227 research outputs found
Challenges in the treatment of HIV-1 infected children with highly active antiretroviral therapy
Nobody could have predicted the tremendous implications of the headline in The New York Times of
July 5, 1981: "Rare cancer in homosexuals". This article contained the first description of the disease
"Acquired Immune Deficiency Syndrome" (AIDS) and marked the beginning of a pandemic by the
Human Immunodeficiency Virus (HIV). (1) Three years after the first adults with AIDS were
identified, similar disease features were reported in children. (2, 3) In general, HIV infection
progresses more rapidly in children than in adults. This progression is associated with a higher viral
burden, a more rapid depletion of CD4+ T-cell lymphocytes and impaired growth characteristics. (4-
8) HN infected children may be divided in three groups on the basis of disease progression: "rapid
progressors" (±20%), "intermediate progressors" (±60%) and "slow progressors" (±20%). (9-12)
The first group shows a rapid decrease in CD4+ T-cells and develops AIDS (CDC classification C
(13)) within the first two years of life. In "intermediate progressors" a more gradual decrease in
CD4+ T-cell counts is observed. These children don't have symptoms of serious immunosuppression
until the age of 7-8 years. The "slow progressors" are asymptomatic at the age of 8 years and have
a normal or slightly decreased CD4+ T-cell count. Symptoms associated with HIV infection in infants
and children are dependent on the extent of immunosuppression. The Centers for Disease Control
and Prevention have developed a pediatric classification sys
Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on Duration of antibiotic Therapy in suspected neonatal early-onset Sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study
Background: Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis.Methods/Design: The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending phy
Liquefaction Characteristics of Sand as Studied by Cyclic Torsional Testing Using Hollow Cylinder Apparatus
The DNA recombination and repair machineries of Mycoplasma genitalium and Mycoplasma pneumoniae differ considerably from those of gram-positive and gram-negative bacteria. Most notably, M. pneumoniae is unable to express a functional RecU Holliday junction (HJ) resolvase. In addition, the RuvB homologues from both M. pneumoniae and M. genitalium only exhibit DNA helicase activity but not HJ branch migration activity in vitro. To identify a putative role of the RuvA homologues of these mycoplasmas in DNA recombination, both proteins (RuvA(Mpn) and RuvA(Mge), respectively) were studied for their ability to bind DNA and to interact with RuvB and RecU. In spite of a high level of sequence conservation between RuvA(Mpn) and RuvA(Mge) (68.8% identity), substantial differences were found between these proteins in their activities. First, RuvA(Mge) was found to preferentially bind to HJs, whereas RuvA(Mpn) displayed similar affinities for both HJs and single-stranded DNA. Second, while RuvA(Mpn) is able to form two distinct complexes with HJs, RuvA(Mge) only produced a single HJ complex. Third, RuvA(Mge) stimulated the DNA helicase and ATPase activities of RuvB(Mge), whereas RuvA(Mpn) did not augment RuvB activity. Finally, while both RuvA(Mge) and RecU(Mge) efficiently bind to HJs, they did not compete with each other for HJ binding, but formed stable complexes with HJs over a wide protein concentration range. This interaction, however, resulted in inhibition of the HJ resolution activity of RecU(Mge)
Treatment with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children is associated with a sustained effect on growth
INTRODUCTION: Growth failure is a common feature of children with human
immunodeficiency virus type 1 (HIV-1) infection. Children who are treated
with mono or dual nucleoside analogue reverse transcriptase inhibitor
(NRTI) therapy show a temporary increase in weight gain and linear growth
rate. In adults, protease-inhibitor-containing antiretroviral therapy is
associated with a sustained weight gain and increased body mass index
(BMI). Experience with protease inhibitors and growth in children is still
limited. The data mainly deal with short-term effects on growth.
OBJECTIVE: To evaluate the effect of highly active antiretroviral therapy
(HAART) on growth in children with HIV-1 infection. DESIGN AND METHODS: We
analyzed selected growth parameters, clinical data, and laboratory results
as part of a prospective, open, uncontrolled, multicenter study to
evaluate the clinical, immunologic, and virologic response to HAART
consisting of indinavir, zidovudine, and lamivudine in children with HIV-1
infection. Height and weight were measured at 0, 12, 24, 36, 48, 60, 72,
84, and 96 weeks after initiation of HAART. Information about the
children's growth before enrollment in the study was retrieved from the
hospital medical records and/or the school doctor or health center. BMI
was calculated. z Scores were used to express the standard deviation (SD)
in SD units from the Dutch reference curves for age and gender. Viral
loads and CD4+ T-cell counts were examined prospectively and related to
these growth parameters. z Scores were also calculated for CD4+ T-cell
counts to correct for age-related differences. A z score of 0 represents
the P50, which is exactly the age/sex-appropriate median. A height z score
of -1 indicates that a child's height is 1 SD below the age- and
gender-specific median height for the normal population. Virologic
responders were defined as those who either reached an undetectable viral
load (1.5 log reduction in viral load compared
with baseline at week 12 after the initiation of HAART, which was
maintained during the follow-up period. RESULTS. PATIENTS: Twenty-four
patients were included (age: 0.4-16.3 years at baseline), with a median
HIV-1 RNA load of 105 925 copies/mL (5.03 log), a median CD4+ T-cell count
of 0.586 x 10(9)/L (median z score: -2.28 SD), a median height z score of
-1.22, a median weight z score of -0.74, and a median baseline BMI z score
of -0.32. Eleven patients were naive to antiretroviral therapy, and 13
patients had received previous treatment with NRTI monotherapy. Twenty
children used indinavir and 4 children used nelfinavir as part of HAART.
VIROLOGIC AND IMMUNOLOGIC RESPONSES TO HAART: Seventeen children were
virologic responders, and 7 children were virologic nonresponders. In
patients naive to NRTIs, median baseline viral loads were significantly
higher than in pretreated patients. However, at weeks 48 and 96, there was
no significant difference between the viral loads of both groups. At
baseline, there was no significant difference in CD4+a T-cell z scores
between virologic responders and nonresponders or between naive and
pretreated patients. During 96 weeks of HAART, the increase of CD4+ T-cell
z score was significantly higher in responders than in nonresponders. The
increase in CD4+ T-cell z score was not significantly different for naive
and pretreated patients. HEIGHT, WEIGHT, AND BMI z SCORE CHANGES: We found
that
Infection with and carriage of Mycoplasma pneumoniae in children
"Atypical" pneumonia was described as a distinct and mild form of community-acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered and recognized as its cause. M. pneumoniae is detected in CAP patients most frequently among school-aged children from 5 to 15 years of age, with a decline after adolescence and tapering off in adulthood. Detection rates by polymerase chain reaction (PCR) or serology in children with CAP admitted to the hospital amount 4-39%. Although the infection is generally mild and self-limiting, patients of every age can develo
Circulating Antibody-Secreting Cell Response During Mycoplasma pneumoniae Childhood Pneumonia
Background. We recently demonstrated that the measurement of Mycoplasma pneumoniae (Mp)-specific immunoglobulin (Ig)
M antibody-secreting cells (ASCs) improved diagnosis o
Viruses as sole causative agents of severe acute respiratory tract infections in children
Background: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. Objective: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Study Design: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. Results: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MCARTI patients. Conclusion: B
Stratified Management for Bacterial Infections in Late Preterm and Term Neonates:Current Strategies and Future Opportunities Toward Precision Medicine
Bacterial infections remain a major cause of morbidity and mortality in the neonatal period. Therefore, many neonates, including late preterm and term neonates, are exposed to antibiotics in the first weeks of life. Data on the importance of inter-individual differences and disease signatures are accumulating. Differences that may potentially influence treatment requirement and success rate. However, currently, many neonates are treated following a “one size fits all” approach, based on general protocols and standard antibiotic treatment regimens. Precision medicine has emerged in the last years and is perceived as a new, holistic, way of stratifying patients based on large-scale data including patient characteristics and disease specific features. Specific to sepsis, differences in disease susceptibility, disease severity, immune response and pharmacokinetics and -dynamics can be used for the development of treatment algorithms helping clinicians decide when and how to treat a specific patient or a specific subpopulation. In this review, we highlight the current and future developments that could allow transition to a more precise manner of antibiotic treatment in late preterm and term neonates, and propose a research agenda toward precision medicine for neonatal bacterial infections.</p
Risk-based maternal group B Streptococcus screening strategy is compatible with the implementation of neonatal early-onset sepsis calculator
Background: The early-onset sepsis (EOS) calculator was
developed and validated in a setting with routine-based group B
Streptococcus (GBS) screening.
Purpose: The study aimed to evaluate the extent of influence
exerted by risk-based GBS screening on management recommendations by the EOS calculator.
Methods: All
Characterization of the nasopharyngeal and middle ear microbiota in gastroesophageal reflux-prone versus gastroesophageal reflux non-prone children
Otitis media (OM) is one of the most common pediatric infections worldwide, but the complex microbiology associated with OM is poorly understood. Previous studies have shown an association between OM and gastroesophageal reflux (GER) in children. Therefore, in order to bridge the gap in our current understanding of the interaction between GER and OM, we investigated the nasopharyngeal and middle ear microbiota of children suffering from GER-associated OM and OM only, using culture-independent 16S rRNA gene sequencing. Middle ear fluid, nasopharyngeal swabs, and clinical data were collected as part of a prospective pilot study conducted at the Department of Otorhinolaryngology of the Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands. A total of 30 children up to 12 years of age who suffered from recurrent acute otitis media (AOM) (5), chronic otitis media with effusion (OME) (23), or both (2), and who were listed for tympanostomy tube placement, were included in the study. Nine children were included in the GER-associated OM cohort and 21 in the OM-only cohort. We found no obvious effect of GER on the nasopharyngeal and middle ear microbiota between the two groups of children. However, our results highlight the need to assess the true role of Alloiococcus spp. and Turicella spp. in children presenting with a high prevalence of recurrent AOM and chronic OME
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