Meningococo y VPH vacunas José Nuñez del Prado Alcoreza Residencia de Pediatría Hospital Ángeles del Pedregal México, Distrito Federal Mayo 2010

Enfermedad por meningococo y vacunas Revised May 2009

Neisseria meningitidis Infección aguda bacteriana severa Causa meningitis, sepsis, e infecciones focales Epidemica en Africa Sub-sahariana Polisacarido licencia 1978/ Conjugada 2005

Neisseria meningitidis Bacteria Aerobia gram-negatia 13 sero-grupos basados en caracteristicas de capsula de polisacarido Enfermedad invasiva sero-grupos A, B, C, Y, y W-135

Patogenia - Enfermedad por meningococo Coloniza nasofaringe Invade torrente sanguíneo y causa infecciones a distancia. Antecedente de IRA alta puede estarrelacionado

Presentación clínica Periodo de Incubación de 3-4 días (ranoe 2-10 días) Fiebre Abrupta, síntomas meningeos, hipotension y rash Indice de Fatalidad 9%-12%; hasta 40% en meningococcemia

Neisseria meningitidis Manifestationes Clinicas* *1992-1996 data

Meningitis Meningococcica Presentación más frecuente Resultado de diseminación hematogena Cuadro Clínico: fiebre Cefalea Rigidez de nuca y cuello

Meningococcemia Infección Hematológica Con o sin meningitis Hallazgos clínicos fiebre Rash petequial y purpúrico hipotension Falla multi-orgánica

Meningococcal Disease Laboratory Diagnosis Bacterial culture Gram stain Non-culture methods Antigen detection in CSF Serology

Neisseria meningitidis Medical Management Initial empiric antibiotic treatment after appropriate cultures are obtained Treatment with penicillin alone recommended after confirmation of N. meningitidis

Meningococcal Disease Epidemiology Reservoir Human Transmission Respiratory droplets Temporal pattern Peaks in late winter–early spring Communicability Generally limited Limited communicability implied from lack of secondary cases in household settings. Secondary cases may occur in some situations, such as day care settings.

Meningococcal Disease - United States, 1972-2007

Meningococcal Disease, 1998 Incidence by Age Group U.S. Rate *Rate per 100,000 population. Source: Active Bacterial Core surveillance/Emerging Infections Program network

Rates of Meningococcal Disease* by Age, United States, 1991-2002 U.S. Rate * Serogroups A/C/Y/W135

Meningococcal Disease in the United States Distribution of cases by serogroup varies by time and age group In 1996-2001: 31% serogroup B 42% serogroup C 21% serogroup Y 65% of cases among children younger than 1 year of age caused by serogroup B

Neisseria meningitidis Risk factors for invasive disease Host factors Terminal complement pathway deficiency Asplenia Genetic risk factors Exposure factors Household exposure Demographic and socioeconomic factors and crowding Concurrent upper respiratory tract infection Active and passive smoking

Meningococcal Disease Among Young Adults, United States, 1998-1999 18-23 years old 1.4 / 100,000 18-23 years old not college student 1.4 / 100,000 Freshmen 1.9 / 100,000 Freshmen in dorm 5.1 / 100,000 Bruce et al, JAMA 2001;286;688-93

Meningococcal Outbreaks in the United States Outbreaks account for less than 5% of reported cases Frequency of localized outbreaks has increased since 1991 Most recent outbreaks caused by serogroup C Since 1997 outbreaks caused by serogroup Y and B organisms have also been reported

Meningococcal Polysaccharide Vaccine (MPSV) Menomune® (sanofi pasteur) Quadrivalent polysaccharide vaccine (A, C, Y, W-135) Administered by subcutaneous injection 10-dose vial contains thimerosal as a preservative

Meningococcal Conjugate Vaccine (MCV) Menactra® (sanofi pasteur) Quadrivalent polysaccharide vaccine (A, C, Y, W-135) conjugated to diphtheria toxoid Administered by intramuscular injection Single dose vials do not contain a preservative

MPSV Recommendations Approved for persons 2 years of age and older Not recommended for routine vaccination of civilians Should be used only for persons at increased risk of N. meningiditis infection who are 56 years of age or older, or if MCV is not available

MCV Recommendations MMWR 2005; 54(RR-7);1-21 Routinely recommended for: All children at 11-18 years of age All college freshmen living in a dormitory Other persons 2 through 55 years of age at increased risk of invasive meningococcal disease At its February 2005 meeting the Advisory Committee on Immunization Practices voted to recommend routine meningococcal vaccination for several other groups. Meningococcal conjugate vaccine is recommended for all persons at their preadolescent visit, which should occur at ages 11 or 12 years. This is also the time when most children should receive their first TD booster dose. In order to produce a more rapid reduction of meningococcal disease among adolescents ACIP also recommended that for the next 2 to 3 years teens about to enter high school also be vaccinated, at about age 15 years. College freshmen living in a dormitory should be routinely vaccinated because of their increased risk of invasive disease. Other adolescents who wish to reduce their risk for meningococcal disease may elect to receive vaccine. MCV is preferred for all these groups. MMWR 2005; 54(RR-7);1-21

Meningococcal Vaccine Recommendations Use of MCV is preferred for persons 2 through 55 years of age for whom meningococcal vaccine is recommended MPSV should be used for persons 56 years and older MMWR 2005; 54(RR-7);1-21

Meningococcal Vaccine Recommendations Recommended for persons at increased risk of meningococcal disease: Microbiologists who are routinely exposed to isolates of N. meningitidis Military recruits Persons who travel to and U.S. citizens who reside in countries in which N. meningitidis is hyperendemic or epidemic terminal complement component deficiency functional or anatomic asplenia MMWR 2005; 54(RR-7);1-21

Meningococcal Endemic Areas 2004 Senegal and Gambia in the west to Ethiopia in the east.

Meningococcal Vaccine Recommendations Both MCV and MPSV recommended for control of outbreaks caused by vaccine-preventable serogroups Outbreak definition: 3 or more confirmed or probable primary cases Period <3 months Primary attack rate >10 cases per 100,000 population* *Population-based rates should be used rather than age-specific attack rates

Meningococcal Vaccine Revaccination Revaccination may be indicated for persons at increased risk for infection* Revaccination may be considered 5 years after receipt of the MPSV MCV is recommended for revaccination of persons 2 through 55 years of age although use of MPSV is acceptable Revaccination after receipt of MCV is not recommended at this time *e.g., asplenic persons and those who reside in areas in which disease is endemic (does not include college settings)

Meningococcal Vaccines Adverse Reactions MPSV MCV Local reactions 4%-48% 11%-59% for 1-2 days Fever >100oF 3% 5% Systemic reactions 3%-60% 4%-62% (headache, malaise fatigue)

Meningococcal Vaccines Contraindications and Precautions Severe allergic reaction to vaccine component or following prior dose of vaccine Moderate or severe acute illness

CDC Vaccines and Immunization Contact Information Telephone 800.CDC.INFO Email nipinfo@cdc.gov Website www.cdc.gov/vaccines

Papiloma-virus Humano y la vacuna VPH

Papiloma-virus Humano VPH Virus DNA, pequeño Más de 100 tipos, por secuencia genética de la proteína de capside externa L1 40 tipos infectan el epitelio mucoso

Tipos de VPH y asociación con enfermedades mucosas/genital(~40 tipos) No-mucoso/cutaneo (~60 tipos) Tipos de alto riesgo 16, 18, 31, 45 (Y otros) Tipos de bajo riesgo 6, 11 (y otros) verrugas cutaneas En Manos y pies Anormalidad cervical de alto grado Precursores de cancer Cancer anogenital Anormalidades cervicales de bajo grado Verrugas genitales Papilomas laringeos

Enfermedades asociadas al VPH Tipo mujeres varones 16/18 70% de Cancer cervical 70% cancer anal-genital 70% transmisión de cancer anal a mujeres 6/11 90% de verrugas genitales 90% verrugas genitales

Historia natural de la infección por VPH 1 año 1 a 5 años décadas Infección inicial por VPH Infección persistente NIC 2/3 CancerCervical NIC 1 Recuperación dela infección

Presentación clínica del VPH Principales manifestaciones: Verrugas ano-genitales Papilomatosis respiratoria recurrente Precursores de cancer: Neoplasia Intraepitelial Cervical NIC Cancer: Cervical, anal, vulvar, penil, y algunas formas de cancer de cabeza y cuello)

Transmision Contacto directo, usualmente sexual HPV Epidemiología reservorio Humano Transmision Contacto directo, usualmente sexual Patron temporal ninguno transmisibilidad Presuntamente alta

Panorama general del VPH Infección ano-genital de transmisión sexual más común en el mundo Aproximadamente 20 millones de infectados 6.2 nuevas infecciones/año Común entre adolecentes y jovenes Cerca al 80% de mueres sexualmente activas tienen la infección a los 50 años Infección frecuente en varones.

Panorama general del VPH Estimación de la ACS 2008 11,070 nuevos casos de cancer 3,870 muertes por cancer cervical Casi 100% causados por los 40 tipos de VPH que infectan mucosa

Monitorización del Cancer Cervical 30% de cancer cervical no prevenible con vacuna tetravalente Tipos no cubiertos por vacuna Infección sexual previa a vacunación

Vacuna VPH HPV L1 Proteina mayor de cápside, base para la vacuna. Proteina L1 expresada en yemas, por tecnología recombinante. Proteina L1 se ensamblan a las partículas virales VLP. Las VLPs son no infeccioas y no oncogénicas

Eficacia de la vacuna VPH meta Eficacia HPV 16/18- NIC 2/3 o AIS 100 HPV 6/11/16/18 NIC relacionado 95 Para verrugas genitales 99 *Entre mujeres de 16-26 años. CIN – neoplasia intraepitelial cervical; AIS – adenocarcinoma in situ

Eficacia para VPH Alta eficacia para mujeres no infectadas por tipos incluidos en la vacuna Infección previa por un tipo no interfiere con inmunogenicidad contra otros tipos incluidos en la vacuna

Vacuna VPH Recomendaciones Rutinaria en mujeres de 11 a 12 años A discreción clínica Refuerzo entre los 13 a los 26 años. MMWR 2007;56(RR-2):1-24

Calendario de vacunación Rutinaria: 0-2 y 6 meses. La tercera dosis, se da 24 semanas despúes de la primera. No usar intervalos abreviados. No reiniciar la serie si se interrumpe.

Consideraciones especiales. La vacuna tetravalente no se recomienda para varones o mujeres menores de 9 o mayores de 26 años.

Situaciones especiales PAP anormal o erroneo Test DNA + VPH Verrugas genitales Inmunosupresión Lactancia

Reacciones adversas Locales 84% (dolor, edema) Fiebre 10%

Contraindicaciones y precauciones Reacción Severa a la vacuna Precaución Enfermedad aguda severa