Swine Flu Infection Research Articles

Pathogenesis of Swine Influenza Infection Produced Experimentally in Suckling Piglets

Summary The development of exrimental swine influenza infection in piglets sucking immune colostrum was studied. Specific antibodies acquired from the colostrum of the infected sow did not prevent viral multiplication in the lung or the development of clinical disease after experimental intranasal infection of piglets with 107 CEID50 of swine influenza virus at 7 days of age. The development of clinical signs and pathomorphological changes during the first five days after infection was the same as in control piglets. The virus content of the lung was, however, 1 to 3 logarithms lower in piglets having colostrum-acquired antibodies than in control piglets beginning day 1 after infection, and no virus could be recovered from the former from day 7 onwards. In spite of a rapid onset of active production of serum antibodies, the virus persisted in the lungs of control piglets up to day 12 after infection. Analogous quantitative differences between the two groups were obtained by immunofluorescent staining of viral antigen in the lung and upper respiratory tract. Zusammenfassung Pathogenese von Schweineinfluenza-Infektionen in experimentell infizierten Ferkeln III. Vermehrung von Schweineinfluenzavirus im Respirationstrakt von Ferkeln mit spezifischen, kolostralen Antikörpern Die durchgeführten Untersuchungen sollten klären, welche Bedeutung kolostrale Antikörper für eine experimentelle Schweineinfluenza-Infektion in Saugferkeln besitzen. Es konnte nachgewiesen werden, daß die Infektion von 7 Tagen alten Ferkeln mit 107 EID50 trotz Vorhandensein von spezifischen, kolostralen Antikörpern möglich ist. Die Entwicklung klinischer Symptome, Virusvermehrung und pathomorphologische Veränderungen konnten sowohl in Ferkeln mit maternalen Antikörpern, als auch in antikörper-freien Kontrollferkeln bis zum 5. Tag p. inf. beobachtet werden. Während aber der Virusgehalt in den Ferkellungen mit Antikörpern um 1 bis 3 log10 niedriger lag und nach dem 5. Tag p. inf. Virus nicht mehr nachweisbar war, persistierte Virus in den Ferkellungen der Kontrollgruppe, trotz rasch einsetzender Anti-körperbildung noch bis zum 12. Tag p. inf. Diese Befunde konnten durch immunfluoreszenz-serologische Untersuchungen der Lunge und des oberen Respirationstraktes bestätigt werden. Résumé Pathogénie de la grippe du porc chez des porcelets infectés expérimentalement III. Multiplication du virus influenza porcin dans le tractus respiratoire des porcelets avec anticorps colostraux spécifiques Les expériences accomplies devraient élucider le rôle des anticorps colostraux dans une infection expérimentale des porcelets par la grippe du porc. On a pu démontrer qu'il est possible d'infecter des porcelets âgés de 7 jours avec 107 EID50 malgré la présence d'anticorps colostraux spécifiques. On a observé jusqu'au 5ème jour p. i. le développement des symptêmes cliniques, la multiplication du virus et les modifications patho-morphologiques et ceci chez les porcelets avec des anticorps maternels, mais aussi chez les porcelets tédnoins exempts d'anticorps. Mais, alors que la teneur en virus dans les poumons des porcelets avec anticorps reste de 1 à 3 log10 plus basse et qu'on ne peut plus déceler de virus après le 5ème jour p. i., celui-ci persiste dans les poumons des porcelets du groupe témoin jusqu'au 12ème jour p. i., malgréune rapide formation d'anticorps. Ces rédultats ont pu être confirmés par des examens des poumons et du tractus respiratoire supérieur a l'immunofluorescence. Resumen Patogenia de las infecciones influenza porcina en lechones infectados artificialmente III. Multiplicación del virus influenza porcina en el tracto respiratorio de lechones con anticuerpos calostrales específicos Los estudios realizados estaban encaminados para aclarar qué importancia le corresponde a los anticuerpos calostrales en la infección experimental de lechones lactantes con influenza porcina. Se pudo probar que resulta posible la infección de lechones de 7 días de edad con 107 DIA50 a pesar de hallarse presentes anticuerpos calostrales específicos. La evolución de los síntomas clínicos, multiplicación virósica y alteraciones patomorfológicas se logró observar tanto en lechones con anticuerpos maternos como en lechones sin anticuerpos hasta el 5° dia p.inf. Pero mientras que el contenido de virus en los pulmones de lechones con anticuerpos se encontraba de 1 a 3 log10 por debajo y despuéd del 5° día p.inf, ya no se identificaba virus, el mismo persistía en los pulmones de lechones del grupo testigo, a pesar de formarse los anticuerpos hasta el 12° día p.inf., operación que se iniciaba con rapidez. Estos hallazgos se consiguieron confirmar por medio de investigaciones inumnofluorescentes- serológicas en pulmones y tractos respiratorios superiores.

Cross-Reactive Antibodies to Pandemic (H1N1) 2009 Virus, Singapore

To the Editor: Accumulating evidence suggests that the degree of serologic cross-reactivity to pandemic (H1N1) 2009 virus varies between populations worldwide. To assess potential serologic cross-reactivity in Singapore, we obtained serum samples during May–June 2009 from 50 randomly recruited, healthy volunteers born mostly before 1958 (i.e., potentially those with some natural exposure to the then circulating H1N1/1918-like subtype viruses) before widespread transmission of pandemic (H1N1) 2009 virus in Singapore. Standard serologic hemagglutination-inhibition (HI) tests (1) were performed in 2 reference laboratories (Singapore during July–October 2009 and Melbourne, Australia, in January 2010), and microneutralization (MN) tests (2) were performed in 1 reference laboratory (Singapore) for each serum sample against pandemic (H1N1) 2009 virus (A/Auckland/1/2009) and seasonal influenza (H1N1) virus (A/Brisbane/59/2007). The study was reviewed and approved by the National Healthcare Group Domain-Specific Review Board (ref no. E/09/289, J.W.T. principal investigator). Mean ± SD age of participants was 60.1 ± 7.4 years (range 45–82 years); 31 (62%) were women, 42 (84%) were born in Singapore (the rest in Hong Kong, Malaysia, or India), and 26 (52%) had not traveled outside Singapore. None of the 50 participants had HI or MN titers >40 against influenza A/Auckland/1/2009 when samples were tested in either laboratory. In contrast, 18 samples had either HI or MN titers >40 against seasonal influenza A/Brisbane/59/2007 (Table). Use of guinea pig or turkey erythrocytes in HI assays had little effect on the results (Table). Thus, our results are similar to those of Chen et al. (3) and Itoh et al. (4) for this small cohort in that none of the participants 40–80 years of age from Southeast Asia had cross-reactive antibodies to pandemic (H1N1) 2009 virus. Table Cross-reactive antibody titers to pandemic (H1N1) 2009 and seasonal influenza viruses for 50 persons, Singapore, May–October 2009* Although differences in population demographics and laboratory methods used make comparisons between studies difficult, one of the most striking observations from various studies has been the higher levels of cross-reactive antibody titers in prepandemic serum samples from older persons (>80 years of age) in western populations (United States and United Kingdom) (5,6) than from persons in eastern populations (China) (3) and Singapore (this study). Although Itoh et al (4) did not find serologic cross-reactivity in the population 80 years of age. Historically, because epidemiologic data suggest that influenza (H1N1)/1918–like viruses were widespread in Asia, these contrasting results are a stimulus for additional large-scale studies to assess the effect of these viruses in these populations. Although the main limitation of our study is the small sample size, several reasons may account for different findings in population studies of serologic cross-reactivity. First, populations may not be comparable in terms of geographic proximity and their potential for community-acquired infection within the same wave of a seasonal influenza epidemic with a virus that was similar to pandemic (H1N1) 2009 virus. Chen et al. (3) reported that their serum samples were obtained mainly from rural farmers in China who lived farther apart than city dwellers, However, Hancock et al. (5) reported that their samples were obtained from vaccine trials conducted in 1976 or 2005–2009 involving academic, government, and industrial workers, which likely indicates that these persons were urban-based (i.e., living and working more closely to each other than rural farmers in China). Thus, results of our study may not be directly comparable with either of these previous studies because our population resided in Southeast Asia and was urban-based. Second, use of seasonal influenza vaccine has varied in different populations, with Singapore having one of the lowest recorded use rates in the Western Pacific region, and far lower than that in the United States (6). If previous seasonal influenza viruses shared a degree of antigenic cross-reactivity with pandemic (H1N1) 2009 virus, contemporary seasonal influenza vaccines, if well-matched, should reflect changing antigenicity of seasonal influenza viruses; thus, vaccinated populations may have acquired some serologic cross-reactivity through previous influenza vaccines. However, it is likely that past infection rather than vaccination results in cross-reactivity, as suggested by Miller et al. (7). Third, because pandemic (H1N1) 2009 virus originated mainly from swine viruses in North America and Europe (8), resident populations in these countries have been exposed to these virus lineages more frequently than populations in Asia, and therefore may have acquired a greater degree of preexisting cross-reactive immunity to pandemic (H1N1) 2009 virus. A recent review of human swine influenza infections suggests that they may not be uncommon (9), although the true incidence of human infections with swine influenza is unknown because of paucity of swine influenza surveillance data worldwide (8). In conclusion, partial cross-immunity and cell-mediated immunity may be present but not detected by HI or MN assays. Thus, results of standard serologic assays may not be providing all relevant data (10).

It's not all swine flu…are we missing opportunities to diagnose primary HIV infection in patients with flu symptoms?

The advantages of diagnosis of primary HIV infection (PHI) for the individual and public health are well documented. However, symptoms of HIV seroconversion are often not recognized by health-care professionals. Also, symptomatic patients themselves often do not present to health-care services. With the emergence of H1N1 infection, many patients with flu-like symptoms are seeking medical advice. Currently in the UK, the management of H1N1 is in the treatment phase, that is, patients are diagnosed and treated for H1N1 influenza based on clinical observation rather than laboratory testing. Symptoms of H1N1 infection are often similar to those of PHI. We present two cases of men who have sex with men from Brighton, UK presenting to general practice and accident and emergency with flu-like symptoms. Both were initially diagnosed on clinical grounds with H1N1 infection and treated empirically with antivirals but were later confirmed to, in fact, have symptomatic PHI. It is important in high-risk patients with flu symptoms attributed to swine flu infection, that PHI is also considered and excluded.

Cytokines and acute phase proteins associated with acute swine influenza infection in pigs.

This study set out to investigate the cytokines and acute phase proteins (APPs) associated with the acute stages of experimentally-induced swine influenza virus (SIV) infection in 3-week-old, colostrum-deprived, caesarean-derived piglets. The piglets were inoculated intratracheally with 107.5 50% egg infective dose [EID50] Swine/Belgium/1/98 (H1N1) SIV and were euthanased at time-points between 0 and 120 h post-inoculation (PI). Broncho-alveolar lavage fluid (BALF), lung homogenates and sera were examined for inflammatory mediators by bioassay or ELISA. Interferon (IFN)-α, interleukin (IL)-6, IL-1 and tumour necrosis factor (TNF)-α peaked in BALF 24–30 h PI, when virus titres and the severity of clinical signs were maximal.Whereas IFN-γ and IL-12, but not IL-18, increased in tandem in BALF, serum cytokine concentrations were either undetectable or were up to 100-fold lower. The APP C-reactive protein (CRP) and haptoglobin peaked 24 h later than the cytokines and reached higher levels in serum than in BALF. In contrast, lipopolysaccharide (LPS)-binding protein (LBP) only increased in BALF. Lung virus titres tightly correlated with BALF IFN-α, IL-6, IL-1, TNF-α, IFN-γ and IL-12, as well as with serum IL-6, IFN-α and IFN-γ. Signs of disease correlated with the same cytokines in BALF and serum, as well as with BALF LBP and serum CRP. The findings suggest that IFN-γ and IL-12 play a role in the pathogenesis of SIV and that APPs are induced by cytokines. This influenza infection model may have value in assessing the therapeutic potential of cytokine antagonists.

Stress-induced Cardiomyopathy Associated with Swine Influenza Infection Which Exacerbated Underlying Emphysema - A Case Report -

Stress-induced cardiomyopathy (SICM) is an acute cardiac condition that causes left ventricular apical ballooning which mimicks acute coronary syndrome. The risk of in-hospital mortality with SICM is generally low (1% to 3%) and supportive care is usually sufficient for resolution. Swine-origin influenza A (H1N1, S-OIV) is a recently spreading pandemic and a serious public health problem. Although most S-OIV infections have a mild, self-limited course, clinical cases resulting in fatalities and associated with variable co-morbidities remain as a serious concern in some individuals. Among such serious complications, there have been few reports of SICM caused by S-OIV infection. We herein report, for the first time in the literature, a case with fatal hemodynamic instability secondary to SICM caused by S-OIV infection with viral pneumonia.

危機的状況での認知，感情，行動の変化―新型インフルエンザへの対応―

Calling attention to potential risks does not always lead to preventative actions. To investigate changes in cognitive, emotional, and behavioral responses towards potential risks, longitudinal studies targeting nonclinical samples of undergraduate students were conducted at 4 time points (April, May, June, and July 2009) during the outbreak of swine flu in 2009, which eventually developed in to a global pandemic. During the course of the study, the risk of swine flu infection for the seventy-nine participants became more and more self-relevant as the situation developed in the news and as their university was temporarily closed off. The results indicate that despite increasing knowledge about the swine flu, the level of anxiety showed steady decrease as the time went by. Similarly, despite the expanding infection around the globe, the level of preventative behavior remained low. Moreover, participants reported perceiving their own risk to be significantly lower than that of average undergraduate students at all time points. These findings indicate that even when potential risks are clearly communicated, too much information, saturated emotions, and optimistic bias may obstruct people from taking appropriate preventative actions.

Swine Influenza (H3N2) Infection in a Child and Possible Community Transmission, Canada

An influenza A virus (H3N2) of probable swine origin, designated A/Canada/1158/2006, was isolated from a 7-month-old hospitalized child who lived on a communal farm in Canada. The child recovered uneventfully. A serosurvey that used a hemagglutination-inhibition assay for A/Canada/1158/2006 was conducted on 54 of the 90 members of the farm. Seropositivity was demonstrated in the index patient, 4 of 7 household members, and 4 of 46 nonhousehold members; none had a history of hospital admission for respiratory illness in the preceding year. Serologic evidence for this strain of swine influenza was also found in 1 of 10 pigs (12 weeks-6 months of age) on the farm. Human infection with swine influenza virus is underrecognized in Canada, and because viral strains could adapt or reassort into a form that results in efficient human-to-human transmission, routine surveillance of swine workers should be considered as part of pandemic influenza preparedness.

An overview of swine influenza

Summary Swine influenza is a highly infectious viral disease of pigs, causing considerable economic impact. The causative agent is known as a type A orthomyxovirus with a segmented RNA genome. Influenza type A virus is a highly contagious pathogen among a limited number of birds and mammals. The objective of this review is to summarize the current knowledge in swine influenza infection in pigs with emphasizing on epidemiology, pathogenesis, diagnostic techniques and control measures.

Serological and virologic surveillance of swine influenza in China from 2000 to 2003

Serological and virologic surveillance of swine influenza in 19 provinces and cities in China was conducted from 2000 to 2003. The serological studies were carried out by hemagglutination inhibition (HI) assay using H1, H3, H5 and H9 subtype influenza viruses as antigens. The positive rates of H1 and H3 subtype influenza were 10.1% and 41.1%, respectively, from a total of 4212 samples. From the samples collected in four different provinces in 2002, 1.9–6.8% of H9 subtype influenza positive were detected, and 3.9% and 9.5% of H5 subtype influenza positive were detected from two separate farms in 2003. A total of 1985 samples, including swabs from nasal tracts, lungs, and tracheas were collected from different farms for virus detection, and 116 strains of swine influenza viruses were isolated. Forty-five strains were identified as the H3N2 subtype, while 25 H1N1 and 2 H1N2 subtype strains were identified. Moreover, the isolation of eight strains of H9N2 and two strains of H5N1 viruses had also been confirmed. In conclusion, H1 and H3 subtype swine influenza infections widely existed in the pig flocks in China, and the emergence of H5 and H9 subtype influenza viruses in the pig farms in some areas are potential disasters for the pig industry and may also turn out to be a threat to public health.

Diagnosis of swine influenza with an immunofluorescence technique using monoclonal antibodies

Direct diagnosis of swine influenza infection by an indirect immunofluorescence technique using anti-nucleoproteine monoclonal antibody was compared with virus isolation. Five 8-week-old pigs were inoculated with 2 x 10(7) EID50 of strain A H1N1Sw/4115/85. Clinical signs developed in only three pigs. Antigen was detected in nasal epithelial cells obtained from all animals the first day after inoculation; the antigen was detected in one pig 6 days after the infection. Fluorescence was present in the nucleus, nucleolus and cytoplasm of infected cells. The indirect immunofluorescence test was specific and as sensitive as virus isolation in embryonated eggs, allowing a rapid diagnosis that could be achieved within hours.

Fatal Swine Influenza Pneumonia During Late Pregnancy

Serious morbidity or death from swine influenza infection is unusual in the immunocompetent host. We present a fatal case of pneumonia caused by this virus in a previously healthy 32-year-old woman during her third trimester of pregnancy, and review all published case reports of swine influenza in United States civilians. Pregnancy may be a predisposing factor to fulminant infection with swine influenza virus.

Swine-Influenza Infection in Civilians

The recent outbreak of influenza due to A/New Jersey/8/76 (HswN1) in a number of recruits at Fort Dix, New Jersey,1 has aroused concern that a new influenza pandemic similar to that of 1918 may be imminent. Only persons living before 1923 have a high prevalence of hemagglutination-inhibition antibody to swine-influenza viruses.2 , 3 No large-scale outbreaks of swine-influenza infection in man have been recognized since 1920, although sporadic transmission of the virus from swine to man has been suspected. The HswN1, strain has remained prevalent among swine, with as many as 50 per cent . . .

THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR SWINE INFLUENZA VIRUS

1. The swine lungworm can serve as intermediate host in transmitting swine influenza virus to swine. The virus is present in a masked non-infective form in the lungworm, however, and, to induce infection, must be rendered active by the application of a provocative stimulus to the swine it infests. Multiple intramuscular injections of H. influenzae suis furnish a means of provoking infection. Swine influenza infections can be provoked in properly prepared swine during the autumn, winter, and spring, but not during the summer. The phenomenon, while not regularly reproducible, occurs in well over half the experiments conducted outside the refractory period of summer. No explanation for the failures is apparent. 2. The virus can persist in its lungworm intermediate host for at least 2 years. 3. Swine infected with swine influenza virus by way of the lungworm intermediate host exhibit a more pronounced pneumonia of the posterior lobes of the lung than do animals infected intranasally with virus. The situation of the worms providing the virus will account for this. 4. Occasional swine infested with lungworms carrying influenza virus fail to become clinically ill after provocation but instead become immune. In these it is believed that lungworms containing the virus are localized outside the respiratory tract at the time of provocation. 5. It is believed that the experiments described furnish an explanation for the findings recorded in the preceding paper, in which swine influenza virus infections were induced in apparently normal swine by multiple injections of H. influenzae suis. 6. In a single experiment swine lungworms failed to transmit hog cholera virus.

THE EFFECT OF HEMOPHILUS INFLUENZAE SUIS VACCINES ON SWINE INFLUENZA

Either living or heat-killed H. influenzae suis vaccines, given intramuscularly to swine, elicit an immune response capable of modifying the course of a later swine influenza infection. The protection afforded is only partial and is in no way comparable to the complete immunity afforded by swine influenza virus vaccines.