Грип: Закана за пандемија Токму на Време (JIT) Ажурирано: 2 Март, 2006 Превод и обработка: Проф. д-р. Елисавета Стикова, MD, PhD estikova@ukim.edu.mk Универзитет „Св. Кирил и Методиј“ – Медицински Факултет д-р. Емилија Мирчевска MD (mircevska@gmail.com) Борче Андоновски - Републички завод за здравствена заштита Сузана Дунгевска -Републички завод за здравствена заштита Rashid A. Chotani, MD, MPH Director, Global Infectious Disease Surveillance & Alert System Johns Hopkins Bloomberg School of Public Health 410-502-3116/410-322-7469 rchotani@jhsph.edu

Вирус на грип Три типа Површински антигени A, B, C Површински антигени H (хемаглутинин) N (неуроминидаза) Тип A вирусот има три подтипа H3N2, H1N1 (чест, хуман подтип) H7N7 (птичји 2003, Холандија) H5N2 (птичја вакцина) H9N2 (случај кај човек во Хонг Конг, Кина 2003) H5N1 (сега присутен, птичји, предмет на загриженост) Credit: L. Stammard, 1995

Вирус на грип Flu strains are named after their types of hemagglutinin and neuraminidase surface proteins, so they will be called, for example, H3N2 for type-3 hemagglutinin and type-2 neuraminidase. If two different strains of influenza infect the same cell simultaneously, their protein capsids and lipid envelopes are removed, exposing their RNA, which is then transcribed to mRNA. The host cell then forms new viruses that combine antigens; for example, H3N2 and H5N1 can form H5N2 this way. Because the human immune system has difficulty recognizing the new influenza strain, it may be highly dangerous.

Природни домаќини на вирусот на грип H1 N1 H2 N2 H3 N3 H4 N4 H5 N5 H6 N6 H7 N7 H8 N8 H9 N9 H10 H11 H12 H13 H14 H15 Природни домаќини на вирусот на грип Хемаглутинински подтип Неуроминидаза подтип

Оптеретување со грип Сезонски грип Пандемиски грип Глобално: 250 000 дo 500 000 смртни случаи секоја година Во САД (годишно) ~35,000 смртни случаи >200 000 хоспитализации $37.5 билиони економски трошоци (грип & пневмонија) Пандемиски грип Постојано присатна закана

“Шпански грип” A(H1N1): 1918-19 Приближно 20-40 милиони луѓе умреа ширум светот и преку 500 000 во САД. It was called the Spanish flu because it was first officially noticed in Spain in May 1918. It went on to kill an estimated eight million people there and 20-40 million people worldwide. . The virus was tracked along international shipping lanes, from Europe to North America, then to Asia, Africa, Brazil and eventually the South Pacific.

Големата пандемија во 1918 This graph demonstrated the US life expectancy over time from 1900 to 1960. The average US Life Expectancy fell sharply during the 1917-18 influenza pandemic – from around 55 years to around 39 years.

Слики од епидемијата на грип во 1918 Национален музеј за здравје и медицина This graph shows the mortality from all causes from June 1918 to March 1919 in New York, Paris, London & Berlin The deaths are expressed in weekly annual rate per 1,000 The first peak is observed during October and November of 1918 and the second peak is seen between February and March of 1919. Critical to note is that in all four cities the first peak appears almost at the same time – between 10 of October to 7 of December, 1918.

Големата пандемија во 1918 This graph demonstrated the age specific death rate in the US due to influenza & pneumonia from 1911 to 1917 and compares it to 1918. The age specific death rate is higher in all age divisions except in the 75+ age strata. The age specific death rate due to influenza and pneumonia was highest in the 25-34 year age strata.

Слики од епидемијата на грип во 1918 Национален музеј за здравје и медицина This slide describes the percent of deaths due to influenza and pneumonia in Boston, 1918. In Boston the age group most affected was between 20 to 29 years followed by age group 0 to 9 years. Furthermore, influenza hit Boston’s healthiest population in September.

This slide series illustrates the spread of influenza in the U. S This slide series illustrates the spread of influenza in the U.S. during the 1918 pandemic. In a matter of weeks, influenza had spread across the entire country. It is thought that this rapid spread may have been facilitated by seeding of the virus the previous spring.

“Азиски грип” A(H2N2) 1957-58 За време на епидемијата на Азиски грип во 1957-58, едно училишно дете во Ислингтон, Лондон, прави гаргара за да го задржи вирусот во испирокот. Повеќе од милион луѓе умреа ширум светот и околу 70 000 во САД. The second pandemic of the 20th century occurred in 1957 claiming around a million lives. This was caused by an antigenic shift as the H2 strain emerged.

Ширење на H2N2 грипот во 1957 “Азиски грип” In the short span of 7 months the H2N2 virus spread across the globe

“Hong Kong Flu” A(H3N2) 1968-69 Членови на црвената гарда во Кина во 1968 година се штитата со маски по наредба на Претседателот Мао. Хонкохгшкиот грип од 1968-69 уби повеќе од 1 милион луѓе низ светот и околу 34 000 во САД. In 1968 there was another antigenic shift and H3 emerged causing another pandemic and claiming over a million lives.

Временска линија на опасноста од Influenza A вирусите кај луѓето Птичји грип H9 H7 Руски грип H5 H5 H1 H3 H2 H1 This illustration depicts the antigenic shifts that occurred during the 20th century. The H1 subtype that circulated starting 1918 was replaced by an H2 subtype in 1957. Of note: when the H1 subtype reappeared in 1977, young persons were disproportionately affected as persons born before 1957 would have had previous exposure to H1 virus. The H5, H7, and H9 subtypes depicted have not caused sustained person-to-person transmission and will be discussed further later on. 1918 1957 1968 1977 1997 2003 Шпански грип H1N1 Азиски грип H2N2 Хонг Конг грип H3N2 1998/9

Регистрирани пандемии на грип 37 Influenza virus which have undergone antigenic shift have also gone on to cause the Asian Flu pandemic of 1957, the Hong Kong Flu pandemic of 1968, and the Swine Flu scare of 1976. It has been over 37 years since the last pandemic in 1968. One increasingly worrying situation is the possible antigenic shift between avian influenza and human influenza. This antigenic shift could cause the formation of a highly virulent virus.

Дефиниции Епидемија – лоцирана група (cluster) на случаи Пандемија – епидемија раширена низ целиот свет Антигенскa варијациja – “drift” Променa во протеинската структура предизвикани од генетски мутации и селекции Основа за постојаните активности за промена на составот на вакцините секоја година Антигенска променa -“shift” Промени во протеинската структура преку генетско прераспределување Создавање на различни вируси кои не се покриени со годишната вакцина

Миграторни водени птици Реасортирање кај луѓе Миграторни водени птици Reassortment: Reassortment, or Viral Subunit Reassortment, is the exchange of DNA between viruses inside a host cell. Two or more viruses of different strains (but usually the same species) infect a single cell and pool their genetic material creating numerous genetically diverse progeny viruses. It is a type of genetic recombination. Reassortment can lead to a viral shifts under some conditions. Source: WHO/WPRO

Реасортирање кај свињи Миграторни водени птици Reassortment: Reassortment, or Viral Subunit Reassortment, is the exchange of DNA between viruses inside a host cell. Two or more viruses of different strains (but usually the same species) infect a single cell and pool their genetic material creating numerous genetically diverse progeny viruses. It is a type of genetic recombination. Reassortment can lead to a viral shifts under some conditions. Source: WHO/WPRO

Миграторни водени птици Мутација кај луѓе Миграторни водени птици Mutation: In general mutations are changes to the DNA or RNA (genetic materials) of viruses. Mutations can be caused by copying errors in the genetic material during cell division and by exposure to elements such as radiation, chemicals, viruses or can occur deliberately under cellular control during the processes such as meiosis or hyper-mutation. Mutations are considered the driving force of evolution, where less favorable (or deleterious) mutations are removed from the gene pool by natural selection, while more favorable (beneficial or advantageous) ones tend to accumulate. Source: WHO/WPRO

Миграторни водени птици Од птици на луѓе Миграторни водени птици Домашни птици Хонг Конг, 1997, H5N1 Хонг Конг, 1999, H9N2 Холандија, 2003, H7N7 Хонг Конг, 2003, H5N1 In 1997 the first H5N1 outbreak in humans was recorded and epidemiological investigations revealed that this outbreak was caused by direct virus transmission from domestic birds to humans. The fear was that the virus could mutate in humans and develop the ability of human-to-human transmission. Only 18 cases and 6 deaths were recorded and the entire poultry population of Hong Kong was destroyed. In 1999 another influenza virus (H9N2) known previously to only infect birds was reported in seven people in China and Hong Kong, serologic evidence suggested no person-to-person transmission. Between February and May of 2003, an extremely pathogenic avian influenza strain A sub-type H7N7 caused an outbreak in the Netherlands causing disease in 89 humans and resulted in the death of a Dutch veterinarian. The H5N1 strain that had caused human illness in 1999 has been observed causing human illness and deaths since 2003. Source: WHO/WPRO

This slide looks at the relationship between pig density and avian influenza outbreaks in Asia. The map shows that the pig density is directly related to avian outbreaks. SOURCE: FAO

This slide looks at the relationship between poultry density and avian influenza outbreaks in Asia. The map shows that the poultry density is directly related to avian outbreaks. Thus both, pig and poultry density play an important role in avian outbreaks in Asia. SOURCE: FAO

There has been a lot of questions regarding how H5N1 is spreading – is it through migratory bird alone?

The role of migratory birds in the spread of highly pathogenic avian influenza (HPAI) is not fully understood. Wild waterfowl are considered the natural reservoir of all influenza A (including H5 & H7 subtypes) viruses. Considerable circumstantial evidence suggests that migratory birds can introduce low pathogenic H5 and H7 viruses to poultry flocks, which then mutate to the highly pathogenic form. In the past, highly pathogenic viruses have been isolated from migratory birds on very rare occasions involving a few birds, usually found dead within the flight range of a poultry outbreak. This finding long suggested that wild waterfowl are not agents for the onward transmission of these viruses. Recent events however make it likely that some migratory birds are now directly spreading the H5N1 virus in its highly pathogenic form. Further spread to new areas is expected.

The role of open bird markets need to be further studied as well as cross-border contamination and poultry export practices.

H5N1 Птичји грип од јули 2004

Never before in the history of this disease have so many countries been simultaneously affected, resulting in the loss of so many birds. The causative agent, the H5N1 virus, has proved to be especially tenacious. Despite the death or destruction of an estimated 150 million birds, the virus is now considered endemic in many parts of Indonesia and Viet Nam and in some parts of Cambodia, China, Thailand, and possibly also the Lao People’s Democratic Republic. Control of the disease in poultry is expected to take several years. The next few maps illustrate the timeline and spread of disease spatiotemporally.