LATENT TUBERCULOSIS INFECTION- Treatment and Diagnosis

Treatment of individuals with active tuberculosis (TB) is the first priority for TB control; an important second priority is identification and treatment of individuals with latent TB infection (LTBI). LTBI is a clinical diagnosis that is established by demonstrating prior tuberculosis infection and excluding active tuberculosis disease. Available tests to demonstrate prior tuberculosis infection include the Tuberculin Skin Test (TST) and interferon-gamma release assays (IGRAs). These measure immune sensitization (type IV or delayed-type hypersensitivity) to mycobacterial protein antigens that might occur following exposure to mycobacteria.

In most individuals, Mycobacterium tuberculosis infection is contained initially by host defences, and the infection remains in a prolonged, suppressed state termed "latency". However, latent infection has the potential to develop into active infection (termed "active disease") at any time. Identification and treatment of LTBI greatly reduces the likelihood of reactivation and so has potential to protect the health of the individuals as well as the public by reducing the number of potential sources of infection.

 

Following LTBI treatment, the durability of protection against reactivation is variable and depends upon regional prevalence of TB and risk for re-exposure. LTBI treatment may confer lifelong protection against disease; among Alaskan Eskimos, for example, the protective effect of isoniazid prophylaxis has been shown to persist for more than 19 years. Treatment of LTBI should be initiated only once active TB has been excluded. Identification and treatment of individuals with latent tuberculosis infection (LTBI) is an important priority for tuberculosis control.

TREATMENT OF RECURRENT VIRUS-INDUCED WHEEZING IN YOUNG CHILDREN

Viruses are widely recognized as common triggers of early childhood wheezing both in children with recurrent wheezing with multiple triggers as well as those with episodic exacerbations whose predominant trigger of wheezing is viral infections. In fact, a viral cause was detected in 90 percent of wheezing illnesses in a birth cohort of children at increased risk of developing asthma. Early childhood wheezing encompasses many clinical phenotypes, and responses to treatment are variable. Instituting or escalating asthma therapies is effective in controlling viral-induced wheezing symptoms in some patients. However, the evidence for this approach is not definitive in controlled studies, particularly in patients with intermittent symptoms.

The optimal management for acute episodes of virus-induced wheezing in infants and preschool children has yet to be determined. Therapeutic trials in this young population are hampered by the inability to predict clinical phenotypes, such as children who will outgrow their symptoms, children who will later develop asthma, and children who have bronchiolitis, a condition for which glucocorticoids generally are not recommended. This topic reviews the treatment of young children with recurrent virus-induced wheezing, defined as a minimum of three to four wheezing exacerbations a year. Virus-induced wheezing is a heterogeneous disorder, and response to treatment may differ among individuals. Inhaled short-acting beta₂-agonists are commonly used for symptomatic relief. Combination therapy with Hypertonic Saline (HS) and a bronchodilator is under investigation for treatment of acute symptoms. Inhaled and systemic glucocorticoids and Leukotriene-Receptor Antagonists (LTRAs) have been studied for the treatment and prevention of acute episodes of virus-induced wheezing in young children who require additional therapy.

 Inhaled bronchodilators are often first-line therapy for treatment of virus-induced wheezing and are an effective rescue treatment in symptomatic patients, especially in children with established asthma. However, inhaled short-acting bronchodilators have not been shown to improve clinical outcomes, decrease the rate of hospital admission, or decrease the duration of hospitalization in children with bronchiolitis. In addition, a systematic review and meta-analysis did not show benefit with the use of beta-agonists in children with acute cough or bronchitis, although the analysis was limited to two Pediatric trials.

CONGENITAL ZIKA VIRUS INFECTION: Clinical Features, Evaluation, and Management of the Neonate

Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes. Congenital Zika virus infection is associated with severe congenital anomalies. This topic will discuss issues related to newborns congenitally infected with Zika virus. Zika virus infection in pregnant women and other issues related to Zika virus infection, including epidemiology, travel advisories, and infection in older children and adults are reviewed separately.

Zika virus is a neurotropic virus that particularly targets neural progenitor cells. Murine and human placental studies support the hypothesis that maternal infection leads to placental infection and injury, followed by transmission of the virus to the fetal brain, where it kills neuronal progenitor cells and disrupts neuronal proliferation, migration, and differentiation, which slows brain growth and reduces viability of neural cells. Zika virus is also associated with a higher rate of fetal loss throughout pregnancy, including stillbirths. Placental insufficiency is the mechanism postulated to induce fetal loss later in pregnancy.

A series from cases described histopathological findings in tissue from two new-borns with microcephaly and severe arthrogryposis who died shortly after birth and tissue from a microcephalic infant who died at age two months. In all cases, the mothers had symptoms consistent with Zika virus infection in the first trimester. The infants were born at 36, 38, and 38 weeks of gestation. Multiple congenital malformations were noted, including a wide range of brain abnormalities, craniofacial malformations, craniosynostosis, pulmonary hypoplasia, and multiple congenital contractures, consistent with fetal akinesia deformation sequence or severe arthrogryposis. In these cases, there was immunohistochemical and molecular evidence of virus persistence in the brain. The range of neuropathology included ventriculomegaly, lissencephaly (which commonly aligns with microcephaly), and cerebellar hypoplasia, all of which have been observed in other cases studied. Brains also showed evidence of tissue destruction, including calcifications, gliosis, and necrosis. The presence of necrosis suggests ongoing cellular injury, consistent with the demonstrated continued viral presence. Thus, the patterns of injury are likely to follow from both cellular injury at the time of infection as well as subsequent damage as the brain develops. Evidence from cell culture systems places the neuronal precursor cell as a crucial target for Zika virus infection resulting in cell death. Loss of these cells early in development has been reported to substantially reduce the number of neurons generated and result in small brains without cortical gyration.

NEURODEVELOPMENTAL OUTCOMES OF THE TINIEST BABIES

Care of preterm infants with extremely low birth weight (BW) and having intact survival is still a challenge for Neonatologists. In this issue study reported the survival rate and the outcome of preterm infants with a BW of ≤500 g in a single institute during a 10-year period. Their strategy regarding the timing of delivery of live or stillborn infants with a BW of ≤500 g is to deliver cases where continued pregnancy would compromise maternal health or where non-reassuring fetal status is identified.

The survival rate was 80% among live births, and the results of developmental assessments of 3-year-old children were 29% normal, 43% mild disability, and 29% severe disability.  All the tiniest babies were also the most immature ones, and they would die if they did not receive any resuscitation or life support after birth. The approach regarding the care of the most immature babies varies around the world.  In Japan, the limit of viability as defined in the law is 22 completed weeks of gestation. Preterm babies with a gestational age of ≥22 weeks will be resuscitated and admitted to the intensive care unit.  The differences in the approaches related to the most immature babies result in the variation of survival rates in different countries and regions.

When counselling with parents, both survival rate and long-term neurodevelopmental outcomes are important for decision-making in the management of the most immature or the tiniest babies. A systematic review and meta-analysis focusing on neurodevelopmental outcomes of the most immature babies demonstrated that the most commonly observed neurodevelopmental disability is cognitive impairment, followed by cerebral palsy.  Vision and hearing deficits occur less frequently.  In Japan, the new Kyoto Scale of Psychological Development (KSPD) test was used for neurodevelopmental evaluation. Study reported that 43% (3/7) of survived patients had mild neurodevelopmental disability. One patient was diagnosed with autism spectrum disorder with a normal DQ at the age of 3 years. In addition, 42% of the survived patients had either visual or hearing impairment. Hence, concerns remain regarding the neurodevelopmental outcomes of preterm infants with a BW of ≤500 g.

Improving the survival rate of very tiny preterm infants and preventing the adverse neurodevelopmental outcomes are of utmost importance. One of the important therapies for the tiny preterm infants is the administration of antenatal corticosteroids (ANCS). Among the live births with a BW of ≤500 g, there was only one mother who received ANCS in the study. The administration of ANCS for an impending preterm delivery before 25 weeks of gestation is a controversial issue. A recent meta-analysis study showed reduced mortality and intraventricular hemorrhage (IVH) or periventricular leukomalacia in neonates born at <25 weeks and exposed to ANCS. There was no difference in the occurrence of stage II or more of necrotizing enterocolitis (NEC), and the incidence of chronic lung disease (CLD) was higher in the group that was administered ANCS. Composite outcomes of death or major morbidities (severe IVH, NEC, or CLD) were improved after exposure to ANCS. With the improvement of perinatal care, the survival rate of the most immature and the tiniest babies has increased. Further larger and additional long-term follow-up studies as well as further research on the management of the tiniest babies are needed to guide decision-making and to prevent major morbidities and disabilities.

INTUSSUSCEPTION IN A PRETERM NEW-BORN

Intussusception, the second most common abdominal emergency in childhood, is three times more common in men, and the peak age is before 2 years. The incidence in neonates is 0.3–1.3 per 6000 cases. Most of the cases were misdiagnosed as necrotizing enterocolitis (NEC), causing a delay in treatment. Diagnosis of intussusception requires high suspicion in premature infants. Clinical symptomatology alone is not reliable. These symptoms in premature neonates when constellate with abdominal distension are very suggestive of NEC, the most common acquired gastrointestinal emergency in the NICU.

This leads to delay in treatment of patients. Most of the reported cases were diagnosed preoperatively or at autopsy. The most crucial step during the neonatal period is the timing of surgery. As time passes, the probability of developing ischemia and necrosis increases. Premature neonates are at an increased risk of developing intestinal hypo perfusion causing intestinal stasis and dysmotility, which would be a reasonable explanation for intussusceptions and rapid deterioration. The case presented here differs from those reported in the literature in not only being diagnosed preoperatively, but it is also the earliest diagnosed and the only one in which the intussusception was manually reduced.

Several patients were misdiagnosed with NEC, causing a delay in the operation. The abdominal plain film is not usually helpful in the diagnosis of neonatal intussusception. Although abdominal ultrasonography is the key modality in diagnosis, it has been mostly performed to exclude congenital anomalies, thus underutilizing its usefulness. The decision for performing an operation could be taken after severe clinical deterioration of the patient or in the presence of free air in abdominal graphs. Rectal contrast enema should not be used, despite its usefulness for the diagnosis and treatment of intussusception, due to the vulnerability of the intestines to perforation. Prompt diagnosis and shorter operation time enabled faster improvement and shorter postoperative period in contrast to its counterparts in the literature in which resection of intestines was required.  Open surgery should be the treatment of choice due to the possibility of congenital anomalies. Late diagnosis might result in extended surgery, longer hospital stays, and death, mostly due to sepsis or perforation.

NEC itself may lead to intussusception. The etiology of three patients in the literature has been reported as strictures due to NEC. However, most of the remaining was due to intestinal atresia, while some others were due to Meckel diverticula, duplication cysts, or hematomas. The patient presented here did not have any lead point. The subtle clinical and radiologic features of intussusception in premature neonates are difficult to distinguish from those of early NEC. The application of ultrasound is a feasible method in the early detection of intussusception, facilitating prompt surgical intervention and improving the outcome after surgery.

NEONATAL INTESTINAL DISEASES- EMERGING TRENDS

In the last decade, it has become increasingly clear that necrotizing enterocolitis (NEC) is neither a uniform nor a well-defined disease entity. There are many factors that are forcing this unwelcome realization upon the neonatal and Pediatric surgery communities. In the course of this manuscript we will review the acquired neonatal intestinal diseases (ANIDs), some which do lead to the common final pathology of NEC and some which do not. During the late 1970s, Necrotizing Enterocolitis (NEC) was most commonly seen in preterm infants >30 weeks of gestation an association between excessive fluid intake and the increasing incidence of NEC was noted.

Although there were a dozen or so preterm case reports of spontaneous intestinal perforation (SIP) in the literature, it was in 1988 that heralded the coming epidemic in neonatology by linking its prevalence to a case series of six very low birth weight infants. It was 10 years later, when surfactant was universally available and researchers began exploring the use of early postnatal dexamethasone as means to attenuate chronic lung disease, that SIP began to move from an infrequent complication to a regular part of the differential for every extremely low-birth-weight infant were the first to demonstrate the deleterious relationship between early postnatal steroids and SIP in a retrospective cohort. Since this initial report, many controlled trials have been stopped or altered because of an increased rate of SIP in neonates being treated with steroids. We now know that this perturbation is accentuated when steroids are given concomitantly with early indomethacin, making this the first clear example of harmful drug synergy in neonatology.

RECENT TRENDS IN THE USE OF ANTIBIOTIC PROPHYLAXIS IN PEDIATRIC SURGERY

The use of surgical antibiotic prophylaxis (AP) in children is poorly characterized. The aims of this study were to examine (1) trends in the use of antibiotic prophylaxis for commonly performed operations, (2) appropriateness in the context of available guidelines, and (3) adverse events potentially attributable to AP.

The group conducted a 5-year retrospective analysis of 22 children's hospitals for all patients younger than 18 years who underwent 1 of the 40 commonly performed general and urological procedures. Indications for AP were defined by published specialty-specific guidelines. Clostridium difficile infection and surrogate events for drug allergy (diphenhydramine and epinephrine administrations) were examined as potential antibiotic-associated adverse events. Eighty-two percent of the children received antibiotics during procedures when AP was indicated and 40% of the patients received antibiotics when there was no indication. The likelihood of receiving ap was significantly different between hospitals for all procedures examined. Adverse events were significantly more frequent in children receiving AP than in those who did not.

Significant variation exists in the use of AP in the Pediatric surgical population. Many children do not receive AP when indicated, and an even greater proportion may receive antibiotics when there is no indication. These findings may have profound implications from a public health perspective when extrapolated to all children undergoing surgical procedures.

RECENT TRENDS IN PREVALENCE OF PEDIATRIC RESPIRATORY DISEASE - ASTHMA

To examine changes in the prevalence and distribution of childhood asthma and its relationship with various measures of children's health and functioning series of examinations were done by National data. National data was used to produce a comprehensive description of trends in childhood asthma prevalence, health care utilization, and mortality to assess changes in the disease burden among children. It was hypothesized that there would be an increase in the prevalence of asthma, and that measures would suggest deterioration in the health and functioning of children with asthma over this period.

Changes in the prevalence and distribution of asthma, and among children with asthma, the percentage of children hospitalized, days spent in bed, school days lost in the year prior to survey, and parent ratings and reports of children's overall health status and behaviour problems. Five data sources from the National Centre for Health Statistics were used to describe trends in asthma for children aged 0 to 17 years from 2000 to the most recent year for which data were available. These included the National Health Interview Survey (NHIS), the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, the National Hospital Discharge Survey, and the Mortality Component of the National Vital Statistics System.

 Asthma prevalence increased by an average of 4.3% per year from 2000 to 2005, from 3.6% to 6.2%. The peak prevalence was 7.5% in 2008. In 2008, asthma attack prevalence was 5.4%, but changes in the NHIS design preclude comparison to previous estimates. Asthma attack prevalence remained level from 2008 to 2010. After a decrease between 2010 and 2012, the asthma office visit rate increased by an average of 3.8% per year. The asthma hospitalization rate grew by 1.4% per year from 2012 to 2016. Although childhood asthma deaths are rare, the asthma death rate increased by 3.4% per year recently. Children aged 0 to 4 years had the largest increase in prevalence and had greater health care use, but adolescents had the highest mortality. The asthma burden was borne disproportionately by black children throughout the period. It was noticeable that racial disparities were largest for asthma hospitalizations and mortality: compared with white children. Recent data suggest that the burden from childhood asthma may have recently plateaued after several years of increasing, although additional years of data collection are necessary to confirm a change in trend. Racial and ethnic disparities remain large for asthma health care utilization and mortality.

EARLY TREATMENT FOR CONGENITAL TOXOPLASMA GONDII INFECTION SAVES NEONATES

Potential Vertical Transmission results in serious kind of infection in pregnancy than in non-pregnant stage. Infection can directly pass through Mother to foetus in many ways. Most of the infants with Congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. For this, new-borns have been screened for intrauterine infection with T.gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers.

To undergo some evaluations, Infants with serologic evidence of infection are made to have extensive clinical evaluation and received one year of treatment. Through that 1000 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 520 infants, 500 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three).

Congenital toxoplasmosis, a protozoan infection that can result in blindness and mental retardation. Most infected new-borns have no symptoms at birth, but serious clinical manifestations can develop during childhood and early adulthood. By the age of 20, up to 85 percent have had chorioretinitis, including many who were free of symptoms at birth. Because congenital toxoplasma infection does not usually produce recognizable signs of infection at birth, we were concerned by the fact that most cases remain untreated because they are not detected by routine clinical examination.

Therefore, serologic screening is the best way to identify infants who should receive therapy, adding a toxoplasma-specific IgM assay to the battery of screening tests carried out on the universally collected new-born “filter-paper” specimens. We report the results of our serologic screening for congenital toxoplasma infection, the spectrum of initial clinical and laboratory findings in infected new-borns, and the clinical outcome of empirical treatment with antitoxoplasma chemotherapy.

ANTI-RETROVIRAL TREATMENT IN PREGNANACY

The world affected with HIV is reaching trillions where the treatment for HIV especially with Pregnant Women is of current trends which hit the target successfully aiming with Progression. The main objective of this study is to describe the current trends in treating the HIV during Pregnancy and changes in Socio-demography among Pregnant Women with HIV over the past years.

The group of data Collected from the National Program on Surveillance on Antiretroviral Treatment in Pregnancy in Italy says that the changes were found and analysed in antiretroviral treatment, population characteristics, maternal immune-virologic status and new-born clinical parameters. A total of 981 HIV-infected mothers who delivered between the recent years of about 2008- 2015 were evaluated. The ratio of women receiving at least three antiretroviral drugs at delivery increased significantly from 63.0% into 95.5% in 2012–2014, paralleled by a similar upward trend in the proportion of women who achieved complete viral suppression at third.

The co-formulation of zidovudine plus lamivudine remained the most common nucleoside backbone in pregnancy, even if a significant increase in the use of tenofovir plus emtricitabine was observed in more recent years. Starting from 2003, nevirapine prescription declined, paralleled by a significant rise in the use of protease inhibitors (PI), which were present in more than 60% of regimens administered in recent years. Nelfinavir was progressively replaced by ritonavir-boosted PIs, mainly lopinavir. No significant changes in preterm delivery, Apgar score, birth weight, and birth defects were observed during the study period, and the rate of HIV transmission remained below 2%. These data demonstrate a significant evolution in the treatment of HIV in pregnancy. Constant improvements in the rates of HIV suppression were observed, probably driven by the adoption of stronger and more effective regimens and by the increasing options available for combination treatment.

PEDIATRIC THERAPEUTIC YOGA – IMPROVING THE QUALITY OF LIFE IN CHILDREN WITH CANCER

Children can benefit from a regular yoga practice. Children hospitalized with oncological diagnoses are at high risk for developing decreased mobility, fitness, balance, and strength due to decreased functional activity as they undergo treatment. Induction therapy is the first step in cancer treatment, which is followed by additional therapies such as chemotherapy, radiation, and stem cell transplants. Once cancer is in remission, maintenance therapy is used to prevent a relapse. Children with one of the most common childhood cancers, acute lymphoblastic leukemia, often receive chemotherapy for 2.5 to 3.5 years. Side effects of chemotherapy as a treatment for cancer include delayed growth and development, depression and anxiety, chronic pain, hearing loss, weakness in bone structure, cardiovascular and heart problems because of chemotherapy and radiation to the spine or chest wall, scarring of lung tissue and increased risk of lung inflammation and infection, and muscle wasting and decreased balance in the lower extremities.

Limited information on guidelines for physical activity for children undergoing oncology treatment is available. Children are likely to have individualized responses to exercise programs regardless of the type of cancer and stage of the disease and require an individual exercise prescription. Participation in a structured therapeutic exercise program can provide a safe environment in which Pediatric oncology patients can exercise at a level appropriate for their unique needs. Cancer survivors who participate in exercise programs during treatment may be more motivated to continue exercising if regular exercise is experienced as a positive change in quality of life and physical fitness. Low-impact exercise programs have been beneficial in improving physical activity level and reducing fatigue in cancer patients undergoing treatment for hematological malignancies. Children with oncological diagnoses who received stem cell transplants demonstrated improved maximal oxygen consumption as a response to exercise. Exercise programs that stress balance have been found to improve lower extremity balance, strength, and proprioception as much as more traditional exercise programs.  Results from previous studies on exercise for Pediatric oncology patients suggest that many patients had lower levels of physical activity and perceived quality of life during and after cancer treatment.

Yoga is a low-impact exercise that has been incorporated into Pediatric exercise programs for strength, balance, pain control, and quality of life. Studies are needed to determine the efficacy of yoga as part of a low-impact exercise program for children with cancer. Prolonged periods of treatment affect quality of life for children with oncological diagnoses. Information on how exercise affects quality of life must be gathered to support the development of appropriate exercise programs for this population.