Purpose of Review
Exanthema subitum, which is caused by primary human herpesvirus 6B (HHV-6B) infection, is generally self-limited. However, disease burden due to primary HHV-6B infection has not yet ...been widely reported. Therefore, we reviewed the burden of emergency room (ER) visits and serious complications by primary HHV-6B infection.
Recent Findings
Around 10% of children with fever under 6 years of age seen in ERs had primary HHV-6B infection prior to the coronavirus disease 2019 (COVID-19) pandemic. Non-pharmacological interventions implemented because of the COVID-19 pandemic decreased the frequency of many viral infections, but not ES. Thus, the relative disease burden of primary HHV-6B infection has increased. Central nervous system diseases including febrile seizure and encephalitis are rare complications. Primary HHV-6B infection is the second cause of pediatric acute encephalopathy after influenza in Japan and there is still no effective treatment.
Summary
The clinical features and disease burden of primary HHV-6B infection in immunocompetent patients are reviewed.
Abstract
Background
Human herpesvirus 6 (HHV-6) can be genetically transmitted from parent to child as inherited chromosomally integrated HHV-6 (iciHHV-6). HHV-6 reactivation occurs in pregnant women ...with iciHHV-6. We found no sex differences in the frequency of index cases with iciHHV-6 but inheritance from the father was more common. We evaluated the association between iciHHV-6 status and spontaneous abortion.
Methods
iciHHV-6 was confirmed by high viral DNA copy numbers in whole blood and somatic cells. The origin of integrated viral genome, paternal or maternal, was examined using the same method. The pregnancy history of 23 mothers in families with iciHHV-6 and 285 mothers in families without iciHHV-6 was abstracted.
Results
Of 23 iciHHV-6 index cases, 8 mothers and 15 fathers had iciHHV-6. Spontaneous abortion rates in mothers with and mothers without/fathers with iciHHV-6 and mothers in families without iciHHV-6 were 27.6%, 10.3%, and 14.8%, respectively (P = .012). Mothers with iciHHV-6 (odds ratio OR, 6.41; 95% confidence interval CI, 1.10–37.4) and maternal age at the most recent pregnancy ≥40 years (OR, 3.91; 95% CI, 1.30–11.8) were associated with 2 or more spontaneous abortions.
Conclusions
Mothers with iciHHV-6 is a risk factor for spontaneous abortion.
The frequency of iciHHV-6 inherited from the mother was lower than expected, and spontaneous abortion rate in mothers with iciHHV-6 was significantly higher than in mothers without/fathers with iciHHV-6 and control mothers.
Here, we present a previously healthy adolescent with aseptic meningitis without skin rash caused by varicella vaccine derived from the Oka/Biken strain; the patient received a single dose of ...varicella vaccine at 1 year of age. Pediatricians should be aware of the potential for reactivation of varicella vaccine derived from the Oka/Biken strain, which can cause aseptic meningitis in vaccinated children even in the absence of a skin rash.
Reassortment is an important mechanism in the evolution of group A rotaviruses (RVAs), yielding viruses with novel genetic and phenotypic traits. The classical methods for generating RVA reassortants ...with the desired genetic combinations are laborious and time-consuming because of the screening and selection processes required to isolate a desired reassortant. Taking advantage of a recently developed RVA reverse genetics system based on just 11 cloned cDNAs encoding the RVA genome (11 plasmid-only system), we prepared a panel of simian SA11-L2 virus-based single-gene reassortants, each containing 1 segment derived from human KU virus of the G1P8 genotype. It was shown that there was no gene-specific restriction of the reassortment potential. In addition to these 11 single-gene reassortants, a triple-gene reassortant with KU-derived core-encoding VP1-3 gene segments with the SA11-L2 genetic background, which make up a virion composed of the KU-based core, and SA11-L2-based intermediate and outer layers, could also be prepared with the 11 plasmid-only system. Finally, for possible clinical application of this system, we generated a series of VP7 reassortants representing all the major human RVA G genotypes (G1-4, G9 and G12) efficiently. The preparation of each of these single-gene reassortants was achieved within just 2 weeks. Our results demonstrate that the 11 plasmid-only system allows the rapid and reliable generation of RVA single-gene reassortants, which will be useful for basic research and clinical applications.
It is well known that febrile seizures are commonly occur in children with exanthem subitum. In this study, we compared the clinical features and backgrounds of patients with complex febrile seizures ...with and without primary human herpesvirus 6B infection.
Sixty-two patients were enrolled after experiencing their first febrile seizure. Primary human herpesvirus 6B infection was confirmed when human herpesvirus 6B DNA was detected and human herpesvirus 6B antibody was negative in serum obtained during the acute phase of infection. Patient age, gender, and features of seizures were evaluated between patients with and without human herpesvirus 6B infection.
Thirty patients with complex febrile seizure were diagnosed with primary human herpesvirus 6B infection. Those with primary human herpesvirus 6B infection (median, 13 months; range, seven to 39 months) were significantly younger than those without primary human herpesvirus 6B infection (median, 19 months; range, 10 to 59 months) (P = 0.001), and the proportion of males was significantly higher in patients without primary human herpesvirus 6B infection (male/female, 25/7) than in those with the infection (male/female, 14/16) (P = 0.017). An interval between fever onset and seizures of more than 24 hours was significantly more common in patients with primary human herpesvirus 6B infection (15 of the 30 patients) than in those without primary HHV-6B infection (two of 32 patients) (P < 0.001).
A younger age at onset, a different gender ratio compared with febrile seizure due to other causes, and the length of interval between fever and seizures were features of complex febrile seizure associated human herpesvirus 6B infection. These findings may suggest a mechanism of complex febrile seizure onset different from that due to other causes.
The exact evolutionary patterns of human G4P6 rotavirus strains remain to be elucidated. Such strains possess unique and strain-specific genotype constellations, raising the question of whether G4P6 ...strains are primarily transmitted via independent interspecies transmission or human-to-human transmission after interspecies transmission. Two G4P6 rotavirus strains were identified in fecal specimens from hospitalized patients with severe diarrhea in Thailand, namely, DU2014-259 (RVA/Human-wt/THA/DU2014-259/2014/G4P6) and PK2015-1-0001 (RVA/Human-wt/THA/PK2015-1-0001/2015/G4P6). Here, we analyzed the full genomes of the two human G4P6 strains, which provided the opportunity to study and confirm their evolutionary origin. On whole genome analysis, both strains exhibited a unique Wa-like genotype constellation of G4-P6-I1-R1-C1-M1-A8-N1-T1-E1-H1. The NSP1 genotype A8 is commonly found in porcine rotavirus strains. Furthermore, on phylogenetic analysis, each of the 11 genes of strains DU2014-259 and PK2015-1-0001 appeared to be of porcine origin. On the other hand, the two study strains consistently formed distinct clusters for nine of the 11 gene segments (VP4, VP6, VP1-VP3, and NSP2-NSP5), strongly indicating the occurrence of independent porcine-to-human interspecies transmission events. Our observations provide important insights into the origin of zoonotic G4P6 strains, and into the dynamic interaction between porcine and human rotavirus strains.
This cohort study, based on the design of a prior study in the United States, was conducted to elucidate the clinical features of primary human herpesvirus-6B (HHV-6B) infection.
Between June 2014 ...and May 2016, febrile children younger than 5 years who visited the emergency room (ER) and underwent blood examination were enrolled in this study.
Fifty-nine (12%) of the 491 patients were diagnosed with primary HHV-6B infection. The rates of both simple and complex febrile seizure were significantly higher in patients with primary HHV-6B infection than in those without (P < 0.001 and P = 0.008, respectively). The median age at primary HHV-6B infection was 15 months. Forty-seven (79.7%) of the 59 patients with primary HHV-6B infection were younger than 2-year-old. Clinical features were compared between HHV-6B-infected patients older and younger than 2 years. The frequency of apparent infection (exanthema subitum) was significantly higher in the younger patients (P = 0.01). The median leukocyte (P = 0.01) and lymphocyte (P < 0.001) counts in the patients older than 2 years were significantly lower than those in the younger patients.
Primary HHV-6B infection accounted for 12% of ER visits. Secondary febrile seizures, in particular the complex type, were considered to be a major contributor to the disease burden of primary HHV-6B infection. The timing of primary HHV-6B infection occurred at older ages than in past reports, and the frequency of inapparent infection was higher in older patients.
Kawasaki disease (KD) is an acute, febrile, systemic vasculitis of unknown etiology that primarily affects the coronary arteries and generally occurs at around 1 year of age. Although the diagnosis ...of KD is generally not difficult, it is challenging in cases of incomplete KD lacking characteristic clinical manifestations. The incidence of incomplete KD is higher in infants younger than 6 months of age. Pneumonia is an extremely rare complication of KD and can be misinterpreted as atypical pneumonia rather than KD. Herein, we report a neonate with atypical KD and severe pneumonia who required mechanical ventilation.
Japanese one-month-old infant had only fever and rash on admission (day 1), and he was transferred to the intensive care unit for severe pneumonia on day 2. Although pneumonia improved following intensive care, he was diagnosed with KD on day 14 because of emerging typical clinical manifestations such as fever, bulbar nonexudative conjunctival injection, desquamation of the fingers, and coronary artery aneurysm. KD symptoms improved after three doses of intravenous immunoglobulin plus cyclosporine. However, small coronary aneurysms were present at the time of discharge. In a retrospective analysis, no pathogens were detected by multiplex real-time PCR in samples collected at admission, and the serum cytokine profile demonstrated prominent elevation of IL-6 as well as elevation of neopterin, sTNF-RI, and sTNF-RII, which suggested KD.
The patient's entire clinical course, including the severe pneumonia, was caused by KD. As in this case, neonatal KD may exhibit atypical manifestations such as severe pneumonia requiring mechanical ventilation.
Background. Human herpesvirus 6B (HHV-6B) is the causative agent for exanthem subitum. HHV-6B was associated with mesial temporal sclerosis (MTS), leading to mesial temporal lobe epilepsy (MTLE). In ...this study, we sought to elucidate the pathogenic role of HHV-6B in patients with MTLE. Methods. Seventy-five intractable MTLE patients, including 52 MTS patients and 23 non-MTS patients, were enrolled in this study. Resected hippocampus, amygdala, and mixed samples of amygdala and uncus samples were examined by real-time polymerase chain reaction (PCR) and reverse-transcriptase PCR to detect viral DNA and messenger RNA (mRNA), respectively. Host gene expressions, including neural markers, were measured using the TaqMan Gene Expression Assay. Results. Detection of HHV-6 DNA was higher in MTS patients than non-MTS patients (median/interquartile range: 19.1/0-89.2 vs 0.0/0.0-0.0 copies/μg DNA; P = .004). HHV-6B viral DNA was determined in 12/27 HHV-6 DNA-positive samples, and no HHV-6B mRNA were detected in all samples. In MTS patients, expression of monocyte chemotactic protein-1 (P = .029) and glial fibrillary acidic protein (P = .043) were significantly higher in the amygdala samples with HHV-6 DNA than those without viral DNA. Conclusions. This study suggests that HHV-6B may play an important role in the pathogenesis of MTS via modification of host gene expression.
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