Marilyn A. Menegus

Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis

During a 2-year period, 233 infants younger than 3 months were prospectively studied to determine whether physical examination, white blood cell and band count, and urinalysis could identify infants unlikely to have serious bacterial infections. Only previously healthy infants (born at term, no perinatal complications, no previous or underlying diseases, no previous antibiotic therapy) were studied. One hundred forty-four (62%) of the 233 infants were considered unlikely to have serious bacterial infections, because they did not have physical findings consistent with ear, soft tissue, or skeletal infection, had between 5000 and 15,000 white blood cells/mm3, had less than 1500 bands/mm3, and urinalysis yielded normal findings. Eighty-nine (38%) infants did not meet one or more of these criteria and were classified as being at high risk for serious bacterial infection. Only one (0.7%) of the 144 infants in the low-risk group had a serious infection, compared with 22 (25%) of the 89 infants in the high risk group (P less than 0.0001). None of the infants in the low-risk group had bacteremia, compared with nine (10%) of the 89 infants in the high-risk group (P less than 0.0005). Neither traditional risk factors, such as age, sex, and temperature, nor other signs, symptoms, or laboratory findings were adequate predictors of serious bacterial infection. We conclude that previously healthy infants younger than 3 months with an acute illness are unlikely to have serious bacterial infection if they have no findings consistent with ear, soft tissue, or skeletal infections and have normal white blood cell and band form counts and normal urine findings.

Epidemiology of neonatal enterovirus infection

During a typical enterovirus season in Rochester, New York, none of 666 neonates or 629 mothers were found to be excreting nonpolio enteroviruses within 1 day of delivery. No enteroviruses were isolated from weekly cultures of the 23 infants who died or remained hospitalized during the first month of life. After discharge, culture specimens were obtained in 586 infants at one to four weekly home visits until 1 month of age. The incidence of acquisition of nonpolio enterovirus infection was 12.8%, and the overall prevalence of enterovirus excretion was 5.3%. Risk of virus infection was associated only with lower socioeconomic status (P less than 0.0001) and lack of breast-feeding (P less than 0.0001). Four percent of all infants and 21% of infants in whom cultures for enterovirus were positive were readmitted to the hospital in the first month of life; 79% of infants with positive enterovirus cultures were asymptomatic. We conclude that enterovirus infection during the first month of life is very common in the late summer and early fall. Most infants are asymptomatic, but the risk of hospitalization is high. Breast-feeding may be associated with protection from infection.

The changing spectrum of group B streptococcal disease in infants: an eleven-year experience in a tertiary care hospital.

Risk factors, clinical syndromes and the case fatality rates associated with Group B Streptococcus (GBS) infections in infants managed at the University of Rochester Medical Center during 1979 to 1989 were reviewed. Overall 92 episodes of early onset disease (EOD) and 54 of late onset disease (LOD) were diagnosed in 143 infants (3 infants with EOD presented later with LOD). About one-third of patients with EOD and controls were non-white compared with two-thirds of patients with LOD that occurred in racial minority groups. Prematurity and low birth weight were significantly more common in patients with invasive GBS disease than in controls. Eighty-three of 92 (90%) cases of EOD were detected during the first day of life and 10 of 54 (19%) cases of LOD occurred in infants older than 3 months of age. At the time of diagnosis 4% of infants with EOD were asymptomatic, 54% had respiratory disease, 27% had sepsis without a focus, 15% had meningitis and 1% had urinary tract infection or omphalitis. Among infants with LOD 46% had sepsis, 37% meningitis, 7% urinary tract infection, 6% osteomyelitis and/or septic arthritis and 4% cellulitis or pneumonia. Leukopenia and shift to the left were observed in 43 and 61% of episodes of EOD and in 28 and 57% of episodes of LOD, respectively. All infants were promptly treated with antibiotics and vigorous supportive therapy. The case-fatality rate was 13% in EOD and 0 in LOD. These data suggest that: (1) the vast majority of patients with EOD are recognized on the first day of life; (2) the occurrence of LOD can extend beyond the third month of life; (3) nonwhite infants and infants born prematurely are at increased risk to develop LOD; (4) The observed case-fatality rate of invasive GBS disease is lower than that reported in the past. These data provide a current and accurate deseription of the clinical spectrum of GBS disease and suggest that early recognition and aggressive supportive therapeutic interventions have resulted in a much lower mortality rate than previously reported.

Association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis in hospitalized infants with enterovirus infection

One hundred eight hospitalized infants with enteroviral infections were studied to determine the association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis. Of 108 infants, 55 (51%) had meningitis. Clinical manifestations on admission did not distinguish between infants with and those without meningitis. Echoviruses 30 and 11 and coxsackie virus B were frequently associated with meningitis (34/38; 90%) whereas echoviruses 18, 24, and 25 were not (5/35; 4%). The virus isolation rate was directly proportional to the number of leukocytes in cerebrospinal fluid: 5 of 58 (9%) when up to 9 cells/mm3 were found, 10 of 21 (48%) when 10 to 99/mm3 cells were found, and 25 of 29 (86%) when greater than equal to 100 cells/mm3 were found. Meningitis is often unsuspected in children hospitalized with enterovirus infection. The frequency of meningitis among hospitalized infants is serotype dependent and is most frequently, but not exclusively, found with pleocytosis of the cerebrospinal fluid.

Nosocomial viral infections: I. Epidemiology and significance.

Viral 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.

Cytomegalovirus infection of the human placenta: An immunocytochemical study

In congenital cytomegalovirus (CMV) infection histologic evaluation of the placenta is often unrevealing. In the present study immunocytochemistry to CMV immediate early and early nuclear antigens was used to characterize placental involvement in six cases of symptomatic intrauterine CMV infection. Histologic examination had demonstrated diagnostic viral inclusions in one placenta and non-specific villitis in another. However, immunocytochemistry revealed CMV infection in five of the six placentas, including three with no pathologic changes on routine histologic evaluation. Infected cells were located primarily in the villous stroma. In one case immunoperoxidase staining showed infection in the syncytiotrophoblast. Infected endothelial cells were demonstrated by double staining for CMV and factor VIII antigen. No double-stained cells were seen in tissue sections stained for CMV immediate early nuclear antigen or the human macrophage-associated CD68 antigen, which is expressed in Hofbauer cells. In conclusion, specific immunoperoxidase staining was more sensitive for demonstrating placental CMV infection than was histologic examination and it aided in the characterization of infected cells.

Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis

A prospective study was conducted to determine the frequency and distribution of bacterial and viral pathogens in infants hospitalized with suspected sepsis and to evaluate the potential of virus detection for improving patient management. A causative organism was detected in 157 (67%) of 233 previously healthy infants less than 3 months of age, who had been hospitalized for suspected sepsis: 19 (8%) had bacterial infections, 135 (58%) had viral infections, and 3 (1%) had mixed viral-bacterial infections. Viral infections occurred in a seasonal pattern: enteroviruses were responsible for most of the hospitalizations during summer and fall (65/110; 63%) and respiratory syncytial and influenza A viruses were responsible for most of the infections during winter (44/81; 55%). In contrast, bacterial infections were not seasonally distributed. Virus was detected in 33% of the 138 infected infants within 24 hours, and in 64% within 3 days. We conclude that viral infections are prevalent among infants hospitalized for suspected sepsis, and most can be detected early enough to influence patient management.

Cytomegalovirus in the Perfused Human Term Placenta In Vitro

Cytomegalovirus (CMV) is one of the most frequent causes of intrauterine-acquired infection in the human species. However, very little is known about the pathophysiology of the transplacental transmission of the virus from the mother to the fetus. In this study, the passage of CMV across the human term placenta, and the susceptibility of the human term trophoblast to infection with CMV was investigated. In vitro dual perfusion of human term placental lobules was performed. In five experiments the perfused tissue was exposed to high titres (10(4)-10(6) 50 per cent tissue culture infective doses) of CMV AD169 for up to 9.5 h. Monitoring included placental functional parameters, and virus titres in the perfused tissue, and in the fetal and maternal circuit. Immunocytochemistry with a monoclonal antibody against CMV immediate early antigen was used to search for placental infection. CMV AD169 did not cross the placenta even during many hours of perfusion, up to 9.5 h, and with exposure to high virus titres. No infected placental cells were detected by immunocytochemistry, although the virus cultures from perfused tissue samples were positive. The perfused human term placenta and the term trophoblast in vitro form an effective barrier to cell-free CMV AD169.

Concurrent outbreaks of rhinovirus and respiratory syncytial virus in an intensive care nursery: epidemiology and associated risk factors.

An outbreak of viral respiratory disease occurred in eight infants in a neonatal intensive care unit during the 1980 winter respiratory season. Four infections with respiratory syncytial virus and four infections with rhinovirus were identified. Epidemiologic investigation revealed that viral respiratory infection was significantly associated with intubation with orotracheal tubes (P = 0.001), with the presence of both a nasal feeding tube plus an orotracheal tube together (P = 0.007), and with assisted ventilation (P = 0.009) when compared to uninfected controls. Twenty-seven of 85 (30.6%) personnel working in the unit at the time of the outbreak reported a history of upper respiratory illness during the week prior to the outbreak, and 46 (54.1%) of them had had contact with patients in areas of the hospital where patients infected with RSV and rhinovirus were housed. The data suggest that both viruses were transmitted to the babies by hospital personnel. Rhinoviruses can be nosocomial pathogen in neonates with compromised pulmonary function, and the clinical presentation of rhinovirus infection in neonates may be difficult to distinguish from that produced by RSV.

Polymerase Chain Reaction and Restriction Fragment Length Polymorphism Analysis of Varicella-Zoster Virus Isolates from the United States and Other Parts of the World

A polymerase chain reaction (PCR) assay that identifies and differentiates wild-type (wt) and vaccine strains of varicella-zoster virus (VZV) was used to determine if VZV strains with restriction fragment length polymorphisms resembling those of the Japanese Oka vaccine strain were present in the wt pool outside of Japan. Virus samples (n = 114) from patients with chickenpox and zoster from various parts of the United States and Australia were analyzed. The assay correctly identified 113 samples as wt strain. The 1 sample identified as Oka vaccine strain came from a child with leukemia who developed a vaccine-associated rash after receiving the live attenuated varicella vaccine. At this point, there is no evidence that wt strains resembling the vaccine are circulating outside of Japan. This indicates that this PCR assay can be utilized to distinguish rashes due to vaccine and wt VZV.