Influenza: Underestimated in Children Below 2 Years of Age.

Children under 2 years of age may receive antiviral therapy when influenza is suspected. Signs of influenza are frequently unclear and testing is indicated. The aim of the study was to assess the usefulness of clinical signs and the rapid influenza diagnostic test (RIDT) in diagnosing influenza and in choosing the appropriate treatment. In the 2015-2016 influenza season, 89 children under 2 years of age (56.7% of 157 children diagnosed with influenza) were hospitalized. There were 74 RIDT and 70 reverse transcription polymerase chain reactions (RT-PCR) performed for the purpose of diagnosis, either test per child. Eighty-three percent of children (74/89) presented with fever, 55.1% (49/89) with cough, and 39.3% (35/89) with both cough and fever. The RIDT was positive in 31.1% (23/74) of cases. The highest percentage of positive RIDT was within the first 24 h of disease, decreasing dramatically thereafter (70% vs. 13-17%, respectively). The RIDT shortened the time to diagnosis by 43.8 h/patient (an average €149 gain in treatment costs). The mean delay for RT-PCR-based diagnosis was 33.5 h/patient (an average €114 loss in treatment costs). We conclude that clinical signs have a low diagnostic sensitivity in children under 2 years of age. Likewise, RIDT is of low sensitivity, being diagnostically useful only in the first 24 h. The PCR is recommended for the diagnosis, but that requires a constant access to the method.

Soluble urokinase plasminogen activator receptor: an indicator of pneumonia severity in children.

Enhanced level of soluble urokinase plasminogen activator receptor (suPAR) level has been associated with activation of the immune system. It may be a novel biomarker for pneumonia severity, yet data on this subject are limited. In the present study we seek to determine the suPAR level in hospitalized children with community-acquired pneumonia (CAP), its correlation with pneumonia severity, and to compare the suPAR level between pneumonia and healthy conditions. The study encompassed a total of 596 children: 447 with pneumonia and 119 healthy. suPAR was measured in 227 out of the 447 pneumonia patients and in all healthy subjects. We used clinical indicators (fever, time for defeverscence, heart and breath rate, saturation, and length of antibiotic treatment and of hospitalization) and laboratory indicators (CRP, procalcitonin, white blood cell count, and sodium) to assess the CAP severity. The finding were that the suPAR concentration in children with pneumonia was significantly higher (median 7.11 ng/mL) than in healthy individuals (4.68 ng/mL). We found a positive correlation between the suPAR and the following factors: fever, time for defeverscence, length of hospital stay, and elevated CRP and procalcitonin levels. There was a reverse correlation with sodium concentration and capillary blood saturation. Moreover, the suPAR level was significantly higher in children with a severe course of pneumonia compared with those having non-severe pneumonia (7.79 vs. 6.87 ng/mL; p = 0.006). In conclusion, suPAR elevation is observed in pneumonia and may reflect its severity.

Hyponatremia in children hospitalized due to pneumonia.

The aim of this study was to evaluate the relation between hyponatremia (HN) and severity of community-acquired pneumonia (CAP) in children. The study consisted of a retrospective analysis of medical records of 312 children (165 boys, 147 girls) aged 33 days to 16 years, hospitalized with CAP. The children were divided into two age-groups: under and over the age of four. Clinical findings such as breath frequency, heart rate, capillary blood saturation, body temperature, time for defeverscence, duration of antibiotic treatment and hospital stay, and the serum inflammatory markers WBC, neutrophil count, CRP, and procalcitonin level were used as the disease severity predictors. The results demonstrate that hyponatremia was observed in 104/312 (33.3 %) patients. Children with HN of both age-groups had higher neutrophil counts (6.96 vs. 5.73*10(3)/µL; p < 0.05 and 12.46 vs. 8.22*10(3)/µL; p = 0.01), those aged > 4 had higher WBC (15.85 vs. 11.0*10(3)/µL; p = 0.02), and those aged < 4 had a lower lymphocyte count (3.74 vs. 4.75*10(3)/µL; p = 0.02) than children without HN. Hyponatremic children had higher CRP (28.82 mg/L vs. 9.18 mg/L; p < 0.01) and tended to have higher procalcitonin (0.31 vs. 0.19 ng/mL) than children without HN. Body temperature was higher (38.6 vs. 37.6 °C; p < 0.01) and duration of hospitalization was longer (9 vs. 8 days, p = 0.01) in hyponatremic compared with non-hyponatremic children. There was no correlation between the sodium level and either breath frequency, heart rate, capillary blood saturation, time for defeverscence, or time of antibiotic treatment. We conclude that hyponatremia is a frequent finding in CAP and seems associated with the disease severity.

Soluble receptor for urokinase plasminogen activator in community-acquired pneumonia in children.

Community-acquired pneumonia (CAP) is a leading single cause of mortality in children under 5 years of age. In search of new diagnostic markers, soluble urokinase plasminogen activator receptor (suPAR) seems to offer promise as a novel clinical tool. The goal of the present study was to assess the relation between suPAR and the severity of CAP. suPAR was measured in 74 (39 males, 35 females) patients aged from 1 month to about 15 years. Correlation between the level of suPAR and inflammatory markers (white blood cell, neutrophil count, C-reactive protein-CRP, and procalcitonin-PCT) was assessed by Spearmann's rank coefficient. We found that the median suPAR level in children with pneumonia was 8.29 ng/mL (range 2.44-18.31 ng/mL). In the multivariate logit model, age and CRP level were statistically important. The older children (age above the median value) had higher suPAR (above the median value) less frequently than the younger children (OR = 0.31), whereas the children with greater CRP values (above the median value) had higher suPAR levels than the children with lower CRP concentration (under the median value) (OR = 4.54). There was also a positive correlation between suPAR and PCT levels. In conclusion, we demonstrate a positive correlation between serum suPAR and the non-specific inflammatory markers CRP and PCT in the community acquired pneumonia in children.

Diminished presentation of complement regulatory protein CD55 on red blood cells from patients with hereditary haemolytic anaemias.

INTRODUCTION: Hereditary haemolytic anaemias (HHA) encompass a heterogeneous group of anaemias characterized by decreased red blood cell survival. The aim of this study was to evaluate the status of red blood cell (RBC) surface molecules known or previously proposed to participate in preventing premature RBC clearance, analysing erythrocytes from patients with two types of HHA: hereditary spherocytosis (HS) and microcytosis. MATERIAL/METHODS: Relative binding of five monoclonal antibodies (mAbs), anti-CD55, anti-CD59, anti-CD44, anti-CD47 and anti-CD58, was evaluated in erythrocytes of patients with HS and hereditary microcytosis, using flow cytometry. The amount of CD55 protein was assessed by semi-quantitative Western blots densitometry analysis. RESULTS: The majority of both HS and microcytic patients demonstrated significant reduction of anti-CD55 binding by erythrocytes (average 23% and 19%, respectively, P < .001), with no concomitant anti-CD59-binding deficiency. Anti-CD44, anti-CD47 and anti-CD58 binding was within the healthy control range or was slightly decreased. CONCLUSIONS: This study provides evidence supporting the presence of erythrocytes deficient in CD55 presentation in HS and hereditary microcytosis. Moreover, deficiency of CD55 antigen presentation on RBC does not correlate with the amount of CD55 in RBC membrane. Further studies using molecular techniques will clarify the exact participation of CD55 deficiency in premature RBC clearance in HHA.

Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

BACKGROUND: Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. METHODS: This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. RESULTS: Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. CONCLUSION: PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.

The role of the soluble urokinase plasminogen activator (suPAR) in children with pneumonia.

Although pneumonia is one of the most important health problems in children, there is still no widely accepted disease severity score, the data on the correlation between the conventional inflammatory markers or chest X-ray and the disease severity remain disputable, and thus, there is an urgent need for a new pneumonia biomarker. The soluble urokinase plasminogen activator (suPAR) is a soluble form of the urokinase plasminogen activator that plays an important role in the innate host defense in the pulmonary tissue. suPAR levels have been associated with a general activation of the immune system rather than with a particular etiological factor. suPAR has a high prognostic value in critically ill patients, especially with sepsis, but there is a growing number of studies focusing on suPAR in respiratory diseases. The aim of this review is to summarize the knowledge on the role of the suPAR/uPAR in lung pathology and its possible use in pneumonia in children.

Immunogenicity of subunit trivalent influenza vaccine in children with acute lymphoblastic leukemia.

BACKGROUND: The aim of this study was to assess humoral response to influenza vaccine in children with acute lymphoblastic leukemia. METHODS: Studies were performed in 25 patients previously vaccinated against influenza (Group A) and in 20 children who had never been immunized before (Group B). In Autumn, 1996, they were vaccinated with subunit trivalent influenza vaccine containing 15 microg of hemagglutinin of A/Singapore/6/86, A/Wuhan/359/95 and B/Beijing(184/93. Antihemagglutinin (HI) and antineuraminidase antibody titers were determined before immunization and 3 weeks and 6 months after vaccination by the hemagglutinin inhibition test and the neuraminidase inhibition test. All results were presented as the geometric mean titer of antibodies, mean fold increase of antibody titer, protection rate and response rate. RESULTS: In Group A mean fold increase of HI antibodies ranged from 17.2 to 26.7 three weeks after vaccination and from 22.1 to 38.2 six months after vaccination, while in Group B it ranged from 15.7 to 22.6 and from 30.3 to 39.3, respectively. In the case of neuraminidase, mean fold increases for Group A varied from 9.2 to 13.2 three weeks after immunization and from 15.6 to 21.1 six months after vaccination, whereas for Group B they varied from 5.5 to 8.3 and from 14.4 to 23.4, respectively. Six months after vaccination the proportion of subjects with HI antibodies > or = 1:40, as well as those with at least 4-fold increase of HI antibody titers, ranged from 68 to 100% in Group A and from 90 to 100% in Group B. No vaccinated child was infected with the influenza virus; the vaccine was well-tolerated and did not cause any adverse reactions. CONCLUSIONS: The results obtained in this study indicate that influenza vaccine is immunogenic in patients with acute lymphoblastic leukemia, despite their serious disease.

Kinetics of humoral response in children with acute lymphoblastic leukemia immunized with influenza vaccine in 1993 in Poland.

A total of 49 children with acute lymphoblastic leukemia were immunized with a purified subvirion trivalent influenza vaccine (Wyeth-USA) and monitored for hemagglutination inhibition (HI) and neuraminidase inhibition (NI) antibodies before vaccination, and then three weeks and six months after vaccination. Results for HI antibodies were evaluated as geometric mean titre (GMT), mean fold antibody increase (MFI), protection and response rates and those for NI antibodies as geometric mean titre (GMT) and mean fold antibody increase (MFI). Six months after vaccination GMT for hemagglutinin 1 (H1) was much higher than previous values. GMT for hemagglutinin 3 (H3) and hemagglutinin B (HB) was lower than three weeks after vaccination, but much higher than the original values. In the control group GMT for H1 was on a low level all the time and for H3 and HB it was lower when compared with the original values. The proportion of vaccines to antibodies > or = 40 ranged between 45% and 88%. Six months after vaccination GMT for neuraminidase 1 (N1) increased when compared with the second sampling; for neuraminidase 2 (N2) and neuraminidase B (NB) it was slightly lower. In the control group GMT for all antigens was on a low level all the time. The results point to a significant seroconversion for both components after vaccination when compared with the control group.

[Vaccination against hepatitis B in children with chronic hematologic diseases treated with immunosuppression]. / Szczepienia przeciw wirusowemu zapaleniu watroby typu B u dzieci z przewleklymi chorobami krwi leczonych immunosupresyjnie.

Prevention of hepatitis B infection is an important factor in the successful management of cancer and aplastic anaemia cases. Our result suggested that children with Hodgkin's disease and solid tumors vaccinated during early stage of immunosuppressive therapy are good responders to hepatitis B vaccine. Active immunisation with hepatitis B vaccine (Engerix B), was also effective in children with leukaemia after completing immunosuppressive therapy. Protective levels of antibodies remained 6 years after vaccination. Vaccination according to shortened schedule (0-10-20 days) was not effective in these children. Passive immunisation is indicated in children with chronic neoplastic haematological diseases during immunosuppressive therapy. In 6 children the lack of seroconversion after vaccination was due to immune disorders.

[Prevention of hepatitis B by passive immunization of children with chronic hematologic disease immunoglobulin]. / Zapobieganie metoda biernej immunizacji zakazeniu wirusem zapalenia watroby typu B u dzieci chorych na przewlekle choroby krwi.

In order to prevent the hepatitis virus B (HBV) infection, in 66 children aged from 6 months to 14 years with acute and chronic leukaemias, Hodgkin's and non-Hodgkin's lymphomas, testicular tumours, and aplastic anaemia a specific immunoglobulin was used intravenously (Hepatect made by Biotest). Hepatect was given every month to children with proliferative diseases throughout the whole time of intensive chemotherapy, and to children with aplastic anaemias during the administration of antilymphocytic globulin, prednisone, and Anapoln. Fourteen children were excluded from the analysis due to lack of systematic follow-up. Among 52 studied children, in most cases considerable fluctuations were observed of antibody concentration, the maximal values of which were of 150 mIU/ml. In 35 children, with the exception of sporadic falls, the anti-HBs antibody level remained level was noted, in two cases the presence of antibodies was revealed only sporadically. One of these children was infected with HBV. In all, three children were infected (5.76% of all children in the studied group). Perhaps the use of higher doses of Hepatect and its more frequent administration in children showing low anti-HBs level after routine doses might reduce further the incidence of infection.

[Hepatitis B in children with leukemia and lymphoma]. / Zakazenie wirusem zapalenia watroby typu B u dzieci chorych na bialaczki i chloniaki.

In the time period from February to October 1988 the indicators of hepatitis virus B infection, transaminase activity, and bilirubin level were studied in 89 children with acute leukaemias and malignant lymphomas. The age of the children was from 7 months to 16 years. Fifteen children were examined before starting the treatment with cytostatics, 48 during intensive chemotherapy, and 26 during maintenance treatment. HBV markers were found in 53 children during intensive therapy and maintenance treatment. Out of 36 children with negative HBV infection markers 31 were examined before starting the treatment with cytostatics or during the first 6 months of treatment. Nine out of 53 children in whom HBV infection markers were found had aminotransferase activity raised over 100 u/l and/or bilirubin level over 5 mg/dl and in nine cases transaminase activity and bilirubin level were raised only slightly (below 100 u/l and below 5 wg/dl). In 53 children the results were normal. The high incidence of HBV infection in children with acute leukaemias and lymphomas indicates the necessity of routine prophylactic treatment in this group of patients.

[How to improve the results of treatment of myelodysplastic syndromes in the studies of Polish pediatric leukemia/lymphoma group]. / Co zrobic dla poprawy wyników leczenia zespolów mielodysplastycznych w Polskiej Pediatrycznej Grupie ds. Leczenia Bialaczek i Chloniaków.

Fourty two children with myelodysplastic syndrome (MDS) treated in seven centres of The Polish Paediatric Leukaemia/Lymphoma Study Group in period 1975-1998 were included in the study. In 16 children RAEB-T, in 3 CMML, in 10 RA and in 13 RAEB were diagnosed. BMT is the best therapy for children with MDS. For children, who have not a donor for BMT, Roacutan therapy seems to be the most effective.

[The fate of children after discontinuation of treatment for acute lymphoblastic leukemia]. / Losy dzieci po odstawieniu leczenia ostrej bialaczki limfoblastycznej.

Among 1879 children with the diagnosis of acute lymphoblastic leukaemia made up to Dec 31 1987 in 863 cases (45.92%) treatment was discontinued. They were followed up till Dec 31 1989. The median follow-up was 3 years and 14 months. In 811 cases the treatment was discontinued during the first complete remission, in 56 cases after a relapse during initial treatment. In the time period when the programmes St. Jude and LSA2L2 were used the per cent of children with treatment withdrawal was 38.22%, but it rose to 53.01% when a more intensive programme BMF had been introduced. The probability of 7-year disease free survival after treatment discontinuation was 69.5% and 76.2% respectively. In 186 cases (21.6%) relapses developed., mostly in the first year after treatment discontinuation, but even after 7 years the risk of relapse was 2.46%. Ninety-six children (11.2%) died, 761 (88.8%) are alive, among them 671 in the first complete remission. Apart from therapy intensity, a statistically significant beneficial effect on disease free survival had discontinuation of treatment during the first complete remission, and sex--the prognosis was better in girls. In three cases secondary neoplasms were found.

[Second cessation of therapy in children with acute lymphoblastic leukemia]. / Drugie odstawienie leczenia u dzieci z ostra bialaczka limfoblastyczna.

In the group of 63 children in whom a relapse of ALL after first suspension of treatment occurred, and in whom a repeated cessation of therapy had place, 46.2% of patients had probability of a prolonged symptomless survival. The children with an isolated extramedullary relapse had a greater chance for a DFS of 7 years, than those with a relapse in the bone marrow (p = 0.05). The patients with a relapse occurring after the first cessation of treatment of ALL should be treated as intensively as newly diagnosed cases, because they have a real possibility for a prolonged survival during remission phase of disease.

[Vaccination against influenza in children with acute lymphoblastic leukemia]. / Szczepienia przeciw grypie dzieci chorych na ostra bialaczke limfoblastyczna.

In November and December 1993, 49 children, ages 4 to 20, suffering from acute lymphoblastic leukemia, were vaccinated against influenza in the Department of Paediatric Haematology and Oncology, Medical Academy in Warsaw. These patients were vaccinated either in the course of maintenance treatment or after treatment. Each dose of Wyeth USA subunit trivalent influenza vaccine contained 15 micrograms of hemagglutinin of strains recommended for that season. The level of antibody production was determined in pre- and post vaccination sera in the group of children with leukemia and the control group. It was determined that in the investigated group, the GMT increased more than four times for hemagglutinins H1N1 and H3N2. A somewhat lower increase was observed in case of hemagglutinin HB. The proportion of subjects protected after vaccination was 35% for hemagglutinin H1N1, 76% for H3N2 and 100% for HB. The response rate was 33% for hemagglutinin H1N1, 47% for H3N2 and 45% for HB. In the control group the proportion of subjects protected and the response rate were very low. The results show the significant immunological efficacy of the vaccine used in the vaccination against influenza in high risk groups.

Acute lymphoblastic leukemia in children below two years of age.

From among 1464 children with ALL 167 (11.4%) at diagnosis had two or less than two years, 53 of them were infants. Most of them had a great tumor bulk, 15 had initial CNS infiltration and 31 WBCc greater than or equal to 100000/ML. 66 were treated according to St. Jude or LSA2L2 programs (the I group), 101 according to BFM programs (the II group). Complete remission was obtained in 85% of patients. In 63 children relapses occurred in the course of treatment whereas in 5 after the therapy cessation. In majority of cases, there were isolated relapses, mostly, they involved bone marrow. CNS involvement was found, in both mixed and isolated relapses, in 28 children (20%). 64 children are alive, in 43 of them the therapy was stopped. Kapla-Meier estimates for event free survival (EFS) after 8 years were 19 +/- 4.7% in the first group vs 37.38 +/- 6.3% in the second group. Due to therapy intensification the treatment results have been improved (p = 0.05) but still they are not satisfactory, particularly in case of infants and children with WBC greater than or equal to 100000/ML. Analysis of the lot of children showed that apart from age at ALL diagnosis and the initial WBC the methods of treatment are also the prognostic factors.

Active immunization of children with leukemias and lymphomas against infection by hepatitis B virus.

Engerix B vaccine was administered to 54 children with leukemias and lymphomas aged from 2 to 15 years. In 36 cases chemotherapy was completely stopped, and 18 cases were receiving maintenance treatment. Engerix B was given at 0, 1, 2 and 6 months in a dose of 20 micrograms to children < 10 years, and 40 micrograms to older patients. The effectiveness of active immunization was demonstrated after complete therapy cessation in 88% of cases. The levels of antibodies determined 1 year after primary vaccination remained high, and in most of the vaccinated children they were > 1000 mIU/mL. In children vaccinated in the course of maintenance treatment the levels of antibodies did not give sufficient protection against infection.