Episodio Hipotonía-Hiporreactividad posterior a la inmunización con vacuna combinada con pertussis de células enteras. Reporte de un caso / Hypotonic-Hyporesponsive Episode after immunization with whole-cell pertussis combination vaccine. Clinical Case Report

Resumen Introducción: El Episodio Hipotonía-Hiporreactividad (EHH) es un efecto adverso tras la vacuna ción, asociado principalmente a vacunas anti-pertussis de células enteras. Se caracteriza por un inicio súbito de flacidez muscular, reducida respuesta a estímulos y palidez cutánea o cianosis. Aunque el EHH es infrecuente, está considerado como un efecto adverso severo. Objetivo: Reportar un caso de EHH posterior a la administración de la vacuna combinada pentavalente con: difteria, tétanos, pertussis celular, hepatitis B y Haemophilus influenzae tipo b (DTwP-HB-Hib), que está incluida en el Programa Nacional de Inmunizaciones (PNI) de Chile, con la finalidad de difundir esta infrecuente complicación de evolución benigna, auto-limitada y de carácter no recurrente. Caso clínico: Lactante de 6 meses de edad, 3 h post-vacunación con la tercera dosis de vacuna DTwP-HB-Hib, presentó compromiso del estado de conciencia interpretado como convulsión atónica y que finalmente se consideró como EHH. El lactante evolucionó favorablemente después de 2 h y fue dado de alta tras 24 h de vigilancia clínica; se cambió el esquema de inmunización del lactante con vacunas anti-per tussis acelulares como medida preventiva. Conclusiones: El desconocimiento sobre el EHH puede desalentar la inmunización infantil. Por lo tanto, es importante que el personal médico informe a los padres de los pacientes sobre este evento benigno, autolimitado y no recurrente. En estos casos, se re comienda continuar con el programa de inmunización del lactante con formulaciones que contengan componentes anti-pertussis acelulares.

Abstract Introduction: Hypotonic-Hyporesponsive Episode (HHE) is an adverse event after vaccination, mainly associated with whole-cell pertussis vaccines. It is characterized by a sudden onset of muscle flaccidity, reduced response to stimuli and pallor or cyanosis. Although the HHE is infrequent, it is considered a severe adverse event. Objective: To report a case of HHE following the administration of the whole-cell pertussis combination vaccine (DTwP-HB-Hib), which is included in National Im munization Program (PNI) of Chile, and to contributing to the knowledge of this adverse event in the country. Case report: A 6-month-old infant, 3 hours post-vaccination with the third dose of DTwP-HB-Hib vaccine, presented a decreased level of consciousness that was interpreted as atonic seizure but finally considered as EHH. The infant progressed favorably after 2 hours of clinical observation and was discharged 24 hours later. Parents were suggested to continue the immunization schedule of the infant with acellular pertussis vaccines as a preventive measure. Conclusions: The lack of knowledge about the EHH may discourage childhood immunization. Therefore, it is important for the medical staff to inform parents of the patients about this benign, self-limited and non-recurrent adverse event. In these cases, it is recommended to continue the immunization schedule of the infant with acellular pertussis vaccines.

Eficácia e segurança da vacina brasileira contra hepatite B em recém-nascidos / Efficacy and safety of the Brazilian vaccine against Hepatitis B in newborns

OBJETIVO: Analisar a eficácia e segurança de vacina recombinante contra hepatite B em recém-nascidos. MÉTODOS: O estudo foi conduzido em hospital geral do município de Guarulhos, SP, entre 2002 e 2005. A vacina recombinante contra hepatite B do Instituto Butantan (VrHB-IB) foi analisada em dois ensaios clínicos. Em ambos os ensaios, os recém-nascidos foram alocados aleatoriamente ao grupo experimental ou controle (vacina de referência). Os recém-nascidos receberam três doses das vacinas, uma em até 24 h após o nascimento e as subseqüentes 30 e 180 dias após. No primeiro ensaio 538 recém-nascidos completaram o protocolo e no segundo ensaio, 486. Considerou-se critério de equivalência a diferença na soroproteção inferior a 5 por cento. RESULTADOS: A soroproteção no primeiro ensaio (anti HBs > 10mUI/ml) foi de 92,5 por cento (247/267) no grupo experimental, comparada a 98,5 por cento (267/271) no grupo controle (p = 0,001). Com este resultado, a VrHB-IB não atingiu o critério de equivalência estabelecido. Após o aumento da concentração de antígeno na vacina para 25»g, a soroproteção no segundo ensaio foi de 100 por cento no grupo experimental e 99,2 por cento no grupo controle. Nenhum evento adverso grave foi registrado. CONCLUSÕES: A vacina VrHB-IB modificada foi considerada equivalente à vacina de referência e seu uso recomendado à vacinação de recém-nascidos.

OBJECTIVE: To analyze the efficacy and safety of a recombinant Hepatitis B vaccine in newborns. METHODS: The study was carried out in a general hospital in the city of Guarulhos, Southeastern Brazil, between 2002 and 2005. The recombinant Hepatitis B vaccine from Instituto Butantan (VrHB-IB) was tested in two clinical trials. In both trials, newborns were randomly allocated to the experimental or control (reference vaccine) groups. Newborns were given three doses of vaccine, one up to 24 hours after birth and the other two 30 and 180 days later. In the first trial, 538 newborns completed the immunization protocol, and 486 in the second. Vaccines were considered equivalent when seroprotection difference was below 5 percent. RESULTS: Seroprotection in the first trial (anti-HBs > 10mUI/ml) was 92.5 percent (247/267) in the experimental group, compared to 98.5 percent (267/271) in the control (p = 0.001). With this result, VrHB-IB did not fulfill the pre-established criterion for equivalence. After increasing the concentration of antigen in the vaccine to 25»g, seroprotection reached 100 percent in the experimental group and 99.2 percent in the control. No severe adverse effects were recorded. CONCLUSIONS: The reformulated VrHB-IB is considered equivalent to the reference vaccine, and its use is recommended in newborns.

Immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type b conjugate combination vaccine (pentaxim™) with hepatitis B vaccine.

Objective: To obtain immunogenicity and safety data for a pentavalent combination vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate). Design: Multicenter, open, Phase III clinical study. A DTaP-IPV//PRP~T vaccine (PentaximTM) was given at 6,10,14 weeks of age; and Hepatitis B vaccine at 0,6,14 or at 6,10,14 weeks of age. Immunogenicity assessed 1 month post-3rd dose; safety assessed for 30 minutes by the investigator, then by parents and investigators to 8 days and 30 days post-vaccination. Setting: Tertiary-care hospitals. Participants/patients: 226 healthy Indian infants (6 weeks of age). Main outcome measures: Immunogenicity and safety. Results: Immunogenicity was high for each vaccine antigen, and similar to a historical control study (France) following a 2,3,4 month of age administration schedule. Post-3rd dose, 98.6% of subjects had anti-PRP ³0.15 mg/mL and 90.0% had titers ³1.0 mg/mL; the anti-PRP GMT was 4.1 µg/mL. Seroprotection rates for diphtheria and tetanus (³0.01 IU/mL) were 99.1% and 100%; and 100%,99.1% and 100%, for polio types 1,2 and 3 (³8 [1/dil]) respectively. Anti-polio GMTs were 440.5,458.9, and 1510.7 (1/dil) for types 1,2 and 3 respectively. The vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 93.7% for PT and 85.7% for FHA; the 2-fold increase was 97.1% and 92.4%. Vaccine reactogenicity was low with adverse reaction incidence not increasing with subsequent doses. Conclusion: The DTaP-IPV//PRP~T vaccine, given concomitantly with monovalent hepatitis B vaccine, was highly immunogenic at 6, 10 and 14 weeks of age in infants in India. The vaccine was well tolerated.

Erythema multiforme following vaccination in an infant.

Erythema multiforme is a cutaneous reaction pattern precipitated by varied agents, notably herpes simplex and drugs. It predominantly occurs in adolescents and young adults but may be seen at other ages also. While vaccination is rarely a precipitating factor for erythema multiforme, it may occasionally be seen in infants and children. We report here a case of a two month-old infant with lesions of erythema multiforme minor appearing after two weeks following vaccination for DPT, Hepatitis B and influenza.

Análise dos eventos adversos pós-vacinais ocorridos em Teresina / Analysis of after-vacination side-effects occurred in Teresina

Este estudo trata do perfil dos eventos adversos pós-vacinais ocorridos em Teresina em 2006. Os dados foram coletados mediante a aplicação de formulário com 73 participantes em 18 Unidades Básicas de Saúde. Os resultados mostram que as vacinas que mais produziram eventos adversos foram a tetravalente, BCG e DPT. Os eventos mais freqüentes foram: febre, episódio hipotônico hiporresponsivo, irritabilidade e manifestações locais moderadas. Dentre as condutas adotadas pelos profissionais de saúde, aproximadamente 80 por cento foram adequadas. Os menores de ano foram os mais acometidos pelos eventos. Todos os eventos evoluíram para a cura. Conclui-se que a ação de vacinação ainda continua requerendo capacitação constante dos profissionais da área. Sugere-se aprofundar o conhecimento com relação ao manejo, diagnóstico, investigação e tratamento.

This study focuses the profile of the adverse events after-vaccine occurrences in Teresina in 2006. The data had been collected by means of the form application with 73 participants in 18 Basic Units of Health. The results show that the vaccines that had more produced events adverse had been tetravalente, BCG and DPT. The events most frequent had been: fever, hiporresponsivo hipotonic episode, moderate irritability and local manifestations. Amongst the behaviors adopted for the health professionals, 80 percent had been approximately adjusted. The year minors had been accomitted by the events. All the events had evolved for the cure. It was concluded that the action of vaccination still continues requiring constant qualification of the professionals of the area. It is suggested to deepen the knowledge with relation to the handling, diagnosis, inquiry and treatment.

El presente estudio trata del perfil de las ocurrencias adversas de la después-vacuna en Teresina en 2006. Los datos fueron recogidos por medio del uso un formulário a lo cual participaran 73 personas en 18 unidades básicas de salud. Los resultados demuestraran que las vacunas que tenían más ocurrencias adversas fueran la tetravalente, BCG y DPT. Las ocurrencias más frecuentes fueran: fiebre, episodio hipotônico hiporresponsivo, irritabilidad moderada y manifestaciones locales. Entre los comportamientos adoptados por los profesionales de salud, 80 por ciento fueran ajustados aproximadamente. Los menores de edad del año habían sido acometidos por los acontecimientos. Todos los acontecimientos fueran desarrollados para la cura. Se hay concluydo que la acción de la vacunación todavía continúa requiriendo la calificación constante de los profesionales de la área. Se sugiere para profundizar el conocimiento en relación a la dirección, a la diagnosis, a la investigación y al tratamiento.

Vacunación contra hepatitis B: veinte años después / Vaccination against hepatitis B: twenty years later

Desde 1984 en que se inició la vacunación contra la hepatitis B, primero con una vacuna derivada de plasma y luego una desarrollada por DNA recombinante, han transcurrido mas de veinte años y en ese lapso se han producido importantes cambios en diferentes aspectos de esta enfermedad, se ha reducido efectivamente las tasas de infección aguda y crónica, la tasa de mortalidad por hepatitis fulminante en infantes y la incidencia de carcinoma hepatocelular en aproximadamente 25 por ciento; la vacunación en la infancia ha producido adecuada protección hasta 20 años después. Se ha confirmado la aparición de mutantes del gen de superficie de hepatitis B en niños DNA VHB positivo, los que gradualmente se incrementaron de 7,8 por ciento antes de la vacunación a 23.1 por ciento 15 años después. A la fecha no hay evidencia que esos virus están alterando los esfuerzos para controlar la hepatitis por virus B a través de los programas de inmunización. También se ha establecido una buena respuesta inmune en la vacunación de niños prematuros y de bajo peso al nacer, retrasando el inicio de la vacunación entre 7 y 30 días después del nacimiento; así mismo se ha sugerido un riesgo incrementado de no respuesta a la vacuna en personas mayores. Finalmente se ha comprobado que la vacuna contra hepatitis B es una de las mas seguras del mundo.

From1984, when begin vaccination against hepatitis B, first with plasma derived vaccine and then with DNA recombinant vaccine up to day, it past 20 years and happened important changes in several topics of this disease : vaccination effectively reduced the acute and chronic infection rates, also fulminant hepatitis B in infancy and the incidence of hepatocellular carcinoma in children; by the other hand, universal vaccination in infancy has produced adequate protection up to 20 years. Also, it was confirmed the appearing of hepatitis B surface gene mutants in DNA HBV positive children and the rate was increased gradually from 7,8 percent before vaccination to 23,1 percent 15 years after vaccination program. To date, there is no evidence that these viruses are disrupt in efforts to control HBV through immunization programs. It was stablished a good immune response to HBV vaccine of preterm children and low birth weigth when delay of 7 to 30 days the initiating of routine chilhood immunization schedule; also was suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals. Finally the hepatitis B vaccine is one of the safest vaccines available in the world.

Polymyositis: rare complication of hepatitis B vaccination. An unusual cause of toxic shock syndrome

Transient weakness of the legs developed in a 17 year-old male high school student three weeks after the initial injection of a hepatitis B vaccine. Seventeen days after the second injection of the vaccine, low-grade fever, a pruritic maculopapular rash appeared and weakness of the legs recurred. This was associated with elevation of the creatinine kinase to 2,406 U/L. The day after admission he became afebrile and in the subsequent four days the rash improved but leg weakness persisted. One-month later, muscle strength had returned; and the creatinine kinase had returned to normal levels. The only case of dermatomyositis associated with hepatitis B vaccination and the findings in the six reported cases of surface antigen-positive hepatitis associated with polyomyositis or dermatomyositis are briefly reviewed. Hepatitis B vaccination should be encouraged, but it is important to be aware that, rarely, dermatomyositis, polymyositis or neurovascular complications may occur. Polymyositis associated with the administration of the hepatitis B vaccine or with hepatitis B virus infection is a rare occurrence. A Medline Search performed from 1960 to January 2002 associating hepatitis B vaccine or hepatitis B virus with myopathy, myositis, polymyositis and dermatomyositis, showed only one case of dermatomyositis related to the hepatitis B vaccine, and six case reports relating polymyositis to hepatitis B virus infection. We present a case where a causal relationship between polymyositis and hepatitis B vaccination appears quite likely

Emergence of vaccine-induced escape mutant of hepatitis b virus with multiple surface gene mutations in a korean child

The S protein of hepatitis B virus is the principal component of virus envelope and the primary target of anti-HBs response. Mutants or variants that escape neutralization by anti-HBs have been selected during immunoprophylaxis of HBV after birth and liver transplantation. We investigated a case of a Korean child who was vaccinated at birth against hepatitis B and also given hepatitis B immunoglobulin, but nevertheless later became infected with the virus. Hepatitis B virus-specific deoxyribonucleic acid covering the region of genome encoding the predominant "a" determinant of hepatitis surface antigen was amplified using polymerase chain reaction, and the nucleotide sequence was determined. We present for the first time in Korea the independent emergence of an escape mutant with substitution of arginine for glycine at amino acid 145 and proline for glutamate at amino acid 120 in "a" determinant after immunization.

Guillain - Barre' syndrome following recombinant hepatitis B vaccine and literature review.

A 17 year-old woman developed progressive quadriparesis with bilateral facial diplegia after immunization with recombinant hepatitis B vaccine 3 days prior. Cerebrospinal fluid analysis revealed acellular fluid with high protein level. The electrodiagnosis was compatible with demyelinating polyneuropathy. Other potential causes of Guillain-Barre' syndrome (GBS) were ruled out. Her motor power gradually improved and returned to normal later. The temporal relationship between GBS and vaccination was suggestive of a vaccine-induced cause. Mechanisms of this very rare complication are proposed with a literature review.

Safety and immunogenicity of hepatitis b vaccine butang in adults

Vacina contra hepatite B, produzida no Instituto Butantan em levedura recombinante, foi administrada em dois grupos de voluntarios adultos (I e II) seguindo dois esquemas diferentes de imunizacao. No primeiro ensaio (doses de 10 ug e esquema de vacinacao de 0, 1, 3 meses). 106 individuos completaram p programa de imunizacao proposto...

Clinical safety and efficacy of first indigenous recombinant hepatitis B vaccine.

A pilot study was conducted to assess the clinical safety and immunogenicity of an indigenously developed recombinant hepatitis B vaccine (Shanvac B) in 18 healthy adults. 20 microg of vaccine was administered at 0, 1 and 2 months. Protective anti HBs titres developed in 22%, 77% and 100% one month after 1st, 2nd and 3rd dose of vaccination, respectively. The geometric mean titre after the 3rd dose was 1015.29 mIu/ml. The vaccine was well tolerated with minor local and systemic side effects in 28% and 22%, respectively. The indigenously developed recombinant hepatitis B vaccine is safe, well tolerated and highly immunogenic.

Respuesta a la vacunación contra la hepatitis B en trabajadores de la salud del Hospital San Juan de Dios de Santa Fe de Bogotá

Objetivo: evaluar la respuesta protectora y la frecuencia de reacciones adversas de la vacuna recombinante cubana Herberbiovac HB contra el virus de la hepatitis B (VHB) en trabajadores de la salud del Hospital San Juan de Dios de Bogotá (HSJD), y estudiar el riesgo que tienen estos trabajadores de contraer la infección por VHB. Método: se utilizaron los marcadores del anticuerpo contra el antígeno de superficie (anti-HBs) y del anticuerpo contra el antígeno central (anti- HBc) del virus de la hepatitis B, los cuales fueron medidos 15 meses después de la vacunación en 132 trabajadores participantes. Resultados: esta vacuna (Heberbiovac HB) produjo una seroprotección de 93,2 por ciento (IC95 por ciento = 87,0 a 96,6 por ciento). El dolor local y el malestar general fueron los síntomas adversos más frecuentes derivados de su aplicación. Los trabajadores estudiados presentaron un alto riesgo para contraer la infección por VHB, ya que 22,2 por ciento (26/132) refirieron accidentes laborales con sangre o secreciones corporales en los últimos 15 meses postvacunación y 7,6 por ciento (2/26) de estos accidentes fueron positivos para el anticore del VHB. Conclusiones: 1) La vacuna estudiada posee cualidades de reactogenicidad e inmunogenecidad similares a las descritas con otras vacunas recombinantes. 2) Los trabajadores del Hospital San Juan de Dios tienen un alto riesgo para contraer la infección por VHB, siendo el grupo de enfermería el de mayor riesgo

Acute Myelitis after hepatitis B vaccination

We report a case of myelitis after plasma-derived hepatitis B vaccination. The patient was a 31-year-old man who presented with progressive sensory symptoms in extremities that developed 2 weeks after a third vaccination. MRI of the cervicothoracic region revealed swelling and T2 high signal at the level of C4 to C5 cord, and isolated enhancement in the posterior columns between C4 and C5 cord. The significance of MRI findings and HLA haplotype of the patient will be briefly discussed.

Reacciones adversas y respuesta inmune de la vacuna Heberbiovac-HB aplicada a lactantes, simultáneamente con la DPT y la VA-MENGOC-BC / Adverse reaction and immune response of the Heberbiovac-HB vaccine administered to infants simultaneously with DPT and VA-MENGOC-BC

Se aplicó la vacuna recombinante cubana (Heberbiovac-HB) derivada de células de levaduras, contra el virus de la hepatitis B, a la dosis de 10µg, a 2 grupos de niños de edades de 3 meses y esquema de 0, 1 y 6, y 0, 1, 2 y 12 en coincidencia con las vacunas DPT y antimeningocócica, según se establece en el programa de inmunizaciones. Se estudió la reactogenicidad e inmunogenicidad en ambos grupos, las reacciones observadas fueron ligeras y similares a otros estudios, donde la febrícula eritema e induración fueron los signos más frecuentes. Ambos grupos mostraron altos porcentajes de niños con títulos de anticuerpos anti-HBs superiores a 100 UI/L-1. Se demuestra la aceptable reactogenicidad de la vacuna y la no interferencia inmunológica por las otras vacunas aplicadas

Hepatite B: imunizaçäo universal / Hepatitis B: universal immunization

Estima-se que mais de dois bilhöes de indivíduos, dois em cada cinco habitantes da Terra, estäo infectados pelo vírus da hepatite B, sendo o mesmo responsável por 1 a 2 milhöes de óbitos/ano em todo o mundo. A disponibilidade de vacinas altamente eficazes e com pequeno número de efeitos colaterais, aparece como a unica forma de controlar tal infecçäo, sendo a estratégia de vacinaçäo universal de todos os lactentes, proposta pela OMS e ja utilizada em cerca de 32 paises em todo o mundo, a mais adequada para o alcance deste objetivo