Abstract Objective: To identify and describe learnings from past pandemics and to suggest a framework for vaccine development as part of epi/pandemic readiness. Source of data: Articles/ reviews/letters on pandemic preparedness/ vaccines published between 2005 and 2022 in PubMed, MEDLINE, MedRxiv, BioRxiv, Research Square, Gates Open Research; who. int, cepi.net, visualcapitalist.com, airfinity.com, ted.com websites; press releases. Summary of findings: Disease pandemics caused by emerging pathogens impacted the social development, health and wealth of most societies in human history. In an outbreak, the first months determine its course. To block an exponential spread and the development of an epi/ pandemic early, vaccine availability in sufficient quantities is of paramount importance. It is inevitable that new human viruses will emerge. Any future pandemic will come likely from RNA viruses through zoonotic or vector transmission, but we cannot predict when or where “Disease X” will strike. Public health, scientific and societal readiness plans need to include: continuous identification of new viruses in common mammalian reservoir hosts; continuous epidemiological surveillance, including wastewater sampling; establishment of prototype vaccine libraries against various virus families sharing functional and structural properties; testing of various and innovative vaccine platforms including mRNA, vector, nasal or oral vaccines for suitability by virus family; functional clinical trial sites and laboratory networks in various geographies; more efficient phasing of preclinical and clinical activities; global harmonization and streamlining of regulatory requirements including pre-established protocols; and societal preparedness including combating any pandemic of misinformation. Conclusions: “Outbreaks are unavoidable, pandemics are optional”. Objective epipandemic epi data Articles reviewsletters reviews letters 200 202 PubMed MEDLINE MedRxiv BioRxiv Square who int cepinet cepi net cepi.net visualcapitalistcom visualcapitalist com visualcapitalist.com airfinitycom airfinity airfinity.com tedcom ted websites releases findings history outbreak course early importance emerge transmission X strike include hosts surveillance sampling properties mRNA family geographies activities preestablished pre established protocols misinformation Conclusions Outbreaks unavoidable optional. optional . optional” 20 2

OBJETIVO: Estimar a soroprevalência de anticorpos por vírus herpes simples (HSV-1 e HSV-2) e analisar fatores associados no Brasil. MÉTODOS: Estudo transversal realizado entre 1996 e 1997 em 1.090 indivíduos com idade entre um e 40 anos da população geral, em quatro diferentes regiões geográficas no Brasil. Foram analisadas amostras sangüíneas para detecção de anticorpos para HSV-1 e HSV-2 com teste tipo-específico Elisa. Foram descritas freqüências e proporções, comparadas entre grupos utilizando o teste de Fisher bilateral exato. Foi realizada análise de regressão logística para avaliar influência das variáveis sociodemográficas e histórico de DST, sobre a soroprevalência de HSV-1 e/ou HSV-2. RESULTADOS: As soroprevalências de anticorpos para HSV-1 e HSV-2, ajustadas por idade, foram 67,2% e 11,3% respectivamente, sem diferença quanto ao sexo e maiores na Região Norte. As soroprevalências aumentaram com a idade, e para HSV-2 o maior aumento ocorreu na adolescência e entre adultos jovens. Indivíduos soropositivos para HSV-1 apresentaram maior risco de serem positivos para HSV-2 (15,7%) quando comparados com os negativos para HSV-1 (4,7%). Na análise multivariada, o histórico de DST aumentou significativamente (OR=3,2) a probabilidade de soropositividade para HSV-2. CONCLUSÕES: As soroprevalências para HSV-1 e para HSV-2 variam com a idade e entre as regiões do Brasil. História pregressa de DST é importante fator de risco para aquisição de infecção por HSV-2.

OBJECTIVE: To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil and to analyze factors associated. METHODS: Cross-sectional study including subjects aged 1-40 years from the general population in four different geographical areas in Brazil between 1996 and 1997. All subjects were stratified by age and gender and 1,090 of them were included in the final analysis. Blood samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2) ELISA. Frequencies and proportions were described and compared among groups using two-sided Fisher's exact test. A logistic regression analysis was performed to assess the influence of the variables age, gender, geographical area, socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV-1 and/or HSV-2. RESULTS: The age-adjusted seroprevalences of HSV-1 and HSV-2 antibodies were 67.2% and 11.3%, respectively, without sex differences and being higher in the North region. Seroprevalences increased with age and, for HSV-2 infection, the higher increase was observed among adolescents and young adults. Subjects who tested positive for HSV-1 were more likely to also test positive for HSV-2 (15.7%) compared to HSV-1 negative subjects (4.7%). In the multivariate analysis past history of STD significantly (OR=3.2) increased the likelihood of HSV-2 infection whereas socioeconomic condition did not affect the results. CONCLUSIONS: HSV-1 and HSV-2 seroprevalences vary with age and among Brazilian regions. Past history of STD is a major risk factor for HSV-2 infection.

OBJETIVO: Estimar la seroprevalencia de anticuerpos por virus herpes simples (HSV-1 y HSV-2) en diferentes áreas geográficas en Brasil y analizar factores asociados. MÉTODOS: Estudio transversal realizado entre 1996 y 1997 con individuos de la población en general en cuatro diferentes áreas geográficas en Brasil y estratificados por edad (de uno a 40 años) y sexo, de los cuales 1.090 fueron incluidos en el análisis final. Fueron analizadas muestras de sangre para detección de anticuerpos para HSV-1 y HSV-2 con prueba tipo-específica ELISA gG1-gG2. Fueron descritas frecuencias y proporciones y comparadas entre grupos utilizando la prueba de Fisher bilateral exacta. Fue realizado análisis de regresión logística para evaluar influencia de las variables edad, sexo, geografía, grupo económico, histórico de DST, seropositividad para anti-HSV-1 o anti-HSV-2 e interacciones de cualquiera de esos factores sobre la seroprevalencia de HSV-1 y/o HSV-2. RESULTADOS: La tasa de seroprevalencia de anticuerpos para HSV-1 ajustada por edad fue de 67,2%, sin diferencia con relación al sexo, siendo mayor en la Región Norte. Las seroprevalencias aumentaron con la edad, y para HSV-2, hube un aumento significativo en la adolescencia y entre adultos jóvenes. Individuos seropositivos para HSV-1 presentaron mayor riesgo de ser positivos para HSV-2 (15,7%) cuando se compararon con los negativos para HSV-1 (4,7%). En el análisis multivariado, el histórico de DST aumentó significativamente (OR=3,2) la probabilidad de seropositividad para HSV-2. CONCLUSIONES: Las seroprevalencias para HSV-1 y para HSV-2 varían con la edad y presentan diferencias significativas entre las regiones de Brasil. Historia anterior de DST es importante factor de riesgo para adquisición de infección por HSV-2.

OBJETIVO: Estimar a soroprevalência de anticorpos por vírus herpes simples (HSV-1 e HSV-2) e analisar fatores associados no Brasil. MÉTODOS: Estudo transversal realizado entre 1996 e 1997 em 1.090 indivíduos com idade entre um e 40 anos da população geral, em quatro diferentes regiões geográficas no Brasil. Foram analisadas amostras sangüíneas para detecção de anticorpos para HSV-1 e HSV-2 com teste tipo-específico Elisa. Foram descritas freqüências e proporções, comparadas entre grupos utilizando o teste de Fisher bilateral exato. Foi realizada análise de regressão logística para avaliar influência das variáveis sociodemográficas e histórico de DST, sobre a soroprevalência de HSV-1 e/ou HSV-2. RESULTADOS: As soroprevalências de anticorpos para HSV-1 e HSV-2, ajustadas por idade, foram 67,2% e 11,3% respectivamente, sem diferença quanto ao sexo e maiores na Região Norte. As soroprevalências aumentaram com a idade, e para HSV-2 o maior aumento ocorreu na adolescência e entre adultos jovens. Indivíduos soropositivos para HSV-1 apresentaram maior risco de serem positivos para HSV-2 (15,7%) quando comparados com os negativos para HSV-1 (4,7%). Na análise multivariada, o histórico de DST aumentou significativamente (OR=3,2) a probabilidade de soropositividade para HSV-2. CONCLUSÕES: As soroprevalências para HSV-1 e para HSV-2 variam com a idade e entre as regiões do Brasil. História pregressa de DST é importante fator de risco para aquisição de infecção por HSV-2.

OBJECTIVE: To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil and to analyze factors associated. METHODS: Cross-sectional study including subjects aged 1-40 years from the general population in four different geographical areas in Brazil between 1996 and 1997. All subjects were stratified by age and gender and 1,090 of them were included in the final analysis. Blood samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2) ELISA. Frequencies and proportions were described and compared among groups using two-sided Fisher's exact test. A logistic regression analysis was performed to assess the influence of the variables age, gender, geographical area, socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV-1 and/or HSV-2. RESULTS: The age-adjusted seroprevalences of HSV-1 and HSV-2 antibodies were 67.2% and 11.3%, respectively, without sex differences and being higher in the North region. Seroprevalences increased with age and, for HSV-2 infection, the higher increase was observed among adolescents and young adults. Subjects who tested positive for HSV-1 were more likely to also test positive for HSV-2 (15.7%) compared to HSV-1 negative subjects (4.7%). In the multivariate analysis past history of STD significantly (OR=3.2) increased the likelihood of HSV-2 infection whereas socioeconomic condition did not affect the results. CONCLUSIONS: HSV-1 and HSV-2 seroprevalences vary with age and among Brazilian regions. Past history of STD is a major risk factor for HSV-2 infection.

OBJETIVO: Estimar la seroprevalencia de anticuerpos por virus herpes simples (HSV-1 y HSV-2) en diferentes áreas geográficas en Brasil y analizar factores asociados. MÉTODOS: Estudio transversal realizado entre 1996 y 1997 con individuos de la población en general en cuatro diferentes áreas geográficas en Brasil y estratificados por edad (de uno a 40 años) y sexo, de los cuales 1.090 fueron incluidos en el análisis final. Fueron analizadas muestras de sangre para detección de anticuerpos para HSV-1 y HSV-2 con prueba tipo-específica ELISA gG1-gG2. Fueron descritas frecuencias y proporciones y comparadas entre grupos utilizando la prueba de Fisher bilateral exacta. Fue realizado análisis de regresión logística para evaluar influencia de las variables edad, sexo, geografía, grupo económico, histórico de DST, seropositividad para anti-HSV-1 o anti-HSV-2 e interacciones de cualquiera de esos factores sobre la seroprevalencia de HSV-1 y/o HSV-2. RESULTADOS: La tasa de seroprevalencia de anticuerpos para HSV-1 ajustada por edad fue de 67,2%, sin diferencia con relación al sexo, siendo mayor en la Región Norte. Las seroprevalencias aumentaron con la edad, y para HSV-2, hube un aumento significativo en la adolescencia y entre adultos jóvenes. Individuos seropositivos para HSV-1 presentaron mayor riesgo de ser positivos para HSV-2 (15,7%) cuando se compararon con los negativos para HSV-1 (4,7%). En el análisis multivariado, el histórico de DST aumentó significativamente (OR=3,2) la probabilidad de seropositividad para HSV-2. CONCLUSIONES: Las seroprevalencias para HSV-1 y para HSV-2 varían con la edad y presentan diferencias significativas entre las regiones de Brasil. Historia anterior de DST es importante factor de riesgo para adquisición de infección por HSV-2.

Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs. The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety. Conclusions. Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory. The pentavalent vaccine was safe both for primary and booster vaccinations. Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.

Objetivos. La vacuna combinada pentavalente DTPw-HB/Hib ha sido creada siguiendo la recomendación de la Organización Mundial de la Salud de añadir las vacunas contra la hepatitis b (HB) y el Haemophilus influenzae tipo b (Hib) a los programas de vacunación infantil. Los objetivos del presente estudio consistieron en: 1) analizar la inmunogenicidad y reactogenicidad de la vacuna combinada pentavalente DTPw-HB/Hib en comparación con las inyecciones separadas de las vacunas DTPw-HB e Hib como vacunación primaria en un grupo de niños que habían recibido al nacer una dosis de vacuna contra la HB, y 2) evaluar la persistencia de anticuerpos en el segundo año de vida, así como la respuesta a las dosis de recuerdo de DTPw-HB/Hib o DTPw/Hib. Métodos. En la primera parte del estudio (fase de vacunación primaria), realizada en 1998-1999, se analizó la inmunogenicidad y reactogenicidad de la vacuna combinada DTPw-HB/Hib en comparación con inyecciones separadas de las vacunas DTPw-HB e Hib como vacunación primaria a los 2, 4 y 6 meses de edad en un grupo de 207 niños costarricenses que habían recibido al nacer una dosis de la vacuna contra la HB. Posteriormente, en la fase de vacunación de recuerdo, realizada en 1999-2000, se midió la persistencia de anticuerpos y se evaluó la respuesta a los recuerdos de DTPw-HB/Hib o DTPw/Hib en un subgrupo de 69 niños que tenían entonces 15 a 18 meses. Resultados. La vacunación primaria proporcionó concentraciones protectoras de anticuerpos frente a los antígenos empleados en las vacunas en al menos el 97,5% de los lactantes de ambos grupos. La vacuna combinada pentavalente DTPw-HB/Hib no originó más reacciones locales que la vacuna DTPw-HB aislada. Con respecto a las reacciones generales, no hubo diferencias clínicamente significativas entre ambas vacunas, y la combinada pentavalente tuvo la ventaja de necesitar una inyección menos. Nueve meses después de la tercera dosis de la vacunación primaria, la persistencia de anticuerpos fue similar en ambos grupos: más del 93% de los niños todavía tenían títulos protectores de anticuerpos frente al Hib, la HB y el tétanos, y cerca del 50% de ellos frente a la difteria y la tos ferina. A los 15 meses de edad, prácticamente todos los niños presentaron una fuerte respuesta de recuerdo a todos los antígenos de las vacunas, independientemente de que recibieran recuerdos de DTPw-HB/Hib pentavalente o DTPw/Hib. Ambos recuerdos fueron igualmente bien tolerados, lo cual indica que se pueden administrar hasta cinco dosis de vacuna contra la hepatitis B sin que haya problemas de seguridad. Conclusiones. Este estudio confirma que la vacuna pentavalente DTPw-HB/Hib es altamente inmunogénica en la vacunación primaria de niños vacunados contra la HB al nacer, y que la combinación pentavalente produce inmunidad persistente y potenciable mediante la administración de dosis de recuerdo. La vacuna pentavalente fue segura en la vacunación tanto primaria como de recuerdo. Por consiguiente, este estudio respalda el uso rutinario de la vacuna pentavalente DTPw-HB/Hib como parte de los programas de vacunación en Latinoamérica y el Caribe.

Objective. To assess the epidemiology and impact of traveler's diarrhea (TD) among visitors to the city of Fortaleza, Ceará, Brazil, as part of a global study on TD carried out in four countries. Methods. Within a cross-sectional survey, questionnaires were completed by departing travelers at the Fortaleza airport between March 1997 and February 1998. The questions inquired about demographics, duration of stay, reason for their visit, pretravel health advice they had received, risky food and beverage consumption while in Fortaleza, and quality of life during the visit to Fortaleza in relation to having or not having contracted TD. Results. A total of 12 499 questionnaires were analyzed. The most common reason that the visitors gave for their travel to Fortaleza was a holiday (60.3%). The total diarrhea attack rate was 13.4%. Younger people (< 36 years) had significantly higher TD attack rates than did older persons. Using a logistic regression model, we investigated the visitors' risk factors, including age, gender, length of stay, and trip's purpose. According to that analysis, characteristics that are slightly predictive of TD are gender, length of stay, and visiting as a tourist rather than for some other purpose. Characteristics that protect against contracting TD include being older and traveling for business rather than for some other reason. Of those who were incapacitated by TD, the mean duration of the impairment was 42 hours. Conclusions. TD affected the travel plans and activities of many of the visitors to Fortaleza. Further, although aware of the health risks, the majority of those travelers did not avoid all potentially contaminated food or beverage items. Given this pattern of behavior, future efforts to combat TD may have to depend on such other alternative strategies as new vaccines.

Objetivo. Evaluar la epidemiología y el impacto de la diarrea del viajero (DV) en personas que visitan Fortaleza, Brasil, como parte de un estudio general sobre la DV efectuado en cuatro países. Métodos. Se realizó una encuesta transversal en la que se pidió a personas en el aeropuerto que salían de Fortaleza entre marzo de 1997 y febrero de 1998 que completaran un cuestionario. Había preguntas sobre sus características demográficas, la duración de su estancia, la razón de la visita, los consejos que habían recibido antes del viaje, el consumo de alimentos y bebidas peligrosas en Fortaleza, y la calidad de vida durante su visita en relación con la presencia o ausencia de DV. Resultados. Se examinó un total de 12 499 cuestionarios. La razón citada con mayor frecuencia para haber viajado a Fortaleza fue tomarse vacaciones (60,3%). La tasa de ataque global fue de 13,4%. Las personas más jóvenes (< 36 años) tuvieron tasas de ataque mucho más altas que las de edad más avanzada. Usamos un modelo de regresión logística para investigar los factores de riesgo que tenían los turistas, entre ellos la edad, el sexo, la duración de la estancia y el motivo del viaje. Según los resultados de ese análisis, las características que predicen levemente la aparición de DV son el sexo, la duración de la estancia y el estar en viaje de turismo y no de cualquier otro tipo. Ser una persona de mayor edad y haber viajado por razones de negocio en lugar de otros motivos son factores que protegen contra la DV. De las personas que sufrieron discapacitación debido a la DV, la duración media del trastorno fue de 42 horas. Conclusiones. La VD afectó a los planes y actividades de turismo de muchas de las personas que visitaron Fortaleza. Aunque sabían que corrían un riesgo, la mayoría de esos viajeros no se abstuvieron de consumir alimentos o bebidas que podían estar contaminados. En vista de que así se comportan los viajeros, en un futuro cualquier iniciativa orientada a combatir la DV deberá depender de estrategias de otra índole, como por ejemplo, la aplicación de una nueva vacuna.

Avaliou-se a prevalência de anticorpos para as hepatites A e B em 3.653 indivíduos, em quatro regiões brasileiras. As prevalências de anti-VHA e de anti-HBc foram 64,7% e 7,9%, respectivamente. Prevalências mais elevadas de anti-VHA (92,8%) e de anti-HBc (21,4%) foram observadas na região Norte. Em outras regiões, prevalências de anti-VHA acima de 90% foram alcançadas apenas em idades mais avançadas, indicando uma endemicidade intermediária e prevalência significativamente mais elevada foi observada no grupo de baixo nível sócio-econômico, entre 1 e 30 anos. Para o anti-HBc observou-se um aumento na prevalência entre adolescentes e uma prevalência significativamente mais elevada no grupo de baixo nível sócio-econômico, entre 1 e 20 anos. Prevalência de 3,1% foi encontrada em crianças de 1 ano, sugerindo a transmissão vertical. Os principais resultados deste estudo, indicam que pré-adolescente/adolescentes de algumas cidades brasileiras estão em risco para as hepatites A e B, mas por diferentes motivos.

The prevalence of antibodies to hepatitis A and B virus was assessed in 3,653 subjects across four regions of Brazil. The anti-HAV and anti-HBc seroprevalence were 64.7% and 7.9%, respectively. The highest anti-HAV (92.8%) and anti-HBc (21.4%) rates were seen in the Northern region. In other regions, anti-HAV seroprevalence over 90% was only reached in the more elderly, indicating an intermediate endemicity and a significantly higher anti-HAV prevalence was seen in the low socioeconomic group between 1-30 years. With respect to anti-HBc seroprevalence an increase was seen in adolescents and there was a significantly higher anti-HBc prevalence in the lower socioeconomic group between 1-20 years. A 3.1% anti-HBc prevalence was seen in one-year-old infants, suggesting a vertical transmission. The major findings of this study indicate that the pre-adolescent and adolescent population in some Brazilian cities are at greatest risk from both hepatitis A and B infection, but for different reasons.

The seroprevalence of hepatitis B was investigated in over 12 000 subjects in six countries of Latin America: Argentina, Brazil, Chile, the Dominican Republic, Mexico, and Venezuela. Each study population was stratified according to age, gender, and socioeconomic status. Antibodies against hepatitis B core antigen (anti-HBc) were measured in order to determine hepatitis B infection. The highest overall seroprevalence was found in the Dominican Republic (21.4%), followed by Brazil (7.9%), Venezuela (3.2%), Argentina (2.1%), Mexico (1.4%), and Chile (0.6%). In all the countries an increase in seroprevalence was found among persons 16 years old and older, suggesting sexual transmission as the major route of infection. In addition, comparatively high seroprevalence levels were seen at an early age in the Dominican Republic and Brazil, implicating a vertical route of transmission.

Se investigó la seroprevalencia de hepatitis B en más de 12 000 sujetos en seis países de América Latina: Argentina, Brasil, Chile, México, República Dominicana y Venezuela. Cada una de las poblaciones estudiadas fue estratificada por edad, sexo y nivel socioeconómico. Se hicieron determinaciones de anticuerpos contra el antígeno nuclear del virus de la hepatitis B (anti-HBc) con el fin de detectar la infección. La seroprevalencia general más alta se encontró en la República Dominicana (21,4%), seguida del Brasil (7,9%), Venezuela (3,2%), Argentina (2,1%), México (1,4%) y Chile (0,6%). En todos los países se encontró un aumento de la seroprevalencia en personas de 16 años de edad o mayores, lo cual indica que la transmisión sexual es la principal fuente de infección. También se hallaron tasas de seroprevalencia elevadas en personas jóvenes en la República Dominicana y el Brasil, fenómeno que apunta hacia la vía de transmisión vertical.