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Leipzig : Vogel, 1886.

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Early detection of patients vulnerable to infections acquired in the hospital environment is a challenge in current health systems given the impact that such infections have on patient mortality and healthcare costs. This work is focused on both the identification of risk factors and the prediction of healthcare-associated infections in intensive-care units by means of machine-learning methods. The aim is to support decision making addressed at reducing the incidence rate of infections. In this field, it is necessary to deal with the problem of building reliable classifiers from imbalanced datasets. We propose a clustering-based undersampling strategy to be used in combination with ensemble classifiers. A comparative study with data from 4616 patients was conducted in order to validate our proposal. We applied several single and ensemble classifiers both to the original dataset and to data preprocessed by means of different resampling methods. The results were analyzed by means of classic and recent metrics specifically designed for imbalanced data classification. They revealed that the proposal is more efficient in comparison with other approaches.

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.

SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity

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Here’s what we should be expecting in the war on Covid-19.

OBJECTIVES:

To determine if a multicomponent intervention was associated with increased use of first-line antibiotics (cephalexin or sulfamethoxazole and trimethoprim) among children with uncomplicated urinary tract infections (UTIs) in outpatient settings.

Almost 1 in 4 adolescents have a sexually transmitted infection (STI). These infections are preventable through safe sexual practices and routine screening. Pediatricians are the first line of clinical care for adolescents and are well positioned to offer sexual and reproductive health care counseling and services to their patients; yet, there is a paucity of sexual health screening provided at routine health supervision visits. This article addresses the epidemiology of STIs in adolescents, reviews the evidence of current clinical practice, presents recommended STI screening from government and medical agencies, and offers strategies to address barriers to providing care for adolescents and for sexual health screening in primary care.

Lactoferrin is a glycoprotein with anti-infective activities being part of the innate defensive network. Bovine and human lactoferrin share high homology. Bovine lactoferrin can prevent late-onset sepsis in preterm very low birth weight neonates.

In preterm very low birth weight infants, bovine lactoferrin is able to prevent not only late-onset sepsis but also systemic fungal infections. This protection is achieved independently from their colonization status. (Read the full article)

Upper respiratory tract infections (URIs) are very common in children. Currently, there are no effective preventive measures for URI. There are no studies on the effect of montelukast for prevention of URI.

In a randomized, double-blind, placebo-controlled study of preschool-aged children, 12-week prophylactic treatment with montelukast did not reduce the incidence of URI. (Read the full article)

The presence of malodorous urine is often mentioned as one of the clinical manifestations of urinary tract infection (UTI) in young children, yet the few studies looking at this symptom are contradictory.

Our study demonstrates that malodorous urine as reported by parents increases the likelihood of UTI among young children evaluated for suspected UTI. However, this association is not strong enough to definitely rule in or out a diagnosis of UTI. (Read the full article)

Some but not all randomized trials have shown effects of probiotics on incidence and duration of diarrhea and respiratory tract infections among children in developing countries. Calcium improves resistance to intestinal infections in adults, but efficacy in children is unknown.

Lactobacillus reuteri DSM17938 may prevent diarrhea, especially in children with lower nutritional status. Regular calcium milk, alone or with Lactobacillus casei CRL431, did not reduce diarrhea. None of the interventions affected respiratory tract infections in these Indonesian children. (Read the full article)

Rural Alaska children have high rates of hospitalization with lower respiratory tract infections from a variety of pathogens. Past studies of risk factors for respiratory syncytial virus infection associated medically high-risk status, household crowding, and infant feeding practices with hospitalization.

This study reveals the importance of medically high-risk status and infant feeding practices as important factors in respiratory hospitalization. In addition, we identified woodstove use and the absence of 2 or more sinks in household as risk factors for hospitalization. (Read the full article)

Emphasis on preventing central line-associated bloodstream infections (CLABSIs) in US health care facilities and prophylactic antifungal medication use in neonates may impact incidence of Candida spp. CLABSIs. However, data on trends in incidence of neonatal Candida spp. CLABSIs are lacking.

Data from a large sample of US NICUs was analyzed to assess trends in incidence over time. This analysis provides a description of the epidemiology of Candida spp. CLABSIs in a national health care-associated infections surveillance system. (Read the full article)

Neonatal sepsis is an important cause of under-5 childhood mortality. Infants born to HIV-infected mothers are at increased risk of morbidity and mortality, even if not having acquired HIV. This association needs further study during the neonatal period.

Maternal HIV infection was associated with increased vaginal colonization by Escherichia ecoli but not group B Streptococcus. Neonates born to HIV-infected mothers were only at increased risk of sepsis if they had acquired HIV-infection, but not if HIV-uninfected. (Read the full article)

A growing number of epidemiologic studies suggest that individuals with lower vitamin D levels are at higher risk of acute respiratory tract infection. Randomized controlled trials are needed to determine if vitamin D supplementation would decrease this risk.

In a randomized controlled trial of 247 Mongolian children with vitamin D deficiency in winter, with double-blinding and 99% follow-up, vitamin D supplementation significantly reduced the risk of acute respiratory tract infections. (Read the full article)

Pediatric osteoarticular infections can be treated with successful microbiologic and clinical outcomes with a transition from parenteral to oral therapy. The best way to determine the timing of this transition is neither well studied nor standardized.

A total of 193 (99.5%) of 194 pediatric patients with acute bacterial osteoarticular infections were successfully transitioned to oral therapy, determined by using a combination of clinical findings and C-reactive protein levels, representing the largest single-center data set analyzed. (Read the full article)

Invasive Cronobacter infection is a rare but devastating disease known to affect hospitalized premature or immunocompromised infants fed powdered infant formulas (PIFs). PIF labels imply that powdered formulas are safe for healthy, term infants if the label instructions are followed.

Cronobacter can also infect healthy, term infants in the first months of life, even if PIF label instructions are followed. Invasive Cronobacter infection is extremely rare in exclusively breastfed infants or those fed commercially sterile, ready-to-feed formulas. (Read the full article)

Several meta-analyses evaluating probiotics in preterm infants suggest a beneficial effect for the prevention of necrotizing enterocolitis and death, but less for nosocomial infection. Lactobacillus reuteri may reduce these outcomes because of its immunomodulation and bactericidal properties.

Although L reuteri did not appear to decrease the rate of death or nosocomial infection, the trends suggest a protective role consistent with the literature. Feeding intolerance and duration of hospitalization were significantly decreased in premature infants ≤1500 g. (Read the full article)

It has been suggested that maternal immune activation during pregnancy is associated with cardinal behaviors of autism in the offspring. Epidemiologic studies have yielded conflicting results concerning the association between any infection during pregnancy and the development of autism.

This population-based cohort study investigated the association between specific common infectious diseases, febrile episodes, or use of antibiotics during pregnancy by using maternal population-based self-reported data. (Read the full article)

There is evidence that Kingella kingae, the major bacterial cause of osteoarticular infection in children <4 years of age, first colonizes the oropharynx before penetrating the bloodstream and invading distant organs. Diagnosis remains challenging because clinical findings at admission may be normal.

Our study demonstrated for the first time that a simple technique of detecting of K kingae DNA in the oropharynx can provide strong evidence that this microorganism is responsible for the OAI, or even stronger evidence that it is not. (Read the full article)

Skin and soft tissue infections (SSTIs) are a common pediatric condition often requiring inpatient management. Several studies describe recent increases in hospitalizations due to SSTIs.

In addition to rising hospitalizations, analysis of pediatric SSTI resource utilization trends revealed a twofold increase in incisions and drainages over a 13-year period. A growing number of incisions and drainages were performed in younger children. (Read the full article)

Although amphibians are known Salmonella carriers, aquatic African dwarf frogs are specifically marketed toward children, who are especially vulnerable to Salmonella infections. Both direct animal contact and indirect contact with animal habitats can lead to human Salmonella infections.

This is the first reported outbreak of human Salmonella infections associated with African dwarf frogs, particularly among young children. Parents should be aware of the risk of Salmonella infections from both direct and indirect animal contact. Pediatricians should regularly inquire about animal contact and advise families about risks. (Read the full article)

Health care–associated infections cause considerable morbidity and mortality among hospitalized children. Simple barrier precautions such as universal gloving of health care workers’ hands may reduce transmission of infectious agents between patients.

Mandatory use of gloves during respiratory syncytial virus season in pediatric units prevented other health care–associated infections such as central line–associated bloodstream infections, particularly in intensive care settings. These secondary benefits suggest continuing mandatory gloving throughout the year. (Read the full article)

Neonatal infections are frequent complications in very preterm infants, already at high risk of neurologic and cognitive disabilities. Few studies have linked neonatal infections and neurodevelopmental outcomes. Those that did evaluated children only to the age of 22 months.

This study assessed the respective effects of early- and late-onset sepsis and their association with 5-year neurodevelopmental outcomes. We identified a significant and cumulative risk of cerebral palsy when episodes of early- and late-onset sepsis were associated. (Read the full article)

Blood cultures are a common investigation in children admitted to the hospital with skin and soft tissue infections. The yield of blood cultures in this condition is unknown.

Blood cultures are not useful in children admitted to the hospital with uncomplicated skin and soft tissue infections, and they may be associated with increased length of hospital stay. (Read the full article)

The diagnosis of urinary tract infection (UTI) is confirmed by urine testing with urinalysis and culture. No study has characterized the use of urine testing in the setting of empirical antibiotic prescription for outpatient UTI in children.

Urine tests are not performed in a substantial percentage of antibiotic-treated pediatric UTIs. Additional research is necessary to determine whether empirical antibiotic prescription for UTI in children without urine testing is safe and effective. (Read the full article)

Invasive methicillin-resistant Staphylococcus aureus (MRSA) in children is associated with high morbidity and mortality. Although reductions in health care–associated MRSA infection among adults are documented, it is unclear if a similar trend is occurring among children.

Data from population-based surveillance were analyzed to assess changes in invasive MRSA infection incidence over time. This analysis describes the epidemiology and trends of invasive MRSA infections among children in 9 US metropolitan areas and estimates national burden. (Read the full article)

Bacille Calmette-Guerin (BCG) vaccination may provide benefits beyond protecting against pediatric tuberculosis. Evidence suggests links between cell-mediated immunity from tuberculosis and bacterial/viral-related pneumonia but the impact of BCG on acute lower respiratory infection is not fully known.

BCG-vaccinated children had a lower risk of suspected acute lower respiratory infection. Protection was amplified when children were vaccinated against diphtheria-tetanus-pertussis (DTP). Number of DTP doses did not modify this effect, but order in which vaccines were received did. (Read the full article)

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss and neurodevelopmental impairment in full-term infants. The incidence of congenital CMV infection in preterm infants and the possible associations with developmental outcomes are unknown.

This study defines the incidence of congenital CMV infection in very low birth weight infants and identifies strong associations of congenital CMV infection with hearing loss and adverse neurodevelopmental outcomes in this population. (Read the full article)

Little is known about the epidemiology and pathogenicity of Clostridium difficile infection among children, particularly those aged ≤3 years in whom colonization is common and pathogenicity uncertain.

Young children, 1 to 3 years of age, had the highest Clostridium difficile infection incidence. Considering that clinical presentation, outcomes, and disease severity were similar across age groups, C difficile infection in the youngest age group likely represents true disease and not asymptomatic colonization. (Read the full article)

Urinary tract infection (UTI) is the most common bacterial infection in febrile infants aged 1 to 90 days. It is unclear if urine microscopy offers significant benefit beyond urine dipstick as a screening test for UTI in this population.

Dipstick may be an adequate screening test for UTI in infants aged 1 to 90 days with a negative predictive value (NPV) of 98.7%. Adding microscopy increases the NPV to 99.2% but results in 8 false-positives for every UTI missed by dipstick. (Read the full article)

Central line–associated bloodstream infections (CLABSI) are common types of hospital-acquired infections associated with high morbidity and cost. In recent years, quality improvement initiatives have demonstrated how to reduce the incidence of CLABSI.

This study presents nationally representative estimates of the cost and length of stay attributable to pediatric CLABSI. We make the business case to justify quality improvement prevention initiatives and the adoption of strategies for cost-effective management of CLABSI. (Read the full article)

Primary HHV-7 infection is almost universal by age 5 years and is causally associated with exanthem subitum, febrile seizures, and febrile status epilepticus. The consequences of delayed primary infection are unknown, although encephalitis has been reported in one adult.

Delayed primary HHV-7 infection can cause serious neurologic disease as identified in 3 adolescents, 2 with encephalitis and 1 with Guillain-Barré syndrome. Serologic tests to distinguish primary from past HHV-7 infection are imperative when HHV-7 DNA is present in CSF. (Read the full article)

Inadequate nutrient intake can compromise a child’s nutritional status, which may affect immune function. Improving dietary intake via a follow-up formula may support appropriate immune responses and improve a child’s ability to resist infection.

Children who consumed an experimental follow-up formula had fewer episodes and shorter duration of acute respiratory infections, as well as less antibiotic treatment, and fewer days missed of day care due to illness. (Read the full article)

Lower respiratory tract infections (LRTIs), including pneumonia, are in the top 10 causes of death among children in the United States. In high-income countries, 3% to 14% of LRTI hospitalizations have been reported to require admission to an ICU.

During 2007–2011, approximately 31 289 hospitalizations for severe LRTI occurred in children each year in the United States. Children <1 year of age had the highest rates of severe LRTI and accounted for 30% of severe LRTI hospitalizations. (Read the full article)

Health care–associated infections are harmful, costly, and preventable, yet there remain limited data as to their population incidence among hospitalized neonates and children in the United States.

Incidence rates of central line–associated bloodstream infections and ventilator-associated pneumonia decreased among critically ill neonates and children during a 5-year period in the United States. National efforts to improve patient safety through decreasing HAIs have been effective. (Read the full article)

Many pediatric acute respiratory tract infections (ARTI) are viral and do not require antimicrobial treatment. Recent estimates of antimicrobial overprescribing for these infections, defined based on the published bacterial disease prevalence among all ARTI, are not available.

Based on the published bacterial prevalence rates for pediatric ARTI, antimicrobial agents are prescribed almost twice as often as expected to outpatients nationally, amounting to an estimated 11.4 million potentially preventable antimicrobial prescriptions annually. (Read the full article)

Neurodevelopment can be adversely affected by viral infections. Human herpesvirus-6 (HHV-6) is similar to cytomegalovirus and can cause central nervous system disease. Congenital HHV-6 infection occurs in ~1% of live births, with unknown neurodevelopmental consequences.

HHV-6 congenital infection is associated with lower scores on the Bayley Scales of Infant Development II Mental Development Index compared with control infants at 12 months of age and may have a detrimental effect on neurodevelopment. (Read the full article)

This is the first population-based study regarding the epidemiologic characteristics of pediatric zoster among only those who had contracted varicella.

The herpes zoster (HZ) incidence among only children with varicella infection is higher than previously reported. The HZ incidence increased for children contracting varicella aged <2 years. After a vaccination program, the HZ risk increased for those contracting varicella aged ≥2 years. (Read the full article)

Myxovirus resistance protein A (MxA) is a protein induced during viral infections. A few small-scale studies have suggested that MxA could be used as a marker of viral infection in clinical routine practice.

This study involves the largest patient population thus far and confirms the usefulness of MxA for diagnosing viral infections in children consulting the emergency department in a clinical routine setting. (Read the full article)

The sensitivity of the urinalysis (UA) traditionally has been considered suboptimal in young infants. Whether the finding of a negative UA and a positive urine culture represents a false-negative UA versus a false-positive urine culture remains unclear.

In infants <3 months with bacteremic urinary tract infection, a condition that represents true infection, the UA sensitivity is higher than previously reported for urinary tract infection in general, suggesting that the UA is reliable even in young infants. (Read the full article)

Vesicoureteral reflux is recognized as an important risk factor for recurrent urinary tract infection and renal scarring. Less is known about the contribution of other risk factors to these outcomes.

This study found that information about vesicoureteral reflux and bladder and bowel dysfunction can be used to identify children at low, medium, and high risk of recurrent urinary tract infection, information that clinicians could use to select children for specific preventive therapies. (Read the full article)