Priorización de nuevas vacunas e innovación al servicio de estrategias de vacunación / New vaccines prioritization and immunization-related innovation

La vacunación es el medio más efectivo para controlar la morbilidad y mortalidad relacionadas con enfermedades infecciosas. Para lograr esto, necesitamos vacunas inmunogénicas y seguras que faciliten y mejoren sus condiciones de transporte, almacenamiento y administración. Gracias a los avances en inmunología y bioinformática, es posible impulsar el descubrimiento de nuevas vacunas para enfrentar la tuberculosis, el virus respiratorio sincicial, el Streptococcus agalactiae, la enfermedad meningocócica invasora, entre otros. Así también, nuevas tecnologías, como la producción de vacunas utilizando plantas transgénicas y parches de microagujas, los cuales podrían facilitar la producción, disminuir los costos y efectos adversos. Sin embargo, no solo necesitamos las vacunas, sino que debemos conocer la epidemiología de las enfermedades prevenibles con vacuna para tomar decisiones fundadas, con el objetivo de planificar estrategias sanitarias, medir su impacto y evaluar la seguridad de su utilización, para alcanzar las metas de salud pública y la confianza de la población.

Vaccination is the most effective strategy to avoid morbidity and mortality related to infectious diseases. To achieve this, we need immunogenic and safe vaccines that facilitate and improve its transport, storage and administration conditions. Thanks to current advances in immunology and bioinformatics, it is possible to boost the discovery of new vaccines to deal with tuberculosis, the respiratory syncytial virus, Streptococcus agalactiae, meningococcal invasive disease, among others. In addition to new technologies such as the production of plant-based vaccines, and microneedles patches, which can facilitate its production, reducing costs and adverse effects. However, vaccines is not the only thing that we need, because we must know the epidemiology and burden of disease to take informed decisions to design optimal strategies, measuring their impact and assessing the safety of their use in order to achieve the goals health and population confidence.

Challenges in new vaccine introduction in a national program in India.

Vaccines have a long history dating back to the days of Edward Jenner (1749-1823) and Louis Pasteur (1822-1895). Vaccines can be viewed from a public health perspective as well as scientific perspective. Public health experts would focus epidemiological relevance, immunological competency, and technological feasibility. Scientists however will look for a good immune response as well as long-lived immunity, stability considerations, and safety issues such as danger of reversion to virulence. In India, the vaccine coverage is far from satisfactory, national average for full immunization being only 65%. Presently, nine vaccines are being used in the Universal Immunization Program. However, some more have started in pilot, and some are still in the pipeline. Although administrative, logistic and operational challenges have to be faced when introducing a new vaccine into the public health system; these are solvable and should not be a hindrance to the introduction. A real-life example of nonintroduction of a lifesaving vaccine is - the oral cholera vaccine. This vaccine which is manufactured and licensed in India has been the World Health Organization (WHO) prequalified, and it is being used worldwide. Although the disease is a major threat, the disease has its stigma and has led to its low reporting even from cholera endemic areas of the country. Thus, in spite of the WHO recommendations, the vaccine is not being introduced into the national program which would take it to people who need it the most only because of apparent lack of sufficient disease burden data and political commitment.

An assessment of hepatitis B vaccine introduction in India: Lessons for roll out and scale up of new vaccines in immunization programs.

Background: Hepatitis B vaccine was introduced in the Universal Immunization Program (UIP) of 10 states of India in the year 2007-08. This assessment was planned and conducted to ascertain the reasons for low reported coverage of Hepatitis B (Hep B) vaccine in comparison of similarly timed diphtheria, pertussis, and tetanus (DPT) vaccine; to identify operational and programmatic challenges in new vaccine introductions, and to derive lessons for further scale up of Hep B vaccination (or for introduction of any new vaccine) in UIP of India. Materials and Methods: Purposive sampling with both quantitative and qualitative data collection. Two districts each were purposively selected from 5 of the 10 states, which introduced Hep B vaccine, in the year 2007-08. A protocol was devised and data was collected through desk review, in-depth interviews and on-site observation at state, districts and facility levels. The assessment was completed in December 2009. Results: Coverage with three doses of Hep B vaccine was lower than similarly timed three doses of DPT vaccine. Poor stock management ("stock outs or nil stocks" at various levels), incomplete recording and reporting, perceived high cost & related fear of wastage of vaccine in 10 dose vial, and incomplete knowledge amongst health functionaries about vaccination schedule were the main reasons cited for reported lower coverage. Hep B vaccine birth dose was introduced in only 3 of 5 states evaluated. The additional reasons for low Hep B birth dose coverage were lack of knowledge amongst Health Workers about birth dose administration, no mechanism for recording birth dose, and insufficient trainings, official communications, and coordination at various levels. Conclusions: This assessment documents challenges faced in the introduction of hepatitis B vaccine in UIP in India and summarizes the lessons learnt. It is concluded that for successful introduction and scale up of any new vaccine in national or state immunization program; clear and timely central level instructions and oversight and improved stock management is required. At state and district levels; quality trainings, effective supervision and monitoring, improving data recording and reporting are key factor for success. The additional focus on Hep B birth dose administration may help in improving coverage. The lessons from this assessment can possibly be utilized for future introduction and scale up of any new vaccine (or other similar interventions) in India or in any other developing country setting.

Vacunas anti neumocócicas / Pneumococcal vaccines

Existen vacunas contra el Streptococcus pneumoniae. Una de polisacáridos capsulares con 23 antígenos y las vacunas conjugadas, denominadas así, porque los polisacáridos están conjugados a una mutante no tóxica de la toxina diftérica o a la proteína D delHaemophilus influenzae no tipificable, a una proteína transportadora del toxoide tetánico y otra de toxoide diftérico. La vacuna de 23 antígenos se recomienda en niños con edad igual y mayor de 24 meses, con alto riesgo para enfermedad neumocócica invasiva y complicaciones, debidas a enfermedades subyacentes y se administra en esquema mixto con vacunas anti neumocócica conjugadas. En 2002, la Organización Mundial de la Salud determinó que la vacuna anti neumocócica heptavalente (Prevenar® 7) es el estándar de oro, con la cual debían ser comparada toda nueva vacuna conjugada, por lo que definieron, necesarios para su aprobación, dos criterios de no inferioridad. Primer criterio: Una vez administrada la vacuna se registren títulos de anticuerpos medidos por ELISA iguales o mayoresde 0,35 μg/mL para los serotipos comunes a ambas vacunas y los adicionales. Segundo criterio: Los anticuerpos deben tener capacidadfuncional, lo cual se establece mediante la cuantificación de la actividad opsonofagocítica que debe ser igual o mayor de 1:8. Las vacunas conjugadas 10valente (Synflorix®) y 13 valente (Prevenar® 13) cumplen ambos criterios. De no ser posible completar el esquema o administrar refuerzo, con el mismo tipo de vacuna conjugada inicial, puede hacerse con cualquier otra vacuna

Several vaccines against Streptococcus pneumoniae are available. One made of capsular polysaccharides with 23 antigens and the conjugated vaccines, thus denominated, because the polysaccharides are conjugated to a nontoxic mutant of the diphteric toxin or to the D protein of the nontipificable Haemophilus influenzae, to a transporting protein of tetanic and diphteric toxoids. The 23 antigens vaccine is recommended for children 24 months of age and older, with high risk for invasive pneumococcal disease and complications due to underlying diseases. It is administered in a mixed scheme with anti pneumococcal conjugated vaccines. In 2002, the World Health Organization (WHO) determined that the heptavalent vaccine (Prevenar® 7) is the gold standard, with which all new conjugated vaccineshould be compared. For this reason, they defined two non inferiority criteria as necessary for the approval. First criterion: Once administered the vaccine and measured the amount of antibodies by ELISA, these must be equal or above 0.35 μg/mL for the common serotypes to both vaccines and to the additional serotypes. Second criterion: The antibodies must have functional capacity, which is determined by the opsonophagocitic activity that must be equal or greater than 1:8. The 10 valent (Synflorix®) and the 13 valent(Prevenar® 13) conjugated vaccines fulfill both criteria. If it is not possible to complete the vaccine scheme or to administer a booster dose, with the same type of conjugated vaccine, this may be done with any other vaccine

Nuevas vacunas de BCG

La tuberculosis continúa con alta prevalencia en los países más pobres del mundo. Aún cuando se cuenta con procedimientos diagnósticos, medicamentos y una vacuna de eficacia limitada que previene las formas graves de la enfermedad, como es la vacuna de Bacilos de Calmette y Guérin; dos factores han generado nuevo interés por la obtención de nuevas vacunas contra el bacilo de la tuberculosis: La coinfección del Virus de Inmunodeficiencia Humana y tuberculosis, y el surgimiento de Mycobacterium tuberculosis multi-resistente a antibióticos. Los objetivos principales de las nuevas vacunas son: prevención de la infección de personas no expuestas previamente, prevención de la reactivación de la infección latente y acción terapéutica para prevenir recaídas de los enfermos de tuberculosis. Actualmente, las líneas de investigación, en más de 12 proyectos, que más apoyo reciben son las vacunas de Bacilos de Calmette y Guérin modificadas por recombinación genética, las cepas atenuadas de M. tuberculosis, las vacunas de subunidades y las vacunas de ADN.

Tuberculosis continues to be highly prevalent in poor countries. Even though the availability of diagnostic procedures, drugs and a vaccine of limited effectiveness that prevents the serious forms with the disease, namely the vaccine of Calmette and Guérin bacilli, two factors have generated new interest for the production of new vaccines against tuberculosis bacilli: the coinfection of the Virus of Human Immunodeficiency and tuberculosis, and the appearance of multi-resistant tuberculosis Mycobacterium. The primary targets of new vaccines are: prevention of the infection in people not previously exposed, prevention of reactivation of latent infection and therapeutic action to prevent relapses in tuberculosis patients. At the moment, the lines of investigation in more than 12 projects, that receive more support are the vaccines of Calmette and Guérin Bacilli modified by genetic recombination, the attenuated stocks of M. tuberculosis, the subunits vaccines and the DNA vaccines.

Nuevos desafíos en tuberculosis / New challenges in tuberculosis

Tuberculosis (TB) is a main cause of disease and death in many countries of the world. The efforts to control this scourge have not been very successful. Even in Chile where we are near to reach the advanced stage of elimination of TB as a public health problem, five persons each week die of this disease. The main challenges for the control of TB and the most recent advances to counteract them are reviewed. A series of modern methods of diagnosis based on the techniques of molecular biology are reviewed. There is a need to develop procedures that can be applied in the so called "point of diagnosis", like the Xpert MTB/RIF test. There are new techniques for the diagnosis of latent TB infection (IGRA's), in order to identify infected subjects of high risk to develop disease to subject them to chemo-profilaxis. We need to develop shorter treatments for new cases and better drugs for multi-resistant patients. Ten new drugs have progressed into the clinical development pipeline for TB. New vaccines against tuberculosis are being investigated. Some of them are already being tried in the field. In the last years two new challenges have appeared: the association TB-AIDS, and the new epidemics of Multi Drug Resistant Tuberculosis (TB MDR and TB XDR). New techniques of diagnosis are described. Our main challenge is to make all this advances available for everybody. In Chile only the private sector has some of these techniques.

La tuberculosis (TBC) sigue siendo una de las principales causas de morbi-mortalidad en el mundo y los esfuerzos para controlarla han demostrado ser insuficientes. Aun en Chile, donde estamos cerca de alcanzar la etapa avanzada de su eliminación como problema de salud pública, fallecen 5 personas por semana de TBC. Este artículo presenta los principales desafíos de los Programas de Control de la TBC y los avances más recientes para enfrentarlos. Se analiza una serie de métodos de diagnóstico basados en técnicas de biología molecular. Se necesitan técnicas más sensibles que la baciloscopia que puedan ser empleadas en la periferia, en el llamado "punto del diagnóstico", como el test Xpert MTB/RIF. Están en estudio nuevos métodos de diagnóstico de la infección tuberculosa latente -los IGRA's - para identificar con mayor especificidad que con el PPD, a los infectados con alto riesgo de progresar a TBC para someterlos a quimioprofilaxis. Necesitamos tratamientos más breves para los casos nuevos, y drogas más eficaces para los enfermos de TBC multi-resistentes. Está en desarrollo la introducción de 10 nuevos medicamentos anti-TBC. Se necesitan vacunas más eficaces que la BCG, capaces no sólo de prevenir la infección, sino también de reforzar la inmunidad de los infectados y aún de los enfermos. Varias de estas vacunas se están ensayando en África. En los últimos decenios han aparecido dos nuevos desafíos: la asociación TBC-SIDA y las epidemias de TBC multi-resistentes (TB MDR y XDR). Se han desarrollado técnicas para identificar polimorfismos del gen rpo B, principal causa de resistencia a la rifampicina, considerada marcador de TB MDR. El principal desafío actual es poner todos estos avances al alcance de los que más los necesitan. En Chile sólo disponemos de algunas de estas nuevas técnicas, en su mayoría en clínicas privadas.

Prevention of childhood tuberculosis / 国际儿科学杂志

In recent years the incidence rate of tuberculosis (TB) has gone up.It was estimated that 1/3of people had asymptomatic latent tuberculosis infection globally.The current widespread use of Bacillus calmetteguerin (BCG) vaccine program against tuberculosis in children has a good preventive effect,but due to the limited duration of the immune responses induced by BCG,there also had situation of prevent failure,so researchers begin to explore new TB vaccines,such as live attenuated mutant strains,subunit vaccines and DNA vaccines,and achieved certain results.For the pure protein derivative tuberculosis skin test positive and immunosuppressed children,in addition to active immunization would also need anti-TB medicine for chemoprophylaxis.