MINIMINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH NATIONAL INSTITUTE OF HYGIENE AND EPIDEMIOLOGY * NGUYEN THI THI THO EPIDEMIOLOGICAL CHARACTERISTICS AND SOME RISK FACTORS OF PANDEMIC INFLUENZA A/H1N1/2009 IN THE NORTHERN AREAS OF VIETNAM, 2009 - 2011 Specialization: Public Health Code: 62.72.03.01 AN EXECUTIVE SUMMARY OF PhD THESIS HANOI - 2012 THE THESIS HAS BEEN COMPLETED IN NATIONAL INSTITUTE OF HYGIENE AND EPIDEMIOLOGY Scientific supervisors: 1. Assoc. Prof. Nguyen Tran Hien, PhD. 2. Dr. Tran Nhu Duong, PhD. Opponent 1: Prof. PhD. Truong Viet Dung Opponent 2: Opponent 3: The thesis shall be defended in the National Doctorate Thesis Grading Committee established by the Decision No. 404/QD – VSDTTƯ dated 19 th November, 2012, at: NATIONAL INSTITUTE OF HYGIENE AND EPIDEMIOLOGY At: 9h00, 19 th October, 2012 This thesis is available to access at: - National Library; - Library of National Institute of Hygiene and Epidemiology. RATIONALE Influenza is an acute infectious disease caused by influenza viruses that attacks mainly the upper respiratory tract infections, but can lead to severe pneumonia and even death if the patients are not detected and treated in time. Influenza is still a public health threat due to their rapidly spreading and causing a pandemic. Influenza pandemics generally occur suddenly and cause heavy losses for people and society, including: significant increase in the number of cases and deaths associated with influenza; overloaded health systems with prevention and treatment activities; a decline in economic activities and cessation of educational activities. In the spring 2009, a new strain of the influenza A/H1N1 virus appeared worldwide, which had shown the ability to cause a pandemic. On 11 June 2009, the World Health Organization (WHO) officially declared the outbreak of influenza A/H1N1 to be the first influenza pandemic of the XXI century, named pandemic influenza A/H1N1/2009 (pH1N1/2009). Six weeks later, this pandemic had spread to 168 countries/overseas territories/communities on all five continents with approximately 162,380 cases and 1,153 deaths. On 31 May 2009, with the recognition of the first case of the pH1N1/2009 in Ho Chi Minh City, Vietnam became the 54 th country to confirm the appearance of the influenza pandemic related to the new strain of the H1N1 influenza virus. The fist case in the north of Vietnam occurred on 8 June 2009. Then this pandemic had rapidly spread to other provinces/cities. In order to provide scientific evidences for effective prevention activities, as well as to retain the important information about the first pandemic influenza in the XXI century, the study "Epidemiological characteristics and some risk factors of pandemic influenza A/H1N1/2009 in the Northern areas of Vietnam, 2009 - 2011" was conducted with two specific objectives: 1. To describe the epidemiological development and characteristics, and to identify the attack rate of pH1N1/2009 in the Northern areas of Vietnam, from 2009 to 2011. 2 2. To identify some risk factors of pH1N1/2009 in the Northern areas of Vietnam, from 2009 to 2011. PRACTICAL IMPLICATIONS AND NEW CONTRIBUTIONS - Novelty: This research provides full information about the epidemiological development and characteristics of cases, deaths, attack rate, transmission pattern, and some risk factors of the pH1N1/2009. This is the first time when the epidemiological information of influenza pandemic is fully retained in our country. - Applicability: The information on epidemiological characteristics of the pH1N1/2009 will provide scientific basis and lessons learned for the development of effective prevention strategies for other pandemics that we will continue to undergo in the future. THESIS STRUCTURE The thesis comprises about 138 pages and is divided into following sessions: Rationale (2 pages); Chapter 1 – Literature review (32 pages), Chapter 2 – Methodology (20 pages); Chapter 3 – Results (40 pages); Chapter 4 – Discussion (44 pages); Conclusions (2 pages); and Recommendations (1 page). There are 19 tables, 20 charts, 2 figures and 135 references in the thesis. CHAPTER 1 – LITURATURE REVIEW 1.1. Some epidemiological characteristics of human influenza 1.1.1. Virology Structure of viruses: Influenza is caused by influenza viruses which are genus of the Orthomyxoviridae family of viruses. These viruses are classified into subtypes depending on which versions of two different surface glycoprotein antigens: Hemagglutinin (HA) and Neuraminidase (NA). A type-specific antigen (S-Antigen), the major component of influenza visions’ core proteins, classifies influenza viruses into type A, B or C. Only type A virus is responsible for influenza epidemics and pandemics in human whereas type B virus affecting only human, primarily children, normally causes milder diseases, but can lead to outbreaks in the winter. There is no evidence that influenza C virus can causes epidemics in humans. 3 Antigen changes of influenza viruses: Influenza A virus is one of the most changeable viruses known with two ways of genetic material changes called drift and shift: - Antigenic drift: this process is due to random mutations in the genes coding hemaglutinin. Antigenic drift is responsible for small seasonal influenza outbreaks. - Antigenic shift: The most important mechanism in antigenic shift is reassortment. This process occurs when two or more strains of a influenza virus, especially strains of different viruses like human influenza virus and avian influenza virus, intrude into the same host where genetic permutations occur to form a new subtype of influenza virus. Antigenic drift is the cause of human influenza pandemics. 1.1.2. Source of infection and mode of transmission Infected patients, and in some specific situations, infected poultry are also recognized as source of disease. Influenza virus is transmitted from infected person to others via respiratory tract and through direct or indirect contact. 1.1.3. Susceptibility, immune response and resistance Anyone can get influenza. After infection, the human body’s immune system becomes resistant to the strain of virus. Only antibodies specific for the viral surface glycoprotein antigens of this virus that person is infected with. The protecting effect against influenza is likely to reduce or even lost if there is a change in the antigens structure of new virus. 1.2. Influenza pandemics before the XXI century Historically, influenza pandemics happened very long ago, only is described, however, from the sixteenth century. In the twentieth century, the world had witnessed three influenza pandemics with different scales and levels. These pandemics were recognized more fully than the previous pandemics by applying technology advancements. The basic epidemiological characteristics of the influenza pandemics in the twentieth century are summarized in the table below: 4 Table 1.1. Summarizes some of the characteristics of influenza pandemics in the XX century Pandemics Started place Influenza virus Case fatality rate Deaths Affected a g e groups Spanish Flu (1918 - 1919) Non- specific A/H1N1 2 - 3% 20 - 50 million Young people Asian Flu (1957 - 1958) South China A/H2N2 <0,2% 1 - 4 million Children, The elderly Hong Kong Flu (1968 - 1969) South China A/H3N2 <0,2% 1 - 4 million All age groups 1.3. The pandemic influenza A/H1N1/2009 and some risk factors 1.3.1. Pandemic influenza A/H1N1/2009 in the world Viral pathogen is pH1N1/2009 with an entirely new genome structure and satisfying virological features of human influenza pandemic mechanism. This new virus is a result of the reassortment, with captaining genes from avian influenza, North American swine influenza, human influenza, and two swine influenza viruses found in Asia and Europe. The origin and development of the pandemic: the first appearance of 2009 pandemic influenza A/H1N1 is in North America in March 2009. On 11 June 2009, WHO has announced a level 6 influenza pandemic for the first time after 41 years. Six weeks later, the pandemic had spread to 168 countries/overseas territories/communities on all five continents with approximately 162,380 cases and 1,153 deaths. Fourteen months later, on 10 August 2010, WHO officially announced that 2009 pandemic influenza A/H1N1 had moved into the post-pandemic period. Some epidemiological characteristics: In the first phase, WHO estimated the attack rate of pH1N1/2009 ranges from 22% to 33%. Hospitalization rates were about 6% in Mexico, 2 - 5% in the U.S. and Canada and 2% in the UK. Case fatality rate did not exceed 0.35%, and highly increase in underlying medical conditions group, children, the people aged 65 or more and pregnant women. Unlike seasonal influenza, 90% of severe cases and deaths of pH1N1/2009 did not occur in the elderly group. 5 1.3.2. Risk factors and high-risk groups Currently, there is not much research related to identifying risk factors for influenza infections, especially for influenza pandemic. Regarding to seasonal influenza, children under 5 years of age was at a 1.85 times (1.09 - 3.26) greater risk of influenza infections as compared to those aged 15 years and over. To contact with children under the age of 5 and children aged 5 - 15 years old getting influenza increases the infection risk to 1.93 and 1.68 times in comparison with adult cases. For pH1N1/2009, age is also a risk factor for the possibility of infection. A research in China shows that the possibility of infection of the age group under 18 years was 15 times as high as that of the group aged 18 years and over. Besides this, a study in Japan also concluded that people under 20 years of age has a higher risk for influenza injection than others (OR = 7.9 [2.24 - 27.8]). Some other factors, such as hand washing (OR = 0.11 [0.04 - 0.28]), regularly opening windows in workplace (OR = 0.14 [0.05 - 0.39]) were proven to be protective factors against influenza infection. Some other studies also identified that occupational status are risk factors for influenza pandemic. CHAPTER 2 - METHODOLOY Objective 1 2.1. To describe epidemiological development and characteristics of pH1N1/2009 cases and deaths 2.1.1. Target groups - Influenza like illness (ILI), suspected cases, confirmed cases, clinical cases and deaths related to pH1N1/2009. - Reports related to pH1N1/2009. 2.1.2.Time and places: The study was conducted from May, 2009 to May, 2011 in 28 provinces in the Northern areas. 2.1.3. Study method: Descriptive study 2.1.4. Sample size and sampling approach - Description of epidemiological development: Select all of 2948 pH1N1/2009 confirmed cases recorded during the duration of the study. - Description of epidemiology of pH1N1/2009 cases: The sample size was calculated by the following formula: 6 n = Z 2 1- α /2 p (1-p) d 2 As a result, 1068 first confirmed cases were selected in the study. - Description of epidemiology of pH1N1/2009 deaths: Select all deaths related to pH1N1/2009 recorded. 2.1.5. Laboratory testing technique: pH1N1/2009 cases and deaths were confirmed by RT-PCR technique. 2.1.6. Data collection method: Interviewing cases or relatives of deaths by using structured questionnaires. 2.2. To identify attack rates of pH1N1/2009 2.2.1. Target groups: pH1N1/2009 outbreaks. In each outbreak, target groups included all subjects, pH1N1/2009 infection cases, clinical cases, confirmed cases. 2.2.2. Study places: - In community: The outbreak occurred in the village number 3, Pha Le Commune, Thuy Nguyen district, Hai Phong city. - In school settings: The outbreaks occurred in Pha Le primary school; Ethnic boarding high school in Muong Nhe district, Dien Bien province and Specialization high school in Lao Cai province. - In special contact- environment: The outbreak occurred in one tourist group. 2.2.3. Study time: In each pH1N1/2009 outbreak, the duration of study was from the onset day of the index case to 2 weeks after the onset day of the last case. 2.2.4. Study method: Descriptive study 2.2.5. Sample size: One pH1N1/2009 outbreak in the community, 3 outbreaks in different kinds of schools, and 1 outbreak in tourist group. 2.2.6. Laboratory testing technique - Confirmation of first pH1N1/2009 cases by RT-PCR technique. - Identification of pH1N1/2009 infection cases by Haemaglutination Inhibition (HI) test. 7 2.2.7. Data collection method: Interviewing cases (clinical and confirmed cases), infection cases by using structured questionnaires. Objective 2 2.3. To identify risk factors of pH1N1/2009 2.3.1. Target groups - Definition of cases: cases were those who were confirmed as being infected with pH1N1/2009 by HI technique. - Definition of controls: controls were those who were confirmed as free of infection with pH1N1/2009 by HI technique, and at the same age group, gender with cases and living near to cases’ houses. 2.3.2. Time and place: The case-control study was nested in the study of the pH1N1/2009 outbreak occurred in village number 3, Pha Le commune, Thuy Nguyen district, Hai Phong city. 2.3.3. Study method: Marching case-control study 2.3.4. Sample size and sampling method: Select all subjects who were confirmed as pH1N1/2009 infection by HI technique. Case/control ratio was 1:1. Controls were marched with cases by age group, gender. 2.3.5. Data collection method: Interviewing cases and controls by using structured questionnaires. 2.4. Data analysis - Using Stata version 9.2 (StataCorp USA) for univariate analysis and conditional logistics analysis, stepwise approach with pe = 0,2 for the optimal model. - Using Arc GIS 9.3 software to build up epidemiological map. - The findings were displayed in the format of rate (%), rate/100.000 inhabitants, OR (95% CI). χ2 tests with p< 0,05 would be significant. 8 CHAPTER 3 - RESULTS 3.1. The epidemiological development and characteristics of cases and deaths caused by the pH1N1/2009 in the Northern areas of Vietnam 3.1.1.The epidemiological development of the pH1N1/2009 in the Northern areas of Vietnam Figure 3.1. Development of pH1N1/2009 in Northern areas of Vietnam in the first five months (from June to November, 2009) Follow by figure 3.1, during June and July 2009, the pH1N1/2009 localized in some provinces, spreading rapidly in August 2009 before occurring in all provinces in Northern areas of Vietnam at the end of October 2009. Chart 3.3. Distribution of cases by date of onset, from 1/6/2009 to 31/5/2011 Changed surveillance strategy 0 20 40 60 80 100 120 140 [...]... optimize the model The last model shows that factors including ‘irregular hand washing’ and ‘regularly going out to outbreaks’ were the independent factors protecting community from the risk infections of pH1N1 /2009 CHAPTER 4 - DISCUSSION 4.1 Epidemiological characteristic of the Pandemic Influenza A/H1N1 4.1.1 The development of pH1N1 /2009 in the Northern areas The first imported pH1N1 /2009 case in the Northern. .. occurred in big cities, provinces with high level of transportation, exchanges and density On the contrary, the pH1N1 /2009 slowly moved to the remote, mountainous and hard to reach areas After 5 months (in October, 2009) , pH1N1 /2009 became over whelming in all cities and provinces in the Northern areas (figure 3.1) With the combination of epidemiological analysis of pH1N1 /2009 confirmed cases and results of. .. Asian flu pandemic (1957 - 1958) and Hongkong flu pandemic 18 included 2 epidemiological waves However, on the contrary to the previous influenza pandemic, in the study, the latter pH1N1 /2009 wave was less serious than the former one 4.1.2 Epidemiological characteristics of pH1N1 /2009 cases and deaths The changes in age distribution Difference from seasonal influenza, in influenza pandemics, young groups... disease A further study may be in requirement CONCLUSIONS 1 Epidemiology of pH1N1 /2009 in the Northen area, Vietnam 1.1 Pandemic Influenza A/H1N1 /2009 was imported to the Northern area, Vietnam in early of June, 2009 The outbreak was firstly occurred in big cities with convenient transportation, then transmitted to nearby provinces, and lastly moved to the remote and mountainous areas There were 2... lowest rate (14.8% [8.0% - 32.0%]) 3.3 Risk factors of pH1N1 /2009 Table 3.15 - 3.18 The association between some factors and risk of getting infection with pH1N1 /2009 (univariate analysis) Infected by Non-infected by 2009 pandemic 2009 pandemic OR Risk factors influenza influenza (95% CI) A(H1N1) A(H1N1) N % N % Occupation Children ( . characteristics, and to identify the attack rate of pH1N1 /2009 in the Northern areas of Vietnam, from 2009 to 2011. 2 2. To identify some risk factors of pH1N1 /2009 in the Northern areas of Vietnam,. DISCUSSION 4.1. Epidemiological characteristic of the Pandemic Influenza A/H1N1 4.1.1. The development of pH1N1 /2009 in the Northern areas The first imported pH1N1 /2009 case in the Northern areas. during June and July 2009, the pH1N1 /2009 localized in some provinces, spreading rapidly in August 2009 before occurring in all provinces in Northern areas of Vietnam at the end of October 2009.