[Quo vadis in vaccines: From the empirical approach to the new wave of technology]. / Quo vadis en vacunas: desde la aproximación empírica a la nueva oleada tecnológica.

The development of vaccines is a multifactorial process that has evolved and expanded, particularly over the last decades. The search for immunogenic vaccines that are also acceptably safe and tolerable enacted continuous technological advances in this field. In this regard, the technology applied to vaccines can historically be divided into 3 approaches: the empirical approach, the modern approach, and the new technological wave. The empirical approach for vaccine development includes whole micro-organisms, attenuation, inactivation, cell cultures and sub-unit vaccines. The modern approach contributed to leaps and bounds to vaccine development using chemical conjugation, as well as recombinant protein DNA technology and reverse vaccinology. Lastly, the new technological wave includes, among others, bioconjugation, viral vectors, synthetic biology, self-amplification of messenger RNA, generalized modules for membrane antigens, structural vaccinology and the new adjuvants.

Conocimiento vaccinal en madres con hijos menores de 5 años / Vaccinal knowledge, in mothers with children under 5 years old

La inmunización, es un mecanismo de defensa que asegura la inmunidad humoral para prevenir enfermedades infantiles graves, y es responsabilidad de los padres. Objetivo: Se plantea indagar el conocimiento vaccinal, en madres con hijos menores de 5 años. Métodos: el estudio se orienta bajo el paradigma cualitativo, enfoque fenomenológico; Los participantes del estudio fueron madres que vacunaron a sus hijos en el centro de salud 20 de febrero, distrito 12D03 Quevedo-Mocache, Ecuador. Para el análisis de los datos se utilizó el soware Atlas ti, vinculando 18 preguntas de reflexión. Resultados: Las categorías emergentes fueron: 1) Las vacunas son muy importantes y necesarias. 2. Vacunaron porque sus hijos crecen sanos y fuertes. 3. para algunas el vacunatorio es agradable y para otras no. 4. Algunas reciben buen trato y atención, otras no. 5. Es insuficiente la información sobre las vacunas. 6. Piden cambios de enfermeras y horarios. Conclusión: el conocimiento vaccinal de las madres, esdeterminante para la protección y la no propagación de enfermedades en sus hijos(AU)

Immunization is a defense mechanism that ensures humoral immunity to prevent serious childhood diseases, and is the responsibility of the parents. Objective: to investigate the vaccine knowledge in mothers with children under 5 years. Methods: the study is oriented under the qualitative paradigm, hermeneutic approach; e study participants were mothers who vaccinated their children in the health center February 20, district 12D03 Quevedo-Mocache, Ecuador. The Atlas ti soware was used to analyze the data, linking 18 reflection questions. Results: The emerging categories were: 1) Vaccines are very important and necessary. 2. They vaccinated because their children grow up healthy and strong. 3. For some the vaccine is nice and for others it is not. 4. Some receive good treatment and attention, others do not. 5. Insufficient information about vaccines. 6. Ask for changes of nurses and schedules. Conclusion: the vaccinal knowledge of the mothers, is decisive for the protection and non-propagation of diseases in their children(AU)

How vaccines work: immune effector mechanisms and designer vaccines.

Introduction: Three major advances have led to increase in length and quality of human life: increased food production, improved sanitation and induction of specific adaptive immune responses to infectious agents (vaccination). Which has had the most impact is subject to debate. The number and variety of infections agents and the mechanisms that they have evolved to allow them to colonize humans remained mysterious and confusing until the last 50 years. Since then science has developed complex and largely successful ways to immunize against many of these infections.Areas covered: Six specific immune defense mechanisms have been identified. neutralization, cytolytic, immune complex, anaphylactic, T-cytotoxicity, and delayed hypersensitivity. The role of each of these immune effector mechanisms in immune responses induced by vaccination against specific infectious agents is the subject of this review.Expertopinion: In the past development of specific vaccines for infections agents was largely by trial and error. With an understanding of the natural history of an infection and the effective immune response to it, one can select the method of vaccination that will elicit the appropriate immune effector mechanisms (designer vaccines). These may act to prevent infection (prevention) or eliminate an established on ongoing infection (therapeutic).Literature search: The primary literature source is Pub Med. Secondary source is Wikipedia.

Efeito da exposição à hidroquinona na resposta imune adaptativa induzida pela vacina contra a influenza / Effects of hydroquinone exposure on the adaptive immune response induced by the influenza vaccine

A gripe é causada pelo vírus Influenza e é um problema de saúde pública mundial, que pode levar a problemas sérios em idosos e crianças. O Brasil implantou a vacinação anual contra influenza a partir de 1999, como ação preventiva contra a doença. A vacina é produzida pelo Instituto Butantan e contém três cepas diferentes do vírus Influenza fragmentado para induzir resposta imune adaptativa, com produção de anticorpos específicos e neutralizantes. A literatura tem mostrado que a exposição à xenobióticos com potencial imunossupressor pode comprometer a eficácia de imunizações ativas, como a imunização contra a gripe. Nosso grupo de pesquisa tem mostrado que a exposição à hidroquinona (HQ), um composto tóxico presente em altas concentrações na fumaça do cigarro, prejudica a resposta imune inata e adquirida. Assim, este trabalho avaliou o efeito da exposição à HQ sobre a resposta imune à vacinação contra influenza. Camundongos machos da linhagem C57BL/6 foram diariamente expostos à HQ (2500 ppm) ou PBS, por 1 hora, por nebulização, por um período de 8 semanas. Durante este período, foram imunizados nas semanas 6 e 8 do início das exposições, pela injeção i.m. de 100µL da vacina. Os parâmetros tóxicos e imunológicos foram avaliados 7, 35 e 70 dias após a segunda dose da vacina. A exposição à HQ não alterou o peso corpóreo dos animais e nem causou alterações morfológicas no pulmão, fígado e rins (histologia por H&E); reduziu a frequência de hemácias (11%), hematócrito (14%), hemoglobina (14%) e volume celular (4%); causou estresse oxidativo no baço (citometria de fluxo); aumentou a área dos folículos de células B no baço e linfonodomegalia (histologia por H&E). Em conjunto, os dados aqui obtidos mostram que a exposição à HQ afetou mecanismos envolvidos na gênese da imunidade ativa contra influenza. Assim, os dados deste trabalho mostram mecanismos tóxicos ainda não descritos para a HQ, e ressalta a HQ como um poluente ambiental que deve ser considerado nas avaliações de risco

The flu is a health problem worldwide which is caused by the Influenza virus and may result in severe illness in infants and the elderly. The annually vaccination against influenza was implemented in Brazil in 1999 as a preventive measure. The vaccine is produced by Butantan Institute and contains three different strains of the inactivated Influenza virus which induce the adaptive immune response along with production of specific and neutralizing antibodies. The literature has shown that exposure to immunosuppressive xenobiotics may compromise the efficacy of active immunizations, such as influenza. Our research group has shown that exposure to hydroquinone (HQ), a toxic constituent of cigarette smoke, impairs both innate and adaptive immune response. Thus, the aim of this work was to evaluate the effects of HQ on the immune response induced by the influenza vaccine. Male C57BL/6 mice were daily exposed to HQ (2500 ppm) or PBS by nebulization, for 1 hour, for 8 weeks. During the exposure period, the animals were vaccinated on weeks 6 and 8 with 100µL of the vaccine. Toxicologic and immunological parameters were assessed 7, 35 and 70 days after boost administration. HQ exposure did not alter body weight and did not cause morphological alterations in the lungs, liver and kidneys (H&E staining); reduced the frequency of erythrocytes (11%), hematocrit (14%), hemoglobin (14%) and cellular volume (4%) and caused oxidative stress on the spleen (Flow Cytometry); increased the area of B cell follicles in the spleen and increased the size of draining lymph nodes (H&E staining). Altogether, these data show that HQ exposure affected mechanisms involved in the genesis of the adaptive immune response. Thus, the data presented in this work show toxic mechanisms of HQ that have not yet been described, and it also points out HQ as an environmental pollutant which should be considered on risk assessments

The landscape of vaccines in China: history, classification, supply, and price.

BACKGROUND: Vaccine regulation in China meets World Health Organization standards, but China's vaccine industry and immunization program have some characteristics that differ from other countries. We described the history, classification, supply and prices of vaccines available and used in China, compared with high-and middle-incomes countries to illustrate the development of Chinese vaccine industry and immunization program. METHODS: Immunization policy documents were obtained from the State Council and the National Health and Family Planning Commission (NHFPC). Numbers of doses of vaccines released in China were obtained from the Biologicals Lot Release Program of the National Institutes for Food and Drug Control (NIFDC). Vaccine prices were obtained from Chinese Central Government Procurement (CCGP). International data were collected from US CDC, Public Health England, European CDC, WHO, and UNICEF. RESULTS: Between 2007 and 2015, the annual supply of vaccines in China ranged between 666 million and 1,190 million doses, with most doses produced domestically. The government's Expanded Program on Immunization (EPI) prevents 12 vaccine preventable diseases (VPD) through routine immunization. China produces vaccines that are in common use globally; however, the number of routinely-prevented diseases is fewer than in high- and middle-income countries. Contract prices for program (EPI) vaccines ranged from 0.1 to 5.7 US dollars per dose - similar to UNICEF prices. Contract prices for private-market vaccines ranged from 2.4 to 102.9 US dollars per dose - often higher than prices for comparable US, European, and UNICEF vaccines. CONCLUSION: China is a well-regulated producer of vaccines, but some vaccines that are important globally are not included in China's EPI system in China. Sustained and coordinated effort will be required to bring Chinese vaccine industry and EPI into an era of global leadership.

Factors Influencing Vaccination in Korea: Findings From Focus Group Interviews.

OBJECTIVES: Immunization is considered one of the most successful and cost-effective public health interventions protecting communities from preventable infectious diseases. The Korean government set up a dedicated workforce for national immunization in 2003, and since then has made strides in improving vaccination coverage across the nation. However, some groups remain relatively vulnerable and require intervention, and it is necessary to address unmet needs to prevent outbreaks of communicable diseases. This study was conducted to characterize persistent challenges to vaccination. METHODS: The study adopted a qualitative method in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist. Three focus group interviews were conducted with 15 professionals in charge of vaccination-related duties. The interviews were conducted according to a semi-structured guideline, and thematic analysis was carried out. Data saturation was confirmed when the researchers agreed that no more new codes could be found. RESULTS: A total of 4 main topics and 11 subtopics were introduced regarding barriers to vaccination. The main topics were vaccine hesitancy, personal circumstances, lack of information, and misclassification. Among them, vaccine hesitancy was confirmed to be the most significant factor impeding vaccination. It was also found that the factors hindering vaccination had changed over time and disproportionately affected certain groups. CONCLUSIONS: The study identified ongoing unmet needs and barriers to vaccination despite the accomplishments of the National Immunization Program. The results have implications for establishing tailored interventions that target context- and group-specific barriers to improve timely and complete vaccination coverage.

Kinetics of rabies antibodies as a strategy for canine active immunization

Rabies, a zoonosis found throughout the globe, is caused by a virus of the Lyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil. During 12 months we evaluated the active immunity of dogs first vaccinated (booster shot at 30 days after first vaccination) against rabies using the Fuenzalida-Palácios modified vaccine in the urban area of Botucatu city, São Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (≥0.5 IU/mL) for 360 days after the first vaccination whereas 51.5% during all the study period. The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30 days after the first and the third dose at 180 days after the first for the maintenance of protective titers during 12 months.

[Vaccination coverage and factors associated with incomplete basic vaccination schedule in 12-month-old children, São Luís, Maranhão State, Brazil, 2006]. / Cobertura vacinal e fatores associados ao esquema vacinal básico incompleto aos 12 meses de idade, São Luís, Maranhão, Brasil, 2006.

The study aimed to evaluate vaccination coverage and factors associated with incomplete basic vaccination schedule at 12 months of age in 427 children aged 12-59 months in São Luis, Maranhão State, Brazil, 2006. This cross-sectional, population-based household survey used complex cluster sampling. Poisson regression with robust adjustment of variance was applied. Complete basic vaccination coverage was 71.9% for applied doses, 61.8% for valid doses, and 23.6% for correct doses. Hepatitis B and tetravalent vaccines showed higher percentages of doses on dates or at intervals lower than recommended. Percentages of delayed vaccination were high, except for BCG. Incomplete basic vaccination was more frequent in girls and children from low-income and black families. Racial, gender, and socioeconomic factors posed barriers to complete vaccination, thus emphasizing the need for policies to address such inequalities.

Cobertura vacinal e fatores associados ao esquema vacinal básico incompleto aos 12 meses de idade, São Luís, Maranhão, Brasil, 2006 / Vaccination coverage and factors associated with incomplete basic vaccination schedule in 12-month-old children, São Luís, Maranhão State, Brazil, 2006 / Cobertura de vacunación y factores asociados con esquemas incompletos de vacunación básica a los 12 meses de edad, São Luis, Maranhão, Brasil, 2006

O estudo objetivou avaliar a cobertura vacinal e os fatores associados ao esquema vacinal básico incompleto aos 12 meses de idade, em 427 crianças de 12 a 59 meses, em São Luís, Maranhão, Brasil, 2006. Trata-se de inquérito domiciliar transversal, de base populacional, com amostragem complexa por conglomerados. Empregou-se regressão de Poisson com ajuste robusto da variância. A cobertura para o esquema básico completo foi de 71,9% segundo doses aplicadas, 61,8% para doses válidas e 23,6% para doses corretas. As vacinas contra hepatite B e tetravalente apresentaram maiores percentuais de doses aplicadas em datas ou intervalos inferiores aos recomendados. Os percentuais de atraso vacinal foram elevados, exceto para a BCG. Percentuais mais elevados de esquema vacinal básico incompleto foram encontrados em crianças das classes econômicas D e E, do sexo feminino e de chefes de família de cor da pele preta. As desigualdades raciais, de gênero e socioeconômicas representaram barreiras à vacinação completa, indicando necessidade de reforçar as políticas equitativas que eliminem essas desigualdades.

The study aimed to evaluate vaccination coverage and factors associated with incomplete basic vaccination schedule at 12 months of age in 427 children aged 12-59 months in São Luis, Maranhão State, Brazil, 2006. This cross-sectional, population-based household survey used complex cluster sampling. Poisson regression with robust adjustment of variance was applied. Complete basic vaccination coverage was 71.9% for applied doses, 61.8% for valid doses, and 23.6% for correct doses. Hepatitis B and tetravalent vaccines showed higher percentages of doses on dates or at intervals lower than recommended. Percentages of delayed vaccination were high, except for BCG. Incomplete basic vaccination was more frequent in girls and children from low-income and black families. Racial, gender, and socioeconomic factors posed barriers to complete vaccination, thus emphasizing the need for policies to address such inequalities.

El estudio tiene como objetivo evaluar la cobertura de vacunación y los factores asociados al esquema incompleto de vacunación básico a los 12 meses de edad, realizado en 427 niños de 12 a 59 meses, en São Luis, Maranhão, Brasil, 2006. Se trata de una encuesta domiciliaria transversal, de base poblacional, con muestreo complejo por conglomerados. Se empleó la regresión de Poisson con un ajuste robusto de variancia. La cobertura para el esquema básico completo fue de un 71,9% según las dosis aplicadas, un 61,8% para dosis válidas y un 23,6% para dosis correctas. Las vacunas contra la hepatitis B y tetravalente presentaron mayores porcentajes de dosis aplicadas en fechas o intervalos inferiores a los recomendados. Los porcentajes de atraso en la vacunación fueron elevados, excepto para la vacuna BCG. Los porcentajes más elevados de esquema incompleto de vacunación básico se encontraron en niños de clases económicas D y E, de sexo femenino y con jefes de familia afrobrasileños. Las desigualdades raciales, de género y socioeconómicas representaron barreras a la vacunación completa, indicando la necesidad de reforzar las políticas equitativas que eliminen esas desigualdades.

Historia clínica pediátrica / Pediatric clinical record

La primera parte de la intervención del médico con un paciente radica en la obtención de información que conduzca al análisis del problema clínico; ésta tarea ha sido trabajada a lo largo del tiempo de formas muy diferentes y ha marcado la manera en cómo se enfocan los problemas de la salud. El eje de ese proceso ha sido la historia clínica, que ha cursado en diferentes modalidades en las diversas escuelas de Medicina; todas ellas conformando el principio de la propedéutica médica.

The first part of the intervention with a patient is to obtain information leading to the analysis of the clinical problem, this task has been worked over time in very different ways and has marked the way how to approach problems health. The heart of this process has been the medical history, which has taken different forms in different medical schools, all of them conforming to the principle of medical propaedeutic.

Vaccination coverage among children under two years of age based on electronic immunization registry in Southern Brazil.

OBJECTIVE: To evaluate the immunization program for 12 and 24-month-old children based on electronic immunization registry. METHODS: A descriptive study of a random sample of 2,637 children born in 2002 living in the city of Curitiba, Southern Brazil was performed. Data was collected from local electronic immunization registers and the National Live Birth Information System, as well as from a household survey for cases with incomplete records. Coverage at 12 and 24 months was estimated and analyzed according to the socioeconomic characteristics of each administrative district and the child's enrollment status in the health care service. The coverage, completeness, and record duplication in the registry were analyzed. RESULTS: Coverage of immunization was 95.3% at 12 months, with no disparities among administrative districts, and 90.3% at 24 months, with higher coverage in a district with lower socioeconomic conditions (p < 0.01). The proportion of vaccines, according to type, given before and after the recommended age reached 0.9% and 32.2%, respectively. In the surveyed sample, electronic immunization registry coverage was 98%, underreporting of vaccine doses was 11%, and record duplication was 20.6%. Groups with highest coverage included children with permanent records, children with three or more appointments through the National Unified Health Care System, and children seen within Primary Health Care Facilities fully adopting the Family Health Strategy. CONCLUSIONS: Vaccination coverage in Curitiba was high and homogeneous among districts, and health service enrollment status was an important factor in these results. The electronic immunization registry was a useful tool for monitoring vaccine coverage; however, it will be important to determine cost-effectiveness prior to wide-scale adoption by the National Immunization Program.

Immunity against infectious diseases: predictive value of self-reported history of vaccination and disease.

OBJECTIVE: To determine whether self-reported history of disease and/or vaccination is predictive of immunity against hepatitis B, varicella, rubella, mumps, and measles. DESIGN: The seroprevalence of viral antibodies and the predictive value of a self-report questionnaire were determined for 616 paramedical students who matriculated into Padua Medical School (Padua, Italy) during 2003-2005. RESULTS: The majority of subjects (86.9%) remembered being vaccinated against hepatitis B but had no recollection of disease. Among vaccinees, 1.5% showed markers of previous infection, 6.7% tested negative for anti-hepatitis B virus surface antigen (anti-HBsAg) antibodies, and 91.8% tested positive for anti-HBsAg. Self-reported vaccination history had a positive predictive value of 93.2% for test results positive for immunity against hepatitis B. Immunity against varicella (93.7% of subjects) and rubella (95.5%) was high, compared with immunity against mumps (79.9%) and measles (83.1%). In addition, results of tests for detection of immunity against mumps and measles were equivocal for more than 7% of subjects, probably because their vaccination regimen was not completed. Self-reported histories of varicella disease and rubella disease and vaccination had high positive predictive values (greater than 98% each) for testing positive for antiviral antibodies, compared with self-reported histories of mumps disease and vaccination and measles disease and vaccination; however, high positive predictive values were observed for self-reported histories of mumps only (92.0%) and measles only (94.7%). CONCLUSIONS: The self-report questionnaire used in this study did not accurately predict immunity against 5 transmittable but vaccine-preventable diseases. A complete serological evaluation of healthcare workers, followed by vaccination of those with negative or equivocal results of serological tests, is an appropriate measure to decrease the risk of infection in this population.

Active immunization of premature and low birth-weight infants: a review of immunogenicity, efficacy, and tolerability.

Preterm infants are at increased risk of disease and hospitalization from a number of vaccine-preventable diseases. However, these same infants have immunologic immaturities that may impact vaccine responses. Larger premature infants mount immune responses to vaccines similar to those of full-term infants, but very premature infants (<28-32 weeks' gestation at birth) may have specific defects in vaccine responsiveness. Although there are minor differences in immunogenicity, the immune responses to diphtheria, tetanus, pertussis, and polio antigens are similar enough between full-term and premature infants that clinical consequences are unlikely to result. However, the immunogenicity of Haemophilus influenzae type b conjugate vaccines varies widely among studies of premature infants, and may be affected by the choice of conjugate protein, inclusion in a combination vaccine, and by an infant's overall health. Pneumococcal conjugate vaccine is efficacious in larger premature infants, but little information is available about immunogenicity in smaller premature infants. Meningococcal group C conjugate vaccine appears immunogenic in even very premature infants, but the duration of immunity may be limited. Hepatitis B vaccine given at birth appears poorly immunogenic in infants with birth weights <1500-2000 g, with delay in the administration of the first dose yielding improved immunogenicity. Few data on influenza vaccine in premature infants are available, but infants with pulmonary disease may respond less robustly than others. Bacille Calmette Guérin vaccine appears to be most immunogenic if delayed until at least 34-35 weeks' postmenstrual age in very premature infants, although there may be non-specific advantages to its earlier administration. Premature infants may have persistently lower antibody titers than full-term infants, even years after initial immunization. Sick premature infants experience increased episodes of apnea or cardiorespiratory compromise following vaccine administration, necessitating careful monitoring. Specific factors that impair immune response, quality of the immune response, and safety and immunogenicity evaluation of new vaccines in premature infants are topics needing further research. Premature infants are at significant risk for decisions from healthcare providers that delay beginning and completing their vaccine regimens. A major challenge facing those who care for these infants is the provision of timely immunization.

Allergic reactions to vaccines.

Vaccines have had a very significant impact in Human Health. Except for public water supply and sanitation measure, no other single public health intervention induced such a significant reduction in disease incidence and child mortality. In Portugal, a National Vaccination Program (NVP) began in 1965 and more recently, in January 2006, the new NVP was implemented. However, it is important to recognize and understand adverse reaction to vaccines, since this therapy is intended to be administered to healthy individuals, a fact which considerably lowers the threshold of acceptability of adverse reactions by the general public. In such a way, better understanding of vaccine adverse reactions allows a correct diagnosis and a more appropriate selection of vaccines, increasing the acceptance of immunization in the community.

Vaccination coverage in the South-East Anatolian Project (SEAP) region and factors influencing low coverage.

OBJECTIVES: To determine the vaccination coverage of children living in the South-east Anatolian Project (SEAP) region; whether the vaccination coverage was similar to formal reports, other studies and other countries; and which factors influence vaccination, in order to indicate how vaccination coverage can be improved. STUDY DESIGN: A descriptive cross-sectional study conducted in nine provinces of the SEAP region in order to determine public health problems and their causes. METHODS: A population-based sample of 1150 houses was selected from rural and urban areas of the SEAP region and visited by the researchers. Questionnaires were applied in 2001 and 2002. RESULTS: In the SEAP region, only 30% of children had received a complete set of vaccines. The vaccination coverage was 76.7% for Bacille Calmette-Guérin; 62.0% for the third doses of diphtheria, tetanus toxoid, pertussis and polio vaccine; 62.7% for measles; 44% for the third dose of hepatitis B vaccine in children aged 12-23 months; and 13.3% for the second dose of tetanus toxoid in women who gave birth in the last 5 years. In logistic regression analysis, residence type, number of siblings, birth interval, follow-up visits of midwives, and maternal level of education were found to influence whether children were completely vaccinated. CONCLUSIONS: The findings of this study indicate that vaccination coverage is not acceptable in the SEAP region. Efforts must focus on family planning services, education of women, follow-up visits and strengthening health facilities, especially in rural regions, to improve vaccination.

Adolescent vaccination.

Indian Academy of Pediatrics (IAP) has taken an important step towards adolescent vaccination. In the present article, the author has briefly described the needs for adolescent immunisation along with the IAP vaccination schedule for adolescents, in details.

La vacunación en algunas situaciones especiales / The vaccine at some situations special

Los lactantes, niños y adolescentes en situaciones especiales constituyen un grupo en aumento sostenido. Esto fundamenta la necesidad de contar con normas estandarizadas e indicadores. La elección de la/s vacuna/s y la oportunidad de su aplicación están determinadas por la condición particular del huésped con alteraciones de la hemostasia; alergia, asplenia; implante coclear; enfermedad crónica - metabólica (fibrosis quística, broncodisplasia); hepática; renal -; enfermedades genéticas (síndrome de Down) y embarazo. Los lactantes, niños y adolescentes son habitualmente asistidos por equipos transdisciplinarios. Ello determina la necesidad de establecer responsabilidades con respecto a la evaluación de los antecedentes de las vacunas recibidas (con certificación) así como también la indicación rutinaria de otras vacunas que estará a cargo del pediatra, infectólogo u otro subespecialista (endocrinólogo, neumonólogo, etc) sugún la modalidad de trabajo con el fin de evitar oportunidades perdidas de vacunación