and can be extremely refractory to the conventional therapy.

Age-Specific Sex-Related Differences in Infections: A Statistical Analysis of National Surveillance Data in Japan

BackgroundTo prevent and control infectious diseases, it is important to understand how sex and age influence morbidity rates, but consistent clear descriptions of differences in the reported incidence of infectious diseases in terms of sex and age are sparse.Methods and FindingsData from the Japanese surveillance system for infectious diseases from 2000 to 2009 were used in the analysis of seven viral and four bacterial infectious diseases with relatively large impact on the Japanese community. The male-to-female morbidity (MFM) ratios in different age groups were estimated to compare incidence rates of symptomatic reported infection between the sexes at different ages. MFM ratios were >1 for five viral infections out of seven in childhood, i.e. male children were more frequently reported as infected than females with pharyngoconjunctival fever, herpangina, hand-foot-and-mouth disease, mumps, and varicella. More males were also reported to be infected with erythema infectiosum and exanthema subitum, but only in children 1 year of age. By contrast, in adulthood the MFM ratios decreased to <1 for all of the viral infections above except varicella, i.e. adult women were more frequently reported to be infected than men. Sex- and age-related differences in reported morbidity were also documented for bacterial infections. Reported morbidity for enterohemorrhagic Escherichia coli infection was higher in adult females and females were reportedly more infected with mycoplasma pneumonia than males in all age groups up to 70 years.ConclusionsSex-related differences in reported morbidity for viral and bacterial infections were documented among different age groups. Changes in MFM ratios with age may reflect differences between the sexes in underlying development processes, including those affecting the immune, endocrine, and reproductive systems, or differences in reporting rates.

Development of quantitative RT‐PCR assays for detection of three classes of HHV‐6B gene transcripts

The monitoring of active human herpesvirus 6 (HHV-6) B infection is important for distinguishing between the reactivation and latent state of the virus. The aim of this present study is to develop a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay for diagnosis of active viral infection. Primers and probes for in house quantitative RT-PCR methods were designed to detect the three kinetic classes of HHV-6B mRNAs (U90, U12, U100). Stored PBMCs samples collected from 10 patients with exanthem subitum (primary HHV-6B infection) and 15 hematopoietic stem cell transplant recipients with HHV-6B reactivation were used to evaluate reliability for testing clinical samples. Excellent linearity was obtained with high correlation efficiency between the diluted RNA (1-100 ng/reaction) and C(t) value of each gene transcript. The U90 and U12 gene transcripts were detected in all of the peripheral blood mononuclear cells (PBMCs) samples collected in acute period of primary HHV-6B infection. Only one convalescent PBMCs sample was positive for the U90 gene transcript. Additionally, the reliability of HHV-6B quantitative RT-PCRs for diagnosis of viral reactivation in hematopoietic transplant recipients was evaluated. Relative to virus culture, U90 quantitative RT-PCR demonstrated the highest assay sensitivity, specificity, positive predictive value, and negative predictive value. Thus, this method could be a rapid and lower cost alternative to virus culture, which is difficult to perform generally, for identifying active HHV-6B infection.

Etiology and Risk Factors of Febrile Seizure – An Update

Febrile seizures (FS) are the most common convulsive event in children. This condition has been described since the time of Hippocrates. The etiology of the febrile seizures are still unclear. In FS, there is a strong familial predisposition. This does not exclude infections as a causative factor because subtle genetic polymorphisms have been demonstrated to affect the course of infections. In an earlier review of the world literature (1924-1964), except for roseola infantum, viral infections as a cause of febrile seizures were rarely diagnosed. Reports of viral infections in the etiology of febrile seizures have increased in number in the past decade. In the first half of the twentieth century, infections identified with febrile seizures were mainly upper respiratory in type and the etiologic agent was unknown or bacterial. We review i) the role of infection – viral and bacterial; ii) the role of genetic and environmental factors; iii) the role of electrolyte and metabolic factors; and iv) the role of cytokines. With the help of new diagnostic tools such as PCR, the viral agents are detected in CSF far more often than previously thought, even in the absence of pleocytosis of the CSF. This makes it difficult to distinguish FS from acute encephalitis. FS may be caused by neuroinvasion or intracerebral activation of viruses. By reviewing etiology and risk factors of FS we can identify the points to be focused in therapeutic interventions and trials and also the fields of future studies will be explored. DOI: http://dx.doi.org/10.3329/bjch.v34i3.10361 BJCH 2010; 34(3): 103-112

Acute Cerebellitis and Concurrent Encephalitis Associated with Parvovirus B19 Infection

To the Editors: Central nervous system (CNS) infections caused by parvovirus B19 (PVB19) have been rarely documented, especially the involvement of the cerebellum.1 We describe an immunocompetent girl with acute cerebellitis associated with PVB19 infection. A 5-year-old girl was hospitalized because of seizures of the upper extremities after a 3-day history of fever. On arrival, consciousness was disturbed (Glasgow coma scale: E2V1M4). Laboratory findings on admission included white blood cells 10.6 ×109/L, blood glucose 74 mg/dL and sodium 130 mmol/L. Cerebrospinal fluid (CSF) examination showed 229 cells/µL with predominance of polymorphonuclear cells, 144 mg/dL protein and 56 mg/dL glucose. A brain computed tomography image was normal. The patient began treatment with intravenous ceftriaxone, panipenem/betamipron, dexamethasone and acyclovir. Owing to persistent consciousness disturbance, methylprednisolone therapy was added on the fourth day in a dose of 30 mg/kg for 3 days. Electroencephalography on the sixth day showed high-voltage delta activity in the bilateral occipital regions, leading to the diagnosis of encephalopathy. On the sixth day, brain diffusion-weighted magnetic resonance images (see Fig. A, Supplemental Digital Content 1, https://links.lww.com/INF/B90) showed marked hyperintensity in the bilateral dentate nuclei in the cerebellum, suggesting a diagnosis of acute cerebellitis. These dentate nuclear lesions disappeared on the 10th day, and instead hyperintensity in the cerebellar hemisphere became prominent (see Fig. B, Supplemental Digital Content 1, https://links.lww.com/INF/B90). Thereafter, the patient could gradually follow simple verbal instructions, could sit alone on the 16th day, and could walk with a wide stance on the 26th day. Mutism had remained until the 20th day. Three months later, slurred speech and intention tremor persisted. A follow-up magnetic resonance study 6 months later showed cerebellar atrophy (see Fig. C, Supplemental Digital Content 1, https://links.lww.com/INF/B90). On the 10th day, maculopapular rash appeared, extending to the face and extremities, suggesting erythema infectiosum. This was confirmed by elevation of serum PVB19 IgM and IgG antibodies (11.63 and 7.79 titers, respectively) using enzyme immunosorbent assay. Polymerase chain reaction analyses detected PVB19 DNA in the CSF (4.5 × 104 copies/mL) and in the plasma (2.8 × 105 copies/mL) samples stored from the time of admission. Polymerase chain reaction was also applied for herpes simplex virus 1 and 2, human herpes virus (HHV) 6, 7 and 8, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, JC virus and BK virus, showing negative results for all viruses examined except for HHV6 (5.5 × 102 and 3.5 × 103 copies/mL in the CSF and plasma, respectively). Serologically, HHV6-IgG antibody was positive and HHV6-IgM antibody was negative, findings consistent with history of exanthema subitum. Collectively, cerebellitis and concurrent encephalitis were likely caused by CNS PVB19 infection with reactivation of latent HHV6. It is important to note that clinical and radiologic features in our patient were consistent with those of rotavirus-associated cerebellitis.2 Takanashi et al2 documented 11 such cases and proposed it as a novel clinicoradiologic entity because of the homogeneous characteristics. Although rotavirus predominated as causative pathogens,2 adenovirus type 3,3 HHV-64 and influenza virus5 have also been reported. Among 31 childhood PVB19 CNS infections,1 only 2 developed ataxia, but their cerebellar involvement was not radiologically demonstrated. Thus, this is the first describing PVB19 as a cause for this novel type of cerebellitis and suggests a wider entity and a common mechanism. Yoshiko Uchida, MD Kousaku Matsubara, MD, PhD Department of Pediatrics Nishi-Kobe Medical Center Kobe, Japan Tomohiro Morio, MD, PhD Department of Pediatrics and Developmental Biology Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo, Japan Yu Kawasaki, MD Aya Iwata, MD Kazuo Yura, MD Katsunori Kamimura, MD Hiroyuki Nigami, MD Takashi Fukaya, MD Department of Pediatrics Nishi-Kobe Medical Center Kobe, Japan

Mutations of the SCN1A gene in acute encephalopathy

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthema subitum. It occurs worldwide, but is most prevalent in East Asia. Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation. To determine whether SCN1A mutations are a predisposing factor of acute encephalopathy, we sought to identify SCN1A mutations in a large case series of acute encephalopathy including various syndromes. We analyzed the SCN1A gene in 87 patients with acute encephalopathy, consisting of 20 with acute necrotizing encephalopathy (ANE), 61 with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and six with nonspecific (unclassified) acute encephalopathy. Three patients had distinct point mutations. Two of them had epileptic seizures prior to acute encephalopathy. Clinical and neuroradiologic findings of acute encephalopathy were diverse among the three patients, although all had a prolonged and generalized seizure at its onset. The first patient with V982L had partial epilepsy and AESD. The second patient with M1977L had febrile seizures and nonspecific acute encephalopathy. The third patient with R1575C had no seizures until the onset of ANE. M1977L was a novel mutation, whereas the remaining two, V982L and R1575C, have previously been reported in cases of Dravet syndrome and acute encephalopathy, respectively. These findings provide further evidence that SCN1A mutations are a predisposing factor for the onset of various types of acute encephalopathy.

Development of a Human Herpesvirus 6 Species-Specific Immunoblotting Assay

In order to assess the full spectrum of human herpesvirus 6A (HHV-6A)- and HHV-6B-associated diseases, we sought to develop an HHV-6 species-specific serological assay based on immunoblot analysis. The immunodominant proteins encoded by open reading frame U11, p100 for HHV-6A (strain U1102) and 101K for HHV-6B (strain Z29), were selected to generate virus species-specific antigens. Recombinant p100 and 101K were produced in a prokaryotic expression system. The expression of these proteins was confirmed by using anti-His tag and 101K-specific monoclonal antibodies. HHV-6 species-specific antibodies were detected by immunoblotting in patient sera. Eighty-seven serum samples obtained from various subjects were utilized to determine the reliability of the method for clinical use. Ten of twelve exanthem subitum convalescent-phase sera reacted exclusively with 101K, whereas none of twelve acute-phase sera reacted with either protein. Two of three sera collected from HHV-6A-infected patients reacted with p100 and 101K. Although all five acute and convalescent-phase sera obtained from transplant recipients reacted exclusively with 101K, two of six convalescent-phase sera obtained from patients with drug-induced hypersensitivity syndrome reacted with both p100 and 101K. Of 38 sera obtained from healthy adults, 31 were positive for 101K antibody, while 4 reacted with both proteins. However, PCR analysis of peripheral blood mononuclear cells and saliva from these subjects did not detect HHV-6A DNA. In conclusion, this novel serological assay based on immunoblot analysis using recombinant HHV-6A p100 and HHV-6B 101K allowed us to discriminate between HHV-6A- and HHV-6B-specific antibodies.

Rash Decisions: Atypical Exanthems in 260 Consecutive Patients

An atypical exanthema (AE) is defined as an eruptive rash morphologically different from the six classical exanthems (measles, scarlet fever, rubella, erythema infectiosum, exanthem subitum, and chicken pox). Although AEs are common, they are diagnostically challenging, and not well studied. To characterize the clinical features and laboratory findings that might help establish the etiology of AEs, investigators studied 260 …

Human Herpes Virus Type 6 Can Cause Skin Lesions at the BCG Inoculation Site Similar to Kawasaki Disease

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. We present an 11-month-old boy who developed fever with redness of the BCG site due to infection with human herpes virus type 6 (HHV6). At the age of 3 months, the patient received BCG. His fever remitted 7 days after the onset of skin redness, with sequential desquamation at the BCG site and extremities, which is not a common feature of HHV6 infection that typically lasts for 3 days. The final diagnosis was exanthema subitum. Characteristically, the HHV6 infection in our patient appeared to be associated with the invigoration of the T cell system, as represented by the elevated serum levels of soluble interleukin-2 receptor (3,490 U/ml vs. normal range 145-519 U/ml). This patient clearly showed redness and crusting at the BCG inoculation site, suggesting that HHV6 infection might cause skin changes similar to those of KD via an unknown mechanism. In addition, we suggest that the activation of the T cell system may account for the skin lesions in KD, characterized by redness and subsequent crusting of the BCG inoculation site and desquamation of the extremities.

HHV-6B脳炎のメカニズムとその診断，治療

Human herpesvirus 6B (HHV-6B) is causative agent for exanthem subitum, which is common febrile illness in infant. This disease is generally benign and self-limited disease, however rarely causes several central nervous system complications. As various types of HHV-6B encephalitis has been demonstrated, pathophysiology of the disease would be complicate. Thus, different therapeutic strategies should be established for each type of HHV-6B encephalitis at the time of primary viral infection. Meanwhile, this virus can reactivate in transplant recipients and cause post-trasplant limbic encephalitis. It has been demonstrated that neuroimaging analysis particularly MRI image is useful for diagnosis of post-transplant HHV-6B encephalitis. As high copies of viral DNA are detected in patient's CSF, direct invasion of HHV-6B might play important role in causing the disease. Ganciclovir or foscarnet could be effective against HHV-6B based on in vitro analysis.

Human herpesvirus 6-associated uveitis with optic neuritis diagnosed by multiplex PCR

Human herpesvirus 6 (HHV-6), which is usually responsible for exanthem subitum in children, can be reactivated from its latent state. We report a case of unilateral optic disc edema and retinal vasculitis associated with HHV-6 infection. A healthy 63-year-old man noted a decrease in the vision of his left eye. On examination, his left eye had moderate mutton-fat keratic precipitates, vitreous opacities, significant optic disc edema surrounded by yellowish-white swelling in the inner retina, retinal arteritis, and cotton-wool-like exudates. He was started on corticosteroid therapy and aspirin. After 1month, the disc edema was reduced, the cotton wool-like exudates had decreased, and his visual acuity had improved to 10/20 OS. Multiplex polymerase chain reaction (PCR) of an aqueous humor sample revealed the presence of genomic DNA of HHV-6 but not of the other HHVs. The HHVs are known to infect the ocular tissues, but the differential diagnostic signs of HHV-6 are still not well known. We recommend that multiplex PCR of the aqueous humor be performed to search for the genomic DNA of HHV-6 in suspected cases of herpesviral infection.

An epidemiological study of children with status epilepticus in Okayama, Japan: Incidence, etiologies, and outcomes

To clarify the incidence of first-ever episodes of status epilepticus (SE), their etiologies and outcomes among Japanese children, we performed an epidemiological study in Okayama City. One hundred and twenty patients (69 males, 51 females) experienced first-ever SE episodes between 2003 and 2005. Overall, the annual incidence of SE was 42.0 per 100,000 population (95% CI: 34.5-49.5). The highest incidence was seen in patients aged <2years, especially in the second year of life. Febrile SE accounted for 59 (49.2%) cases, and acute-symptomatic etiologies accounted for 21. Ten were considered to have remote-symptomatic etiologies, and eight to have acute-on-remote-symptomatic etiologies. Ten were classified as cryptogenic/idiopathic epilepsy-related, and 12 were unclassified. Nineteen (15.8%) patients were diagnosed with exanthema subitum, including three with encephalitis/encephalopathy, and 17 (14.2%) patients with influenza, including four with encephalitis/encephalopathy. After SE, eight (6.7%) patients suffered from motor disturbance with or without mental disturbance. One of these died during the follow-up period. Ultimately 34 (28.3%) of the 120 patients had been diagnosed with epilepsy by the end of the follow-up. We conclude that the incidence of SE among Japanese children is higher than the reported incidence among Caucasian children. Febrile SE accounted for approximately half of the cases. Among the etiologies, exanthema subitum was the most important infectious disease, followed by influenza. Both types of infection caused encephalitis/encephalopathy associated with SE as well as febrile SE.

Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants

The birth cohort BraMat (n=205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n=195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life.

Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum

In this study, we assessed the prevalence of human herpesvirus-7 (HHV-7) in 141 serum samples from children less than four years of age with exanthematic disease. All samples were negative for measles, rubella, dengue fever and parvovirus B19 infection. Testing for the presence of human herpesvirus-6 (HHV-6)-specific high avidity IgG antibodies by indirect immunofluorescence assay (IFA) revealed two main groups: one composed of 57 patients with recent primary HHV-6 infection and another group of 68 patients showing signs of past HHV-6 infection. Another 16 samples had indeterminate primary HHV-6 infection, by both IgG IFA and IgM IFA. Serum samples were subjected to a nested polymerase chain reaction to detect the presence of HHV-7 DNA. Among patients with a recent primary HHV-6 infection, HHV-7 DNA was present in 1.7% of individuals; however, 5.8% of individuals tested positive for HHV-7 DNA in the group with past primary HHV-6 infection. Among the 16 samples with indeterminate diagnosis, 25% (4/16) had HHV-7 DNA (p < 0.002). We hypothesise that HHV-7 might be the agent that causes exanthema. However, a relationship between clinical manifestations and the detection of virus DNA does not always exist. Therefore, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease. In conclusion, we detected HHV-7 DNA in young children from the state of Rio de Janeiro, Brazil.