Management of children with human immunodeficiency virus infection.
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Biomedical subjects
Publications and source records attributed to M T Brady.
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Providing care to human immunodeficiency virus (HIV)-infected children requires a comprehensive, multidisciplinary approach. This review will address the current status of supportive care, treatment of HIV-associated complications and specific antiretroviral therapy. HIV affects multiple locations in the body resulting in a myriad of possible complications. These include opportunistic infections and malignancies secondary to immunodeficiency and central nervous system or other specific organ-related disease secondary to direct HIV involvement. Recent scientific advances have markedly enhanced the quantity and quality of life of HIV-infected children. Prophylaxis of Pneumocystis carinii pneumonia is the single most important therapeutic advance for the HIV-infected patient. Other advances for the treatment and prevention of HIV-related infections should similarly improve survival and reduce hospital stays. Antiretroviral therapy is relatively new. The currently available nucleoside reverse transcriptase inhibitors have proven efficacy. The role of single agents or combinations is being established. However, this group of antivirals has limitations that make alternate approaches essential. Augmentation of the patient's immune response will likely be a key to any future successful treatment regimen.
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Infections with nontuberculous mycobacteria (NTM) are being identified with increasing frequency, but the otologic manifestations of NTM infection are not well defined. Mycobacterium abscessus is a ubiquitous rapidly growing mycobacterium (RGM) known to cause disease by inoculation after trauma. Though reported following open heart and breast augmentation surgery, it is not recognized as a cause of sporadic post-tympanostomy tube otorrhea. This report presents detailed clinical information on six sporadic cases and partial information on 15 additional cases of ear infection caused by RGM over the past 7 years. Of these, 20 of 21 cases (95%) were attributable to M. abscessus, 14 of 21 (67%) subjects lived in a southern coastal state and 16 of 16 with available histories had previously undergone placement of tympanostomy tubes. Each isolate exhibited resistance to many antibiotics, with 50 percent exhibiting high level mutational resistance to aminoglycosides related to prior topical aminoglycoside use. Therapy was difficult, requiring debridement and prolonged antibiotic therapy. M. abscessus is a problematic infection requiring specific diagnosis and treatment and should be sought as a cause of refractory post-tympanostomy tube otorrhea.
We attempted to determine the occurrence of transfusion-acquired HIV-1 infection in multiply-transfused pediatric oncology patients receiving blood products prior to donor HIV antibody screening in March 1985. We identified 85 multiply-transfused pediatric oncology patients (initially HIV-1 antibody negative) who had received 4,346 transfusions (968 red blood cells, 3,192 platelets, 137 fresh frozen plasma, and 49 leukocytes). Only one (1.2%) of these multiply-transfused pediatric oncology patients seroconverted following transfusion. Transfusion-acquired HIV-1 infection in our multiply-transfused pediatric oncology patients was infrequent despite marked exposure to blood products (average 51.2 donor exposures per multiply transfused pediatric oncology patients) and occurred at a frequency consistent with the prevalence of HIV-1 infection in our donor population (Central Ohio--2 of 10,000 donors were HIV-1 antibody positive). While our findings may not be unexpected, they offer documentation of a lower risk for transfusion-acquired HIV infection in our blood recipients than in some previous studies conducted in areas where donor HIV antibody prevalence is higher. We also document that the efforts associated with performing "Lookback" evaluations (contacting recipients of blood products from donors subsequently identified as HIV antibody positive) are valuable since our only HIV-1-infected, multiply-transfused pediatric oncology patient was identified in this manner.
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Metabolites of arachidonic acid have been implicated in the regulation of aldosterone release. To form a basis for further investigations in this area, the present study has isolated and identified the metabolites formed from exogenous arachidonic acid by adrenal zona glomerulosa cells and characterized the effects of several inhibitors on the synthesis of these eicosanoids. Rat adrenal glomerulosa cells metabolized exogenous [14C]arachidonic acid to products comigrating with the prostaglandins (PGs), hydroxyeicosatatraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs). The metabolites were found in the cells and the incubation media; however, none of the metabolites were found esterified to cellular lipids. The major metabolites were identified as 6-keto PGF1 alpha, PGE2, PGF2 alpha, PGD2, 12(S)-HETE, 15(S)-HETE, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET. The identities of the HETEs and EETs were confirmed by gas chromatography/mass spectrometry. There was no evidence for the synthesis of leukotrienes. The cyclooxygenase inhibitor, indomethacin, the lipoxygenase inhibitors, nordihydroguaiaretic acid, baicalein and AA861, and the combined cyclooxygenase/lipoxygenase inhibitors, BW755C and eicosatetrayenoic acid, inhibited the formation of the [14C]PGs, the [14C]HETEs, and the [14C]EETs. Metyrapone and clotrimazole, inhibitors of cytochrome P450, increased the synthesis of [14C]PGs and [14C]HETEs and reduced the synthesis of [14C] EETs. Superoxide dismutase did not alter arachidonic acid metabolism. In contrast, arachidonic acid metabolism was increased in cells pretreated with catalase. These data indicate that adrenal glomerulosa cells metabolize exogenous arachidonic acid to a number of oxygenated metabolites including PGs, HETEs, and EETs. From studies with inhibitors, the EETs appear to be synthesized by a cytochrome P450 epoxygenase and the HETEs by lipoxygenases.
Three dilutions of each of three parainfluenza strains were placed on nonabsorptive (stainless steel, laminated plastic, skin) and absorptive (hospital gown, facial tissue, laboratory coat) surfaces to assess persistence of virus recovery at 0, 0.5, 1, 2, 4, 6, 8, and 10 hours. Virus persisted longest on stainless steel. Additionally, the ability to recover virus was enhanced by increasing the initial concentration of virus in the initial inoculum. Drying of the inoculum on surfaces reduced but did not immediately eliminate the ability to recover virus. Cleaning the contaminated surface with a number of commonly available disinfectant or antiseptic agents reduced or eliminated virus with only short exposure times. It is likely that removal of contaminated material by vigorous cleaning was as important as the actual disinfecting substance. In general, all three strains of parainfluenza virus responded similarly. Persistence of all three strains of parainfluenza virus for up to 10 hours on nonabsorptive surfaces and up to 4 hours on absorptive surfaces suggests a need to consider fomites a possible source of transmission of the parainfluenza viruses inside and outside the hospital.
A placebo-controlled, double-blind study to evaluate the safety and prophylactic efficacy of a low dose (100 mg) of rimantadine hydrochloride against naturally occurring influenza in adults was conducted at two sites. After the onset of the influenza season, volunteers (ages, 18 to 55 years) were assigned randomly to receive rimantadine or placebo daily. Subjects were monitored for adverse effects and evidence of influenza virus infection weekly for six weeks. Only 10 (8.7%) of 114 rimantadine recipients and 5 (4.4%) of 114 placebo control recipients reported one or more mild to moderate adverse symptoms, most of which were related to the gastrointestinal or central nervous system. Compared with placebo, low-dose rimantadine was highly effective in the prevention of influenza A virus infection (20 of 110 versus 7 of 112 participants; P less than 0.01) and influenza illness (7 of 110 versus 1 of 112 participants; P = 0.04). Influenza A/Leningrad/87-like (H3N2) virus was recovered from the nasopharynxes of only five placebo recipients. These findings indicate that low-dose rimantadine is well tolerated and highly effective for the prevention of influenza A illness in healthy adults.
During a 17-month period (01/11/85-05/31/86) 225 cases of nosocomial diarrhea were identified in a children's hospital. Diarrhea was considered to be nosocomial if it began at least 72 hours after the patient's hospital admission or within 3 days after discharge. One or more routine diagnostic studies for identification of a pathogen were performed in 195 (87%) cases. The most commonly performed test was the bacterial stool culture. None of these samples yielded a bacterial pathogen. The only pathogens detected by routine laboratory studies were rotavirus (61/137 [45%] samples were positive for rotavirus by ELISA) and Clostridium difficile (9/54 [17%] positive for toxin). Of the patients whose tests were positive for rotavirus 56 were younger than 2 years of age, and all were identified in the winter and spring. When multiple stool samples were tested by the diagnostic laboratory, rotavirus was identified in an additional 14 patients whose initial stool samples were negative for rotavirus. All patients whose tests were positive for C. difficile toxin had received antibiotics within the previous 3 months. Ova/parasites were not detected in 53 of the tested stools. We also identified enteric adenovirus in six patients. Viruses were identified in 95 (42%) of the 225 cases of nosocomial gastroenteritis. Nosocomial diarrhea is common in a children's hospital. Rotavirus is the most commonly identified pathogen. Rotavirus testing is valuable in children with nosocomial diarrhea who are younger than 2 years of age, especially in the winter and spring. Multiple samples may be necessary to identify rotavirus. C. difficile toxin assay should be considered for patients who are receiving or who have received antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
Between August 1982 and December 1985, seven patients at a children's hospital developed hospital-acquired pneumonia caused by Legionella pneumophila. Demographic data included the following: mean age 12.3 years (range 9 months to 20.5 years); male/female ratio 5:2; all patients were white. Some previously identified risk factors present in our patients included high-dose corticosteroid therapy (five patients), other immunosuppressive therapy (four), and chronic lung (five) or kidney (three) disease. Symptoms and signs included rapid onset, fever, cough, pleuritic chest pain, dyspnea, abdominal pain, diarrhea, and headache. Rhinitis, myalgia, and neurologic abnormalities were not noted. Chest roentgenograms revealed single-lobe consolidation in three patients, diffuse bilateral alveolar infiltrates in three, and pleural effusion in three. All patients were treated with erythromycin; three patients also received rifampin. Tracheal intubation and mechanical ventilation were required by four patients. Six patients improved after therapy. One child died of persistent lung disease 1 month after the onset of legionnaires disease. L. pneumophila was isolated from potable water in the hospital. Aerosol equipment cleansed with tap water and the showers were implicated as means of exposure by patients to contaminated potable water. No new nosocomial cases were seen after immunocompromised children were prohibited from taking showers, and sterile water was used to cleanse equipment for administering aerosol medications.
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Hospital employees, especially pregnant women, have expressed concern over exposure to patients excreting cytomegalovirus (CMV). However, the vast majority of CMV excreters are asymptomatic and are not identified while hospitalized. As part of a 2-year, longitudinal study of nosocomial transmission of CMV in a children's hospital, the prevalence rates of CMV excretion by patients in different areas of the hospital were determined. The average prevalence rates were neonatal intensive care unit, 5.7%; intermediate care nurseries, 4%; premature nursery, 6.3%; normal newborn nursery, 3%; hematology-oncology, 3.7%; pediatric intensive care unit, 3.6%; general pediatric ward, 6%; and a chronic care unit, 16%. During this 2-year study, 315 patients admitted to the chronic care unit were investigated to determine which clinical factors might help predict children likely to excrete CMV. With the use of multiple logistic regression analysis of variables, prior excretion of CMV, multiple hospital admissions, female sex, and Hispanic ethnic background were correlated with excretion. Although not identified as significant factors, a history of premature, bronchopulmonary dysplasia and positive results of CMV serologic studies were more commonly associated with excretion. CMV excretion occurred in all areas within a children's hospital, and certain factors were associated with excretion, but it is unlikely that this information could adequately identify "safe" patients or safe areas within a hospital. This study reinforces the need to follow proper precautions with all patients.
Polyacrylamide gel electrophoresis (PAGE) of rotaviral RNA, a sensitive and highly specific test for detecting rotavirus in stool, was compared with two commercially available enzyme immunoassays (EIAs), monoclonal (Pathfinder) and polyclonal (Rotazyme II). Stool samples from 204 children with nosocomial diarrhea were tested for rotavirus by both EIAs and by PAGE of RNA extracted from raw stools or 10% stool suspensions. Samples which tested positive by either EIA but were negative by PAGE were subjected to blocking EIA with rabbit or goat anti-SA11. Rotavirus was detected by PAGE and Pathfinder in 62 stools, but only 47 of these were positive by Rotazyme II. Blocking assays of EIA-positive, PAGE-negative samples suggested the presence of rotavirus in four additional stools. Sensitivity and specificity measured against PAGE and blocking assays were: Pathfinder, 0.985 and 0.934; and Rotazyme II, 0.731 and 0.927, respectively. False-positive rates were 0.134 for Pathfinder and 0.149 for Rotazyme II. The specificity and rate of false-positive results of Pathfinder were improved by using an adjusted optical density cutoff 4.36 times greater than that recommended by the manufacturer (specificity, 0.993; sensitivity, 0.985; false-positive rate, 0.015).
During a 1-year period from October 1986 through September 1987, we recovered 116 mucoid, hemolytic Streptococcus pyogenes isolates from clinical specimens collected from patients seen at our pediatric institution. A total of 102 isolates were from throat cultures (101 for pharyngitis, 1 for acute rheumatic fever), 13 were from other superficial body sites, and 1 was from pleural fluid. All of 40 mucoid isolates tested to date were determined to be M-type 18 strains. A direct latex agglutination test for group A carbohydrate antigen in throat swab specimens was equally sensitive in detecting M-18 mucoid and nonmucoid strains (45 of 77 [58%] and 795 of 1,186 [67%], respectively; not significant, P greater than 0.05). Antimicrobial susceptibility tests performed with 40 mucoid and 40 nonmucoid isolates against penicillin and nine other antimicrobial agents showed all strains to be susceptible, with no difference in MICs. All isolates tested were also considered fully susceptible to the bactericidal activity of penicillin. Further studies are needed to establish the relative virulence of M-18 strains and their possible association with the resurgence of acute rheumatic fever in central Ohio and other areas of the United States.
Cardiac involvement in patients with acquired immunodeficiency syndrome (AIDS) is being reported with increasing frequency, although the factors responsible for the cardiac abnormalities are rarely identified. We report a case of sudden and unexpected death of an infant with AIDS in whom histologic and virologic studies documented generalized infection with cytomegalovirus (CMV), including pancarditis, sialitis, nephritis, colitis, hepatitis, prostatitis, orchitis, myositis, pneumonitis, and meningoencephalitis. CMV was isolated from four of five tissues cultured. Lymphocytic infiltration in the region of the sinoatrial node could have been responsible for the development of a fatal cardiac arrhythmia, and the autopsy failed to reveal any other cause of death in this infant. Children infected with the human immunodeficiency virus (HIV) need to be closely monitored for cardiac complications bearing in mind that opportunistic infections in AIDS patients may cause cardiac involvement that is atypical or that is overshadowed by the primary manifestations of the infection.
Nosocomial gastroenteritis in a 315-bed hospital for children was examined prospectively from January 11 through May 31, 1985. There were 85 cases of nosocomial diarrhea during the study period, and these were identified on each of the 13 hospital wards. Rotavirus was identified in 40% of cases. Incidence of nosocomial rotavirus was highest on wards where most children were less than 2 years of age, except for the infectious diseases (isolation) ward (0.24 versus 2.30 cases per 100 admissions, p = 1.70 x 10(-4), Fisher exact test). The lower incidence on the infectious diseases ward occurred despite the greater potential for exposure to rotavirus, since 70% of children admitted with community-acquired rotavirus diarrhea were placed on the infectious diseases ward. Better infection control, especially hand washing, aided by the structure of the infectious diseases ward, may have been responsible for this difference.