Gram-negative bacillary bacteremia in human immunodeficiency virus type 1-infected children

BACKGROUND: HIV-infected children are particularly susceptible to serious bacterial infections including Gram-negative bacillary bacteremia (GNB). However, the information available on GNB in these children is limited. METHODS: Retrospective review of hospital charts of HIV-infected children with GNB diagnosed between 1980 and 1997. The association between bacteremic episodes, degree of immunosuppression, HIV severity, medical treatment and clinical outcome was assessed. RESULTS: Of 680 HIV-infected children, 72 (10.6%) had 95 episodes of GNB. Statistical analyses were restricted to data from the first episode. The mean age (+/-SD) at diagnosis of GNB was 2.5 +/- 2.7 years (median, 1.6). The predominant organisms were Pseudomonas aeruginosa (26.4%), nontyphoidal Salmonella (15.3%), Escherichia coli (15.3%) and Haemophilus influenzae (12.5%). The relative frequency, per 5-year interval, of P. aeruginosa bacteremia steadily increased from 13% during 1980 through 1984 to 56% during 1995 through 1997. There were no cases of H. influenzae bacteremia after January 1, 1990. Eighty percent of GNB developed in children with AIDS and 72.2% developed in those with severe immunosuppression. Hypogamma-globulinemia and neutropenia were present in only 4.9 and 10.4% of first episodes, respectively. The overall case-fatality rate of GNB was 43.0%, and in children younger than 12 months it was 54.2%. CONCLUSIONS: A diagnosis of AIDS and/or severe immunosuppression was associated with increased risk of GNB, especially among younger children. Because of the high mortality of GNB, a broad spectrum antimicrobial therapy that effectively covers these organisms should be promptly instituted when bacteremia is suspected in HIV-infected children.     

Virologic and host characteristics of human immunodeficiency virus type 1-infected pediatric long term survivors

BACKGROUND: There are limited data concerning determinants of varying clinical progression rates in human immunodeficiency virus type 1 (HIV-1)-infected children. Therefore, we sought to determine whether viral or host factors associated with nonprogressive HIV-1 infection in adults play a role in limiting progression of infection in 5 vertically infected youths, ages 12-18 years, who have displayed no signs of advanced HIV-1 disease or acquired immunodeficiency syndrome despite having received minimal treatment with antiretroviral drugs. RESULTS: The 5 individuals, whom we characterize as long term survivors, have maintained low loads of HIV-1 RNA in plasma when compared to many of their peers, and have also maintained normal and stable CD4 T-lymphocyte numbers and percentages throughout their lives. Determination of their predominant HIV-1 sequences revealed that 4 of 5 patients harbor virus with markers of resistance to their therapy (one was never treated). Furthermore 2 harbored viral isolates that contained insertions in Gag or Vif that inhibit HIV-1 replication. Moreover, 2 were found to be heterozygous for the CCR2 polymorphism 64I, a genotype associated with slower progression to acquired immunodeficiency syndrome in adults. All 5 expressed the histocompatibility leukocyte antigen DQ1 and 2 had unusual DR/DQ1 phenotypes. CONCLUSIONS: We believe that the limited antiretroviral therapy received by the long term survivors cannot solely account for their benign clinical status. Therefore, we conclude that other factors, including gene polymorphisms that affect viral replicative capacity, account for the long term survival in some, and deduce that, as in adults, no single factor (virologic or host) can account for this clinical phenotype in all cases.     

Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi

BACKGROUND: Reference lymphocyte subset values for African children are lacking. This study documents these values as well as their alterations associated with perinatal and postnatal HIV-1 transmission and with protection from HIV-1 infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative nonpregnant women and their children (controls) and for uninfected, perinatally infected and postnatally infected children born to HIV-1-seropositive mothers in Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and CD8+ lymphocyte counts and percentages were determined and compared at the age ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6 to 10 years of age. RESULTS: Among control children counts differed from published values of other populations. In all age ranges, whereas the absolute values were significantly higher than adult values, the percentages were significantly lower. Children perinatally infected with HIV-1 had clearly distinguishable differences in lymphocyte subset percentages by 3 months of age, when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%) for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%) for control children, P < 0.001; whereas the median CD8+ percentage was 37.0% (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5% (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected and control children disappeared after 1 year of age. CONCLUSIONS: Normal lymphocyte subset values among African children differ from those in other populations. Significant differences are detectable by 3 months of age in CD4+ and CD8+ lymphocyte percentages among perinatally infected infants, which may be useful as an adjunct in diagnosis. Transient differences observed among HIV-1-exposed but uninfected infants could reflect a successful immune response to HIV-1 challenge.     

Predictors of early mortality in a cohort of human immunodeficiency virus type 1-infected african children

BACKGROUND: Pediatric human immunodeficiency virus type 1 (HIV-1) infection follows a bimodal clinical course with rapid progression in 10-45% of children before the age of 2 years and slower progression in the remainder. A prospective observational study was undertaken to determine predictors of mortality in HIV-1-infected African infants during the first 2 years of life. METHODS: Infants in a perinatal cohort identified to be HIV-1-infected by DNA PCR were followed monthly to 1 year, then quarterly to 2 years or death. RESULTS: Among 62 HIV-1-infected infants, infection occurred by the age of 1 month in 56 (90%) infants, and 32 (52%) died at median age of 6.2 months. All infant deaths were caused by infectious diseases, most frequently pneumonia (75%) and diarrhea (41%). Univariate predictors of infant mortality included maternal CD4 count <200 cells/microl [hazard ratio (HR), 3.4; P = 0.008], maternal anemia (HR = 3.7; P = 0.005), delivery complications (HR = 2.7; P = 0.01), low birth weight (HR = 4.1; P = 0.001), weight, length and head circumference 相似文献   

Differing manifestations of respiratory syncytial virus-associated severe lower respiratory tract infections in human immunodeficiency virus type 1-infected and uninfected children

BACKGROUND: Respiratory syncytial virus (RSV) causes increased morbidity and mortality in immunocompromised children. The outcome of RSV-associated lower respiratory tract infections (LRTI) in HIV-infected children, is less well described. METHODS: Children from a prospective study evaluating the etiology of     

Apparent life-threatening events presenting to a pediatric emergency department.

OBJECTIVE: To review the etiology, clinical decision-making process, and outcomes of apparent life-threatening events (ALTEs) presenting to a children's hospital emergency department (ED). DESIGN: Retrospective patient record review. SUBJECTS: One hundred thirty infants under the age of 1 year fulfilling the diagnostic definition of an apparent life-threatening event. RESULTS: In a calendar year, 130 infants presented to a large children's hospital ED. The total number of ALTEs studied was 196. The median age was 2 months, and 50% of infants had a normal clinical examination. Eighty-three percent of ALTEs resulted in admission to the hospital. The approach to investigation and management of an ALTE during admission appeared unstructured. Discharge diagnoses, both from the ED and the inpatient service, were numerous, the most common being convulsion, febrile convulsion, GOR, and lower respiratory tract infection. The diagnosis frequently changed in those attending more than once. Eighteen months after cessation of data collection, no infants had died. Follow-up information revealed a higher-than-expected prevalence of asthma and seizures. CONCLUSIONS: This is a diverse group of infants, many of whom appear normal following the ALTE. There are many possible diagnoses, but diagnosis correlates poorly with presenting symptoms. It also appears that many commonly performed investigations conducted in this group of infants may not be those that are most helpful for diagnosis, and doctors may be making diagnoses with little supportive evidence. Until research on this group of "first-presentation" infants provides management guidelines for family and emergency doctors, it may be prudent to advise that all such infants presenting with an ALTE should be admitted for a period of observation and further investigation. This would help ensure more accurate diagnosis, as well as provide reassurance for the family.     

Low immunologic response to highly active antiretroviral therapy in naive vertically human immunodeficiency virus type 1-infected children with severe immunodeficiency

We conducted a retrospective study to analyze the CD4 recovery of naive vertically human immunodeficiency virus-infected children with severe immunodeficiency who were followed up during at least 4 years of receiving highly active antiretroviral therapy (HAART). Children with baseline CD4 of <15% did not reach a mean CD4 of > or =25% after the 4th year on HAART. We conclude that starting HAART after severe immunosuppression of naive HIV-infected children may not be effective for recovery of normal %CD4.     

Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children

OBJECTIVES: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. METHODS: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. RESULTS: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy. CONCLUSIONS: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.     

Utilization of a pediatric emergency department education computer

OBJECTIVE: To describe the use of a computer education station placed within a pediatric emergency department. DESIGN: Prospective tracking of computer tutorial use. SETTING: A tertiary care pediatric emergency department. METHODS: A computer with two 30-minute multimedia computer tutorials was installed in the emergency department. The tutorials were designed for residents to use on a voluntary basis but were available to medical students and allied health professionals as well. Software tracked time, date, duration of use, and the user's path through each tutorial. Data were collected from July 15, 1996, through April 30, 1997. RESULTS: Twenty-eight residents interacted 71 times with the computer during the study. The mean duration of interactions was 22 minutes (SD, 18 minutes; range, 0-75 minutes), but many lasted less than 5 minutes (15 [21%] of 71). Twenty-four (34%) of the interactions led to tutorial completion. Residents were more likely to complete a tutorial during the day shift (22 [40%] of 55) compared with the evening shift (1 [7%] of 14) (P =.02). A third of the interactions were during evenings and weekends. The education station delivered 26.1 hours of instruction in total. Of 32 first-year pediatric and emergency medicine residents, 22 attempted the tutorials; 4 completed both, and 10 completed one. Allied health professionals were responsible for 28% of the total interactions. They were significantly more likely than medical trainees to have brief interactions, but they were no less likely to complete the tutorials (10 [22%] of 46 vs 31 [27%] of 115; P =.44). CONCLUSIONS: Pediatric residents are willing to use an educational computer placed in the emergency department. Choice of form and content should take into account the likelihood of short interactions and the demonstrated interest of allied health professionals.     

Virus burden in human immunodeficiency virus type 1-infected children: relationship to disease status and effect of antiviral therapy

The human immunodeficiency virus type 1 (HIV-1) was isolated from the plasma and peripheral blood mononuclear cells (PBMCs) from each of 21 infected children. The mean titers in plasma were 7 and 165 tissue culture-infective doses per milliliter in 9 children with asymptomatic (P-1) and 12 with symptomatic (P-2) infection, respectively (P = .0013). Significantly higher viral titers were found in PBMCs obtained from P-2 compared with P-1 children: 1920 vs 25 tissue culture-infective doses per 10(6) PBMC (P = .0018). In symptomatic patients at least 1 in 520 circulating mononuclear cells harbored HIV-1. No correlation was found between the viral burden and CD4+ lymphocyte counts. A decrease in the HIV-1 titers was noted both in PBMCs and plasma of symptomatic patients treated with zidovudine for 2 to 7 months. It is concluded that symptomatic children harbor a higher amount of the virus in plasma and PBMCs than asymptomatic children. Zidovudine treatment for 2 months or more decreased the amount of HIV-1 in PBMCs and plasma.     

Pharmacokinetics of enfuvirtide in pediatric human immunodeficiency virus 1-infected patients receiving combination therapy

BACKGROUND: Enfuvirtide is the first of a new class of antiretroviral agents, the fusion inhibitors. OBJECTIVES: The primary objective of this analysis was to evaluate the pharmacokinetics of 2.0 mg/kg enfuvirtide in human immunodeficiency virus 1 (HIV-1)-infected children and adolescents when administered in combination with at least 3 other antiretrovirals. METHODS: Twenty-five HIV-1-infected pediatric patients (5-16 years of age) enrolled in an ongoing phase I/II study were included in this analysis. Patients received enfuvirtide 2.0 mg/kg sc twice daily (bid) for at least 7 days. Blood samples were collected on day 7, and plasma concentrations of enfuvirtide and its metabolite were measured by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetics measures [Cmax, tmax, Ctrough, and area under the concentration time curve time 0 to 12 hours (AUC12 hours)] were calculated from plasma concentration-time data by standard noncompartmental methods. RESULTS: There was no significant difference between children and adolescents for enfuvirtide Cmax (6.43 versus 5.88 microg/mL), Ctrough (2.87 versus 2.98 microg/mL) and AUC12 hours (56.1 versus 52.7 hours . microg/mL). Similarly no significant differences were found when the pharmacokinetic measures were compared based on sexual maturity stages. A post hoc regression analysis based on AUC12 hours showed that body weight-adjusted dosing of enfuvirtide provides drug exposure that is independent of age group, body weight and body surface area. CONCLUSIONS: Body weight-adjusted dosing of enfuvirtide, at a dose of 2.0 mg/kg sc bid, in HIV-1-infected pediatric patients at least 5 years of age, provides drug exposure comparable with that previously observed in HIV-1-infected adults after 90 mg sc bid dosing. Drug exposure in children and adolescents is independent of age group, body weight, body surface area and sexual maturity stage.     

The spectrum and frequency of illness presenting to a pediatric emergency department

Knowledge of the spectrum and relative frequencies of pediatric emergencies is an important factor in developing appropriate training curricula for physicians treating children in emergency departments. To provide these data, we reviewed the records for four one-week periods (January, April, July, and October) of a large pediatric emergency department to describe the population in terms of age, chief complaints, diagnoses, time of arrival, seasonal variation, and disposition. There were 3796 log entries. Complete information on all variables was obtained on 3784 patients. Age ranged from one day to 39 years, and the mean age was 6.0 +/- 6.15 years. One half of all emergency department visits were by children three years old or younger. On the other hand, 12% of visits were by adolescents (ages 13 to 18), and one in 25 visits was made by an adult (greater than 18 years old). The majority of chief complaints and final diagnoses were related to infection and trauma. More than half of the patients arrived on the evening shift, between 4 pm and 12 am. Eleven percent of the children seen on day and evening shifts and 13% from the night shift were admitted. From the analysis of our data we recommend expanded skills in the management of minor trauma for pediatric residents, an emphasis on management of infections for nonpediatric emergency specialists, and extensive training in both pediatric and adult trauma for physicians in pediatric emergency medicine fellowships.     

Mortality after the first year of life among human immunodeficiency virus type 1-infected and uninfected children.

BACKGROUND: HIV-infected and uninfected children who survived their first year of life were prospectively followed in Malawi to assess levels of mortality and related risk factors during the second and third years of life. METHODS: Children with known HIV status from an earlier perinatal intervention trial were enrolled. These children [HIV-infected (Group A); HIV-uninfected but born to HIV-seropositive mothers (Group B); and children born to HIV-seronegative mothers (Group C)] were followed every 3 months until age 36 months. Mortality data were collected at each visit. Immunologic data (CD4+ percent) were collected at or immediately after enrollment. RESULTS: Overall 702 children were enrolled and 83 children died during follow-up. The mortality rate per 1000 person years of observation was 339.3 among Group A children, 46.3 among Group B children and 35.7 among Group C children. Among HIV-infected children the cumulative proportion surviving to age 24 months was 70% and those surviving to age 36 months was 55%. By age 32 months none of the severely immunosuppressed (CD4% < 15%) children had survived. The mortality differentials between HIV-infected and uninfected children persisted after adjusting for several risk factors. The major causes of death among infected children (n = 52) were wasting and respiratory conditions. CONCLUSIONS: Although all HIV-infected children had received childhood immunizations, mortality was high. Management of these children should include aggressive antimicrobial treatment, and evaluation of prophylactic regimens should be considered.     

Antiphospholipid syndrome in a human immunodeficiency virus 1-infected child

High prevalence of anticardiolipin antibodies and antiphospholipid antibodies has been reported in human immunodeficiency virus (HIV)-infected patients. A full blown clinical picture of antiphospholipid syndrome (APLS) is rare and rarely reported, even in HIV-infected adults and has never been reported in HIV-infected children. We report an HIV-infected child with left sided choreoathetosis associated with APLS.     

Extreme leukocytosis in patients presenting to a pediatric emergency department.

We determined the frequency and clinical significance of white blood cell (WBC) counts greater than or equal to 25,000/microliters in children presenting to an emergency department (ED) and defined a degree of leukocytosis which might be considered extreme in this setting. Records of all patients seen in the ED between February 1985 and December 1986 with WBC counts greater than or equal to 25,000/microliters were identified. Each patient was paired with the chronologically nearest patient with a WBC count between 15,000 and 25,000/microliters. Of the total WBCs obtained, 5.8% were greater than or equal to 25,000/microliters; only 1% were greater than or equal to 35,000/microliters. Eighteen percent of patients with counts greater than or equal to 25,000/microliters had a serious disease, and 6% had bacteremia. Twenty-six percent of patients with counts greater than or equal to 35,000/microliters had a serious disease, and 10% had bacteremia. On the basis of infrequency and severity of illness, we suggest that, in children presenting to a pediatric emergency department, WBC counts greater than or equal to 35,000/microliters be considered extreme leukocytosis.