Prolonged croup due to herpes simplex virus infection

Herpes simplex virus (HSV) is an uncommon cause of acute laryngitis in immunocompetent patients since it mostly occurs in immunocompromised subjects. We present two previously healthy children with prolonged gingivostomatitis and stridor (lasting 3 and 4 weeks) in whom HSV-1 was isolated from subglottal ulcers. Conclusion HSV should be considered a possible pathogen in cases of prolonged or atypical croup not only in immunocompromised or elderly patients but also in otherwise healthy children. Received: 10 March 1997 / Accepted: 20 September 1997     

Herpes Simplex Virus Type 1 (HSV-1) and Varicellazoster Virus (VZV) Infections in Saudi Arabia

The seroepidemiology of infection due to herpes simplex type 1 (HSV-1) and varicella-zoster (VZV) viruses was investigated in 224 Saudi children aged from under 1 year to 15 years and 452 adults (healthy male blood donors and pregnant women) using a presently available sensitive indirect immunofluorescence technique to detect antibodies to these viruses in order to determine the age of primary infection. Age-specific prevalence of IgG antibodies to HSV-1 and VZV showed a progressive increase with age in both males and females with no obvious sex-related variation in the level. The overall prevalence of antibodies was 60 per cent for HSV-1 and 68 per cent for VZV in children whereas about 90 per cent of the adults showed the presence of antibodies to both viruses. Virological and serological confirmation of two cases in children of herpes simplex encephalitis (HSE) due to HSV-1 and VZV reactivation in two adults is described.     

Herpes simplex viral pneumonitis in childhood

We report two cases of herpes simplex pneumonia in children. One patient had Down syndrome, and the other was immunosuppressed by cancer therapy. Both had interstitial pneumonitis with nonspecific physical, radiographic, and laboratory findings, and both died. The diagnosis of herpes simplex pneumonia was made by isolation of herpes simplex virus from autopsy lung cultures as well as by demonstration of antigen in the tissue with an immunoperoxidase procedure. Inasmuch as herpes simplex pneumonia is a potentially treatable infection, early virologic studies are recommended in immunocompromised children with progressive pneumonitis of undetermined cause.     

Croup: an 11-year study in a pediatric practice

The etiology and epidemiology of croup were studied in a pediatric group practice over an 11-year period, 1964 to 1975. Croup was diagnosed in 951 instances in 6,165 cases of lower respiratory tract infection (LRI) studied. As census figures of the practice clientele were available, attack rates were calculated. The incidence of total LRI was highest in the first year of life. In contrast, the attack rate for croup was highest in the second year of life; the rate declined gradually after that age. Croup was not diagnosed in the first month of life. Boys were 1.43 times more likely to develop croup than were girls. Three hundred sixty agents were isolated from the 951 croup cases. The parainfluenza viruses accounted for 74.2% of all isolates; 65% of the parainfluenza isolates were classified as parainfluenza virus type 1. Respiratory syncytial virus, influenza viruses A and B, and Mycoplasma pneumoniae were the only other agents isolated in appreciable numbers. The propensity of various agents to produce croup symptoms in children with LRI due to specific microorganisms was 58% for parainfluenzae type 1,60% for parainfluenzae type 2, and 29% for parainfluenzae type 3; similar figures for the other agents varied from 5% to 16%. The role of the various agents in the etiology of croup varied with patient age and depended on the propensity of the agent to produce the croup syndrome and the frequency of isolation of the agent at that age. The parainfluenza viruses were the most important croup agents at all ages; respiratory syncytial virus caused croup in children less than 5 years of age whereas the influenza viruses and M pneumoniae were significant causes of croup only in children more than 5 to 6 years old. Croup occurred predominately in late fall and early winter, times when the parainfluenza viruses, especially type 1, occurred most frequently. The epidemiology of croup differs from that of bronchiolitis, pneumonia, and tracheobronchitis; knowledge of this should be helpful to the clinician caring for children with LRI.     

Clinical courses of croup caused by influenza and parainfluenza viruses.

Influenza viruses have occasionally been associated with severe manifestations of croup, but no comparative studies of different viral etiologies are available. In a retrospective study we compared the clinical courses of croup caused by influenza and parainfluenza viruses in hospitalized children. By several indicators the clinical picture of croup caused by influenza viruses was significantly more severe than that caused by parainfluenza viruses.     

Herpetic meningitis in the child]

In children, viral meningitis is usually caused by Enteroviruses. Herpes simplex viruses (HSV) are known to be a cause of meningo-encephalitis. HSV-2 has been reported to cause recurrent meningitis (Mollaret's meningitis) in adults. CASE REPORT: We report the case of a three-year-old girl with HSV-1 meningitis, whose evolution with treatment by aciclovir was good. CONCLUSION: HSV-1 has rarely been reported as a cause of isolated aseptic meningitis in children. Primary phase of herpes simplex virus infection is not usually associated with neurologic complications.     

Choreoathetosis after herpes simplex encephalitis with basal ganglia involvement on MRI

Children with herpes simplex virus encephalitis have a relapse in approximately 25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for herpes simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after herpes simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-herpes simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and herpes simplex virus encephalitis. Current understanding of the pathophysiology of post-herpes simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.     

Non-invasive method for early diagnosis of herpes simplex encephalitis.

For the early diagnosis of herpes simplex encephalitis IgG and IgM antibodies to herpes simplex virus in cerebrospinal fluid were measured by an enzyme linked immunosorbent assay (ELISA) and a local production index was calculated. Using these three criteria, 31 cases of various neurological illnesses were analysed. All eight cases of herpes simplex encephalitis were diagnosed correctly in the acute phase, and there were no false positive results.     

Preliminary clinical experiences with adenine arabinoside monophosphate (ARA-AMP) in encephalitis due to viruses of the herpes group and varicella/zoster infections (author's transl)]

Adenine arabinoside monophosphate (ARA-AMP) is a new antiviral agent with significant activity against DNA viruses of the herpes group. It appears to be superior to cytosine arabinoside and iodoxuridine in severe herpes simplex infections. Unlike cytosine arabinoside and idoxuridine ARA-AMP has only minimal myelosuppressive and immunosuppressive properties. The original compound, adenine arabinoside (ARA-A) which has been used in the United States in the last years had the disadvantage of poor solubility and tissue penetrance. Compared to adenine arabinoside the monophosphate ester of this compound has the advantage of better solubility and is more slowly metabolized in humans. In eight children with virus induced encephalitis ARA-AMP was well tolerated, we could not observe any severe side effects. A case of herpes simplex encephalitis showed a complete recovery. However it has to be pointed out that in herpes simplex encephalitis ARA-AMP should be given early in the course of infection to have a beneficial effect, therefore an early diagnosis is of utmost importance. A case of generalized herpes zoster healed up within about a week. Of course these are very preliminary results which must be confirmed by further experiences.     

Herpes simplex virus: fetal and decidual infection

We report 2 cases of probable in-utero transmission of herpes simplex virus. Herpes viral antigen was localized in these cases to the decidualized endometrium, using an immunoperoxidase staining technique. Routine histology did not show herpes inclusions in the decidual or glandular cells. This finding suggests that herpes virus may infect endometrial cells during pregnancy.     

Rapid diagnosis of herpetic encephalitis in children by PCR-microarray technology for simultaneous detection of seven human herpes viruses

The aim of the study was to evaluate retrospectively the usefulness of polymerase chain reaction (PCR)-microarray technology, which can simultaneously detect seven human herpes viruses for rapid and accurate diagnosis of herpetic encephalitis in children. We simultaneously amplified herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2); varicella-zoster virus; Epstein–Barr virus (EBV); cytomegalovirus (CMV); and human herpes virus 6 (HHV-6A and HHV-6B) by multiplex PCR, and genotyped by DNA microarray technology. The multiplex primers and oligonucleotide probes were designed and synthesized based on the highly conserved regions of the DNA polymerase gene in human herpes viruses. Two hundred ninety cerebrospinal fluid (CSF) specimens from children with clinical suspicion of viral encephalitis were screened by PCR-microarray technology. The results were compared with those of TaqMan PCR kits of common herpes virus. The PCR-microarray technology could detect as few as 10 copies of viral loads. There was no nonspecific hybridizing signal between probes and no cross-reaction to DNA extracted from the pathogens we used. Of 290 cases, 11 were tested positive by PCR-microarray technology. Among them, three were positive for HSV-1, two were positive for HSV-2, one was positive for EBV, two were positive for CMV, two were positive for HHV-6A, one was positive for HHV-6B, and one showed mixed infection of HSV-2 and CMV, and the positive rate was 3.8%. Compared with the results of TaqMan PCR, the sensitivity of PCR-microarray technology was 91.7%, the specificity was 100%, and the index of accurate diagnosis was 0.917. None of the 30 control CSF specimens was tested positive in both methods. Our study suggests that the simultaneous detection of seven human herpes viruses by PCR-microarray technology is the method of choice for rapid, accurate, and specific etiological diagnosis of herpetic encephalitis in children.     

Immunological and virological investigations in Down's syndrome

Lymphocyte responsiveness to phytohaemagglutinin and viral antigens was studied in children with Down's syndrome and in controls. Mitogen-responsiveness in the patients was significantly reduced as compared to the control values. Using the lymphocyte transformation test, trisomic patients showed more than a twofold increase in sensitivity to herpes simplex virus as compared to controls. The same test did not show any essential difference between the two groups when adeno- and influenza viruses were used. Immunofluorescence technique, with specifically conjugated antiviral sera, permitted the detection of specific fluorescence in 30% of the patients with Down's syndrome indicating the presence of oncogenic adenovirus type 12 antigen in the circulating lymphocytes. No antibodies—or only very low titres—against adeno- and herpes simplex viruses were demonstrated in the sera of trisomic patients. Mononuclear leukocytes from these patients often showed structural alterations. The incidence of infectious herpes simplex virus and Candida albicans in the saliva of patients was higher than in the control group.It seems that Down's syndrome involves partial disturbance of both the cellular and humoral immune functions—at least with respect to certain viral antigens.     

Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by HSV DNA detection in blood and successfully managed by liver transplantation

We report a case of neonatal herpes presenting with liver failure and disseminated coagulopathy which followed unrecognised maternal primary genital herpes and was diagnosed by herpes simplex virus DNA detection in blood by polymerase chain reaction 2 weeks after initiation of empiric intravenous aciclovir. The child underwent liver transplantation while receiving suppressive antiviral therapy and remains well after 10 months of follow-up. Conclusion:our case highlights potential pitfalls in the diagnosis of neonatal herpes and indicates a role for blood herpes simplex virus polymerase chain reaction as a sensitive diagnostic tool in disseminated infection. It is one of very few reports where liver transplantation has been successfully carried out in a neonate with herpes simplex virus-induced liver failure.Abbreviations HSV herpes simplex virus - PCR polymerase chain reaction     

Multiple herpetic whitlow lesions in a 4-year-old girl: case report and review of the literature

Herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles. In children it typically occurs after auto-inoculation from herpes stomatitis, herpes labialis or genitalis. Occasionally, person-to-person transmission occurs from family members with herpes labialis. We report a 4-year-old girl with multiple herpetic whitlows secondary to herpetic stomatitis and present a review of the medical literature based on a systematic MEDLINE search of published paediatric patients (English, French and German language). Of 42 identified patients, 72% were younger than 2 years, most had endogenous or exogenous inoculation of herpes simplex virus type 1 and 65% were initially misdiagnosed as having "bacterial felon". Recurrences were reported in 23%. CONCLUSION: herpetic whitlow should be suspected based on clinical signs. Specific diagnosis can be made by polymerase chain reaction or culture. The high rate of misdiagnosed cases indicates that this entity is not sufficiently known. Lesions are self-limited; surgical interventions can be harmful and should be avoided. Recurrences occur as frequently as in adults.     

Viral isolates during febrile neutropaenia in children with cancer

We prospectively studied South African children with cancer for viral isolates during episodes of febrile neutropaenia. Viruses were found in seven (31.8 per cent) and bacteria in five (22.7 per cent) of 22 episodes. The most common isolate was the herpes simplex virus and the most common source was from nasopharyngeal aspirates. There was no dual detection of viral and bacterial isolates. This study emphasizes the important contribution of viruses to febrile neutropaenia.     

Occurrence of childhood encephalitis: a population-based study

The occurrence of childhood encephalitis was evaluated in a population-based study in an area with no arboviral infections. Ninety-five children were treated for encephalitis during 1973 to 1987, giving an annual incidence of 8.8/100,000 children younger than 16 years of age (95% confidence interval, 6.7 to 10.1). Based on virologic and serologic studies the most common etiologic agents were varicella (24 cases), mumps (8), herpes simplex (7) and measles (4). The etiology remained unknown in 37 children. No cases of encephalitis caused by mumps, measles or rubella were found in the population after 1982, when vaccination against these viruses was introduced.     

Herpes simplex virus type 1 infections presenting at birth

Two cases of intra-uterine acquired neonatal herpes simplex type I presented with atypical skin lesions apparent at or shortly after birth; the timing and appearance of the lesions meant that herpes virus infections were not considered to be the most likely diagnosis. Once herpes simplex was diagnosed, both infants were treated with acyclovir. Prompt diagnosis and institution of acyclovir are imperative for a favourable outcome from neonatal herpes infections.     

Herpes simplex (author's transl)]

About 1-2% recurrent herpes simplex infections are seen in adults. In childhood, secondary herpetic infections are very rare. In contrast, primary infections by herpes simplex virus are of great importance: herpes disseminatus neonatorum (type 2), gingivostomatitis herpetica (type 1), eczema herpeticum (type 1; in some cases, also type 2) and keratoconjunctivitis herpetica (type 1). The clinical and therapeutic data are discussed.     

Exogenous causes of disordered embryonal morphogenesis

Recent advances in exogenous factors known to cause embryopathies are reviewed. Among the non-infectious agents alcohol is the most important, followed by a combination of anticonvulsant drugs, valproic acid, retinoic acid, lithium, coumarin derivates, methyl mercury, aminopterin and methotrexate, cocaine and amniogenic bands. Rubella embryopathy is well known. Varicella zoster and herpes simplex type II viruses are now also known to be teratogenic in some cases. Erythema infectiosum has recently been detected as a cause of embryonic death. Diabetic women and women with phenylketonuria must be carefully examined before and during pregnancy. There does not seem to be a world trend towards increased frequency of genetically and non genetically conditioned malformations.