Barbara W. Stechenberg

Neonatal Serologic Screening and Early Treatment for Congenital Toxoplasma gondii Infection

BACKGROUND Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. METHODS In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. RESULTS Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three). CONCLUSIONS Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.

Prospective Evaluation of Hearing Impairment as a Sequela of Acute Bacterial Meningitis

As part of a prospective study of acute bacterial meningitis in children, we studied for five years the hearing of 185 infants and children who had acute bacterial meningitis when they were more than one month of age. Nineteen (10.3 per cent) of the patients had persistent bilateral or unilateral sensorineural hearing loss. The incidence of hearing loss as determined by electric-response audiometry and conventional tests was 31 per cent with Streptococcus pneumoniae, 10.5 per cent with Neisseria meningitidis, and 6 per cent with Hemophilus influenzae infections. Transient conductive hearing impairment was found in 16 per cent of the sample, but in no case was there apparent improvement in a sensorineural deficit over time. The site of disease resulting in impaired hearing cannot be stated with certainty, but involvement of the inner ear or auditory nerve was suspected. The number of days of illness (symptoms) before hospitalization and institution of antibacterial treatment was not correlated with the development of sensorineural deafness.

Combination Treatment with Zidovudine, Didanosine, and Nevirapine in Infants with Human Immunodeficiency Virus Type 1 Infection

BACKGROUND In infants and children with maternally acquired human immunodeficiency virus type 1 (HIV-1) infection, treatment with a single antiretroviral agent has limited efficacy. We evaluated the safety and efficacy of a three-drug regimen in a small group of maternally infected infants. METHODS Zidovudine, didanosine, and nevirapine were administered in combination orally to eight infants 2 to 16 months of age. The efficacy of antiretroviral treatment was evaluated by serial measurements of plasma HIV-1 RNA, quantitative plasma cultures, and quantitative cultures of peripheral-blood mononuclear cells. RESULTS The three-drug regimen was well tolerated, without clinically important adverse events. Within four weeks, there were reductions in plasma levels of HIV-1 RNA of at least 96 percent (1.5 log) in seven of the eight study patients. Over the 6-month study period, replication of HIV-1 was controlled in two infants who began therapy at 2 1/2 months of age. Plasma RNA levels were reduced by 0.5 to 1.5 log in five of the other six infants. CONCLUSIONS Although further observations are needed, it appears that in infants with maternally acquired HIV-1 infection, combined treatment with zidovudine, didanosine, and nevirapine is well tolerated and has sustained efficacy against HIV-1.

Serratia marcescens outbreak associated with extrinsic contamination of 1% chlorxylenol soap.

OBJECTIVES To determine risk factors for Serratia marcescens infection or colonization, and to identify the source of the pathogen and factors facilitating its persistence in a neonatal intensive-care unit (NICU) during an outbreak. DESIGN Retrospective case-control study; review of NICU infection control policies, soap use, and handwashing practices among healthcare workers (HCWs); and selected environmental cultures. SETTING A university-affiliated tertiary-care hospital NICU. PATIENTS All NICU infants with at least one positive culture for S marcescens during August 1994 to October 1995. Infants who did not develop S marcescens infection or colonization were selected randomly as controls. RESULTS Thirty-two patients met the case definition. On multivariate analysis, independent risk factors for S marcescens infection or colonization were having very low birth weight (< 1,500 g), a patent ductus arteriosus, a mother with chorioamnionitis, or exposure to a single HCW. During January to July 1995, NICU HCWs carried their own bottles of 1% chlorxylenol soap, which often were left standing inverted in the NICU sink and work areas. Cultures of 16 (31%) of 52 samples of soap and 1 (8%) of 13 sinks yielded S marcescens. The 16 samples of soap all came from opened 4-oz bottles carried by HCWs. DNA banding patterns of case infant, HCW soap bottle, and sink isolates were identical. CONCLUSIONS Extrinsically contaminated soap contributed to an outbreak of S marcescens infection. Very-low-birth-weight infants with multiple invasive procedures and exposures to certain HCWs were at greatest risk of S marcescens infection or colonization.

Prospective evaluation of treatment of Hemophilus influenzae meningitis

Fifty children with Hemophilus influenzae meningitis have been enrolled in a prospective study. Patients were randomly assigned chloramphenicol or ampicillin treatment; there were no significant differences between groups in other respects. Countercurrent immunoelectrophoresis proved to be a valuable tool for rapid diagnosis of the causative agent even in pretreated patients. Increasing quantities of capsular polyribosephosphate antigen detected in the initial cerebrospinal fluid correlated significantly (r=0.62419; p less than 0.01) with early and late sequelae of meningitis. None of the patients died. Severe and persistent neurologic or intellectual deficits were noted in four (8%) of the children, and an additional 14 (28%) had IQ scores between 70 and 90. The presence of bactericidal antibody in serum was not protective. Anti-PRP antibody generally was not present in acute serum specimens and irrespective of the quantity of antigenic stimulus provided by the disease was nondetectable in 21 of 24 children less than 17 months of age following recovery.

Leptospirosis: a childhood disease.

A diagnosis of leptospirosis was confirmed in nine children who were admitted to St. Louis Childrens Hospital during the past 54 months. Epidemiologic, clinical, cultural, and serologic data which were obtained emphasize (1) the high incidence of urban cases; (2) contact with dogs as the most likely source of infection; and (3) that serotypes other than Leptospira icterohaemorrhagiae may produce severe clinical disease. Unusual or previously unreported manifestations of leptospirosis including acalculous cholecystitis, pancreatitis, abdominal causalgia, desquamating skin rashes, and infarction of the extremities which were noted in these children are discussed.

Evidence of human immunodeficiency virus-associated lipodystrophy syndrome in children treated with protease inhibitors.

We conducted a prospective evaluation for evidence of the HIV-associated lipodystrophy syndrome of 26 children infected with HIV-1. Six children had evidence of body fat redistribution. Nine children showed laboratory evidence of insulin resistance. All children with body fat distribution or insulin resistance had been treated with protease inhibitors. Children treated with protease inhibitors had higher total cholesterol, higher low density lipoprotein-cholesterol and higher triglycerides than untreated children.

Quantitation of human immunodeficiency virus in vertically infected infants and children

We used a quantitative human immunodeficiency virus, type 1 (HIV-1) culture method to determine whether there is a relationship between the amount of replicating virus in the blood of vertically infected children and the relatively short latency period before development of symptomatic disease in these children. HIV-1 titers were determined by end point dilution in the peripheral blood mononuclear cells and the plasma of 30 infected (CDC class P1 and P2), 36 indeterminate (CDC class PO), and 19 uninfected (CDC class P3) infants and children born to HIV-1 seropositive mothers. HIV-1 was recovered from 35 (90%) of 39 PBMC cultures and 23 (60%) of 38 plasma cultures of infected patients not receiving antiretroviral therapy. The mean HIV-1 titers tended to be higher in patients with more advanced disease (P2, D, E, or F: 1760 TCID/10(6) PBMC, 460 TCID/ml plasma) than in asymptomatic or mildly symptomatic patients (P1; P2, A or C: 90 TCID/10(6) PBMC; 60 TCID/ml plasma). A poor correlation between HIV-1 titers and serum p24 antigen levels was found. No correlation was observed between viral titers and relative or absolute numbers of CD4 lymphocytes. Plasma virus titers were lower in 9 patients receiving zidovudine (ZDV) therapy (mean 2 TCID/ml) than in untreated patients of similar clinical status. The viral titers measured in the blood of vertically infected infants and children were on the same order of magnitude as the viral titers measured in HIV-infected adults. We conclude that the relatively rapid progression to symptomatic disease of the majority of vertically infected patients is not due to a higher load of replicating virus in blood.

Lyme disease: the latest great imitator

Lyme disease is caused by the spirochete B. burgdorferi. Like its counterpart syphilis, it causes multisystem disease particularly affecting the skin, nervous system, heart and musculoskeletal system. It is endemic in several areas of the United States as well as in Europe. The prompt recognition of this disease and its diverse manifestations should lead to early treatment and resolution. Prevention is aimed at avoidance of the tick vector.

Effects of Local Variation, Specialty, and Beliefs on Antiviral Prescribing for Influenza

In 2004, we conducted a survey of physician knowledge, attitudes, and practices regarding influenza diagnosis and treatment at Baystate Medical Center in Massachusetts and Scott & White Hospital and Clinic in Texas. Of the 579 physicians we contacted, 336 completed the survey. Sixty-one percent of the respondents prescribed antivirals, and 62% used rapid testing. Prescribing practices were associated with location, practice size, use of rapid testing, and belief in the efficacy of antivirals.