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The Beneficial Effects of Early Dexamethasone Administration in Infants and Children with Bacterial Meningitis

BACKGROUND In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Childrens Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.

Serial serum C-reactive protein to monitor recovery from acute hematogenous osteomyelitis in children

Serial C‐reactive protein (CRP) and erythrocyte sedimentation rate determinations were compared with clinical course and outcome at 1 to 2 months in 63 children with acute hematogenous osteomyelitis. High CRP values (163 \pm 108 mg/liter) on admission began to descend after the second day of treatment. From the fourth day on higher (P = 0.03 to P = 0.0001) CRP values distinguished a complicated from an uneventful course of acute hematogenous osteomyelitis and the patients symptomatic at follow‐up (P = 0.003 to P = 0.0001) from asymptomatic ones. Children who developed extensive radiographic changes had elevated CRP values for a longer time (32 \pm 13 days) than children with typical changes (11 \pm 6 days, P = 0.0001). Erythrocyte sedimentation rates did not identify the type of clinical course but higher values on Days 4 to 7 distinguished children symptomatic at follow‐up (P = 0.02) from asymptomatic ones. Monitoring serial CRP values can alert the physician to complications and predict outcome earlier than clinical signs or roentgenograms.

Systemic cytokine response in children bitten by snakes in Costa Rica

Background To characterize the host response to venom from snakes of the familyViperidaein Costa Rica, we investigated the release of cytokines: IL-1, IL-6, IL-8, TNF-α, MIP-1β, and RANTES in pediatric patients who were bitten by a snake. Methods Patients were included in this study if they were admitted to the hospital within 24 hours of the snakebite. Blood samples were taken immediately on admission to the hospital, and then at intervals of 3, 12, and 24 hours, and on days 3, 5, and 7 after the accident. Patients received gentamicin plus clindamycin or gentamicin plus penicillin intravenously for a minimum of 3 days or longer if necessary. IL-1, IL-8, TNF-α, MIP-1β, and RANTES were determined by monoclonal antibody-based ELISAs, while IL-6 was determined by bioassay. Results Eighteen patients were included in this study; 15 were bitten byBothrops asperand three byB. lateralis. Eleven patients were male. Median (range) age was 9 (1–12) years. Nine patients had detectable serum concentrations of IL-6 (200 pg/ mL) and IL-8 (51 pg/mL) on admission, increasing to 500 pg/mL and 115 pg/mL for IL-6 and IL-8, respectively, during the first 12–24 hours. Cytokine concentrations returned to normal or undetectable ranges by 72 hours. TNF-α concentrations peaked at 12 hours (mean: 48 pg/mL). Low, but detectable concentrations of MIP-1β were observed in some patients at various time intervals (48 pg/mL), whereas IL-1 was not detectable at any time point. Regulated on Activation Normal T cell Expressed and Secreted (RANTES) concentrations were evaluated in only five patients, being elevated in all of them. Patients with elevated cytokine concentrations required early fasciotomy (<24 hours after the accident) more often than those who had normal or undetectable cytokine concentrations (P < 0.05). There were no statistically significant associations between severity of envenomation, or outcome, and elevated serum cytokine concentrations (P > 0.05). Conclusions Bothropssp snake venoms induce clinical and pathophysiologic alterations similar to acute trauma, with release of proinflammatory cytokines. A better understanding of the role of the inflammatory response could lead to the development of new therapeutic strategies to improve the outcome in snakebitten patients.

Albendazole therapy for Microsporidium diarrhea in immunocompetent Costa Rican children.

Background: Microsporidia comprise a large group of obligate intracellular parasites. Although several species have emerged as opportunistic agents in immunocompromised patients, cases have also been reported in immunocompetent patients. Methods: During 21 months, we conducted a randomized, open label study in 200 children hospitalized with Microsporidium subacute diarrhea. Patients had prolonged, nonbloody, nonmucoid diarrhea, with ≥10 bowel movements/day for >10 days. Patients had negative rotavirus tests, bacterial stool cultures and sugar reductive tests in feces. Stool examinations to rule out Giardia intestinalis and intestinal nematodes were performed. Microsporidium was identified by light microscopy in stool specimens stained with Giemsa and Weber techniques. One hundred patients received oral albendazole (15 mg/kg/day twice a day for 7 days) and 100 patients received only supportive therapy. Results: Both groups were comparable regarding gender, age, clinical evolution and weight. Median (range) age was 24 (6–36) months. All children had abdominal pain, nausea, vomiting and anorexia. The primary endpoint, defined as clinical improvement within 48 h of initial therapy, occurred in 95 and 30% of the albendazole-treated and untreated patients, respectively (P < 0.05). There was a significant decrease in stool frequency, reduction of clinical findings and decrease in Microsporidium parasites in stool specimens of children treated with albendazole compared with the untreated group. Median (range) duration of diarrhea was 5 (3–7) days in albendazole-treated patients versus 10 (8–15) days in untreated patients (P < 0.05). Conclusion: Albendazole therapy was effective in improving the clinical manifestations and decreasing the duration of the illness of children with diarrhea caused by Microsporidium.

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Abstract Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661.

Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial

In children aged 6 months to <10 years, the incidence of influenza-like illness associated with respiratory syncytial virus was 7.0 per 100 person-years. The highest burden occurred in older infants and children, which may inform vaccination strategies.

Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

Summary Background Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children.