Ptasia grypa (grypa ptasia) – Patofizjologia i mechanizm

Ptasia grypa (grypa ptasia)
Patofizjologia i mechanizm

Ptasia grypa, wywoływana przez wirusy grypy typu A, charakteryzuje się segmentowanym genomem RNA, co umożliwia rearanżację genetyczną i przesunięcia antygenowe, zwiększając potencjał pandemiczny. Wirusy te dzielą się na nisko patogenne (LPAI) i wysoce patogenne (HPAI), przy czym HPAI, np. podtyp H5N1, wywołuje u drobiu śmiertelność sięgającą 90-100% w ciągu 48 godzin. U ludzi zakażenia mogą przebiegać od bezobjawowych do ciężkich, z dominującym zajęciem dolnych dróg oddechowych, co wynika z preferencji wirusa do receptorów kwasu sialowego α-2,3 obecnych głównie w oskrzelach końcowych i pęcherzykach płucnych. Patogeneza obejmuje rozlane uszkodzenie pęcherzyków płucnych, krwotoki oraz dysregulację cytokin i chemokin, co prowadzi do ciężkiego zapalenia płuc i zespołu ostrej niewydolności oddechowej (ARDS). Wskaźnik śmiertelności ptasiej grypy A(H5N1) u ludzi wynosi około 52%, a najczęstszą przyczyną zgonu jest niewydolność oddechowa.

Mechanizm patogenezy ptasiej grypy (grypy ptasiej)

Ptasia grypa (grypa ptasia) jest chorobą zakaźną wywoływaną przez wirusy grypy typu A, które pierwotnie zakażają ptaki, ale w rzadkich przypadkach mogą przenosić się na inne gatunki, w tym ssaki i ludzi. Mechanizm patogenezy tego wirusa jest złożonym procesem obejmującym wiele czynników wirusowych i odpowiedzi gospodarza, które determinują ciężkość choroby i jej przebieg¹².

Właściwości molekularne wirusa

Wirus grypy typu A jest ortomyksowirusem charakteryzującym się segmentowanym genomem RNA, co umożliwia rearanżację genetyczną i przesunięcia antygenowe. Te cechy czynią wirusa ptasiej grypy potencjalnym i nieprzewidywalnym zagrożeniem dla zdrowia ludzkiego¹. Genom wirusa składa się z ośmiu segmentów jednoniciowego RNA o ujemnej polarności, kodujących 10 białek wirusowych²³.

Wirusy grypy ptasiej są klasyfikowane na dwie główne kategorie w zależności od ich zjadliwości¹:

Nisko patogenne wirusy grypy ptasiej (LPAI – Low Pathogenicity Avian Influenza) – powodują łagodne objawy lub bezobjawowe zakażenia u ptaków¹
Wysoce patogenne wirusy grypy ptasiej (HPAI – Highly Pathogenic Avian Influenza) – wywołują ciężką chorobę i wysoką śmiertelność u zakażonego drobiu, sięgającą 90-100% w ciągu 48 godzin¹

Należy podkreślić, że oznaczenia HPAI i LPAI nie odnoszą się do ciężkości choroby u ludzi – zarówno wirusy LPAI, jak i HPAI mogą powodować łagodne do ciężkich zachorowania u zakażonych ludzi¹.

Mechanizm zakażenia i tropizm tkankowy

Kluczowym czynnikiem w patogenezie wirusa ptasiej grypy jest jego zdolność do przyłączania się do specyficznych receptorów kwasu sialowego na komórkach gospodarza. Białka hemaglutyniny (HA) wirusów ptasiej grypy preferencyjnie wiążą się z receptorami kwasu sialowego α-2,3, które występują głównie w przewodzie pokarmowym ptaków¹.

U ludzi receptory kwasu sialowego α-2,3 znajdują się przede wszystkim w dolnych drogach oddechowych, w tym w oskrzelach końcowych i pęcherzykach płucnych, co może tłumaczyć ciężkie zapalenie płuc często obserwowane w ludzkich przypadkach ptasiej grypy¹². Natomiast wirusy grypy ludzkiej preferencyjnie wiążą się z receptorami kwasu sialowego α-2,6, które występują na komórkach nabłonkowych w górnych drogach oddechowych²³.

Ta różnica w powinowactwie receptorowym powoduje, że wirusy ptasiej grypy zazwyczaj powodują cięższe zakażenia dolnych dróg oddechowych, ale jednocześnie utrudnia efektywne przenoszenie się wirusa między ludźmi, ponieważ do skutecznego rozprzestrzeniania się poprzez kaszel i kichanie prawdopodobnie wymagane jest zakażenie górnych dróg oddechowych¹.

Mechanizmy replikacji i patogeneza komórkowa

Po wniknięciu do organizmu gospodarza, wirus ptasiej grypy zakaża pojedyncze komórki nabłonka płucnego i powoduje rozlane uszkodzenie pęcherzyków płucnych oraz krwotoki w płucach zakażonych pacjentów¹. Dynamika replikacji wirusów ptasiej grypy w komórkach gospodarza różni się od dynamiki wirusów grypy przystosowanych do ludzi. Określone podtypy, takie jak H5N1, wykazują przedłużoną replikację wirusa u ludzi².

Proces replikacji wirusa można podsumować w następujących krokach¹:

HA wirusa przyłącza się do receptorów komórki gospodarza zawierających kwas sialowy, inicjując endocytozę
W endocytach zachodzi fuzja zależna od niskiego pH za pośrednictwem HA
Proteolityczne rozszczepienie HA na HA1 i HA2 jest niezbędnym warunkiem fuzji i zakaźności
Nukleokapsydy wirusowe są transportowane do jądra, gdzie kompleks transkryptazy wirusowej syntetyzuje mRNA
Produkcja sześciu monocistronowych mRNA w jądrze i ich transport do cytoplazmy w celu translacji na białka HA, NA, NP, PB1, PB2 i PA
mRNA segmentów genowych NS i M ulegają splicingowi, każdy produkując dwa mRNA, które są tłumaczone na NS1, NS2, M1 i M2
Białka HA i NA są glikozylowane w szorstkiej siateczce endoplazmatycznej, przycinane w aparacie Golgiego i transportowane na powierzchnię, gdzie są osadzane w błonie komórkowej
Osiem segmentów genowych wirusa wraz z wewnętrznymi białkami wirusowymi gromadzi się i migruje do obszarów błony komórkowej zawierających zintegrowane białka HA, NA i M2
Białko M1 sprzyja ścisłemu połączeniu z błoną komórkową i pączkowaniu wirionów

Rola genu HA w patogenności

Gen HA jest głównym determinantem wysokiej patogenności u drobiu¹. Rozszczepienie białka HA na białka HA1 i HA2 jest niezbędne, aby wirus był zakaźny i produkował wiele cykli replikacji. Różnica między miejscem rozszczepienia wirusów LPAI i HPAI polega na liczbie zasadowych aminokwasów w HA1 w pobliżu miejsca rozszczepienia, co determinuje, czy proteazy podobne do trypsyny, czy proteazy podobne do furyny mogą rozszczepiać białko¹.

Wirusy LPAI mają zwykle tylko dwa niesąsiadujące zasadowe aminokwasy na końcu karboksylowym HA1, które mogą być rozszczeplane tylko przez proteazy podobne do trypsyny. Natomiast wirusy HPAI H5 i H7 mają albo wiele zasadowych aminokwasów, albo wstawkę aminokwasów na końcu karboksylowym białka HA1, co umożliwia proteolityczne rozszczepienie przez wszechobecne proteazy furynowe obecne w wielu komórkach w całym organizmie¹.

W przypadku wirusów HPAI, HA jest rozszczepiany wewnątrz komórki przed montażem wirusa i jest zakaźny, gdy jest uwalniany z komórki gospodarza. Efektywnie zwiększa to tropizm komórkowy wirusa, prowadząc do replikacji wirusa w licznych narządach trzewnych, układzie nerwowym i układzie sercowo-naczyniowym, wywołując chorobę ogólnoustrojową z wysoką śmiertelnością¹.

Dysregulacja cytokin i chemokin

Badania wykazały, że dysregulacja cytokin i chemokin jest prawdopodobnie jednym z kluczowych mechanizmów w patogenezie grypy H5N1, oprócz uszkodzeń wynikających z replikacji wirusa¹². Odpowiedź immunologiczna gospodarza ma kluczowe znaczenie dla ciężkości choroby, przy czym podwyższone poziomy markerów zapalnych są powiązane z cięższym przebiegiem choroby¹.

Różne badania wskazują, że nieprawidłowa produkcja prozapalnych cytokin i chemokin może odgrywać ważną rolę w patogenezie grypy H5N1². Regulacja w górę funkcjonalnego TRAIL w makrofagach zakażonych wirusem H5N1 może być kolejnym ważnym czynnikiem w patogenezie zakażenia wirusem grypy H5N1¹.

Rozprzestrzenianie się wirusa i uszkodzenie narządów

Replikacja wirusa H5N1 wydaje się być przedłużona z wysokimi poziomami wirusowego RNA, a wirus może rozprzestrzeniać się do narządów pozapłucnych¹. Niewydolność oddechowa spowodowana pierwotnym wirusowym zapaleniem płuc jest najczęstszą przyczyną śmierci, często wynikającą z rozlanego uszkodzenia pęcherzyków płucnych i krwotoków spowodowanych replikacją wirusa i uszkodzeniem wywołanym przez układ odpornościowy¹.

Badania na zwierzętach sugerują, że wirusy ptasiej grypy mogą również uszkadzać neurony w kompleksie pre-Bötzingera, odpowiedzialnym za generowanie rytmu oddechowego. To uszkodzenie może przyczyniać się do ataksycznego oddychania i załamania oddechowego w ciężkich przypadkach².

W przeciwieństwie do ludzkiej grypy, większość zgonów związanych z ptasią grypą była spowodowana pierwotnym wirusowym zapaleniem płuc, bez dowodów wtórnego zakażenia bakteryjnego².

Patogeneza w różnych gatunkach

Patogeneza u ptaków

U ptaków, wirusa ptasiej grypy infekuje pierwotnie układ oddechowy i pokarmowy¹. Wirus wiąże się ze specyficznymi białkami powierzchniowymi komórek gospodarza. Po wniknięciu do komórek, replikuje się i rozprzestrzenia, powodując uszkodzenia układu oddechowego i pokarmowego¹.

Objawy kliniczne i zmiany patologiczne u ptaków zależą od zjadliwości szczepu wirusa¹:

W przypadkach nadostrych, objawy kliniczne lub zmiany makroskopowe mogą nie występować przed śmiercią
W przypadkach ostrych, zmiany mogą obejmować sinicę i obrzęk głowy, grzebienia, koralików; martwicę niedokrwienną grzebienia i koralików; obrzęk i czerwone przebarwienie skóry podudzia i stóp z powodu podskórnych wylewów krwawych; wybroczyny na narządach trzewnych i w mięśniach; oraz krwiste wydzieliny z jamy ustnej i nosa¹
Ptaki, które przeżyją nadostre zakażenie, mogą rozwinąć objawy ze strony ośrodkowego układu nerwowego, takie jak kręcz szyi, opistotonus, zaburzenia koordynacji, paraliż i opadanie skrzydeł²

Zmiany mikroskopowe są bardzo zróżnicowane zarówno pod względem lokalizacji, jak i nasilenia, i mogą składać się z obrzęku, krwotoku i martwicy komórek miąższowych wielu narządów trzewnych, skóry i ośrodkowego układu nerwowego³.

Patogeneza u ludzi

U ludzi, patofizjologia ptasiej grypy różni się od zwykłej grypy. Ptasia grypa pozostaje przede wszystkim zakażeniem układu oddechowego, ale obejmuje więcej dolnych dróg oddechowych niż zwykle ludzka grypa¹. Wynika to z różnic w białku hemaglutyniny i typów reszt kwasu sialowego, do których białko się wiąże¹.

Zakażenia ptasią grypą u ludzi mogą być bezobjawowe lub powodować łagodną chorobę, ale mogą również prowadzić do ciężkiego zapalenia płuc, zespołu ostrej niewydolności oddechowej (ARDS), wstrząsu, a nawet śmierci¹². Przebieg kliniczny przypadków H5N1 u ludzi charakteryzuje się początkową gorączką i kaszlem, z szybkim postępem do choroby dolnych dróg oddechowych. Objawy górnych dróg oddechowych, takie jak wyciek z nosa i ból gardła, mogą nie być powszechne u wszystkich pacjentów, ale choroba może postępować do niewydolności oddechowej, ARDS i niewydolności wielonarządowej¹.

Patogeneza u ssaków

Niedawne badania wykazały, że wysoce patogenny wirus ptasiej grypy H5N1 może zakażać różne gatunki ssaków, w tym bydło, koty i inne ssaki domowe oraz dzikie¹². U makaków cynomolgus, które służą jako model zastępczy zakażenia u ludzi, wykazano, że zakażenie donosowe lub dotchawicze może powodować zakażenie ogólnoustrojowe prowadzące do łagodnej i ciężkiej choroby układu oddechowego¹.

Badania patogenności u myszy i fretek ujawniły, że HPAI H5N1 pochodzący od krów mlecznych może wywoływać ciężką chorobę po spożyciu doustnym lub zakażeniu dróg oddechowych, a zakażenie drogą doustną lub oddechową może prowadzić do ogólnoustrojowego rozprzestrzeniania się wirusa do tkanek pozaoddechowych, w tym oka, gruczołu sutkowego, strzyku i/lub mięśni².

Czynniki wpływające na patogenezę

Czynniki genetyczne i mutacje

Wirusy grypy stale się zmieniają w wyniku małych mutacji genetycznych, procesu znanego jako dryf antygenowy. Z czasem mutacje mogą prowadzić do zmiany właściwości antygenowych, tak że przeciwciała gospodarza (nabyte przez szczepienie lub wcześniejsze zakażenie) nie zapewniają skutecznej ochrony, powodując świeży wybuch choroby¹.

Segmentowany genom wirusów grypy ułatwia rearanżację genetyczną. Może to nastąpić, jeśli gospodarz jest zakażony jednocześnie dwoma różnymi szczepami wirusa grypy; wtedy wirusy mogą wymieniać materiał genetyczny podczas reprodukcji w komórkach gospodarza¹. W ten sposób wirus ptasiej grypy może nabyć cechy, takie jak zdolność do zakażania ludzi, od innego szczepu wirusa².

Różnice w genach PA, NP, M1, NS1 i PB2 zwykle korelują z ludzkimi szczepami grypy, w tym z ludzkimi zakażeniami ptasią grypą. Funkcjonalna rola tych markerów genetycznych nie została jeszcze określona, ale prawdopodobnie obejmuje zwiększenie replikacji i supresję immunologiczną¹.

Adaptacja do ssaków i potencjał pandemiczny

Głównym powodem obaw związanych z wirusem H5N1 jest jego potencjał pandemiczny. Ze względu na wysoką śmiertelność i zjadliwość HPAI A(H5N1), jego obecność na całym świecie, coraz bardziej zróżnicowany rezerwuar gospodarzy i znaczące trwające mutacje, wirus H5N1 jest uważany za największe zagrożenie pandemiczne na świecie¹.

Naukowcy zidentyfikowali mutacje, które mogą zwiększać zdolność wirusa do zakażania ssaków. Mutacja (PB2 D701N) została zidentyfikowana w niektórych sekwencjach genetycznych genotypu D1.1 H5N1 od bydła mlecznego i jednego przypadku ludzkiego w Stanach Zjednoczonych. Inna mutacja (PB2 E627K) została zidentyfikowana w pojedynczej sekwencji genotypu B3.13 u krowy mlecznej i w dwóch przypadkach ludzkich. Obie mutacje poprawiają wydajność replikacji w komórkach ssaków i zostały powiązane z adaptacją do ssaków¹.

Naukowcy obawią się, że rozprzestrzenianie się na bydło mleczne może wskazywać, że wirus zmienia się w sposób sprzyjający przenoszeniu do innych ssaków, w tym ludzi¹. Krytyczną kwestią jest zrozumienie, czy wirus, który znajduje się obecnie u krów mlecznych, nabędzie mutacji, które pomogą mu stać się bardziej przenośnym u ssaków¹.

Rola receptorów i czynników gospodarza

Naukowcy zidentyfikowali białko BTN3A3 (Butyrophilina podrodziny 3, członek A3), które działa jako silny inhibitor wirusów grypy ptasiej, ale nie ludzkich wirusów grypy¹. Mechanizm działania BTN3A3 działa we wczesnych stadiach cyklu wirusa, hamując replikację wirusowego RNA¹. Zmiany, czyli uniknięcie bariery gatunkowej stanowionej przez gen BTN3A3, są kluczowym mechanizmem, który może nadawać potencjał zoonotyczny wirusom ptasiej grypy A².

Interesujące jest również odkrycie enzymu znanego jako aromataza. Po zakażeniu SARS-CoV-2 jest on nagle produkowany w większych ilościach w płucach. Płuca stają się organem endokrynnym, który przekształca hormony, a dokładniej, testosteron w estradiol. Ta nowo utworzona fabryka hormonów ma dramatyczne konsekwencje, prowadząc do cięższego przebiegu choroby u mężczyzn¹. Wirusy ptasiej grypy w szczególności wydają się mieć niebezpieczną zdolność do silnego indukowania aromatazy w płucach, co sugeruje znacznie zwiększone ryzyko długotrwałego uszkodzenia płuc – konsekwencji, która dotychczas była prawie nie badana².

Drogi transmisji i czynniki ryzyka

Transmisja między ptakami

U drobiu, ptasia grypa jest najczęściej rozprzestrzeniana przez bliski kontakt między zakażonymi ptakami a zdrowymi ptakami. Może być również rozprzestrzeniana pośrednio przez kontakt z zanieczyszczonym sprzętem oraz z wydzielinami biologicznymi i/lub wydalinami zakażonych ptaków¹.

Wirus można znaleźć w wydzielinach z nozdrzy, jamy ustnej i oczu zakażonych ptaków oraz w ich odchodach. Kontakt z odchodami zakażonych ptaków jest najczęstszym sposobem przenoszenia wirusa z ptaka na ptaka, chociaż wydzieliny przenoszone drogą powietrzną są innym ważnym sposobem przenoszenia, zwłaszcza w kurnikach¹.

Badania wykazały również, że wirus H5N1 może być przenoszony przez wiatr, choć ta droga transmisji wymaga „konstelacji wielu specyficznych warunków” i wymaga dalszych badań¹²³.

Przenoszenie z ptaków na ludzi

Wirusy HPAI mogą przenosić się z ptaków na ludzi w wyniku rozległego bliskiego kontaktu z zakażonymi ptakami, na przykład podczas domowego uboju lub odpierzania zakażonego drobiu¹. Głównym czynnikiem ryzyka przenoszenia wirusa z ptaków na ludzi jest bezpośredni lub pośredni kontakt z zakażonymi zwierzętami lub ze środowiskami i powierzchniami zanieczyszczonymi odchodami¹.

Zakażenia ludzi wirusem ptasiej grypy mogą wystąpić, gdy wirus dostanie się do oczu, nosa lub ust osoby, lub jest wdychany¹. Ludzie mający niezabezpieczony kontakt (brak rękawiczek lub innych środków ochrony osobistej) z zakażonymi zwierzętami lub ich produktami (np. surowe mleko, surowe sery, surowe jaja) są narażeni na zakażenie¹.

Przenoszenie między ludźmi

Rozprzestrzenianie się wirusów ptasiej grypy od jednej zakażonej osoby do bliskiego kontaktu jest bardzo rzadkie, a gdy już się zdarzyło, rozprzestrzeniło się tylko na kilka osób¹. Wirusy ptasiej grypy nie wydają się łatwo przenosić między ludźmi¹.

Jednak główne obawy o zdrowie publiczne koncentrują się wokół potencjału wirusa do mutacji lub łączenia się z innymi wirusami grypy w formę nowego szczepu, który mógłby łatwo rozprzestrzeniać się od osoby do osoby².

Implikacje kliniczne i leczenie

Objawy kliniczne u ludzi

Kliniczne manifestacje ptasiej grypy A(H5N1) mogą obejmować¹:

Kaszel, gorączka, duszność
Biegunka (w ciężkich przypadkach)
Ból głowy, bóle mięśni, ból gardła
Wyciek z nosa, krwawienie z błon śluzowych
Zmęczenie, żółtaczka, zapalenie spojówek

Na podstawie dostępnych danych o przypadkach ludzkich, wskaźnik śmiertelności ptasiej grypy A(H5N1) wynosi około 52%. Niewydolność oddechowa jest najczęstszą przyczyną śmierci. Inne powikłania mogą obejmować niewydolność wielonarządową, krwotok płucny, odmę opłucnową, pancytopenię².

Diagnostyka

Zakażenie wirusem ptasiej grypy u ludzi nie może być diagnozowane wyłącznie na podstawie objawów klinicznych; wymagane są badania laboratoryjne¹. Zakażenie wirusem ptasiej grypy jest zwykle diagnozowane przez pobranie wymazu z górnych dróg oddechowych (nos lub gardło) od chorej osoby². W przypadku pacjentów w stanie krytycznym, pobranie i badanie próbek z dolnych dróg oddechowych może również prowadzić do diagnozy zakażenia wirusem ptasiej grypy³.

Leczenie i profilaktyka

Leki przeciwwirusowe mogą być stosowane do leczenia podejrzewanych, prawdopodobnych lub potwierdzonych przypadków ptasiej grypy A(H5N1)¹. Do tej pory nie przeprowadzono badań klinicznych mierzących wynik stosowania leków przeciwwirusowych u osób zakażonych ptasią grypą A(H5N1). Jednakże dane z modeli zwierzęcych i badań obserwacyjnych u ludzi sugerowały korzyść dla chorobowości i śmiertelności wynikającą ze stosowania oseltamiwiru jako środka przeciwwirusowego².

Oprócz leków przeciwwirusowych, niektóre przypadki mogą wymagać wsparcia oddechowego. Obecnie brak wystarczających dowodów na dodatkowe korzyści z terapii uzupełniających u pacjentów z ptasią grypą A(H5N1) (tj. kortykosteroidy, antybiotyki makrolidowe i terapia immunologiczna bierna)³.

Wirusy HPAI A(H5N1) do tej pory okazały się wrażliwe na inhibitory neuraminidazy, choć kilka wirusów z egipskiego klade wykazało oporność².

Znaczenie dla zdrowia publicznego

Ptasia grypa pozostaje stosunkowo nową chorobą o słabo poznanej patologii i patogenezie². Niedawne badania w połączeniu z wcześniejszymi odkryciami stopniowo przyczyniły się do lepszego zrozumienia patologii komórkowej i narządowej powodowanej przez wirusa H5N1, a także tropizmu tkankowego wirusa³.

Ze względu na rozszerzający się zakres gospodarzy i geograficzny tego podtypu wirusa, istnieje pilna potrzeba lepszego zrozumienia wkładu zarówno reakcji wirusa, jak i gospodarza¹. Prace badawcze nad ptasią grypą są ukierunkowane na zrozumienie, dlaczego i jak łagodne wirusy stają się wysoce patogenne, opracowanie lepszych testów diagnostycznych i ulepszonych szczepionek oraz wyjaśnienie molekularnych i patologicznych podstaw zjadliwości¹.

Kolejne rozdziały

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Materiały źródłowe

#1 Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans
https://pmc.ncbi.nlm.nih.gov/articles/PMC2329826/
H5N1 avian influenza is a highly fatal infectious disease that could cause a potentially devastating pandemic if the H5N1 virus mutates into a form that spreads efficiently among humans. […] Here we review the pathology of H5N1 avian influenza reported in postmortem and clinical studies and discuss the key pathogenetic mechanisms. Specifically, the virus infects isolated pulmonary epithelial cells and causes diffuse alveolar damage and hemorrhage in the lungs of infected patients. […] Dysregulation of cytokines and chemokines is likely to be one of the key mechanisms in the pathogenesis of H5N1 influenza. […] H5N1 influenza is still a relatively novel disease with poorly understood pathology and pathogenesis. […] Recent studies combined with early findings have gradually resulted in a better understanding of the cell and organ pathology caused by the H5N1 virus, as well as the viral tissue tropism.
#1 Avian Influenza (Bird Flu): Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/2500029-overview
Avian influenza, commonly referred to as bird flu, describes a group of viral infections primarily affecting birds, particularly domestic poultry. However, the term can be misleading, as it encompasses zoonotic infections in humans caused by strains of the influenza A virus. Influenza A is an orthomyxovirus characterized by a segmented RNA genome, which allows for genetic reassortment and antigenic shifts. These characteristics make avian influenza a potential and unpredictable threat to human health. […] The pathophysiology of avian influenza differs from that of normal influenza. Avian influenza remains primarily a respiratory infection but involves more of the lower airways than human influenza typically does. This likely is due to differences in the hemagglutinin protein and the types of sialic acid residues to which the protein binds. Avian viruses tend to prefer sialic acid alpha(2-3) galactose, which, in humans, is found in the terminal bronchi and alveoli. Conversely, human viruses prefer sialic acid alpha(2-6) galactose, which is found on epithelial cells in the upper respiratory tract. One group has reported that ex vivo cultures of human tonsillar, adenoidal, and nasopharyngeal tissues can support replication of H5N1 avian influenza.
#1 Avian Influenza in Birds: Causes and How It Spreads | Bird Flu | CDC
https://www.cdc.gov/bird-flu/virus-transmission/avian-in-birds.html
Avian influenza refers to disease in birds caused by infection with avian (bird) influenza (flu) Type A viruses. […] Avian influenza A viruses are classified into the following two categories: low pathogenicity avian influenza (LPAI) A viruses, and highly pathogenic avian influenza (HPAI) A viruses. The categories refer to molecular characteristics of a virus and the virus’ ability to cause disease and mortality in chickens in a laboratory setting. […] Highly pathogenic avian influenza viruses cause severe disease and high mortality in infected poultry. Only some avian influenza A(H5) and A(H7) viruses are classified as HPAI A viruses, while most A(H5) and A(H7) viruses circulating among birds are LPAI A viruses. HPAI A(H5) or A(H7) virus infections can cause disease that affects multiple internal organs with mortality up to 90% to 100% in chickens, often within 48 hours. […] HPAI and LPAI designations do not refer to or correlate with the severity of illness in cases of human infection with these viruses; both LPAI and HPAI A viruses have caused mild to severe illness in infected humans. […] Both HPAI and LPAI viruses can spread rapidly through poultry flocks.
#1 Avian Influenza – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK553072/
Avian influenza, commonly known as „bird flu,” is a zoonotic disease caused by avian influenza A viruses. […] The infective and pathogenic capabilities of avian influenza viruses are influenced by their tendency to attach to specific sialic acid receptors on host cells. The hemagglutinin proteins of these viruses preferentially bind to -2,3-linked sialic acid receptors, primarily found in the gastrointestinal tracts of birds. In humans, the -2,3-linked sialic acid receptors are predominantly located in the lower respiratory tract, including the terminal bronchi and alveoli, which may account for the severe pneumonia commonly observed in human cases of avian influenza. […] Once avian influenza viruses enter human host cells, their replication dynamics differ from those of human-adapted influenza viruses. Specific subtypes, such as H5N1, have shown prolonged viral replication in humans.
#1 Avian Influenza (Bird Flu): Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/2500029-overview
Although this results in a more severe respiratory infection, it probably explains why few, if any, definite human-to-human transmissions of avian influenza have been reported; infection of the upper airways probably required for efficient spread via coughing and sneezing. Many are concerned that subtle mutation of the hemagglutinin protein through antigenic drift will result in a virus capable of binding to upper and lower respiratory epithelium. The 1918 pandemic strain was so lethal partially because the receptor utilization of the hemagglutinin differed from that of other strains, and H5N1 has that potential to acquire that same biology through mutation. […] Differences in the PA, NP, M1, NS1, and PB2 genes tend to correlate with human is strains of influenza, including human infections with avian influenza. The functional role of these genetic markers has yet to be determined but likely involves replication enhancement and immune suppression. […] Unlike with human influenza, most deaths associated with avian influenza have been due to primary viral pneumonia, with no evidence of secondary bacterial infection.
#1 Molecular mechanisms in the pathogenesis of avian influenza Pashu Sandesh
https://pashusandesh.com/avian-influenza-pathogenesis
Virus replication: In brief, AI virus HA adsorbs to host cell receptors containing sialic acid, thus initiating receptor-mediated endocytosis. In the endocytes, low-pH-dependent fusion occurs via HA-mediated fusion of the envelope with the endogenous membrane Proteolytic cleavage of HA into HA1and HA2 is an essential prerequisite for fusion and infectivity. The viral nucleocapsids are transported to the nucleus where viral transcriptase complex synthesizes mRNA. Six monocistronic mRNAs are produced in the nucleus and transported to the cytoplasm for translation into HA, NA, NP, PB1, PB2, and PA proteins. The m RNA of NS and M gene segments undergo splicing with each producing two mRNAs, which are translated to NS1, NS2, M1, and M2. The HA and NA proteins are glycosylated in the rough endoplasmic reticulum, trimmed in the Golgi, and transported to the surface where they are embedded in the plasma membrane. The eight viral gene segments along with internal viral proteins (NP, PB1, PB2, PA, and M2) assemble and migrate to areas of the plasma membrane containing the integrated HA, NA, and M2 proteins. The M1 protein promotes close association with the plasma membrane and budding of the virions.
#1 Molecular mechanisms in the pathogenesis of avian influenza Pashu Sandesh
https://pashusandesh.com/avian-influenza-pathogenesis
The HA gene is the primary determinant of high pathogenicity in chickens. In brief, the cleavage of the HA protein into the HA1 and HA2 proteins is essential for the virus to be infectious and produce multiple replication cycles. […] With LPAI viruses, they are released from the host cell with an uncleaved HA protein and are not infectious. The protein can be cleaved by trypsin-like proteases found in restricted anatomical sites, such as respiratory and intestinal epithelial cells, which accounts for the restricted replication and lower virulence. The difference between the cleavage site of LPAI and HPAI viruses is the number of basic amino acids in the HA1 near the cleavage site that determines whether trypsin-like proteases or furin-like proteases can cleave the protein. The LPAI viruses generally have only two non-consecutive basic amino acids at the carboxy-terminus of the HA1 which is cleavable only by trypsin-like proteases. In contrast, H5 and H7 HPAI viruses have either multiple basic amino acids or an insertion of amino acids at the carboxy-terminal of the HA1 protein that allows proteolytic cleavage by ubiquitous furin proteases that are present in many cells throughout the body.
#1 Molecular mechanisms in the pathogenesis of avian influenza Pashu Sandesh
https://pashusandesh.com/avian-influenza-pathogenesis
With HPAI viruses, the HA is cleaved inside the cell before virus assembly and is infectious when it is released from the host cell. This effectively increases the cell tropism of the virus leading to virus replication in numerous visceral organs, the nervous system, and the cardiovascular system, leading to systemic disease with high mortality. HPAI viruses are not believed to normally circulate in wild birds, but LPAI viruses can mutate under some circumstances to the HPAI form by changes in the HA cleavage site including: (1) substitution of non-basic with basic amino acids, (2) insertions of multiple basic amino acids from codons duplicated at the haemagglutinin cleavage site, or (3) short inserts of basic and non-basic amino acids from unknown source. […] One additional factor, the presence or absence of a glycosylation site, can shield the cleavage so that furin-like proteases cannot function, and the viruses may have an LPAI phenotype even with multiple basic amino acids at the cleavage site.
#1 Avian Influenza – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK553072/
The host immune response is crucial in disease severity, with elevated levels of inflammatory markers linked to more severe disease courses. […] Respiratory failure due to primary viral pneumonia is the most common cause of death, often resulting from diffuse alveolar damage and hemorrhage caused by viral replication and immune-mediated injury. […] Animal studies suggest that avian influenza viruses may also damage neurons in the pre-BÃ¶tzinger complex, which is responsible for generating respiratory rhythm. This damage could contribute to ataxic breathing and respiratory collapse in severe cases.
#1 Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans
https://pmc.ncbi.nlm.nih.gov/articles/PMC2329826/
Up-regulation of functional TRAIL in macrophages infected with the H5N1 virus may be another important factor in the pathogenesis of H5N1 influenza virus infection. […] H5N1 viral replication appears to be prolonged with high levels of viral RNA, and the virus may disseminate to extra-pulmonary organs.
#1 Pathogenesis of influenza virus in Avian – Institute of International Peace Leaders
https://internationalpeaceleaders.com/pathogenesis-of-influenza-virus-in-avian/
Following respiratory transmission, the virus attaches to and penetrates respiratory epithelial cells in the trachea and bronchi. The pathogenesis of Avian Influenza involves the entry of the virus into the respiratory and gastrointestinal tracts of birds. The virus binds to host cells using specific surface proteins. Once inside the cells, it replicates and spreads, causing damage to the respiratory and digestive systems. Highly Pathogenic Avian Influenza (HPAI) strains can lead to severe disease, affecting multiple organs and often resulting in high mortality rates.
#1 Avian Influenza in Poultry and Wild Birds – Poultry – Merck Veterinary Manual
https://www.merckvetmanual.com/poultry/avian-influenza-in-poultry-and-wild-birds/avian-influenza-in-poultry-and-wild-birds
Avian influenza is a viral infection found in domestic poultry and a wide range of other birds, with some strains sporadically spilling over into wild and domestic mammals and humans. […] High-pathogenicity strains may cause widespread organ failure and sudden death, often with high mortality rates. […] A few AI viruses, however, have high pathogenicity (HPAI), causing severe systemic disease with multiple organ failure and high mortality rates. […] High-pathogenicity avian influenza (HPAI) viruses arise from the mutation of some H5 and H7 LPAI viruses. […] The morbidity and mortality rates of LPAI viral infections are usually low, unless the infection is accompanied by secondary bacterial or viral infections or aggravated by environmental stressors. […] Even in the absence of secondary pathogens, HPAI viruses cause severe, systemic disease with high mortality rates in chickens, turkeys, and other gallinaceous poultry; mortality rates can be as high as 100% in a few days.
#1 Avian Influenza in Poultry and Wild Birds – Poultry – Merck Veterinary Manual
https://www.merckvetmanual.com/poultry/avian-influenza-in-poultry-and-wild-birds/avian-influenza-in-poultry-and-wild-birds
In peracute cases, clinical signs or gross lesions of avian influenza may be lacking before death. In acute cases, however, lesions may include cyanosis and edema of the head, comb, wattle, and snood (turkey); ischemic necrosis of the comb, wattles, or snood; edema and red discoloration of the shanks and feet due to subcutaneous ecchymotic hemorrhages; petechial hemorrhages on visceral organs and in muscles; and blood-tinged oral and nasal discharges. […] Birds that survive peracute AI infection may develop CNS involvement evident as torticollis, opisthotonos, incoordination, paralysis, and drooping wings. Microscopic lesions are highly variable in both location and severity, and they may consist of edema, hemorrhage, and necrosis in parenchymal cells of multiple visceral organs, the skin, and the CNS.
#1 Avian Influenza – PAHO/WHO | Pan American Health Organization
https://www.paho.org/en/topics/avian-influenza
When avian influenza is transmitted to humans, symptoms in people can range from mild upper respiratory tract infection (fever and cough) to severe pneumonia, acute respiratory distress syndrome (difficulty breathing), shock, and even death. […] PAHO works with countries in the region and other agencies to strengthen avian influenza virus surveillance in animals and humans, and provides technical assistance for the timely detection, treatment and investigation of avian influenza A(H5N1) virus infection in humans. […] The organization also works to strengthen laboratory capacity in national veterinary and public health services so that they have the diagnostic capability to identify the presence of the avian influenza virus and detect changes in its genetic makeup.
#1 Factsheet on A(H5N1)
https://www.ecdc.europa.eu/en/zoonotic-influenza/facts/factsheet-h5n1
The clinical course of human cases of A(H5N1) is characterised by initial fever and cough, with rapid progression to lower respiratory disease. Upper respiratory tract symptoms of rhinorrhoea and sore throat might not be common in all patients, but the disease can progress to respiratory failure, acute respiratory distress syndrome (ARDS) and multi-organ failure [5]. […] A subset of avian influenza viruses may infect humans; whenever such viruses are circulating in poultry, sporadic infections or small clusters of human cases are possible in people exposed to infected poultry or contaminated environments, especially related to backyard settings. Human infections remain rare, and influenza A(H5N1) viruses do not appear to transmit easily between people. […] HPAI A(H5N1) viruses have so far been reported to be sensitive to neuraminidase inhibitors, even though a few viruses of the Egyptian clade showed resistance.
#1 Pathogenicity and transmissibility of bovine H5N1 influenza virus | Nature
https://www.nature.com/articles/s41586-024-07766-6
Highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses occasionally infect, but typically do not transmit, in mammals. […] Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection). […] Bovine HPAI H5N1 virus thus possesses features that may facilitate infection and transmission in mammals. […] HPAI H5N1 viruses rarely infect mammals and typically do not transmit among them. […] Together, our pathogenicity studies in mice and ferrets revealed that (1) HPAI H5N1 derived from lactating dairy cattle may induce severe disease after oral ingestion or respiratory infection; and (2) infection by either the oral or respiratory route can lead to systemic spread of virus to non-respiratory tissues including the eye, mammary gland, teat and/or muscle.
#1 Pathogenesis of bovine H5N1 clade 2.3.4.4b infection in macaques | Nature
https://www.nature.com/articles/s41586-025-08609-8
Since early 2022, highly pathogenic avian influenza (HPAI) H5N1 virus infections have been reported in wild aquatic birds and poultry throughout the USA with spillover into several mammalian species. […] Here we investigated routes of infection with bovine HPAIV H5N1 clade 2.3.4.4b in cynomolgus macaques, a surrogate model for human infection. […] We show that intranasal or intratracheal inoculation of macaques could cause systemic infection resulting in mild and severe respiratory disease, respectively. […] By contrast, infection by the orogastric route resulted in limited infection and seroconversion of macaques that remained subclinical.
#1 Avian influenza – Wikipedia
https://en.wikipedia.org/wiki/Avian_influenza
Influenza A is an RNA virus with a genome comprising a negative-sense, RNA segmented genome that encodes 11 viral genes. […] Hemagglutinin (H) is an antigenic glycoprotein which allows the virus to bind to and enter the host cell. Neuraminidase (N) is an antigenic glycosylated enzyme which facilitates the release of progeny viruses from infected cells. […] Genetic variations are important because they can change amino acids that make up the influenza virus proteins, resulting in structural changes to the proteins, and thereby altering properties of the virus. Some of these properties include the ability to evade immunity and the ability to cause severe disease. […] Influenza viruses are constantly changing as small genetic mutations accumulate, a process known as antigenic drift. Over time, mutation may lead to a change in antigenic properties such that host antibodies (acquired through vaccination or prior infection) do not provide effective protection, causing a fresh outbreak of disease.
#1 Avian influenza – Wikipedia
https://en.wikipedia.org/wiki/Avian_influenza
The segmented genome of influenza viruses facilitates genetic reassortment. This can occur if a host is infected simultaneously with two different strains of influenza virus; then it is possible for the viruses to interchange genetic material as they reproduce in the host cells. […] Thus, an avian influenza virus can acquire characteristics, such as the ability to infect humans, from a different virus strain.
#1 Influenza A virus subtype H5N1 – Wikipedia
https://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1
Due to the high lethality and virulence of HPAI A(H5N1), its worldwide presence, its increasingly diverse host reservoir, and its significant ongoing mutations, the H5N1 virus is regarded as the world’s largest pandemic threat. […] The avian influenza hemagglutinin prefers to bind to alpha-2,3 sialic acid receptors, while the human influenza hemagglutinin prefers to bind to alpha-2,6 sialic acid receptors. This means that when the H5N1 strain infects humans, it will replicate in the lower respiratory tract (where alpha-2,3 sialic acid receptors are more plentiful in humans) and consequently cause viral pneumonia. […] Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different strains of influenza viruses at the same time. Through a combination of mutation and genetic reassortment the virus can evolve to acquire new characteristics, enabling it to evade host immunity and occasionally to jump from one species of host to another.
#1 Avian influenza | American Veterinary Medical Associationmultiple-users-1addaddaddaddadd
https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza
Contact with excrement from infected birds is the most common means of bird-to-bird transmission, although airborne secretions are another important mode of transmission, especially within poultry houses. Excrement from wild ducks can introduce avian influenza into domestic flocks raised on ranges or in open flight pens. […] HPAI viruses can spread from birds to people as a result of extensive close contact with infected birds, such as during home slaughter or defeathering of infected poultry. The current H5N1 outbreak is different in that dozens of people are known to have become infected with avian influenza virus type A (H5), including a few without any known animal contact. The majority have been farm workers on poultry or dairy cattle premises. […] Public health concerns center around the potential for the virus to mutate or combine with other influenza viruses to a form a new strain that could easily spread from person to person. A mutation (PB2 D701N) has been identified in some genetic sequences of the D1.1 genotype of H5N1 from dairy cattle and one human case in the United States. A different mutation (PB2 E627K) has been identified in a single sequence of the B3.13 genotype in a dairy cow and in two human cases (one with the D1.1 genotype and the other with the B3.13 genotype). Both mutations improve replication efficiency in mammalian cells and have been associated with mammalian adaptation. Neither mutation has been reported in D1.1 or B3.13 viruses from wild birds. […] Biosecurity is the first line of defense against transmission of avian influenza to birds, including companion birds and commercial and backyard poultry, and to cattle. Early detection allows actions to be taken quickly to protect poultry and cattle and prevent infections from spreading.
#1 What We Knowâand Donât KnowâAbout H5N1 Bird Flu | SPH
https://www.bu.edu/sph/news/articles/2024/what-we-know-and-dont-know-about-h5n1-bird-flu/
One month since the H5N1 strain of bird flu was first spotted in US dairy cows, fragments of the virus have been detected in commercial milk, increasing the already heightened concern among experts about the extent of the virus national and global spread, as well as its potential to mutate and spread to humans. […] The concern is that the spillover into dairy cows may indicate the virus is changing in ways that promote transmissibility in other mammals, including humans. […] Influenza A viruses mutate rapidly, so the central concern right now is whether this H5N1 virus has evolved a mechanism to transmit between cowsâwhich it appears it hasâand whether intensified transmission among cows increases human exposure. […] Over the years, H5N1 has not to date evolved in a direction that has allowed for sustained human-to-human transmission, despite widespread human exposure from poultry.
#1 Bird Flu Is Raising Red Flags Among Health Officials | Johns Hopkins | Bloomberg School of Public Health
https://publichealth.jhu.edu/2025/bird-flu-is-raising-red-flags-among-health-officials
The critical thing is understanding whether the virus that’s in dairy cows right now will pick up mutations that will help it to be more transmissible in mammals. […] If the virus changes the way it transmits and becomes a respiratory pathogen among dairy cows, that would be another sign that this virus is changing and posing more of a risk to the human population.
#1 Protein prevents transmission avian influenza viruses in humans
https://sciencemediacentre.es/en/reactions-protein-identified-prevents-transmission-and-replication-avian-influenza-viruses-humans
Reactions: a protein is identified that prevents transmission and replication of avian influenza viruses in humans […] The authors propose that this protein with antiviral activity evolved in primates and consider that resistance or sensitivity to it should be taken into account when assessing the zoonotic potential of avian influenza viruses. […] But of added concern is that this virus has demonstrated the ability to severely infect several mammalian species, which is a first step towards crossing the species barrier and causing effective and virulent infections in humans. […] In this article, the authors describe the identification of the protein BTN3A3 (Butyrophilin subfamily 3, member A3), which acts as a potent inhibitor of avian influenza viruses, but not of human influenza viruses.
#1 Protein prevents transmission avian influenza viruses in humans
https://sciencemediacentre.es/en/reactions-protein-identified-prevents-transmission-and-replication-avian-influenza-viruses-humans
Specifically, the researchers show that the mechanism of action of BTN3A3 acts in the early stages of the virus cycle, inhibiting viral RNA replication. […] In summary, this study provides a breakthrough in the understanding of the innate molecular mechanisms by which humans defend against avian influenza viruses. […] Understanding the virus evasion mechanisms and the evolution of proteins involved in evading the immune response is of vital importance, as this provides a tool with great potential to assess the impact of the different bird-to-human virus transmissions that we have been analysing worldwide. […] The study published by an established group dedicated to the investigation of zoonotic virus characteristics and host immune response reports the finding of a new gene that adds to the already known mechanisms involved in the so-called species barrier that prevents avian influenza A viruses from easily infecting humans. […] They conclude that these changes – that is, evasion of the species-hopping barrier constituted by the BTN3A3 gene – are a key mechanism that may confer zoonotic potential to avian influenza A viruses.
#1 Gender-specific personalised medicine: when viruses awaken the hormones | VolkswagenStiftung
https://www.volkswagenstiftung.de/en/news/news/gender-specific-personalised-medicine-when-viruses-awaken-hormones
What we discovered in the human lung was mind blowing. […] The decisive breakthrough came with the discovery of an enzyme known as aromatase. After infection with SARS-CoV-2, it is suddenly produced in greater quantities in the lungs. 'The lungs become an endocrine organ that converts hormones more precisely, testosterone into oestradiol,’ explains Gabriel. […] The newly created hormone factory had dramatic consequences: 'It led to more severe disease progression in men,’ explains Gabriel. […] Oestradiol apparently activates inflammatory signals and thus leads to long-term damage to the lung tissue. […] Bird flu viruses in particular appear to have the dangerous ability to strongly induce aromatase in the lungs, which suggests a significantly increased risk of long-term lung damage a consequence that has hardly been researched to date. […] The research team wants to use the project to develop innovative approaches to inhibit aromatase-dependent, gender-specific pneumonia in infections with avian influenza viruses.
#1 Avian influenza | American Veterinary Medical Associationmultiple-users-1addaddaddaddadd
https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza
The latest example is avian influenza type A H5N1 (clade 2.3.4.4b), which has been responsible for the loss of millions of birds since early 2022, impacting commercial and backyard flocks in all 50 states. This virus was found in U.S. dairy cattle in March 2024 and has since spread to hundreds of dairy herds as well as people, cats, and other mammals. Most affected dairy cattle have had only mild signs, but severe disease and death have occurred in many cats, including barn and feral cats, indoor cats, and big cats (e.g., mountain lions, tigers, leopards, and bobcats). […] For poultry, avian influenza is most often spread by close contact between infected birds and healthy birds. It may also be spread indirectly through contact with contaminated equipment and with biological secretions and/or excretions from infected birds. The virus can be found in secretions from the nares, mouth, and eyes of infected birds and in their excrement.
#1 Can avian flu spread via the wind? Can’t be ruled out, experts say | CIDRAP
https://www.cidrap.umn.edu/avian-influenza-bird-flu/can-avian-flu-spread-wind-cant-be-ruled-out-experts-say
A nonpeer-reviewed study published on the preprint server bioRxiv suggests that highly pathogenic avian influenza (HPAI) virus shed in poultry droppings can be transmitted by the wind, a possibility that other experts say can’t be ruled out but is also very difficult to prove. […] The researchers, from the State Veterinary Institute Prague, used genetic, epizootiologic, meteorologic, and geographic data to reconstruct events suggesting that wind was the mechanism of H5N1 transmission between poultry on at least two of the farms. […] Our results suggest that the contaminated plume emitted from the infected fattening duck farm was the critical medium of HPAI transmission, rather than the dust generated during depopulation. […] „They also strongly implicate the role of confined mechanically-ventilated buildings with high population densities in facilitating windborne transmission and propagating virus concentrations below the minimum infectious dose at the recipient sites.”
#1 Avian Influenza – PAHO/WHO | Pan American Health Organization
https://www.paho.org/en/topics/avian-influenza
Avian influenza, also known as 'bird flu’, is a disease primarily affecting birds and is caused by a virus of the Orthomyxoviridae family. […] According to its subtype, it may be classified as high or low pathogenicity, presenting different symptoms in infected birds. The Highly Pathogenic Avian Influenza Virus (HPAIV) caused by subtypes (H5 and H7) of type A, causes serious illness in birds that can spread rapidly, resulting in high death rates in different species of birds. […] Most of the influenza viruses circulating in birds are not zoonotic. However, some HPAI strains have the ability to infect humans, posing a threat to public health. […] The main risk factor for transmission from birds to humans is direct or indirect contact with infected animals or with environments and surfaces contaminated by feces.
#1 What Causes Bird Flu Virus Infections in Humans | Bird Flu | CDC
https://www.cdc.gov/bird-flu/virus-transmission/avian-in-humans.html
Avian influenza A viruses usually do not infect people, but there have been some rare human cases. […] Illness in humans from avian influenza virus infections have ranged in severity from no symptoms or mild illness to severe disease that resulted in death. […] Human infections with avian influenza viruses can happen when virus gets into a person’s eyes, nose or mouth, or is inhaled. […] The spread of bird flu viruses from one infected person to a close contact is very rare, and when it has happened, it has only spread to a few people. […] Bird flu virus infection in people cannot be diagnosed by clinical signs and symptoms alone; laboratory testing is needed. […] Bird flu virus infection is usually diagnosed by collecting a swab from the upper respiratory tract (nose or throat) of the sick person. […] For critically ill patients, collection and testing of lower respiratory tract specimens also may lead to diagnosis of bird flu virus infection. […] Avian influenza or bird flu refers to the disease caused by infection with avian (bird) influenza (flu) Type A viruses.
#1 Avian Influenza – Overview | Occupational Safety and Health Administration
http://www.osha.gov/avian-flu
People should avoid unprotected exposure to dead animals/birds, animal waste, bedding, raw milk/uncooked animal products, or materials touched by, or close to animals with suspected or confirmed avian influenza. Workers who have unprotected exposure (no gloves or other personal protective equipment) with infected animals or their products (e.g. raw milk, raw cheeses, raw eggs) are at risk of infection.
#1 Avian influenza A(H5N1): For health professionals – Canada.ca
https://www.canada.ca/en/public-health/services/diseases/avian-influenza-h5n1/health-professionals.html
Avian influenza A(H5N1) is classified as highly pathogenic avian influenza (HPAI), based on the severity of illness caused in birds. […] The clinical manifestations of avian influenza A(H5N1) may include: cough, fever, shortness of breath, diarrhea (in severe cases), headache, myalgia, sore throat, rhinorrhea, mucosal bleeding, fatigue, jaundice, conjunctivitis. […] Based on available human case data to date, the case fatality rate of avian influenza A(H5N1) is approximately 52%. […] Respiratory failure is the most common cause of death. Other complications may include: multiorgan failure, pulmonary hemorrhage, pneumothorax, pancytopenia. […] Antiviral agents can be used to treat suspected, probable, or confirmed avian influenza A(H5N1) cases. […] To date, there have been no clinical trials measuring the outcome of antiviral use in individuals infected with avian influenza A(H5N1). However, data from animal models and human observational studies have suggested a morbidity and mortality benefit to the use of oseltamivir as an antiviral agent. […] In addition to antivirals, some cases may require respiratory support. Presently, there is insufficient evidence to suggest added benefit from adjunctive therapies in patients with avian influenza A(H5N1) (i.e., corticosteroids, macrolide antibiotics, and passive immune therapy).
#1 Avian Influenza Published Research | The Transmission | University of Nebraska Medical Center
https://www.unmc.edu/healthsecurity/transmission/category/emerging-infectious-diseases/avian-influenza-published-research/
H5N1 pathogenesis studies in mammalian models […] H5N1 influenza viruses are capable of causing severe disease and death in humans, and represent a potential pandemic subtype should they acquire a transmissible phenotype. Due to the expanding host and geographic range of this virus subtype, there is an urgent need to better understand the contribution of both virus and host responses. […] Phenotypic effects of mutations observed in the neuraminidase of human origin H5N1 influenza A viruses […] Little is known about the role of mutations in the viral neuraminidase (NA) that accompanied bird-to-human transmission to support AIV infection of mammals.
#1 Avian Influenza : USDA ARS
https://www.ars.usda.gov/oc/br/ai/avian-influenza/
Avian influenza (AI) is a virus-caused disease usually infecting birds. AI viruses can infect chickens, turkeys, pheasants, quail, ducks, geese and guinea fowl as well as a wide variety of other birds, including migratory waterfowl. […] AI strains are also divided into two groups based on pathogenicity-the ability of the virus to produce disease. Most AI strains are classified as low pathogenicity (LP) avian influenza and cause little or no clinical signs in infected birds. LPAI poses no serious threat to humans. Some strains of LPAI-H5 and H7-can mutate to the more highly pathogenic forms. Birds with HPAI get a more virulent form of avian influenza. […] ARS is developing new information and important tools to help control this disease in poultry. ARS supports USDA’s Animal and Plant Health Inspection Service, The Centers for Disease Control and Prevention, and poultry industry action programs with epidemiology, molecular virology, pathogenesis research, and technical assistance on avian influenza. […] The Southeast Poultry Research Lab (SEPRL) research efforts on avian influenza are directed toward understanding why and how mild viruses become highly pathogenic, developing better diagnostic tests and improved vaccines, and elucidating the molecular and pathological basis for virulence.
#2 Avian Influenza – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK553072/
Avian influenza, commonly known as „bird flu,” is a zoonotic disease caused by avian influenza A viruses. […] The infective and pathogenic capabilities of avian influenza viruses are influenced by their tendency to attach to specific sialic acid receptors on host cells. The hemagglutinin proteins of these viruses preferentially bind to -2,3-linked sialic acid receptors, primarily found in the gastrointestinal tracts of birds. In humans, the -2,3-linked sialic acid receptors are predominantly located in the lower respiratory tract, including the terminal bronchi and alveoli, which may account for the severe pneumonia commonly observed in human cases of avian influenza. […] Once avian influenza viruses enter human host cells, their replication dynamics differ from those of human-adapted influenza viruses. Specific subtypes, such as H5N1, have shown prolonged viral replication in humans.
#2 Avian influenza – Wikipedia
https://en.wikipedia.org/wiki/Avian_influenza
Influenza A is an RNA virus with a genome comprising a negative-sense, RNA segmented genome that encodes 11 viral genes. […] Hemagglutinin (H) is an antigenic glycoprotein which allows the virus to bind to and enter the host cell. Neuraminidase (N) is an antigenic glycosylated enzyme which facilitates the release of progeny viruses from infected cells. […] Genetic variations are important because they can change amino acids that make up the influenza virus proteins, resulting in structural changes to the proteins, and thereby altering properties of the virus. Some of these properties include the ability to evade immunity and the ability to cause severe disease. […] Influenza viruses are constantly changing as small genetic mutations accumulate, a process known as antigenic drift. Over time, mutation may lead to a change in antigenic properties such that host antibodies (acquired through vaccination or prior infection) do not provide effective protection, causing a fresh outbreak of disease.
#2 Avian Influenza (Bird Flu): Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/2500029-overview
Avian influenza, commonly referred to as bird flu, describes a group of viral infections primarily affecting birds, particularly domestic poultry. However, the term can be misleading, as it encompasses zoonotic infections in humans caused by strains of the influenza A virus. Influenza A is an orthomyxovirus characterized by a segmented RNA genome, which allows for genetic reassortment and antigenic shifts. These characteristics make avian influenza a potential and unpredictable threat to human health. […] The pathophysiology of avian influenza differs from that of normal influenza. Avian influenza remains primarily a respiratory infection but involves more of the lower airways than human influenza typically does. This likely is due to differences in the hemagglutinin protein and the types of sialic acid residues to which the protein binds. Avian viruses tend to prefer sialic acid alpha(2-3) galactose, which, in humans, is found in the terminal bronchi and alveoli. Conversely, human viruses prefer sialic acid alpha(2-6) galactose, which is found on epithelial cells in the upper respiratory tract. One group has reported that ex vivo cultures of human tonsillar, adenoidal, and nasopharyngeal tissues can support replication of H5N1 avian influenza.
#2 Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans
https://pmc.ncbi.nlm.nih.gov/articles/PMC2329826/
The major pathogenetic mechanisms and etiological factors of H5N1 influenza are discussed. […] Various factors are thought to be involved in the pathogenesis of H5N1 influenza, and a combination of these factors most likely determines the extent of tissue injury and disease outcome. […] The role of dysregulation of cytokines and chemokines has been studied extensively and may be one of the key mechanisms in the pathogenesis of H5N1 influenza, in addition to injury resulting from viral replication. […] It is generally thought that replication of the H5N1 virus results in cell and organ damage by either cytolytic or apoptotic mechanisms, similar to human influenza infections. […] Various studies indicate that aberrant production of proinflammatory cytokines and chemokines may play an important role in the pathogenesis of H5N1 influenza.
#2 Avian Influenza – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK553072/
The host immune response is crucial in disease severity, with elevated levels of inflammatory markers linked to more severe disease courses. […] Respiratory failure due to primary viral pneumonia is the most common cause of death, often resulting from diffuse alveolar damage and hemorrhage caused by viral replication and immune-mediated injury. […] Animal studies suggest that avian influenza viruses may also damage neurons in the pre-BÃ¶tzinger complex, which is responsible for generating respiratory rhythm. This damage could contribute to ataxic breathing and respiratory collapse in severe cases.
#2 Avian Influenza (Bird Flu): Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/2500029-overview
Although this results in a more severe respiratory infection, it probably explains why few, if any, definite human-to-human transmissions of avian influenza have been reported; infection of the upper airways probably required for efficient spread via coughing and sneezing. Many are concerned that subtle mutation of the hemagglutinin protein through antigenic drift will result in a virus capable of binding to upper and lower respiratory epithelium. The 1918 pandemic strain was so lethal partially because the receptor utilization of the hemagglutinin differed from that of other strains, and H5N1 has that potential to acquire that same biology through mutation. […] Differences in the PA, NP, M1, NS1, and PB2 genes tend to correlate with human is strains of influenza, including human infections with avian influenza. The functional role of these genetic markers has yet to be determined but likely involves replication enhancement and immune suppression. […] Unlike with human influenza, most deaths associated with avian influenza have been due to primary viral pneumonia, with no evidence of secondary bacterial infection.
#2 Avian Influenza in Poultry and Wild Birds – Poultry – Merck Veterinary Manual
https://www.merckvetmanual.com/poultry/avian-influenza-in-poultry-and-wild-birds/avian-influenza-in-poultry-and-wild-birds
In peracute cases, clinical signs or gross lesions of avian influenza may be lacking before death. In acute cases, however, lesions may include cyanosis and edema of the head, comb, wattle, and snood (turkey); ischemic necrosis of the comb, wattles, or snood; edema and red discoloration of the shanks and feet due to subcutaneous ecchymotic hemorrhages; petechial hemorrhages on visceral organs and in muscles; and blood-tinged oral and nasal discharges. […] Birds that survive peracute AI infection may develop CNS involvement evident as torticollis, opisthotonos, incoordination, paralysis, and drooping wings. Microscopic lesions are highly variable in both location and severity, and they may consist of edema, hemorrhage, and necrosis in parenchymal cells of multiple visceral organs, the skin, and the CNS.
#2 Factsheet on A(H5N1)
https://www.ecdc.europa.eu/en/zoonotic-influenza/facts/factsheet-h5n1
The clinical course of human cases of A(H5N1) is characterised by initial fever and cough, with rapid progression to lower respiratory disease. Upper respiratory tract symptoms of rhinorrhoea and sore throat might not be common in all patients, but the disease can progress to respiratory failure, acute respiratory distress syndrome (ARDS) and multi-organ failure [5]. […] A subset of avian influenza viruses may infect humans; whenever such viruses are circulating in poultry, sporadic infections or small clusters of human cases are possible in people exposed to infected poultry or contaminated environments, especially related to backyard settings. Human infections remain rare, and influenza A(H5N1) viruses do not appear to transmit easily between people. […] HPAI A(H5N1) viruses have so far been reported to be sensitive to neuraminidase inhibitors, even though a few viruses of the Egyptian clade showed resistance.
#2 Avian influenza | American Veterinary Medical Associationmultiple-users-1addaddaddaddadd
https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza
The latest example is avian influenza type A H5N1 (clade 2.3.4.4b), which has been responsible for the loss of millions of birds since early 2022, impacting commercial and backyard flocks in all 50 states. This virus was found in U.S. dairy cattle in March 2024 and has since spread to hundreds of dairy herds as well as people, cats, and other mammals. Most affected dairy cattle have had only mild signs, but severe disease and death have occurred in many cats, including barn and feral cats, indoor cats, and big cats (e.g., mountain lions, tigers, leopards, and bobcats). […] For poultry, avian influenza is most often spread by close contact between infected birds and healthy birds. It may also be spread indirectly through contact with contaminated equipment and with biological secretions and/or excretions from infected birds. The virus can be found in secretions from the nares, mouth, and eyes of infected birds and in their excrement.
#2 Pathogenicity and transmissibility of bovine H5N1 influenza virus | Nature
https://www.nature.com/articles/s41586-024-07766-6
Highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses occasionally infect, but typically do not transmit, in mammals. […] Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection). […] Bovine HPAI H5N1 virus thus possesses features that may facilitate infection and transmission in mammals. […] HPAI H5N1 viruses rarely infect mammals and typically do not transmit among them. […] Together, our pathogenicity studies in mice and ferrets revealed that (1) HPAI H5N1 derived from lactating dairy cattle may induce severe disease after oral ingestion or respiratory infection; and (2) infection by either the oral or respiratory route can lead to systemic spread of virus to non-respiratory tissues including the eye, mammary gland, teat and/or muscle.
#2 Avian influenza – Wikipedia
https://en.wikipedia.org/wiki/Avian_influenza
The segmented genome of influenza viruses facilitates genetic reassortment. This can occur if a host is infected simultaneously with two different strains of influenza virus; then it is possible for the viruses to interchange genetic material as they reproduce in the host cells. […] Thus, an avian influenza virus can acquire characteristics, such as the ability to infect humans, from a different virus strain.
#2 Protein prevents transmission avian influenza viruses in humans
https://sciencemediacentre.es/en/reactions-protein-identified-prevents-transmission-and-replication-avian-influenza-viruses-humans
Specifically, the researchers show that the mechanism of action of BTN3A3 acts in the early stages of the virus cycle, inhibiting viral RNA replication. […] In summary, this study provides a breakthrough in the understanding of the innate molecular mechanisms by which humans defend against avian influenza viruses. […] Understanding the virus evasion mechanisms and the evolution of proteins involved in evading the immune response is of vital importance, as this provides a tool with great potential to assess the impact of the different bird-to-human virus transmissions that we have been analysing worldwide. […] The study published by an established group dedicated to the investigation of zoonotic virus characteristics and host immune response reports the finding of a new gene that adds to the already known mechanisms involved in the so-called species barrier that prevents avian influenza A viruses from easily infecting humans. […] They conclude that these changes – that is, evasion of the species-hopping barrier constituted by the BTN3A3 gene – are a key mechanism that may confer zoonotic potential to avian influenza A viruses.
#2 Gender-specific personalised medicine: when viruses awaken the hormones | VolkswagenStiftung
https://www.volkswagenstiftung.de/en/news/news/gender-specific-personalised-medicine-when-viruses-awaken-hormones
What we discovered in the human lung was mind blowing. […] The decisive breakthrough came with the discovery of an enzyme known as aromatase. After infection with SARS-CoV-2, it is suddenly produced in greater quantities in the lungs. 'The lungs become an endocrine organ that converts hormones more precisely, testosterone into oestradiol,’ explains Gabriel. […] The newly created hormone factory had dramatic consequences: 'It led to more severe disease progression in men,’ explains Gabriel. […] Oestradiol apparently activates inflammatory signals and thus leads to long-term damage to the lung tissue. […] Bird flu viruses in particular appear to have the dangerous ability to strongly induce aromatase in the lungs, which suggests a significantly increased risk of long-term lung damage a consequence that has hardly been researched to date. […] The research team wants to use the project to develop innovative approaches to inhibit aromatase-dependent, gender-specific pneumonia in infections with avian influenza viruses.
#2 Can avian flu spread via the wind? Can’t be ruled out, experts say | CIDRAP
https://www.cidrap.umn.edu/avian-influenza-bird-flu/can-avian-flu-spread-wind-cant-be-ruled-out-experts-say
Lead study author Alexander Nagy, PhD, told CIDRAP News that he and his team became convinced about the role of windborne transmission in these outbreaks when they confirmed the identical identity of the H5N1 strain in the donor and recipient farms, the nearly ideal weather conditions during the transmission event, and the slow disease progression in the chicken barns characterized by feed and water consumption before clinical signs appeared. […] „The windborne route is important to consider in cases when the infection emerges in new locations without obvious links to other farms or when illness and mortality are first observed near the air inlets.” […] Nagy acknowledged that airborne spread isn’t typically considered a primary route of infection in poultry, and windborne spread requires „a constellation of many specific conditions” that behooves further research.
#2 Avian influenza | American Veterinary Medical Associationmultiple-users-1addaddaddaddadd
https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza
Contact with excrement from infected birds is the most common means of bird-to-bird transmission, although airborne secretions are another important mode of transmission, especially within poultry houses. Excrement from wild ducks can introduce avian influenza into domestic flocks raised on ranges or in open flight pens. […] HPAI viruses can spread from birds to people as a result of extensive close contact with infected birds, such as during home slaughter or defeathering of infected poultry. The current H5N1 outbreak is different in that dozens of people are known to have become infected with avian influenza virus type A (H5), including a few without any known animal contact. The majority have been farm workers on poultry or dairy cattle premises. […] Public health concerns center around the potential for the virus to mutate or combine with other influenza viruses to a form a new strain that could easily spread from person to person. A mutation (PB2 D701N) has been identified in some genetic sequences of the D1.1 genotype of H5N1 from dairy cattle and one human case in the United States. A different mutation (PB2 E627K) has been identified in a single sequence of the B3.13 genotype in a dairy cow and in two human cases (one with the D1.1 genotype and the other with the B3.13 genotype). Both mutations improve replication efficiency in mammalian cells and have been associated with mammalian adaptation. Neither mutation has been reported in D1.1 or B3.13 viruses from wild birds. […] Biosecurity is the first line of defense against transmission of avian influenza to birds, including companion birds and commercial and backyard poultry, and to cattle. Early detection allows actions to be taken quickly to protect poultry and cattle and prevent infections from spreading.
#2 Avian influenza A(H5N1): For health professionals – Canada.ca
https://www.canada.ca/en/public-health/services/diseases/avian-influenza-h5n1/health-professionals.html
Avian influenza A(H5N1) is classified as highly pathogenic avian influenza (HPAI), based on the severity of illness caused in birds. […] The clinical manifestations of avian influenza A(H5N1) may include: cough, fever, shortness of breath, diarrhea (in severe cases), headache, myalgia, sore throat, rhinorrhea, mucosal bleeding, fatigue, jaundice, conjunctivitis. […] Based on available human case data to date, the case fatality rate of avian influenza A(H5N1) is approximately 52%. […] Respiratory failure is the most common cause of death. Other complications may include: multiorgan failure, pulmonary hemorrhage, pneumothorax, pancytopenia. […] Antiviral agents can be used to treat suspected, probable, or confirmed avian influenza A(H5N1) cases. […] To date, there have been no clinical trials measuring the outcome of antiviral use in individuals infected with avian influenza A(H5N1). However, data from animal models and human observational studies have suggested a morbidity and mortality benefit to the use of oseltamivir as an antiviral agent. […] In addition to antivirals, some cases may require respiratory support. Presently, there is insufficient evidence to suggest added benefit from adjunctive therapies in patients with avian influenza A(H5N1) (i.e., corticosteroids, macrolide antibiotics, and passive immune therapy).
#2 What Causes Bird Flu Virus Infections in Humans | Bird Flu | CDC
https://www.cdc.gov/bird-flu/virus-transmission/avian-in-humans.html
Avian influenza A viruses usually do not infect people, but there have been some rare human cases. […] Illness in humans from avian influenza virus infections have ranged in severity from no symptoms or mild illness to severe disease that resulted in death. […] Human infections with avian influenza viruses can happen when virus gets into a person’s eyes, nose or mouth, or is inhaled. […] The spread of bird flu viruses from one infected person to a close contact is very rare, and when it has happened, it has only spread to a few people. […] Bird flu virus infection in people cannot be diagnosed by clinical signs and symptoms alone; laboratory testing is needed. […] Bird flu virus infection is usually diagnosed by collecting a swab from the upper respiratory tract (nose or throat) of the sick person. […] For critically ill patients, collection and testing of lower respiratory tract specimens also may lead to diagnosis of bird flu virus infection. […] Avian influenza or bird flu refers to the disease caused by infection with avian (bird) influenza (flu) Type A viruses.
#2 Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans
https://pmc.ncbi.nlm.nih.gov/articles/PMC2329826/
H5N1 avian influenza is a highly fatal infectious disease that could cause a potentially devastating pandemic if the H5N1 virus mutates into a form that spreads efficiently among humans. […] Here we review the pathology of H5N1 avian influenza reported in postmortem and clinical studies and discuss the key pathogenetic mechanisms. Specifically, the virus infects isolated pulmonary epithelial cells and causes diffuse alveolar damage and hemorrhage in the lungs of infected patients. […] Dysregulation of cytokines and chemokines is likely to be one of the key mechanisms in the pathogenesis of H5N1 influenza. […] H5N1 influenza is still a relatively novel disease with poorly understood pathology and pathogenesis. […] Recent studies combined with early findings have gradually resulted in a better understanding of the cell and organ pathology caused by the H5N1 virus, as well as the viral tissue tropism.
#3 Molecular mechanisms in the pathogenesis of avian influenza Pashu Sandesh
https://pashusandesh.com/avian-influenza-pathogenesis
Molecular mechanisms in the pathogenesis of avian influenza […] Certain important features of the avian influenza viruses are considered briefly since this would be helpful in understanding the molecular mechanism involved in the pathogenesis of avian influenza. […] Influenza viruses that infect poultry are pided into two groups: (1) Highly pathogenic avian influenza (HPAI) viruses with flock mortality as high as 100%, and (2) Low pathogenic avian influenza (LPAI) viruses with flock mortality of 1-2%, unless complicated. […] Avian influenza (AI) virus is an RNA virus. Its RNA is single-stranded, segmented and of negative-sense. Its genetic material is composed of eight segments of single-stranded RNA. These eight segments, which are in fact eight genes, encode 10 proteins of the virus. The eight segments are surrounded by an envelope. The envelope is covered by two different surface projections. These projections are glycoprotein and are of two different shapes. They are (1) haemagglutinin (HA), and neuraminidase (NA). Avian influenza viruses are further pided into subtypes on the basis of HA and NA surface glycoprotein. Each virus has one HA and one NA antigen in any combination. Thus, avian influenza viruses can exist in 144 different possible combinations.
#3 Influenza A virus subtype H5N1 – Wikipedia
https://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1
Due to the high lethality and virulence of HPAI A(H5N1), its worldwide presence, its increasingly diverse host reservoir, and its significant ongoing mutations, the H5N1 virus is regarded as the world’s largest pandemic threat. […] The avian influenza hemagglutinin prefers to bind to alpha-2,3 sialic acid receptors, while the human influenza hemagglutinin prefers to bind to alpha-2,6 sialic acid receptors. This means that when the H5N1 strain infects humans, it will replicate in the lower respiratory tract (where alpha-2,3 sialic acid receptors are more plentiful in humans) and consequently cause viral pneumonia. […] Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different strains of influenza viruses at the same time. Through a combination of mutation and genetic reassortment the virus can evolve to acquire new characteristics, enabling it to evade host immunity and occasionally to jump from one species of host to another.
#3 Avian Influenza in Poultry and Wild Birds – Poultry – Merck Veterinary Manual
https://www.merckvetmanual.com/poultry/avian-influenza-in-poultry-and-wild-birds/avian-influenza-in-poultry-and-wild-birds
In peracute cases, clinical signs or gross lesions of avian influenza may be lacking before death. In acute cases, however, lesions may include cyanosis and edema of the head, comb, wattle, and snood (turkey); ischemic necrosis of the comb, wattles, or snood; edema and red discoloration of the shanks and feet due to subcutaneous ecchymotic hemorrhages; petechial hemorrhages on visceral organs and in muscles; and blood-tinged oral and nasal discharges. […] Birds that survive peracute AI infection may develop CNS involvement evident as torticollis, opisthotonos, incoordination, paralysis, and drooping wings. Microscopic lesions are highly variable in both location and severity, and they may consist of edema, hemorrhage, and necrosis in parenchymal cells of multiple visceral organs, the skin, and the CNS.
#3 Can avian flu spread via the wind? Can’t be ruled out, experts say | CIDRAP
https://www.cidrap.umn.edu/avian-influenza-bird-flu/can-avian-flu-spread-wind-cant-be-ruled-out-experts-say
„However, when all conditions align, windborne transmission becomes a feasible mode of spread and could play a more significant role than previously thought, especially in densely populated poultry areas,” he said. […] The significance of any windborne H5N1 spread to poultry farms is unknown at this point, and the likely limited zoonotic potential that between animals and people of currently circulating viral variants means that the implications for public health are probably minimal, Nagy said. […] The historical resistance to considering airborne viral spread, such as that encountered with SARS-CoV-2, the virus that causes COVID-19, may be due to the usual focus on direct contact and fomites, or contaminated objects, Nagy said.
#3 What Causes Bird Flu Virus Infections in Humans | Bird Flu | CDC
https://www.cdc.gov/bird-flu/virus-transmission/avian-in-humans.html
Avian influenza A viruses usually do not infect people, but there have been some rare human cases. […] Illness in humans from avian influenza virus infections have ranged in severity from no symptoms or mild illness to severe disease that resulted in death. […] Human infections with avian influenza viruses can happen when virus gets into a person’s eyes, nose or mouth, or is inhaled. […] The spread of bird flu viruses from one infected person to a close contact is very rare, and when it has happened, it has only spread to a few people. […] Bird flu virus infection in people cannot be diagnosed by clinical signs and symptoms alone; laboratory testing is needed. […] Bird flu virus infection is usually diagnosed by collecting a swab from the upper respiratory tract (nose or throat) of the sick person. […] For critically ill patients, collection and testing of lower respiratory tract specimens also may lead to diagnosis of bird flu virus infection. […] Avian influenza or bird flu refers to the disease caused by infection with avian (bird) influenza (flu) Type A viruses.
#3 Avian influenza A(H5N1): For health professionals – Canada.ca
https://www.canada.ca/en/public-health/services/diseases/avian-influenza-h5n1/health-professionals.html
Avian influenza A(H5N1) is classified as highly pathogenic avian influenza (HPAI), based on the severity of illness caused in birds. […] The clinical manifestations of avian influenza A(H5N1) may include: cough, fever, shortness of breath, diarrhea (in severe cases), headache, myalgia, sore throat, rhinorrhea, mucosal bleeding, fatigue, jaundice, conjunctivitis. […] Based on available human case data to date, the case fatality rate of avian influenza A(H5N1) is approximately 52%. […] Respiratory failure is the most common cause of death. Other complications may include: multiorgan failure, pulmonary hemorrhage, pneumothorax, pancytopenia. […] Antiviral agents can be used to treat suspected, probable, or confirmed avian influenza A(H5N1) cases. […] To date, there have been no clinical trials measuring the outcome of antiviral use in individuals infected with avian influenza A(H5N1). However, data from animal models and human observational studies have suggested a morbidity and mortality benefit to the use of oseltamivir as an antiviral agent. […] In addition to antivirals, some cases may require respiratory support. Presently, there is insufficient evidence to suggest added benefit from adjunctive therapies in patients with avian influenza A(H5N1) (i.e., corticosteroids, macrolide antibiotics, and passive immune therapy).
#3 Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans
https://pmc.ncbi.nlm.nih.gov/articles/PMC2329826/
H5N1 avian influenza is a highly fatal infectious disease that could cause a potentially devastating pandemic if the H5N1 virus mutates into a form that spreads efficiently among humans. […] Here we review the pathology of H5N1 avian influenza reported in postmortem and clinical studies and discuss the key pathogenetic mechanisms. Specifically, the virus infects isolated pulmonary epithelial cells and causes diffuse alveolar damage and hemorrhage in the lungs of infected patients. […] Dysregulation of cytokines and chemokines is likely to be one of the key mechanisms in the pathogenesis of H5N1 influenza. […] H5N1 influenza is still a relatively novel disease with poorly understood pathology and pathogenesis. […] Recent studies combined with early findings have gradually resulted in a better understanding of the cell and organ pathology caused by the H5N1 virus, as well as the viral tissue tropism.