Burden of influenza-associated deaths in the Americas, 2002-2008.

BACKGROUND: Influenza disease is a vaccine-preventable cause of morbidity and mortality. The Pan American Health Organization (PAHO) region has invested in influenza vaccines, but few estimates of influenza burden exist to justify these investments. We estimated influenza-associated deaths for 35 PAHO countries during 2002-2008. METHODS: Annually, PAHO countries report registered deaths. We used respiratory and circulatory (R&C) codes from seven countries with distinct influenza seasonality and high-quality mortality data to estimate influenza-associated mortality rates by age group (0-64, 65-74, and ≥ 75 years) with a Serfling regression model or a negative binomial model. We calculated the percent of all R&C deaths attributable to influenza by age group in these countries (etiologic fraction) and applied it to the age-specific mortality in 13 countries with good mortality data but poorly defined seasonality. Lastly, we grouped the remaining 15 countries into WHO mortality strata and applied the age and mortality stratum-specific rate of influenza mortality calculated from the 20 countries. We summed each country's estimate to arrive at an average total annual number and rate of influenza deaths in the Americas. RESULTS: For the 35 PAHO countries, we estimated an annual mean influenza-associated mortality rate of 2·1/100,000 among <65-year olds, 31·9/100 000 among those 65-74 years, and 161·8/100,000 among those ≥ 75 years. We estimated that annually between 40,880 and 160,270 persons (mean, 85,100) die of influenza illness in the PAHO region. CONCLUSION: Influenza remains an important cause of mortality in the Americas.

Trends in mortality from respiratory disease in Latin America since 1998 and the impact of the 2009 influenza pandemic.

OBJECTIVE: To determine trends in mortality from respiratory disease in several areas of Latin America between 1998 and 2009. METHODS: The numbers of deaths attributed to respiratory disease between 1998 and 2009 were extracted from mortality data from Argentina, southern Brazil, Chile, Costa Rica, Ecuador, Mexico and Paraguay. Robust linear models were then fitted to the rates of mortality from respiratory disease recorded between 2003 and 2009. FINDINGS: Between 1998 and 2008, rates of mortality from respiratory disease gradually decreased in all age groups in most of the study areas. Among children younger than 5 years, for example, the annual rates of such mortality - across all seven study areas - fell from 56.9 deaths per 100,000 in 1998 to 26.6 deaths per 100,000 in 2008. Over this period, rates of mortality from respiratory disease were generally highest among adults older than 65 years and lowest among individuals aged 5 to 49 years. In 2009, mortality from respiratory disease was either similar to that recorded in 2008 or showed an increase - significant increases were seen among children younger than 5 years in Paraguay, among those aged 5 to 49 years in southern Brazil, Mexico and Paraguay and among adults aged 50 to 64 years in Mexico and Paraguay. CONCLUSION: In much of Latin America, mortality from respiratory disease gradually fell between 1998 and 2008. However, this downward trend came to a halt in 2009, probably as a result of the (H1N1) 2009 pandemic.

Incidence of influenza-associated mortality and hospitalizations in Argentina during 2002-2009.

BACKGROUND: We estimated rates of influenza-associated deaths and hospitalizations in Argentina, a country that recommends annual influenza vaccination for persons at high risk of complications from influenza illness. METHODS: We identified hospitalized persons and deaths in persons diagnosed with pneumonia and influenza (P&I, ICD-10 codes J10-J18) and respiratory and circulatory illness (R&C, codes I00-I99 and J00-J99). We defined the influenza season as the months when the proportion of samples that tested positive for influenza exceeded the annual median. We used hospitalizations and deaths during the influenza off-season to estimate, using linear regression, the number of excess deaths that occurred during the influenza season. To explore whether excess mortality varied by sex and whether people were age <65 or ≥ 65 years, we used Poisson regression of the influenza-associated rates. RESULTS: During 2002-2009, 2411 P&I and 8527 R&C mean excess deaths occurred annually from May to October. If all of these excess deaths were associated with influenza, the influenza-associated mortality rate was 6/100,000 person-years (95% CI 4-8/100,000 person-years for P&I and 21/100,000 person-years (95% CI 12-31/100,000 person-years) for R&C. During 2005-2008, we identified an average of 7868 P&I excess hospitalizations and 22,994 R&C hospitalizations per year, resulting in an influenza-associated hospitalization rate of 2/10,000 person-years (95% CI 1-3/10,000 person-years) for P&I and 6/10,000 person-years (95% CI 3-8/10,000 person-years) for R&C. CONCLUSION: Our findings suggest that annual rates of influenza-associated hospitalizations and death in Argentina were substantial and similar to neighboring Brazil.

Global health security and the International Health Regulations.

Global nuclear proliferation, bioterrorism, and emerging infections have challenged national capacities to achieve and maintain global security. Over the last century, emerging infectious disease threats resulted in the development of the preliminary versions of the International Health Regulations (IHR) of the World Health Organization (WHO). The current HR(2005) contain major differences compared to earlier versions, including: substantial shifts from containment at the border to containment at the source of the event; shifts from a rather small disease list (smallpox, plague, cholera, and yellow fever) required to be reported, to all public health threats; and shifts from preset measures to tailored responses with more flexibility to deal with the local situations on the ground. The new IHR(2005) call for accountability. They also call for strengthened national capacity for surveillance and control; prevention, alert, and response to international public health emergencies beyond the traditional short list of required reporting; global partnership and collaboration; and human rights, obligations, accountability, and procedures of monitoring. Under these evolved regulations, as well as other measures, such as the Revolving Fund for vaccine procurement of the Pan American Health Organization (PAHO), global health security could be maintained in the response to urban yellow fever in Paraguay in 2008 and the influenza (H1N1) pandemic of 2009-2010.

Epidemiology of Saint Louis encephalitis virus in the Brazilian Amazon region and in the State of Mato Grosso do Sul, Brazil: elevated prevalence of antibodies in horses / Epidemiologia do vírus da encefalite Saint Louis na Amazônia brasileira e no Estado do Mato Grosso do Sul, Brasil: elevada prevalência de anticorpos em equinos

The immunity of horses (n = 1401) against Saint Louis encephalitis virus (SLEV) was investigated in the Brazilian Amazon region (Bragança/Pará, Salvaterra/Pará, Macapá/Amapá and Rio Branco/Acre) and Maracaju, State of Mato Grosso do Sul, by the hemagglutination inhibition (HI) and plaque reduction neutralization (PRNT) tests. HI and neutralizing antibodies specific (monotypic reactivity, MR) for SLEV and other flaviviruses included in the tests were detected, as was cross-reactivity (CR) against flaviviruses. In the HI test, MR was observed in 248 (17.7 percent) serum samples, 137 of which were (55.2 percent) againstSLEV; CR was detected in 380 (27.1 percent). The frequency of MR against SLEV was significantly higher in Macapá and CR was significantly higher in Salvaterra. In the PRNT, neutralization of SLEV was observed in 713 (50.9 percent) samples, and the prevalence of neutralizing antibodies was significantly higher in Macapá than in Salvaterra (p = 0.0083). This study adds new data regarding the immunity of horses against SLEV in Brazil, and it confirms the wide distribution of SLEV and the diversity of flaviviruses in the country, as well as the apparent absence of disease in SLEV-infected horses.

A imunidade de equinos (n = 1401) contra o vírus da encefalite Saint Louis (SLEV) foi investigada na Amazônia brasileira (Bragança/PA, Salvaterra/PA, Macapá/AP e Rio Branco/AC) e Maracaju, no Estado do Mato Grosso do Sul, por meio detestes de inibição da hemaglutinação (IH) e neutralização por redução de placas (PRNT). Foram detectados anticorpos IH e neutralizantes específicos (reações monotípicas – RM) para SLEV e outros flavivírus incluídos nos testes, assim como reações cruzadas para flavivírus. Pelo teste de IH, RM foram observadas em 248 (17,7 por cento) amostras de soro, 137 (55,2 por cento) para SLEV, e RC para flavivírus foram detectadas em 380 (27,1 por cento). A frequência de RM para SLEV e de RC foi significativamente maior em Macapá e Salvaterra, respectivamente. Pelo PRNT, foi observada a neutralização do SLEV em 713 (50,9 por cento) amostras, e a prevalência de anticorpos neutralizantes foi significativamente maior em Macapá, em comparação com Salvaterra (p = 0,0083). Este estudo traz novos dados a respeito da imunidade de equinos contra SLEV no Brasil, e confirma a ampla distribuição de SLEV e a diversidade de flavivírus no País, bem como a aparente ausência de doenças em equinos infectados por SLEV.

Strategy to enhance influenza surveillance worldwide.

The emergence of a novel strain of influenza virus A (H1N1) in April 2009 focused attention on influenza surveillance capabilities worldwide. In consultations before the 2009 outbreak of influenza subtype H1N1, the World Health Organization had concluded that the world was unprepared to respond to an influenza pandemic, due in part to inadequate global surveillance and response capacity. We describe a sentinel surveillance system that could enhance the quality of influenza epidemiologic and laboratory data and strengthen a country's capacity for seasonal, novel, and pandemic influenza detection and prevention. Such a system would 1) provide data for a better understanding of the epidemiology and extent of seasonal influenza, 2) provide a platform for the study of other acute febrile respiratory illnesses, 3) provide virus isolates for the development of vaccines, 4) inform local pandemic planning and vaccine policy, 5) monitor influenza epidemics and pandemics, and 6) provide infrastructure for an early warning system for outbreaks of new virus subtypes.

[Preparedness planning for an influenza pandemic: regional efforts]. / Planificación de la preparación para la influenza pandémica: esfuerzos regionales.

Failure to establish a contingency plan prior to a public health emergency can have catastrophic consequences. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, mitigate, and recover from a potential influenza pandemic. This paper examines these preparations in Latin America and the Caribbean and describes potential scenarios of pandemic impact on the burden of mortality and on health services in the Region. In particular, the paper reports on the progress made by Member States in developing national influenza pandemic preparedness plans and implementation mechanisms at both the national and local levels. These achievements were facilitated through a series of planning workshops and self-assessment exercises conducted by PAHO for intersectoral country teams and guided by the WHO global influenza preparedness plan. Although significant progress has been made in plan completeness, intercountry preparedness planning and local level implementation remain key challenges. Multisectoral partnerships are clearly paramount to securing the commitment and resources needed to reach and sustain effective pandemic preparedness in the Americas.

[Technological development: a weak link in vaccine innovation in Brazil]. / Desenvolvimento tecnológico: elo deficiente na inovação tecnológica de vacinas no Brasil.

In very recent years, the federal government has launched important initiatives mean to strengthen science, technology, and innovation in Brazil and thus enhance the results of technological innovation in key areas of the country's economy. Yet these initiatives have not been enough to reduce Brazil's heavy dependence on goods and technology from more developed nations. The article describes the current state of vaccination, production, and technological development of vaccines both internationally and nationally. Some thoughts are also offered on the complexity of vaccine innovation and the various stages whose completion is essential to the whole process of technological development. An analysis is made of the parameters and factors involved in each stage; technical requirements for facilities and equipment; good manufacturing practice guidelines; organizational, infrastructural, and managerial needs; and the lengthy time periods adn high costs entailed in these activities.

Desenvolvimento tecnológico: elo deficiente na inovaçäo tecnológica de vacinas no Brasil / Technological development: a weak link in vaccine innovation in Brazil

Apresenta-se neste trabalho a situaçäo da vacinaçäo, produçäo e desenvolvimento tecnológico de vacinas no mundo e no Brasil; também säo feitas algumas reflexöes sobre a complexidade da inovaçäo tecnológica de vacinas e as diversas etapas do processo de desenvolvimento tecnológico requeridas para esse completo desenvolvimento. Descrevem-se várias etapas envolvidas, com análise dos parâmetros e fatores integrantes em cada etapa, os requisitos técnicos de instalaçöes e equipamentos, as normas de boas práticas de fabricaçäo(BPF_), a necessidade organizacional, de infra-estrutura e de gestäo, o longo período e o alto custo demandados para essa atividade.

Technical analysis of the state of DTP vaccine production in Latin America and the Caribbean

This report will also be published in Spanish in the BOSP. Vol. 117(3), September 1994

Imunizaçäo anti-rábica em humanos / Anti-rabies immunization in humans

Foi desenvolvido um estudo imunológico em amostras de soro colhidas de pacientes agredidos por animais suspeitos ou comprovadamente raivosos, tratados pelo Serviço de Prevençäo da Raiva Humana do Rio de Janeiro, com vacina anti-rábica do tipo Fuenzalida & Palácios. Foram pesquisados os anticorpos neutralizantes dos pacientes, utilizando-se o teste de neutralizaçäo em camundongos, segundo a metodologia recomendada pela OMS. O objetivo foi estabelecer o número de doses de vacina capaz de induzir a formaçäo de anticorpos neutralizantes que protejam o indivíduo de uma infecçäo rábica. O estudo envolveu um grupo de pacientes primovacinados que receberam nove doses de vacina e duas doses de reforço. As amostras de sangue foram colhidas durante o esquema vacinaçäo nos dias 6, 16, 26 e 36, a contar do início do tratamento e os títulos de anticorpos neutralizantes foram calculados pelo teste de Reed & Muench, variando nas amostras de soro entre menor que 1:5 e maior que 1:15625. Foi observado que o esquema de sete doses e dois reforços apresentou bons resultados no que se refere aos níveis de anticorpos e principalmente porque, em nenhum dos pacientes submetidos a esse esquema vacinal ocorreu reaçäo pós-vacinal séria que necessitasse de tratamento ou mesmo suspensäo temporária da vacinaçäo. Foi também observado que sete doses mais uma única de reforço foram suficientes para induzir níveis satisfatórios de anticorpos neutralizantes em todos os pacientes