Safety and immunogenicity of a quadrivalent meningococcal conjugate vaccine (MenACYW-DT): a multicenter, open-label, non-randomized, phase III clinical trial.

OBJECTIVE: To assess the safety and immunogenicity of a quadrivalent meningococcal (groups A,C,Y,W) polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-DT) in India. DESIGN: Open-label, descriptive, non-randomized study. SETTING: Three medical college hospitals, one each in New Delhi, Bengaluru and Mumbai, India. PARTICIPANTS: 300 healthy, vaccine-naïve participants (100 children aged 2-11 years, 100 adolescents aged 12-17 years, and 100 adults aged 18-55 years). INTERVENTION: One dose (0.5 mL) of MenACYW-DT administered intramuscularly. MAIN OUTCOME MEASURES: Serum bactericidal antibody titers against A, C, Y, and W were measured before and after MenACWY-DT vaccination. Safety data were also collected. RESULTS: Thirty days post-vaccination, geometric mean titers rose across all serogroups. Most participants had protective titers >8 (1/dil) across the four serogroups. The percentage (95% CI) achieving >8 (1/dil) in the Adolescent Group was typical - A: 96.9% (91.2%; 99.4%); C: 96.9% (91.2%; 99.4%); Y:100% (96.3%; 100%); W:100% (96.3%; 100%). In general, solicited reactions were mild and short-lived. Unsolicited events were uncommon and unrelated to vaccination. CONCLUSIONS: MenACYW-DT was well tolerated and elicited a robust and protective immune response 30 days post-vaccination against meningococcal serogroups A, C, Y, and W-135 in the Indian study participants aged 2-55 years.

Immunoglobulin levels and CD4 / CD8 counts in ß- thalassemia major.

OBJECTIVE: This cross-sectional study determined the CD4, CD8 counts and serum immunoglobulins in transfusion dependent b - thalassemic patients, and correlated them with anti-HIV, anti-HCV and HBsAg status, number of transfusions, iron overload and splenectomy. METHODS: Patients with acute or chronic diseases (except HIV, Hepatitis B and C), on immunosuppressive drugs or vaccinated within one month prior to study were excluded. CD4, CD8 counts and serum Immunoglobulins were documented. RESULTS: Increasing transfusions led to higher IgA and IgM as well as a decline in CD4 and CD8 levels. Higher ferritin correlated with high IgM. CD4, CD8 and IgA were significantly higher in splenectomized subjects. HCV correlated significantly with lower IgA values. CONCLUSION: Higher transfusion requirement, iron overload, splenectomy and HCV infection correlated with alterations in different immunological parameters.

Hidradenitis suppurativa in a HIV-infected child.

Hidradenitis suppurativa (HS), a painful and chronic condition, commonly occurs in women and coincides with post-pubertal increase in sex hormones. A 13-year-old pre-pubertal HIV-infected male child presented to our clinic with a discharging right axillary lymph node swelling. The biopsy of the lesion showed features of HS. The patient was treated with oral antibiotics, oral steroids, and local antibiotic wash. Though the patient responded to this treatment, the clinical response was not adequate and the lesion recurred. Subsequently, the child was started on antiretroviral therapy (zidovudine, lamivudine, and nevirapine). Following these medications, the lesions healed and had not recurred till we last examined the child. Thus, this is a rare presentation of a known condition in an HIV-infected pre-pubertal male child, which did not respond to usual modalities of treatment and had to be treated with antiretroviral therapy.

Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial performance in mice.

Developmental reading disorder (RD) affects 5-10% of school aged children, with a heritability of approximately 60%. Genetic association studies have identified several candidate RD susceptibility genes, including DCDC2; however, a direct connection between the function of these genes and cognitive or learning impairments remains unclear. Variants in DCDC2, a member of the doublecortin family of genes, have been associated in humans with RD and ADHD and Dcdc2 may play a role in neuronal migration in rats. In this study, we examined the effect of Dcdc2 mutation on cognitive abilities in mice using a visual attention and visuo-spatial learning and memory task. We show that both heterozygous and homozygous mutations of Dcdc2 result in persistent visuo-spatial memory deficits, as well as visual discrimination and long-term memory deficits. These behavioral deficits occur in the absence of neuronal migration disruption in the mutant mice, and may be comorbid with an anxiety phenotype. These are the first results to suggest a direct relationship between induced mutation in Dcdc2 and changes in behavioral measures. Dcdc2 mutant mice should prove useful in future studies designed to further dissect the underlying neural mechanisms that are impaired following Dcdc2 mutation.

Isolation of Streptobacillus moniliformis from the blood of a child with acute lymphoblastic leukaemia.

This is an unusual report of isolation of Streptobacillus moniliformis from the blood of a male child with acute lymphoblastic leukaemia. No history of rat bite was there, but rats were present in the house. The possible source of infection may be food or water contaminated with rat excreta. Whether this bacteria can cause opportunistic infection in leukaemic patients, need to be evaluated further.

Pseudomonas diarrhea in a child suffering from acute lymphatic leukemia.

A female child admitted to hospital, diagnosed with acute lymphatic leukemia - CALLA positive, developed loose motions. Her stool culture and blood culture grew Pseudomonas aeruginosa. Although the diarrhea subsided after five days, the stool culture repeatedly grewP. aeruginosa for more than one month, in spite of treatment. Even though diarrhea due to Pseudomonas is rare, it can yet be seen in immunocompromised patients and is also associated with neutropenic enterocolitis. Stool specimens of all leukemia patients on chemotherapy and suffering from diarrhea, should be sent routinely for culture, so as to find out the exact cause of the diarrhea. Proper reporting will enable the clinicians to start appropriate antibiotics, thereby, reducing the morbidity and mortality of the leukemia patients.

Acquired pure red cell aplasia in a child.

Primary acquired pure red cell aplasia is a rare occurrence in childhood. An eleven-year old boy presented to us with pallor, which required multiple packed red cell transfusions. He did not have hepatosplenomegaly, jaundice or lymphadenopathy. Bone marrow examination revealed the diagnosis of pure red cell aplasia. All possible investigations were done to exclude secondary causes of pure red cell aplasia. No secondary cause was found on investigations. Rheumatoid factor and anti-nuclear antibodies were positive. He was started on oral steroids, to which he did not respond. He was then given cyclosporine A. Response to cyclosporine was dramatic and the child now does not require any transfusions.

Clinical spectrum of HIV infection.

OBJECTIVE: To study the modes of transmission of pediatric HIV infection, to categorize clinical manifestations and to compare clinical spectrum of perinatal with transfusion acquired HIV infection. DESIGN: Case series study. SETTING: Hospital based pediatric HIV clinic. METHODS: Children confirmed to have HIV infection were evaluated and relevant details recorded. RESULTS: 55 children were enrolled of whom 41 (74.5%) had perinatal transmission of HIV, 12 (21.8%) were infected through blood transfusions and 2 (3.6%) through other routes. Thirty-seven (90.2%) of the 41 perinatally infected children were symptomatic. Tuberculosis was seen in 25 (67.5%) of these children and failure to thrive in 18 (48.6%). Nonspecific features such as recurrent bacterial infection, oral candidiasis and chronic diarrhea were other manifestations. Eight (26.3%) of the 30 children available for follow up for a median period of 9 months died at the median age of 8.5 months. Amongst the transfusion acquired HIV infection, 11 (91.6%) of the 12 were asymptomatic at presentation. Six (50%) of these children died at the median age of 3 years and the remaining 6 had no major symptoms at a median follow up of 3.5 years. CONCLUSION: Perinatal route is the major route of HIV transmission in children and clinical manifestations are different from those of adults.

Congenital erythrocytosis with elevated erythropoietin level: an incorrectly set "erythrostat"?

PURPOSE: A child who was extensively evaluated for polycythemia is reported. Polycythemia, or erythrocytosis, is seen rarely in children. The mechanisms for congenital and/or familial erythrocytosis are discussed. PATIENT AND METHODS: A 10 1/2-year-old white girl was referred for evaluation of polycythemia, which was detected incidentally during an emergency room visit for a febrile illness. She underwent extensive evaluation to determine the cause of the polycythemia. The literature was reviewed to determine the occurrence of congenital and/or familial erythrocytosis in children and its various causes. RESULTS: Despite extensive evaluation, no specific cause of the erythrocytosis could be determined in our patient. The erythrocytosis appeared to be secondary to an inappropriately elevated serum erythropoietin concentration. Serum erythropoietin rose further after phlebotomy, suggesting nonautonomous hypersecretion. After a review of the literature, we hypothesize that she had an inappropriate erythropoietin expression related to an abnormality in the renal oxygen-sensing mechanism governing erythropoietin synthesis. DISCUSSION: A discussion of congenital and familial erythrocytosis is presented, and a review of the literature regarding the possible mechanisms causing erythrocytosis is included.

Intussusception in an infant with acute lymphoblastic leukemia: a case report and review of the literature.

PURPOSE: An ileocecal intussusception developed in a 7-month-old infant with acute lymphoblastic leukemia (ALL) during induction therapy. Gastrointestinal complications, especially intussusception, are rare in children with ALL. PATIENT AND METHODS: The history of a 7-month-old white boy with ALL in whom an ileocecal intussusception developed 1 week into induction chemotherapy was reviewed. In addition, a literature search was performed to determine the prevalence of this complication in children with acute leukemia. RESULTS: On day 4 of induction chemotherapy for B-lineage ALL, the infant developed abdominal distension with hypoactive bowel sounds. After a barium enema and abdominal computed tomography scan, the symptoms were determined to be caused by an ileocecal intussusception. Chemotherapy was resumed 1 week after immediate surgical intervention (reduction of intussusception and resection of the "leading edge") with an uneventful post-operative recovery. Histopathologic examination of the resected edge revealed an intact mucosa with areas of necrosis in the submucosa. This was associated with a dense lymphoid infiltrate composed of mature lymphocytes and leukemic cells, edema, and focal necrosis. Despite a 1-week delay in chemotherapy, a complete remission was documented at day 32. DISCUSSION: The prevalence of intussusception in children with ALL and its possible etiology are discussed. The pathologic changes, clinical manifestations, and treatment outcome are briefly mentioned.

Anemia in newborn.

Various blood indices vary in a newborn as compared to older child or adult. It depends on the gestational age, day of life, maternal factors, mode of delivery and site of blood collection. Hemoglobin, HCT & MCV tend to be higher in newborns. They further increase in first 2 days of life. Reticulocytosis and presence of nucleated red cells are normally seen in first week of life. Neonatal anemia is a common problem in NICU. It is usually caused by either hemorrhage or hemolysis and rarely due to decreased production. Hemorrhage can be ante or intra or post natal and it could be external or internal. It could be acute or chronic. Management of acute severe hemorrhage includes packed cell transfusion. Hemolysis is usually due to isoimmune hemolysis, G6PD deficiency or rarely due to the hemoglobinopathy like alpha-thalassemia or due to spherocytosis. Usually patients will have indirect hyperbilirubinemia which needs phototherapy or exchange transfusion. Rarely congenital pure red cell aplasia can present at birth with physical anomalies and anemia. Treatment of neonatal anemia depends on the arteriology.

'NESTROFT'--an effective screening test for beta thalassemia trait.

OBJECTIVE: To evaluate the efficacy of NESTROFT (Naked Eye Single Tube Red Cell Osmotic Fragility Test) as a screening tool for detection of beta thalassemia trait. DESIGN: Prospective study. SETTING: Field camps in various parts of Gujarat and Maharashtra States. METHODS: A total of 2525 subjects were screened. NESTROFT, complete hemogram including red cell indices and calculation of Mentzer's Fraction (MF) and discriminant functions (DF1-4) were done in all subjects. HbA2 was performed in 830 initial subjects to compute sensitivity, specificity and predictive values for various parameters. RESULTS: NESTROFT (sensitivity 94.4%), as a single screening parameter was superior to any of the other evaluated parameters individually, besides being cost effective. Mean corpuscular volume (MCV) < 80 fl followed NESTROFT closely (sensitivity 93.7; p > 0.05). MCV < 75 fl had a significantly (p < 0.001) lower sensitivity (87.3%) in comparison to both of these parameters. In contrast, MF, DF1, DF2, DF3 and DF4 did not meet the requirements of a good screening test with sensitivity values of 66.2%, 54.9%, 47.2%, 64.1% and 55.6%, respectively. NESTROFT in combination with MCV < 80 fl proved 100% sensitive. However, the combination was not cost effective. CONCLUSION: NESTROFT is a sensitive, cost effective, rapid and reliable screening test for detection of beta thalassemia trait in a population.

Evaluation of naked eye single tube red cell osmotic fragility test in detecting beta-thalassemia trait.

The Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) was applied to 4 groups of subjects: (i) Normal; (ii) Proven beta-thalassemia trait carriers; (iii) Iron deficiency anemia; and (iv) other hemoglobinopathies, to evaluate its effectiveness as a screening test for beta-thalassemia minor. The test was successful in detecting 105/110 subjects with beta-thalassemia trait. The sensitivity of the test was 95.5% and specificity was 87%. The predictive value of the positive test was 70.5% and that of the negative test was 98.3%. NESTROFT was also positive in 9/17 subjects with HbS trait, in 3/3 subjects with HbD trait and in 1/1 subjects with HbE trait. The test proved to be simple, cheap, easy to perform and adaptable for field surveys, coming close to an ideal screening test for beta-thalassemia minor.