Marcela Potin

Efficacy of a vancomycin solution to prevent bacteremia associated with an indwelling central venous catheter in neutropenic and non-Neutropenic cancer patients

We evaluated the efficacy of a vancomycin solution in the prevention of bacteremia caused by vancomycin-sensitive organisms (VSO) in cancer patients with a tunneled central venous catheter (CVC). Eighty-three patients who had a single lumen CVC were randomized to use a heparin solution (25 U/ml) for daily catheter flush with (HepVan) or without (Hep) vancomycin, 25 mcg/ml. Febrile episodes were recorded, and central and peripheral blood cultures were drawn before beginning antibiotic therapy. Patients participated in follow-up to 16,677 catheter days (8,666 Hep and 8,011 HepVan), and 143 febrile episodes were recorded (82 Hep and 61 HepVan). Forty-four episodes of bacteremia occurred, 23 of them due to VSO (16 occurred in the Hep group and 7 in the HepVan group (P = 0.19). VSO bacteremia occurred in 14 neutropenic (absolute neutrophil count < 500 x 10(9)/l) episodes (7 Hep vs. 7 HepVan) and in 9 non-neutropenic episodes (9 Hep vs. O HepVan; P = 0.013). Vancomycin effectively prevented bacteremia by VSO in non-neutropenic patients, supporting the idea that intraluminal colonization of indwelling CVCs contributes to bacteremia only in these patients.

Efficacy of Hepatitis A Vaccination in Children Aged 12 to 24 Months

Abstract Background Current hepatitis A vaccines are either licensed for children >2 years of age, as in the U.S. or Chile, or >1 year of age, as in Europe and other parts of the world. Recent recommendations for immunization against hepatitis A have included routine vaccination of children in areas or regions of higher endemicity. However, data on hepatitis A vaccination in toddlers aged between 1 and 2 years are scarce. Methods This open clinical study investigated the reactogenicity and immunogenicity of two doses (0, 6-month schedule) of an inactivated hepatitis A vaccine (Havrix™ pediatric, Glaxco SmithKline Biologicals, Rixensart, Belgium) in 120 seronegative children aged 12–24 months. Results Pain at the injection site and irritability were the most frequently reported local and general symptoms, respectively. No serious adverse events related to the study vaccine were reported. One month after the first dose, all but one subject had antibodies against hepatitis A with a GMT of 159 mIU/mL. After the booster dose, all had antibodies with a GMT of 2,939 mIU/mL. Conclusions Our data show that the inactivated hepatitis A vaccine was well tolerated by these toddlers and that the vaccine elicits a good immune response.

Presencia de Bordetella holmesii en brote epidémico de coqueluche en Chile

The incidence of whooping cough in Chile ranges from 4.1 and 7.5 per hundred thousand inhabitants. B. pertussis detection is performed by Real Time PCR (Q-PCR) directed to the insertion sequence IS481. However, this sequence is also found in the genome of B. bronchiseptica and B. holmesii. The latter is also a respiratory pathogen whose clinical features are similar to B. pertussis. However, it is important to differentiate between these species because in immunosuppressed patients B. holmesii is more likely to cause bacteremia and is less susceptible to erythromycin. The goal of this work is to measure prospectively and retrospectively the presence of B. holmesii in samples reported positive for B. pertussis in the period 2010-2011. During this period, 1994 nasopharyngeal specimens entered the laboratory for Bordetella sp. PCR, of which 224 were positive. The analysis by Q-PCR directed to the recA gene of B. holmesii of all 224 positive samples determined a prevalence of B. holmesii of 0.6% (12/1994). Because of its more aggressive behavior in immunosupressed patients and its different resistance pattern, routine screening of B. pertussis and B. holmesii is currently performed for all samples in which Bordetella sp PCR is initially detected.

Infección respiratoria por virus influenza en niños: ¿Qué aprendimos durante el año 2004?

BACKGROUND Infants and toddlers have the highest influenza hospitalization rate in pediatrics. Although the impact of this virus in children has been recognized, there is no defined statement related to vaccination in this population. AIM To describe clinical and epidemiological characteristics of complicated influenza infections in hospitalized children. MATERIAL AND METHODS All hospitalizations due to influenza virus were recorded prospectively between March and June 2004. RESULTS We registered 40 laboratory-confirmed influenza admissions. Median age was 24 months (range: 15 days-14.5 years), 52% males, 18 younger than 2 years. Most of them had an underlying medical condition. The most common conditions were recurrent wheeze in 17, a neurological disease in 7 and asthma in 6. Twenty had more than one condition and 15 were previously healthy. The average days of respiratory symptoms and fever prior to admission were 5 and 3, respectively. The most common discharge diagnoses were concomitant viral-bacterial pneumonia in 53%, viral pneumonia in 38% and laryngitis in 8%. Influenza virus A was identified in 34/40 children. Oxygen supplementation was required by 34 cases; 20% of which required an O2 inspired fraction over 40%. The average days of hospitalization and oxygen were 4 and 3, respectively. Eleven children were treated with amantadine and 21 with antimicrobials. Four children were admitted to pediatric intensive care units and two cases required non-invasive ventilatory support. No deaths were recorded. CONCLUSIONS Our data confirms the importance of influenza virus infection in children, as measured by admission rates, complications and length of hospital stay. Young children are a risk group for which immunization is recognized as protective.

Opinión del Comité Consultivo de Inmunizaciones Sociedad Chilena de Infectología: Vacuna neumocóccica conjugada en niños y la emergencia de serotipo 19A

Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.: Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.

Pneumococcal vaccines in children: an update

Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

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.

Estrategias para proteger al recién nacido y lactante menor de 6 meses de la coqueluche: Posición del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología (CCI)

In recent years there have been Pertussis outbreaks not seen in the last 50 years affecting adults, adolescents and children and causing deaths in young unvaccinated infants. In Chile an outbreak of Pertussis started in year 2011, leaving 16 infants less than 3 months dead during this year, twice the number seen in a non epidemic year. These children were infected before receiving the programmatic vaccines indicated at 2, 4 and 6 months of age, usually from close contacts, especially their mothers. Pertussis control has not been possible for several reasons, such as limited immunity duration of available vaccines and their poor impact on nasopharyngeal carriage, situation that keeps the agents circulation and transmission, condition often asymptomatic or unrecognized. Additionally, the use of acellular vaccines appears to be a determining factor because they induce an immune response with poor immune memory and consequently a short time duration. The acellular vaccines with reduced antigen content, available for adolescents and adults, has allowed the evaluation of various strategies but none has succeeded in reducing infant mortality. Recently a new strategy of vaccinating pregnant women against Pertussis in the second or third semester has shown remarkable results reducing up to 90% infant deaths due to Pertussis infection. This strategy prevents mothers infection avoiding child infection through respiratory droplets and also provides the child with antibodies from placental transmission. Improved pertussis vaccines are required, in the meantime the Committee considers that the pregnant immunization strategy, between the 27 and 36 weeks, with acellular pertussis vaccine should be included in our national vaccine program.

Réplica: Opinión del Comité Consultivo de Inmunizaciones, Sociedad Chilena de Infectología

En respuesta a la carta de Lepetic y colaboradores, en la cual discuten y critican nuestra preferencia como Comité Consultivo de Inmunizaciones de la SOCHINF por la vacuna antineumocócica conjugada 13 valente (PCV13) en lugar de la vacuna 10 valente (PCV10)1, quisiéramos precisar los siguientes puntos: Concordamos en que la introducción de PCV10 en Chile, y su posterior incorporación como vacuna programática en 2011, ha sido una medida de salud pública muy beneficiosa e incuestionable a la luz de los datos de vigilancia disponibles que muestran un claro descenso en las enfermedades neumocócicas invasoras (ENI), neumonías y muertes por neumonias en menores de 2 años2,3. Sin embargo, el impacto de las vacunas neumocócicas conjugadas que contienen múltiples serotipos debe ser evaluado también considerando la mejor cobertura de serotipos circulantes y emergentes en cada región. En Chile, los serotipos que más han aumentado son el 3 y 19A no contenidos en PCV10, y concordamos con los autores en que el serotipo 3 ha sido difícil de reducir con las vacunas disponibles; sin embargo, la situación del serotipo 19A es completamente distinta. Si bien existe información inmunológica de protección cruzada de PCV10 contra el serotipo 19A, y autoridades regulatorias de varios países han registrado esta indicación, la evidencia clínica y epidemiológica en nuestro país indica que esta protección cruzada no está ocurriendo habiendo transcurrido 5 años desde la incorporación de PCV10 en nuestro Plan Nacional de Inmunizaciones. Al respecto, existe información reciente que complementa los datos epidemiológicos chilenos que mencionamos en nuestra publicación y que confirman que entre enero 2014 y junio de 2016 se han registrado 105 menores de 6 años con ENI por serotipo 19A4. De ellos hay 94 niños con datos de vacunación disponible, de los cuales solo 2/94 no tenían ninguna dosis de vacuna, 28/94 (30%) tenían 2 dosis y el 63/94 (67%) tenían esquema completo de 2 dosis +1 refuerzo. En esta serie se registraron incluso dos niños fallecidos4. En relación a la protección indirecta de grupos no vacunados otorgada por las vacunas neumocócicas conjugadas, que consideramos en Chile ha sido insuficiente, si bien es cierto que en algunos países que usan PCV13 no se ha mostrado impacto, como por ejemplo Francia o Noruega5 en la gran mayoría de ellos el efecto ha sido notable5-8. En cambio en países que utilizan PCV10 el efecto ha sido más discreto y muy variable de una región a otra. Así en Finlandia, país que usa PCV10 en esquema 2+1 en niños desde 2011, se evidencia efecto sobre ST contenidos en PCV10 en población no vacunada pero a partir del año 2014 se observa un aumento de casos por serotipos no contenidos pero relacionados lo que finalmente mantiene en mayores de 64 años números absolutos de ENI sin modificaciones, con 279 casos como promedio anual entre los años 2004-2010 y 348 casos promedio entre 2011-20159. Por otra parte en Brasil, país que también usa PCV10 muestra impacto, en algunas regiones, en ENI en individuos sobre 65 años10 pero otras no10-12. En gran medida el efecto se ve reducido por el aumento de serotipos 19A, 6 A y 6C lo que es explicable por el escaso efecto de PCV10 en portación nasofaríngea de estos ST no incluidos en la formulación de PCV1014. Esto puede también explicar lo que ocurre en Chile por lo que parece muy razonable el optar por una vacuna que sí ha mostrado en forma consistente una reducción de carga de enfermedad neumocócica en adultos y adultos mayores5-7. Tal como precisan Lepetic y cols el efecto global de estas vacunas es indiscutible, pero también concordamos con lo que señala la OMS de que si bien PCV10 y PCV13 tienen perfiles de seguridad y eficacia similar para los serotipos contenidos en cada vacuna, la elección de la vacuna neumocócica conjugada dependerá de factores como los serotipos contenidos en las vacunas y los prevalentes en los grupos objetivo15. De modo que existiendo en nuestro país casos de niños vacunados adecuadamente con PCV10 que han presentado infecciones invasoras graves por el serotipo 19A, y disponiendo de una vacuna que brinda protección contra dicho serotipo, consideramos técnica y éticamente mandatorio proponer un cambio desde PCV10 a PCV13. Los programas de inmunización modernos han de ser dinámicos, vale decir, deben ser revisados periódicamente a la luz de la nueva evidencia disponible y de la información epidemiológica local. Este proceder permite proponer cambios en un sentido que consideramos correcto.

Razones para recomendar la vacunación contra el dengue en Isla de Pascua: Opinión del Comité de Inmunizaciones de la Sociedad Chilena de Infectología

Dengue was first diagnosed on Easter Island on year 2002 and thereafter recurrent outbreaks have occurred involving different serotypes of dengue virus. Its vector, Aedes aegypti has not been eliminated despite the small size of the island. Conditions at the local hospital preclude adequate management of severe and hemorrhagic cases due to the absence of a Critical Care Unit as well as no availability of platelets, or plasma units for transfusion. Besides, transfer, of severely affected patients to continental Chile is cumbersome, slow and expensive. In this scenario, it is advisable to implement selective vaccination of Easter Island habitants with an available quadrivalent attenuated dengue vaccine with the aim to reduce hemorrhagic and severe dengue cases. This strategy should not replace permanent efforts to control waste disposal sites, water sources, maintain vector surveillance and increase education of the population.