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1.
Chakraborty R Pulver A Pulver LS Musoke R Palakudy T D'Agostino A Rana F 《Annals of tropical paediatrics》2002,22(2):125-131
A retrospective review of autopsy findings and medical records in 33 HIV-infected children living in a Kenyan orphanage is described. Their ages ranged from 1 month to 18 years and median age at death was 71 months (range 7-156). Respiratory disorders were probably the primary cause of death in 21 (64%), in 19 (90%) of whom pyogenic parenchymal lung disease was detected. A presumptive clinical diagnosis of pulmonary tuberculosis had been made in 14 (67%); these children also had a history of recurrent acute lower respiratory tract infections (more than four infections/year). At autopsy, however, only one case of tuberculosis was identified (disseminated disease). Pneumocystis carinii pneumonia was not identified. Primary bacterial meningitis was detected in 33%. The associated findings included disseminated Kaposi sarcoma in two children and cryptococcal meningitis in one child. It is concluded that pyogenic infections are common causes of morbidity and mortality in HIV-1-infected African children. Management should include prompt treatment and, if indicated, prophylaxis for recurrent bacterial infections, and early evaluation and treatment of pulmonary tuberculosis. 相似文献
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P Gallo A M Laverda A De Rossi S Pagni A Del Mistro P Cogo M G Piccinno A Plebani B Tavolato L Chieco-Bianchi 《Acta paediatrica Scandinavica》1991,80(6-7):659-666
Several immunological abnormalities were detected in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected children. Intrathecal synthesis of immunoglobulins, free light chains (FLC), IL-1 beta, IL-6, and M-CSF were demonstrated both in asymptomatic children and children with subacute encephalopathy. Our findings further support the hypothesis that an immunopathological subclinical process within the central nervous system (CNS) may be an early manifestation of acquired immunodeficiency syndrome (AIDS). Cytokine detection in the CSF may represent a useful diagnostic tool in evaluating the outcome of HIV-1-infected patients. 相似文献
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Pneumococcal disease is a major cause of childhood morbidity and mortality worldwide. However, there is a lack of epidemiological data to describe the vaccine-preventable burden of disease. New pneumococcal conjugate vaccines offer hope of preventing infant pneumococcal disease. The efficacy of the 7- and 9-valent pneumococcal conjugate vaccine (PCV) against invasive vaccine-type pneumococcal disease in young children is between 77 and 97%. The PCV vaccine efficacy against radiological pneumonia in HIV-negative infants for the 7- or 9-valent PCV is 23-30%. The vaccine efficacy in HIV-positive infants is lower--65% against invasive vaccine-type pneumococcal disease and no significant efficacy against radiological pneumonia. The 7-valent PCV showed modest efficacy against acute otitis media (7%) but seems to be more effective in preventing recurrent or severe disease. The high cost of these new vaccines is a barrier to their widespread introduction. The development of other pneumococcal vaccine candidates with wider serotype coverage should be encouraged. These vaccines should be affordable for all countries, particularly those with the highest burden of disease. In addition, other vaccination strategies such as maternal and neonatal immunisation and combinations of fewer doses of the PCV combined with an early dose of the cheaper pneumococcal polysaccharide vaccine need to be assessed further. 相似文献
4.
Chakraborty R Smith CJ Dunn D Green H Duong T Doerholt K Riordon A Lyall H Tookey P Butler K Sabin CA Gibb D Pillay D;Collaborative HIV Paediatric Study;UK Collaborative Group on HIV Drug Resistance 《The Pediatric infectious disease journal》2008,27(5):457-459
We reviewed HIV-1 genotypes from 200 of 979 (20%) HIV-infected children in the U.K. Collaborative HIV in Pediatric Study (CHIPS) cohort (343 resistance tests). Three of 44 samples had major primary resistance mutations before antiretroviral therapy. Three-class resistance was noted in 42 samples (14.1%). Our study also highlighted underutilization of testing and the need for prompt genotyping after drug discontinuation which may have lead to an underestimation of HIV-1 resistance. 相似文献
5.
Macassa E Delaugerre C Teglas JP Jullien V Tréluyer JM Veber F Rouzioux C Blanche S 《The Pediatric infectious disease journal》2006,25(9):809-814
BACKGROUND: Pediatric experience with atazanavir combined with antiretroviral drugs administered once daily is very limited. OBJECTIVE: The objective of this prospective, single-center observation study was to evaluate efficacy and tolerance of once-a-day ritonavir-boosted atazanavir, including treatment. RESULTS: Antiretroviral treatment of 23 children and adolescents with a median age of 16 years (range, 10-19 years) was changed to a single daily dose of a combination of ritonavir-boosted atazanavir and 2 other nucleoside or nonnucleoside analogs. The single daily dosing was expected to improve adherence to treatment. The mean follow-up period was 12 months (range, 6-17 months). At the time of the treatment switch, the previous treatment had been effective in 11 children (plasma viral load [pVL] <50 copies/mL) and not effective in 12 (pVL >50 copies/mL). None of the viral genotypes had resistance to atazanavir. The susceptibility score for the drugs used in combination with atazanavir (GSS) was at least 1.5 in 12 of 20 children. The atazanavir dose was 300 mg per day for children weighing more than 50 kg and 200 mg per day for children weighing 30 to 50 kg, in all cases associated with 100 mg ritonavir. During follow up, the mean atazanavir plasma concentration at 12 to 15 hours was 2.18 +/- 1.19 mg/L. Tolerance was good in most patients, but 4 children chose to stop treatment because of icterus (n = 2) or persistent nausea and vomiting (n = 2). In 6 of the 12 children in whom treatment was not virologically effective before the switch, pVL was below 50 copies/mL after 1 to 3 months of treatment. Poor compliance and virologic failure persisted in the other 6 children. Seven of the 11 children with good virologic control before the switch continued to have undetectable pVL but 4 experienced virologic failure after 1, 1, 3 or 12 months of treatment despite good compliance. Insufficient antiviral potency of associated drugs could have been the cause of 2 of these 4 unexpected virologic failures. CONCLUSION: In these children with extensive previous treatment, the change to a once-daily treatment, including ritonavir-boosted atazanavir, was associated with a significant risk of virologic failure. 相似文献
6.
Interferon-gamma and interleukin-10 production among HIV-1-infected and uninfected infants of HIV-1-infected mothers 总被引:3,自引:0,他引:3
Kuhn L Coutsoudis A Moodley D Mngqundaniso N Trabattoni D Shearer GM Clerici M Coovadia HM 《Pediatric research》2001,50(3):412-416
Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-1 [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers were followed prospectively after birth to determine HIV vertical transmission, and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA-stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10 production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production alone were not significantly associated with transmission, but relationships between the two cytokines differed among infected and uninfected infants of HIV-1-infected mothers. PHA-stimulated IFN-gamma and IL-10 production was positively correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03 at 6 mo) but not uninfected infants, and stronger relative production of IFN-gamma to IL-10 was observed among exposed uninfected than among infected infants (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord blood cells from infants of HIV-1-infected mothers may be associated with protection against perinatal HIV infection. 相似文献
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S Resino JM Bellon D Gurbindo MA Muñoz-Fernández 《Acta paediatrica (Oslo, Norway : 1992)》2001,90(9):989-997
This study measured cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-infected children born to HIV-infected mothers, and compared it with vertically exposed but uninfected age-matched children. A significant defect was observed in Th1 cytokine production [interferon-gamma and interleukin-2 (IL-2)] in HIV-infected children compared with controls, but without a concomitant increase in Th2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an increased release of tumour necrosis factor-alpha (TNF-alpha) that correlated well with CD4+ levels, and a positive correlation of the TNF-alpha/IL-10 ratio with disease progression was observed. A correlation between AIDS-free status and higher %CD4+ and %CD8+ T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also found. Conclusion: A dysfunctional cytokine production of PBMCs was observed in HIV-infected children in both Th1 and Th2 cytokines due to quantitative and qualitative defects induced by HIV-1. An important observation was an increased RANTES production associated with viral isolates of NSI/R5 phenotype and S/L kinetics. 相似文献
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Chattopadhya D Grover SS Sharma M Ichhpujani RL Baveja UK 《Annals of tropical paediatrics》2003,23(4):279-292
The effect of HIV infection on immune response to diphtheria and tetanus primary immunisation was investigated in 24 HIV-1-positive multi-transfused (MT) children with thalassaemia and compared with 48 HIV-1-negative MT thalassaemic children and 36 HIV-1-negative non-transfused (NT) children in the community. Diphtheria and tetanus antibody levels in the HIV-1-positive MT group were comparable with the two HIV-negative groups. The proportions of children with antibody titres below the protective level (i.e. <0.01 IU/ml) for antidiphtheria antibodies were 20.8, 16.6 and 16.6%, and 12.5, 12.5 and 13.9% for anti-tetanus antibodies in the three groups, respectively. On the other hand, delayed-type hypersensitivity (DTH) response to diphtheria and tetanus antigens was significantly depressed in the HIV-1-positive group compared with the HIV-negative controls. The mean percentages of both mature (CD20+) and immature (CD10+) B-cell counts were significantly higher in the HIV-1-positive group than in the HIV-negative MT and NT groups (p<0.05). Levels of serum immunoglobulins and spontaneously secreted immunoglobulins were significantly higher in the HIV-1-positive group compared with both HIV-negative groups. The HIV-1-positive group showed a mean (SD) IL-6 of 52.9 (28.8) pg/ml compared with 23.7 (12.1) pg/ml and a detection rate of 54.2% in the HIV-negative MT group, and 23.6 (8.2) pg/ml and a 50% detection rate in the HIV-negative NT group. The IL-2 level was significantly lower (p<0.05) in the HIV-1-positive group [41.7% detection rate and mean (SD) 28.8 (17.1) pg/ml] than in the HIV-negative MT and NT groups [75% and 83.3% detection rates and mean (SD) 57.2 (42.3) pg/ml and 99.3 (51.1) pg/ml, respectively]. During follow-up for 3 years, the frequency of major infections was significantly higher in the HIV-1-positive group than in the other two groups. Acute pneumonia and acute sinusitis were the predominant infections regardless of HIV status while primary bacteraemia, osteomyelitis, pyogenic meningitis and septic arthritis were common in the HIV-1-positive group. We conclude that, in HIV-1-infected children pre-immunised with DPT, DTH response to diphtheria and tetanus antigens might be more reliable than anti-diphtheria and anti-tetanus antibody levels in predicting susceptibility to major bacterial infections. 相似文献
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Background: During the past two decades, the incidence of paediatric empyema has increased in many countries. Purpose: The aim of this retrospective hospital chart review was to evaluate the incidence, aetiology and clinical and laboratory characteristics of parapneumonic empyema in children. Subjects and methods: Twenty‐one patients were admitted to a university hospital from the area with a population of 84 000 children in 1991–2009. Results: The annual incidence of parapneumonic empyema was 1.6/100 000 children in 1991–1998, 0.2/100 000 children in 1999–2005 and 2.7/100 000 children in 2006–2009. Bacterial aetiology was identified in 52% of the cases, and pneumococcus caused 45% of the cases with bacterial aetiology detected. The clinical and laboratory findings in children with and without pleural effusion on admission were surprisingly similar. The development of empyema in hospital during antibiotic therapy was associated with persistent fever and serum C‐reactive protein (CRP) >200 mg/L for 48 h after admission. Conclusion: The incidence of parapneumonic empyema in children fluctuated but in the long run, increased in 1991–2009. Pneumococcus caused half of the cases with bacterial diagnosis available. Since 2010, pneumococcal vaccination has belonged to the general vaccination programme, and the effect on the incidence of empyema remains to be seen. 相似文献
13.
Streptococcus pneumoniae is a common cause of meningitis, sepsis, pneumonia, acute otitis media, and sinusitis in children. Children younger than 24 months have the highest rates of invasive pneumococcal infections (Germany 1997-1999: 19.5/100,000/year). Pneumococcal infections cause in Germany 220-250 cases of meningitis, about 50,000 of pneumonia (children younger than 5 years) and more than 1 million cases of otitis media (children) annually. The case-fatality rate for invasive pneumococcal diseases is high (1997-1999 5.5%, meningitis 8.3%). 20-30% of survivors from meningitis suffer from CNS-related sequelea. In children up to 2 years vaccination with the heptavalent pneumococcal conjugate vaccine can reduce invasive pneumococcal diseases by about 80% and otitis media and recurrent otitis media by 6% and 9-16%, respectively. Due to the increased risk of pneumococcal infections in the first two years of live all children of this age group should be vaccinated. The high rate of resistance of pneumococci against macrolides in Germany, the high rate of non-licensed antibiotics in infants and the inefficacy of the 23-valent vaccine in children younger than 2 years makes the new vaccine to a necessary alternative. 相似文献
14.
Bunders MJ Bekker V Scherpbier HJ Boer K Godfried M Kuijpers TW 《Acta paediatrica (Oslo, Norway : 1992)》2005,94(11):1571-1577
Aim: To investigate haematological parameters in infants born to HIV-1-infected mothers and exposed to combination antiretroviral therapy (ART) used to prevent mother-to-child transmission (MTCT). Methods: A 2-y single-centre follow-up study performed in 109 infants born to HIV-1-positive mothers. Exclusion criteria for the infants were HIV-1 infection, perinatal death, or insufficient information. Haematological parameters of the remainder of 92 infants born to HIV-1-infected mothers and exposed to ART in utero and neonatally were compared with 75 matched non-ART-exposed children. Results: Transmission rate of HIV-1 was 1.8% and occurred when the mother was not compliant with the treatment. In the HIV-1/ART-exposed children there was a long-lasting reduction in absolute neutrophil counts (ANC) until at least 8 mo of age. According to PACTG toxicity scores, 16 infants were suffering from grade II or more (moderate-to-severe) toxicity of ART on ANC. In a multivariable analysis of maternal and neonatal risk factors, pregnancy duration was correlated with moderate-to-severe toxicity on ANC. There were no clinical implications detected, e.g. increased infections or antibiotic treatment.
Conclusion: ART is successful in preventing MTCT, but alterations in haematological parameters may persist for a long period. The clinical implications remain uncertain. This suggestion increases the importance to continue prospective follow-up on the haematological parameters in ART/HIV-exposed children. 相似文献
Conclusion: ART is successful in preventing MTCT, but alterations in haematological parameters may persist for a long period. The clinical implications remain uncertain. This suggestion increases the importance to continue prospective follow-up on the haematological parameters in ART/HIV-exposed children. 相似文献
15.
Anita De Rossi Lucia Ometto Carlo Zanotto Francesca Salvatori Sara Masiero Fabrizio Mammano Luigi Chieco-Bianchi 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(S400):25-28
Polymerase chain reaction was performed in 251 infants born to HIV-1-seropositive mothers to diagnose HIV-1 infection. Assay specificity was invariably > 95%, regardless of age at testing, while sensitivity ranged from 15% in neonates (within 48 h of birth) to > 95% in infants over 1 month of age. Evaluation of viral burden in 43 infected infants by means of quantitative DNA-PCR disclosed that the number of HIV-1 proviruses ranged from 5 to 947 per 100,000 peripheral blood mononuclear cells. Clinical follow-up demonstrated that a high viral burden was associated significantly with disease onset. 相似文献
16.
Le TM Rovers MM Veenhoven RH Sanders EA Schilder AG 《European journal of pediatrics》2007,166(10):1049-1052
Pneumococcal vaccines may be effective in preventing or decreasing the burden of disease related to otitis media. In study
reported here, we investigated the effectiveness of pneumococcal vaccination on otitis media with effusion (OME) in children
(n = 383 children aged 1–7 years) with a history of recurrent otitis media within the framework of a randomized double blind
placebo controlled trial. Children were randomized to be immunized with either a 7-valent pneumococcal conjugate vaccine followed
by the 23-valent pneumococcal polysaccharide vaccine, or by hepatitis A or B vaccines. The proportion of children diagnosed
with OME at the scheduled follow-up visits – 7, 14, 20 and 26 months after randomization – was then calculated. OME was diagnosed
according to an algorithm combining tympanometry and otoscopy. The percentage of children diagnosed with OME was similar in
the pneumococcal vaccination group and control group at both baseline and the follow-up visits at 7, 14, 20 and 26 months
– 52.9 versus 52.7, 44.9 versus 44.2, 34.9 versus 31.5, 40.8 versus 32.2 and 31.4 versus 26.1, respectively (corresponding
to p-values of 0.96, 0.89, 0.51, 0.13 and 0.36, respectively). We conclude that the combined pneumococcal conjugate and the polysaccharide
vaccination have no beneficial effect on OME in children aged 1 year or older with a history of recurrent otitis media. Therefore,
these vaccinations are not indicated in the prevention of OME in these children. 相似文献
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Resino S Bellón JM Sánchez-Ramón S Gurbindo D León JA Muñoz-Fernández MA 《Pediatric research》2003,53(2):309-312
Our objective was to study the probability of achieving undetectable viral load levels in HIV-1-infected children after 36 mo of highly active antiretroviral therapy (HAART). A prospective, multicenter, longitudinal study in 41 HIV-1-infected children on HAART was undertaken. Viral load was quantified using standard molecular assay. CD4+ and CD8+ T cell subsets were determined by flow cytometry. The probability of achieving undetectable viral load was determined using Kaplan-Meier curves according to groups by percentage CD8+ at baseline (CD8+ <25% or >25%). Lower baseline CD8+ T cell levels conditioned a less effective virological response to HAART in children, independent of baseline CD4+ T cell numbers and viral load levels. A greater number of children (81%) from CD8+ >25% group than from the CD8+ <25% (40%) presented undetectable viral load levels (p = 0.013). Additionally, the CD8+ >25% group showed a 4.5-fold higher (95% confidence interval: 1.1-19.2) relative proportion for achieving viral load <400 copies/mL than the CD8+ <25% group (p = 0.039). We concluded that monitoring CD8+ T cell numbers may be valuable in deciding when to start HAART in vertically HIV-1-infected children. 相似文献
19.
Lima M De Menezes Succi RC Nunes Dos Santos AM Weckx LY De Moraes-Pinto MI 《The Pediatric infectious disease journal》2004,23(7):604-607
BACKGROUND: HIV infection can have important although sometimes unexpected consequences, such as contributing to enlargement of the pool of rubella-susceptible children. METHODS: At the Federal University of S?o Paulo, Brazil, we assessed response to rubella immunization at 15 months of age in 15 human immunodeficiency virus type 1 (HIV)-infected children, 20 seroreverted children (SR) and 18 healthy control children born to HIV-seronegative mothers (CON). Blood samples were collected before and 3 months after vaccination. All HIV-infected children had started highly active antiretroviral therapy during their first 6 months of life. Serum samples were tested with a rubella IgG enzyme-linked immunosorbent assay kit. RESULTS: HIV children in immunologic categories 2/3 had lower rubella antibody titers (geometric mean, 33 IU/mL) than those from CON (125 IU/mL) and SR group (236 IU/mL) (Tukey, P = 0.01). Antibody values after vaccination were positively associated with CD4 T cell numbers and negatively associated with HIV viral load assessed immediately before vaccination. The percentage of children with protective antibodies after vaccination (above 10.0 IU/mL) was also significantly different among groups (Fisher's exact test, P = 0.013): CON, 94%; SR, 100%; HIV category 1, 100%; HIV category 2/3, 62%. CONCLUSIONS: HIV-infected children with a preserved immune system at measles-mumps-rubella immunization can have a good response to rubella vaccine. In contrast, those in more advanced categories for HIV infection respond poorly. 相似文献
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Crommentuyn KM Scherpbier HJ Kuijpers TW Mathôt RA Huitema AD Beijnen JH 《The Pediatric infectious disease journal》2006,25(6):538-543
BACKGROUND: The objectives of this study are to develop and validate a population pharmacokinetic model that adequately describes the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected children; to define factors involved in the pharmacokinetic variability, which could aid in defining dosing strategies; and to correlate the pharmacokinetics to the treatment response. METHODS: Protease inhibitor-naive, HIV-1-infected children were included. A population pharmacokinetic model of nelfinavir and M8 was developed using NONMEM. Bayesian analysis was used to estimate pharmacokinetic values. A pharmacokinetic-pharmacodynamic analysis was performed to study relationships between these values and the virologic response to therapy. RESULTS: From 38 children, 724 nelfinavir and 636 M8 plasma concentrations were available. The pharmacokinetics of both compounds were described simultaneously with a one-compartment model with first-order elimination. Clearance (CL/F) and volume of distribution (V/F) were 32.6 L/h (interindividual variability [IIV]: 31.6%) and 281 L/h (IIV: 29.7%) for nelfinavir and 86.2 L/h (IIV: 43.1%) and 42.3 L/h for M8. No factors could be defined that affected the pharmacokinetics of nelfinavir or M8. The overall virologic response was 78% (HIV-1 RNA <500 copies/mL, on-treatment analysis). No differences in exposure to nelfinavir and M8 were observed between responders and nonresponders. The only factor distinguishing the two groups was a higher baseline HIV-1 RNA concentration in nonresponders. CONCLUSION: A model was developed and validated that adequately described the population pharmacokinetics of nelfinavir and M8 in a childhood population. No factors affecting dosing strategies were identified, and no correlation could be demonstrated between the exposure to nelfinavir and M8 and the virologic treatment response. 相似文献