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"Doctor, there's a man on the phone who's offering you $500 to give his child a flu shot. His child isn't one of our patients." "Please tell him we only [...]

This single most important pediatric respiratory pathogen is ubiquitous, highly contagious, and potentially devastating in adults as well. But drug treatment is now a reality, and research holds the promise [...]

The discovery of three new human herpesviruses (HHV-6, -7, and -8) has led to more questions than answers. HHV-6 can cause roseola, and is found in adults with immune deficiencies, although its role in these patients is unknown. The action of HHV-7 in disease is even less clear, but it may play a part in roseola also. HHV-8 is strongly linked to Kaposi sarcoma lesions; in one study, 97% of these lesions contained the virus. Improved diagnostic tests are needed to provide more information on this family of viruses.

Respiratory syncytial virus (RSV) infection in the United States and worldwide is a major cause of morbidity and mortality and of outpatient visits, hospitalizations, and increased healthcare costs. Effective diagnosis of viral respiratory infections, as well as recognition and understanding of the benefits and limitations of diagnostic laboratory testing, is essential. Serology is not useful for diagnosing acute respiratory illness. Antigen-based assays are widely available, easy to use, provide rapid results, and are inexpensive; however, they are less sensitive than cell culture utilizing good specimen collection and processing techniques. Cell culture, which was previously considered the gold standard for identification of respiratory viruses, in many settings is being replaced by nucleic acid amplification assays that have even greater sensitivity and provide more rapid results. Although available chiefly at large hospitals and reference laboratories, molecular assays may fulfill the need for more sensitive and rapid diagnosis of illnesses caused by respiratory viruses. The seasonality of RSV as measured by nucleic acid amplification-based assays appears to be broader with better identification of patient populations that harbor RSV between yearly epidemic peaks compared with the seasonality of RSV as measured by the older techniques. As these new diagnostic methodologies emerge, guidelines will be needed to direct their appropriate use in the diagnostic laboratory.

ABSTRACTThe role of human herpesvirus 6 (HHV-6) in disease beyond primary infection remains unclear. We have developed and validated a new reverse transcription-PCR (RT-PCR) assay for HHV-6 that can determine the presence of HHV-6 in clinical specimens and differentiate between latent and replicating virus. Peripheral blood mononuclear cells from 109 children were evaluated for HHV-6 by RT-PCR, DNA PCR, and viral culture. Of these samples, 106 were suitable for analysis. A total of 20 samples were positive for HHV-6 by culture and DNA PCR, of which 19 were positive by RT-PCR (sensitivity, 95%). All 28 samples from children that were negative by viral culture, but positive by DNA PCR, were negative for viral transcripts by our RT-PCR assay. One positive RT-PCR result was observed in 56 samples that were negative by tissue culture and DNA PCR. This indicates a low rate of false-positive results (1.2%) and a specificity of 98.8%. This RT-PCR assay can reliably differentiate between latent and actively replicating HHV-6 and should allow insight into the pathogenesis of this ubiquitous virus.

To test the hypothesis that children experiencing first febrile seizures caused by human herpesvirus 6 (HHV-6) have an increased risk for recurrent seizures when compared with children experiencing first febrile seizures attributed to other illnesses.

Aerosolized ribavirin was evaluated in the treatment of respiratory syncytial virus lower respiratory tract disease in 53 infants, 36 of whom had underlying diseases. Of the total infants, 26 were studied in a double-blind, placebo-controlled manner; 14 received ribavirin and 12 received placebo, a water aerosol, for an average of five days. When the infants with bronchopulmonary dysplasia and congenital heart disease treated with ribavirin were compared with those receiving placebo, the treated infants showed a significantly faster rate of improvement in their illness severity score. The degree of improvement in the total group of infants receiving ribavirin compared with those receiving placebo was similarly greater, and at the end of therapy significantly greater improvement was also demonstrated in their arterial blood gas values and in the amount of virus shed from their nasal washes. No toxic or adverse effects of the aerosol therapy were observed in any of the 53 infants studied, and resistance to ribavirin did not develop in any of the respiratory syncytial virus strains isolated, despite prolonged treatment in some of the more ill infants.(JAMA 1985;254:3047-3051)

AbstractThis article reviews the most likely mechanisms of transmission of the commonly encountered respiratory viruses (influenza, respiratory syncytial virus, parainfluenza, rhinovirus), herpesviruses, and hepatitis viruses, and presents the guidelines used currently for prevention and control that are in use at Strong Memorial Hospital.

• Although the "Boston exanthem" has been seen rarely over the past 20 years, in the summer of 1974 we identified ten children, aged 1 week to 7 years with echovirus 16 infections. Seven of the children had rashes, and in four, the illnesses suggested roseola infantum. Five of these children were neonates, all with illnesses severe enough to mimic sepsis. In addition, information obtained on echovirus 16 isolations occurring in 1974 elsewhere in the country showed an additional 27 isolations from eight states. It is postulated that more outbreaks of the Boston exanthem or other echovirus 16 illnesses will appear during the next several years, before the virus again "disappears."(Am J Dis Child 131:323-326, 1977)

Parainfluenza types 1, 2 and 3 were studied in a pediatric outpatient population from 1976 to 1992 to compare seasonal patterns over time and to define better the spectrum of illness in all ages of children caused by these viruses. Parainfluenza type 1 occurred in the fall of odd numbered years; parainfluenza type 2 was less predictable; and parainfluenza type 3 appeared yearly with peak activity in spring or summer. The parainfluenza viruses were the major cause of croup and also accounted for one-half of the cases of laryngitis and over one-third of all lower respiratory tract illness in children from whom a virus was isolated. The major clinical manifestations of infection with parainfluenza types 1 and 2 were croup, upper respiratory infections and pharyngitis; for parainfluenza type 3 upper respiratory tract infection was predominant in all age groups.

Clinical and laboratory data of 12 previously healthy infants under 3 months of age hospitalized for suspected sepsis and subsequently diagnosed as suffering from influenza A viral infection were obtained prospectively during two epidemics of influenza A/Bangkok/H3N2epidemics. The onset of the illness was generally acute, and the infants presented with high fever, lethargy often alternating with irritability, anorexia and signs of upper respiratory tract infection. History of contact with at least one person with signs and symptoms consistent with viral disease was present in all infants. White blood cell counts were within normal limits. Only one child had pneumonia and all had normal cerebrospinal fluid findings. Viral diagnosis was made by immunofluorescent testing of nasopharyngeal specimens within several hours of admission in 7 of the 9 infants tested and was isolated within 5 days from admission in 6 of 10 infants. Increasing awareness of the possible viral etiology of acute fever along with a greater availability of rapid viral diagnosis should result in better management of these young infants.

• The efficacy of infection control procedures utilizing gowns and masks in the control of nosocomial respiratory syncytial virus (RSV) infections was evaluated by comparing the rate of nosocomial RSV infections in infants and ward personnel during two sequential periods when gowns and masks were used (period 1) and not used (period 2). All patients (162) and staff (36) on our infants' ward were examined for signs of respiratory infection and had nasal washes obtained for viral isolation every two to four days for two months. Nosocomial RSV infection was identified in a total of 19 infants. Eight of these occurred in period 1 for a nosocomial infection rate of 32% of contact infants who were hospitalized for seven or more days. In comparison, 11 (41%) of the contact infants hospitalized for seven or more days in period 2 became infected. These findings suggest that the additional routine use of masks and gowns does not result in measurable benefit in controlling the nosocomial spread of RSV infection to infants or to ward personnel.(Am J Dis Child 1981;135:512-515)

• The physiological abnormalities and clinical correlates of 32 infants consecutively hospitalized with lower respiratory tract disease from respiratory syncytial virus (RSV) were studied in an attempt to characterize the infant most at risk for the acute and long-term complications of RSV infection. Arterial oxygen saturation (Sao2) determinations were obtained daily by means of an ear oximeter. On admission all infants were hypoxemic with a mean Sao2 of 87% (range, 74% to 95%). The mean of the lowest Sao2 recorded during their hospitalization was 85.5% (range, 53% to 96%). The hypoxemia improved little during hospitalization but showed improvement three to seven weeks later. The severity of the hypoxemia correlated significantly with the duration of viral shedding, occurrence of apnea, respiratory rate, age, and percentage of immature neutrophils. Clinical severity did not correlate with the degree of hypoxemia.(Am J Dis Child 133:798-802, 1979)

• Concurrent and sequential outbreaks of infection with respiratory syncytial virus (RSV) and influenza A virus were studied, utilizing a local surveillance system for infectious diseases that involved weekly reports from primary care physicians. The patterns of illness in the community and in hospital admissions were relatively specific for these two viruses, and differed according to whether RSV and influenza A virus occurred together or separately. This surveillance system appeared to be a practical and accurate indicator of the activity of RSV and influenza A virus in the community. Such a system may serve as a valuable means of relatively early detection of the local arrival of these viruses, and recognition of these illness patterns might aid the physician in diagnosis.(Am J Dis Child 130:615-620, 1976)

AbstractViral illnesses in Strong Memorial Hospital were monitored over a 17-month period. Using criteria based primarily on the incubation periods for a number of common virus infections, the infections we found were classified as hospital- or community-acquired. Hospital-acquired viral infections occurred on most hospital services; the majority of infections occurred on the pediatric and psychiatric services. Infections due to herpesviruses were seen more frequently in a group of patients aged 14 years or older, while infections in patients aged three years or younger were more likely to be due to respiratory syncytial virus, influenzavirus, adenovirus, or parainfluenza virus. Patients with nosocomial infections due to viruses were hospitalized an average of 9.3 days longer than uninfected controls; thus nosocomial viral infections result in increased costs of hospitalization.

• A 9-month-old boy developed encephalopathy associated with the onset of erythema infectiosum, which resulted in permanent neurologic sequelae. This is the second reported case of encephalitis following erythema infectiosum and the first, to our knowledge with permanent sequelae.(Am J Dis Child 131:65-67, 1977)

Children to whom books are read aloud from a young age are more likely to become readers for life than are children whose parents do not read to them or who have no books in their homes. Reading with a child provides the opportunity for an intimate, shared experience and is a relief from active games, cross tempers, or boredom.How does an adult know what makes a good book for children? For young children, ages 2 to 5, the visual quality is very important. The illustrations should be bright, colorful, and clear (not abstract). Of special importance in books to read aloud, pictures should be closely related to the text so that they really help tell the story and do not merely decorate. Vocabulary ought to be simple and clear, yet rich enough not to be dull. Texts in some of the best picture books read like poetic prose;

There is no Frigate like a Book To take us Lands away Nor any Coursers like a Page Of prancing PoetryEMILY DICKENSONFor generations, the "bedtime hour" evoked visions of mother and her brood snuggled about the hearth as she read the tales spun by Rudyard Kipling or Hans Christian Andersen to the glow of young eyes. But if Wee Willie Winkie were to peer through the shutters of today's town, he would be apt to see a different twilight scene—little faces immobilized by the flickering steel gray light of the television screen. TODAY'S CHILD Our preschool children of almost a decade ago watched an average of 3⅓ hours of television each day, according to the Neilsen Television Index. One fifth of these children, classified as the most ardent television devotees, spent seven hours in front of the television each day. By 1970, four years later, our average preschooler

We are all diseas'd and with our surfeiting and wonton hours Have brought ourselves into a burning fever, and we must bleed for it. William Shakespeare (Henry IV)Polymicrobial infections with organisms derived from the mouth occur in wounds inflicted by a human bite. These infections may be contiguous to the mouth or at a distance. We observed two instances of infections with bacteria consistent with oral flora, without a clearly established route of infection. Unrecognized, inconsequential habits of these children were responsible for self-inoculation with their own saliva. These cases demonstrate the importance of rigorous pursuit of the pathogenesis of infections with agents known to reside in specific locations in the body, even in the absence of an obvious connection.Report of Cases.—Case 1.—An 18-month-old male infant was hospitalized in September 1982, with bilateral orbital and left flank masses and intermittent fever for four days. Acute

Exanthems from an ancient family of five1,2Achieved great fame; though now just four remain alive.Rubella, Measles, Scarlet Fever are the threeFirst christened, since the fourth succumbed in infancy.Yet little Fifth Disease cannot assume Fourth's name,Just as the "junior" would not then the "senior" claim.Instead, a new fourth member we might now adopt,And for the orphan, Roseola, I would opt.(Though it was called the Sixth disease by just a few,3 Procedures for adoption were not carried through.)Or should the fourth become that diagnostic cache—The MD's sage pronouncement, "It's a 'Viral Rash'..."?

Control of infections due to respiratory syncytial virus (RSV) by immunization poses special problems. First, the peak period of serious illness due to RSVis during the first few months of life, and thus a vaccine would have to be administered during the neonatal period. Second, we understand little of the pathogenesis of and immunity to RSV disease in new borns, and an immune reaction may even play a role in the development of the lower respiratory tract disease seen in infancy. Third, immunity to RSVis imperfect even after naturally acquired, severe infection of the lower respiratory tract. Therefore, it is difficult to envision a vaccine that is safe in the infant and that will engender more complete immunity than the disease itself. However, if the goals are limited to protection of certain high-riskgroups or to protection of infants during the first year of life only, immunization might be both feasible and effective in reducing the morbidity and mortality associated with this ubiquitous virus.

To test whether nosocomial spread of respiratory syncytial virus (RSV) could occur through contact with environmental surfaces contaminated by RSV-infected nasal secretions, survival in the environment of RSV isolated from media, pooled adult secretions, and secretions from hospitalized infants was examined. RSV in freshly obtained infant secretions was recovered from countertops for up to 6 hr, from rubber gloves for up to 1 1/2 hr, from cloth gowns and paper tissue for 30–45 min, and from skin for up to 20 min. RSV in media and pooled secretions survived for slightly longer periods. Further experiments demonstrated that infectious virus could be transferred to hands touching these contaminated surfaces and could be recovered from these hands for up to 25 min. These studies suggest that survival of RSV in the environment of infected infant secretions is sufficient to allow transfer of infectious virus to the hands of hospital personnel. Thus, self-inoculation by contact with contaminated infant secretions may be a potential mode of nosocomial transmission of RSV.

Little is known of the persistence and pathogenicity of human herpesvirus 6 (HHV-6) after primary infection, including the role of strain variant. Over 2 to 5 years, 2,716 children and 149 families were studied. Peripheral blood mononuclear cell (PBMC), saliva, and cerebrospinal fluid (CSF) specimens were examined for HHV-6 DNA and variant. Ninety-nine percent of isolates causing primary infection were HHV-6 variant B (HHV-6B), which predominated in 95%–98% of the variants persisting in PBMC and saliva specimens from children and adults. Of 668 CSF samples, 13% contained HHV-6 DNA; of 77 children examined after primary infection, 61% had HHV-6 DNA detected only in their CSF and 39% had HHV-6 DNA in both CSF and PBMCs. HHV-6 variant A (HHV-6A) was detected significantly (P = .0001) more frequently in CSF than in PBMCs or saliva. In children for whom HHV-6 was identified in both CSF and PBMCs, PBMCs contained only HHV-6B, while CSF contained HHV-6A or HHV-6B, not both. Thus, in patients with dual infection, only HHV-6A persisted in CSF, which suggests that HHV-6A has greater neurotropism. Findings for adults indicate that dual infection occurs; variant persistence is similar to that for children. The frequency of HHV-6A infection increased little with age, thereby indicating that HHV- 6A infection remains uncommon into adulthood. This study suggests that HHV-6 variants have different immunobiologic courses and neurotropism.

To better understand the duration of immunity against respiratory syncytial virus (RSV) and the role of serum antibodies to the surface glycoproteins, F and G, in susceptibility to reinfection, 15 adults with previous natural RSV infection were challenged with RSV of the same strain group (A) at 2, 4, 8, 14, 20, and 26 months after natural infection. By 2 months about one-half and by 8 months two-thirds of the subjects became reinfected. Each challenge resulted in infection in at least one-fourth of the subjects. Within 26 months 73% had two or more and 47% had three or more infections. The duration of immunity tended to increase after two closely spaced infections. Higher neutralizing, F and GAantibody levels before challenge correlated significantly with protection against infection. However, even in subjects with the highest antibody levels, the risk of reinfection was 25%. Specific nasal 19A antibody titers did not correlate significantly with protection. This suggests that humoral neutralizing, F, and G antibodies correlate with resistance to reinfection, but protection is far from complete and is of short duration.

Over 15 years respiratory syncytial virus (RSV) isolates from 1209 hospitalized and ambulatory children were examined for strain group and in a subset for subgroup to determine the associated epidemiologic and clinical characteristics. Three patterns of yearly outbreaks existed: (1) strong predominance of group A strains (9 years with 83%–100% A strains), (2) relatively equal proportions of group A and B strains (4 years), and (3) strong predominance of group B strains (78%–85%) in 2 years, separated by a decade. The first pattern of highly dominant A strains occurred in cycles of 1 or 2 consecutive years with a single intervening year in which B strains were 40% of the isolates. Subgroups Al and A2 predominated, while B2, 3, and 4 occurred almost equally. A greater clinical severity for Group A strains was suggested bychildren with group A infections requiring intensive care significantly more often (15.4 vs. 8.3%, P = .(08). Further, strongly dominant A strain years were associated with higher proportions of RSV admissions requiring intensive care (16.6% vs. 5.5%, P < .01). Strains of subgroups A2 and B4 were more frequently found in hospitalized patients and Al in outpatients, and the 2 years with the highest rates of intensive care admissions were those in which subgroup A2 dominated.

Human herpesvirus 6 (HHV-6) causes a febrile illness in children and has been implicated as a cause of encephalitis and recurrent seizures. Paired samples of cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) from 487 children were evaluated by nested polymerase chain reaction (PCR) for evidence of current or past infection with HHV-6. PBMC were also cultured for isolation of HHV-6. These data were correlated with the patients' clinical information. HHV-6 DNA was detected in 72 (14.8%) of 487 CSF samples. HHV-6 persistence was documented in 142 children by PCR detection ofHHV-6 DNA in PBMC or CSF (or both) in the absence of primary HHV-6 infection; the central nervous system was the only site of HHV-6 DNA persistence in 28.9%. HHV-6 DNA can be detected in the CSF of children during and after primary infection, and the central nervous system may be the sole site of persistence.

In Reply.—Our children should hear fairie tales, we're much agreed,And hope that we adults have just as great a need.Should not at times our own Promethean worlds be sought?For rich is he who nutures yet prelogic thought.Have not great men dared use the dreamer's scanning scope?Only those who've sailed beyond our earth's terrain could hopeTo envision life within the soul of each small cell,Or capture unseen rays to make the hopeless well.The well-spun tales where fantasy and truth entwineAre sources of the miracles of future time.

During an epidemic of influenza B, 43 ambulatory children were prospectively followed to determine the quantitative shedding patterns of influenza B viral infection, because these have not been previously described. The spectrum of illness included 74% with a typical influenzalike illness, 7% with an afebrile infection of the upper respiratory tract, and 19% with croup. Mild myositis occurred in 21%. For the first three days of illness, 93% of the children shed virus, and 74% shed on day 4. The average peak quantity of virus shed in the nasal wash was 4.0 log10 50% tissue culture infective doses/ml (range,1.5–6.0), which gradually declined over four days to 2.4 log10 50% tissue culture infective doses/ml. The quantities of virus shed correlated significantly with severity of illness and fever score, but not with sex, type of illness, or occurrence of myositis. These results suggest that the degree of clinical illness may be directly related to the cytotoxic effects of the virus and to the transmissibility of the disease.