Rodolfo Villena

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study

BACKGROUND Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. METHODS We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. FINDINGS Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assays upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). INTERPRETATION Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. FUNDING Bill & Melinda Gates Foundation.

Rotavirus Serum IgA Immune Response in Children Receiving Rotarix Coadministered With bOPV or IPV.

Background: Vaccine schedules including bivalent oral and inactivated poliovirus vaccines will replace trivalent oral poliovirus vaccines in 2016. Methods: We evaluated rotavirus immunoglobulin A seroresponses when the second dose of Rotarix at 16 weeks was given concomitantly with inactivated or bivalent oral poliovirus vaccines. Results: Rotavirus immunoglobulin A seroresponse rate at week 28 was 15% lower in recipients of bivalent oral poliovirus vaccines compared with inactivated poliovirus vaccines. Conclusion: Bivalent oral poliovirus vaccine decreases rotavirus IgA seroresponse rates when coadministered at 16 weeks of age.

Interacción entre meropenem y ácido valproico: A propósito de dos casos pediátricos

The pharmacological interaction between meropenem and valproic acid is potentially serious, especially in critically ill patients, resulting in low plasmatic levels of the anticonvulsant. However, to our knowledge, this interaction between meropenem and reduced valproic acid plasma levels has not been reported in the pediatric chilean population. We present two clinical cases of chilean children, thus reporting that this interaction is present in our population, with an aim at educating physicians about the possibility of such interaction.The pharmacological interaction between meropenem and valproic acid is potentially serious, especially in critically ill patients, resulting in low plasmatic levels of the anticonvulsant. However, to our knowledge, this interaction between meropenem and reduced valproic acid plasma levels has not been reported in the pediatric chilean population. We present two clinical cases of chilean children, thus reporting that this interaction is present in our population, with an aim at educating physicians about the possibility of such interaction.

Global epidemiology of serogroup B meningococcal disease and opportunities for prevention with novel recombinant protein vaccines

ABSTRACT Background: Meningococcal disease (MD) is a major cause of meningitis and sepsis worldwide, with a high case fatality rate and frequent sequelae. Neisseria meningitidis serogroups A, B, C, W, X and Y are responsible for most of these life-threatening infections, and its unpredictable epidemiology can cause outbreaks in communities, with significant health, social and economic impact. Currently, serogroup B is the main cause of MD in Europe and North America and one of the most prevalent serogroups in Latin America. Mass vaccination strategies using polysaccharide vaccines have been deployed since the 1970s and the use of conjugate vaccines has controlled endemic and epidemic disease caused by serogroups A, C, W and Y and more recently serogroup B using geographically-specific outer membrane vesicle based vaccines. Two novel protein-based vaccines are a significant addition to our armamentarium against N. meningitidis as they provide broad coverage against highly diverse strains in serogroup B and other groups. Early safety, effectiveness and impact data of these vaccines are encouraging. These novel serogroup B vaccines should be actively considered for individuals at increased risk of disease and to control serogroup B outbreaks occurring in institutions or specific regions, as they are likely to save lives and prevent severe sequelae. Incorporation into national programs will require thorough country-specific analysis.

Monitoreo terapéutico de vancomicina intravenosa en una unidad de paciente crítico pediátrico

BACKGROUND In critically ill pediatric patients vancomycin distribution and elimination is altered underscoring the need for pharmacokinetic monitoring; however the therapeutic trough ranges have not been validated for children. OBJECTIVE To describe the pharmacokinetics of intravenous vancomycin in critically ill pediatric patients using plasmatic vancomycin monitoring. METHODS Retrospective, descriptive study performed in a paediatric critical care unit. Vancomycin serum levels (Cmin and Cpeak), t ½ and Vd were determined in 1 month to 12 year old patients receiving ≥ 40 mg per-kg-per day. Plasmatic levels were measured at therapy onset and during follow up, evaluating the proportion of trough level determinations within therapeutic range, the average trough concentration, and the Cpeak achieved. RESULTS A total of 65 plasmatic vancomycin monitorings were analysed in 45 patients. The average values for Ctrough, Cpeak, t1/2 and Vd were 10.4 μg/mL, 22.7 μg/mL, 3,1 h and 0.7 L/kg, respectively. An average dose of 47,1 mg/kg/day achieved initial Ctrough levels < 10 mg/mL in 60% of patients (n = 27), between 10 and 14,9 μg/mL in 22,2% (n = 10), between 15 to 20 μg/mL in 4% (n: 2), and > 20 μg/mL in 13,3% (n: 6). CONCLUSIONS Vancomycin doses of 40 mg/kg/day are insufficient for critically ill paediatric patients without renal failure. A higher starting dose and monitoring of plasma levels must be considered in this population.

Vacunación con pertussis en el embarazo: una estrategia segura y efectiva para proteger al lactante menor

Whooping cough is an immune preventable disease that can be life threatening. Despite infant immunization starting at 2 month of age, there are many cases and outbreaks in our country and also around the world, with a high risk of mortality specially in infants under 6 month of age. It has been proposed that antenatal vaccination with acellular pertussis component (Tdap) would be useful, safe and effective since it transfers a high antibody rate to the child, reducing the incidence of pertussis in this group by 85%. No higher incidence of adverse effects has been found in pregnant women with this vaccine. This strategy has been implemented in several developed and Latin American countries. The purpose of this manuscript is to review and discuss the benefits of antenatal vaccination with Tdap. It was concluded that maternal immunization with Tdap vaccine should be promoted to prevent infection and associated mortality in the less than 6 months of age by Bordetella pertussis .Whooping cough is an immune preventable disease that can be life threatening. Despite infant immunization starting at 2 month of age, there are many cases and outbreaks in our country and also around the world, with a high risk of mortality specially in infants under 6 month of age. It has been proposed that antenatal vaccination with acellular pertussis component (Tdap) would be useful, safe and effective since it transfers a high antibody rate to the child, reducing the incidence of pertussis in this group by 85%. No higher incidence of adverse effects has been found in pregnant women with this vaccine. This strategy has been implemented in several developed and Latin American countries. The purpose of this manuscript is to review and discuss the benefits of antenatal vaccination with Tdap. It was concluded that maternal immunization with Tdap vaccine should be promoted to prevent infection and associated mortality in the less than 6 months of age by Bordetella pertussis.

Resultado de un modelo de gestión de vacunas especiales.

Introduction: Special vaccines recommendation patients are a growing population. The Ministry of Health has developed a special vaccination program for these cases, through which our hospital manages vaccine forms by an established flowchart. Objective: To describe the special vaccines model of management results in the period between March 2015 and September 2016, and the clinical and demographics characterization of the pediatric population benefited with this program in Dr. Exequiel Gonzalez Cortes Children´s Hospital. Patients and Methods: We performed a descriptive observational study, which covers the chronically ill patient’s population who received special vaccines during the period between March 2015 to September 2016. Results: A total of 367 vaccine schemes were administered to 215 patients, with a total of 405 vaccines administered during the period. The medical specialties that most requested vaccines were infectology (39.1%), immune-rheumatology (24.2%) and bronchopulmonary specialists (20%). The National Immunization Program authorized 97.8% of the requested schemes (n = 359), the response time had a median of 15 days (range 0-174 days), the vaccination opportunity had a median of 41 days (range 0-287 days) and the total of schemes completed at the time of tabulating the results was 52.8%. Conclusions: Vaccines are one of the main public health equity policies and Chile has special vaccines request flowchart a flow chart, which requires a multidisciplinary work to provide coverage to this vulnerable child population.INTRODUCTION Special vaccines recommendation patients are a growing population. The Ministry of Health has developed a special vaccination program for these cases, through which our hospital manages vaccine forms by an established flowchart. OBJECTIVE To describe the special vaccines model of management results in the period between March 2015 and September 2016, and the clinical and demographics characterization of the pediatric population benefited with this program in Dr. Exe-quiel González Cortés Childrens Hospital. PATIENTS AND METHODS We performed a descriptive ob servational study, which covers the chronically ill patients population who received special vaccines during the period between March 2015 to September 2016. RESULTS A total of 367 vaccine schemes were administered to 215 patients, with a total of 405 vaccines administered during the period. The medical specialties that most requested vaccines were infectology (39.1%), immune-rheumatology (24.2%) and bronchopulmonary specialists (20%). The National Immunization Program authorized 97.8% of the requested schemes (n = 359), the response time had a median of 15 days (range 0-174 days), the vaccination opportunity had a median of 41 days (range 0-287 days) and the total of sche mes completed at the time of tabulating the results was 52.8%. CONCLUSIONS Vaccines are one of the main public health equity policies and Chile has special vaccines request flowchart a flow chart, which requires a multidisciplinary work to provide coverage to this vulnerable child population.

Statement from the Immunization Committee of the Chilean Infectious Diseases Society in reference to vaccine refusal and mandatory policy on vaccination

Although vaccines have had a tremendous impact in public health they are questioned by certain groups that consider them unnecessary or unsafe and argue in favor of the right to decide to be vaccinated or not. However vaccines must have special considerations because unlike other medical decisions, not vaccinating has consequences not only for the individual but also for other members of the community. Immunizing a high proportion of the population limits the circulation of an infectious agent attaining what is called herd immunity that protects the susceptible members of the group. For this reason many countries consider vaccination mandatory as a responsibility of every citizen. This committee agrees with this view but thinks other strategies should be implemented as well, such as special educational efforts for the public and parents addressing benefits and real risks of vaccinating. Also health care professionals should be trained in vaccines. The notification system for adverse events currently available should be improved and be more accessible. Persons truly affected by adverse events due to vaccination should receive on time responses and be offered psychological and financial support. Finally all stakeholders should make coordinated efforts to work together to deliver messages that answer concerns on vaccines and bring confidence back to the public.Although vaccines have had a tremendous impact in public health they are questioned by certain groups that consider them unnecessary or unsafe and argue in favor of the right to decide to be vaccinated or not. However vaccines must have special considerations because unlike other medical decisions, not vaccinating has consequences not only for the individual but also for other members of the community. Immunizing a high proportion of the population limits the circulation of an infectious agent attaining what is called herd immunity that protects the susceptible members of the group. For this reason many countries consider vaccination mandatory as a responsibility of every citizen. This committee agrees with this view but thinks other strategies should be implemented as well, such as special educational efforts for the public and parents addressing benefits and real risks of vaccinating. Also health care professionals should be trained in vaccines. The notification system for adverse events currently available should be improved and be more accessible. Persons truly affected by adverse events due to vaccination should receive on time responses and be offered psychological and financial support. Finally all stakeholders should make coordinated efforts to work together to deliver messages that answer concerns on vaccines and bring confidence back to the public.

Enfermedad meningocóccica invasora por serogrupo B en dos niños chilenos vacunados contra serogrupos ACWY

Invasive meningococcal disease (IMD) by serogroup W has become predominant in Chile since 2012, prompting vaccination with conjugate ACWY. We reported two pediatric cases in patients already vaccinated, which evolved with IMD by serogroup B. This should remind us to keep the alertness with this pathology, despite the current vaccination system in Chile, emphasizing in improve our epidemiological case definition and its diagnosis.

Seroconversión frente a primovacunación reforzada contra hepatitis B en niños con cáncer

INTRODUCTION Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. PATIENTS AND METHOD Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. RESULTS A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml. CONCLUSIONS Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses.