Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.

A comparative trial of albendazole alone versus combination of albendazole and praziquantel for treatment of Trichuris trichiura infection.

A randomized clinical trial was conducted to compare the effectiveness of albendazole alone and albendazole combined with praziquantel in the treatment of Trichuris trichiura infection. The drug regimens consisted of single dose of albendazole 400 mg (A1, n=34), 3 days of albendazole 400 mg daily (A3, n=34), 5 days of albendazole 400 mg daily (A5, n=35), single dose of albendazole 400 mg plus praziquantel 40 mg/kg (AIP1, n=34), and 3 days of albendazole 400 mg plus praziquantel 40 mg/kg daily (A3P3, n=36). It was found that treatment with 3 or more consecutive days of albendazole with or without praziquantel resulted in a significant reduction in density of Trichuris eggs in stools while a single dose of such drug did not. Praziquantel was not shown to have synergistic or antagonistic effects with albendazole. A regimen of 400 mg of albendazole daily for 3 days was found to be the most suitable therapy for Trichuris infection.

Fluticasone propionate and bronchial hyperresponsiveness in childhood asthma.

Bronchial asthma is now agreed as being a chronic inflammatory disease of the airways. Inhaled steroids are widely accepted as a preventive medication in asthmatic patients of all ages and severity. However, the optimal use of inhaled steroids and the important issue of safety and efficacy still remain of concern, particularly in children. Recently, fluticasone propionate (FP) has been developed for use as an inhaled preparation for the treatment of asthma. Because of its high topical potency and increased lipophilicity, it is claimed that FP has an improved risk/benefit compared with other inhaled steroids. In order to evaluate the use of FP in children, we have studied the efficacy of high dose FP (500 microg/day) in asthmatic children. Thirteen children (9 boys and 4 girls), aged 7-17 years (10.8 +/- 2.6), were instructed to use a pressurized metered-dose inhaler connected to a Volumetric spacer. The standard methacholine bronchial challenge test was used as a principal outcome parameter. The PD20, a cumulative dose of methacholine inducing a 20% decrease in FEV1, was measured pre- and post-treatment with inhaled FP. After 4 weeks of FP, PD20 significantly increased from 21.6 +/- 14.3 inhalation unit to 106.6 +/- 78.5 inhalation unit (4.9 fold, p = 0.004) reflecting the improvement of airway reactivity. All subjects improved clinically. These results demonstrate that the anti-inflammatory action of FP 500 microg a day for four weeks can markedly reduce bronchial hyperresponsiveness, the basic physiologic abnormality in bronchial asthma.

A comparison of pain scales in Thai children.

Three commonly used pain scales, the visual analogue scale, the Wong-Baker Faces Pain Scale, and the Faces Pain Scale Revised were administered to 122 Thai children, of whom half were HIV infected, in order to assess their validity. These scales presented moderate to good correlation and moderate agreement, sufficient for valid use in Thai children.

Pain: a common symptom in human immunodeficiency virus-infected Thai children.

AIM: To determine the prevalence and characteristics of pain in Thai human immunodeficiency virus-infected children. METHODS: A cross-sectional study was performed at the HIV/AIDS outpatient clinic at the Queen Sirikit National Institute of Child Health, Bangkok, Thailand from November 2002 to January 2003. Sixty-one human immunodeficiency virus-infected patients aged 4 to 15 y, an equal number of age-matched children with no chronic disease and their caregivers participated. We interviewed children and their caregivers using a structured questionnaire on pain. The main outcome measure was the percentage of human immunodeficiency virus-infected children reporting pain. RESULTS: Forty-four percent of the human immunodeficiency virus-infected children reported pain compared to 13% of the children with no chronic disease (odds ratio, OR = 5.3; 95% CI: 2.0-14.3). Seven percent of the infected children experienced chronic pain. Children in human immunodeficiency virus clinical categories B and C reported more pain than children in categories N and A (OR = 4.0, 95% CI: 1.1-14.7). Pain in infected children tended to occur in the abdomen, lower limbs or head. Only 44 percent of the infected children experiencing pain received analgesic medication. CONCLUSION: Despite being a common experience, pain is insufficiently taken into account and treated in Thai children with HIV/AIDS. Therefore, adequate pain identification, assessment and management should be systemically considered in their routine care.

The effectiveness of 3, 5 or 7 days of albendazole for the treatment of Trichuris trichiura infection.

A randomized clinical trial was carried out to study the relationship between the duration of albendazole therapy, at 400 mg/day, and its effectiveness in the treatment of Trichuris trichiura infection. The 168 patients were treated for three (N=56), five (N=56) or seven (N=56) consecutive days. Compared with both of the shorter regimens, treatment for 7 days resulted in a significantly higher cure 'rate' and significantly greater reductions in the level of egg excretion. The advantage of using the longer (5- or 7-day) regimens was most apparent among the patients who had heavy infections (at least 1000 Trichuris eggs/g faeces) when treated. It is therefore suggested that albendazole be given for at least 3 days to those with light infections and for 5-7 days to patients with heavy infections.

Pharmacokinetic investigation of albendazole and praziquantel in Thai children infected with Giardia intestinalis.

The pharmacokinetics of albendazole/albendazole sulphoxide and praziquantel were investigated in Thai children with Giardia infection. Twenty school-age children were randomly allocated to receive either a single oral dose of albendazole (400 mg/child) or the same dose of albendazole given concurrently with a single oral dose of praziquantel (20 mg/kg). The concentrations of albendazole/albendazole sulphoxide and praziquantel in plasma samples, collected at intervals in the first 24 h post-treatment, were then quantified using HPLC with ultra-violet detection. No significant pharmacokinetic interaction between the albendazole and praziquantel was demonstrated. For albendazole sulphoxide, the active metabolite of albendazole, there was marked inter-individual variation in the maximum plasma concentration and the 'area under the curve'. The pharmacokinetics of albendazole sulphoxide were similar whether albendazole was given alone or in combination with praziquantel.