2009 flu pandemic

Scientists take big step towards universal flu vaccine

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Scientists say they have made a significant leap towards creating a vaccine that would protect against every form of flu.

The influenza virus is a constantly shifting target so seasonal flu vaccines rapidly become useless and new ones are needed each year.

A team at Imperial College London say they have made a “blueprint” for a universal flu vaccine.

Their discovery is published in the journal Nature Medicine.

Influenza is able to change the proteins that protrude from the surface of the virus as readily as people change outfits.

However, the material on the inside is common to many strains of flu. Vaccine researchers believe targeting the core of the virus may be the way to develop a universal vaccine.

“Start Quote

We have the know-how, we know what needs to be in the vaccine and we can just get on and do it”

Prof Ajit Lalvani Imperial College London

A specific part of the immune system, called T-cells, is thought to be able to recognise proteins in the core. A team at Imperial used the 2009 swine flu pandemic to test the theory.

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Milder symptoms

Swine flu was a new virus from a mix of bird and pig flu.

The outer shell should have been a completely new experience to the immune system, but the core may have been encountered before in other flu viruses.

The team compared levels of one kind of T-cells at the start of the pandemic with symptoms of flu in 342 staff and students at the university.

They showed that the higher the levels of the T-cells a patient had, the milder their symptoms were.

Researchers then teased out the specific part of the immune system that offered some pandemic flu protection and which part of the virus it was attacking.

Prof Ajit Lalvani, who led the study, told the BBC: “It’s a blueprint for a vaccine. We know the exact subgroup of the immune system and we’ve identified the key fragments in the internal core of the virus. These should be included in a vaccine.

“In truth, in this case it is about five years [away from a vaccine]. We have the know-how, we know what needs to be in the vaccine and we can just get on and do it.”

‘Long journey’

This would be a distinct approach compared with other forms of vaccination, such as the MMR jab. These trigger the immune system to produce antibodies that can attack an invader.

The prize could be huge. Seasonal flu kills between 250,000 and 500,000 people each year and new pandemics have the potential to take doctors by surprise and kill large numbers of people.

Yet the researchers admit it is “generally harder” to develop a T-cell vaccine than provoke an antibody response. The challenge will be to get a big enough T-cell response to offer protection and a response that will last.

Prof John Oxford, of Queen Mary University of London, said: “This sort of effect can’t be that powerful or we’d never have pandemics. It’s not going to solve all the problems of influenza, but could add to the range of vaccines.

“It’s going to be a long journey from this sort of paper to translating it into a vaccine that works.”

Prof Sarah Gilbert, who is developing a universal flu vaccine at the

Jenner Institute in Oxford, said: “Live attenuated influenza vaccines which are given by nasal spray and will be used in children in the UK from this autumn are much better at increasing the number of influenza-specific T cells, but these vaccines only work in young children who haven’t yet had much exposure to influenza virus, so we need an alternative approach for adults.

“The new publication contains information on the precise characteristics of the influenza-specific T cells which were protective, and this information will be useful in monitoring the immune response to vaccination when testing novel influenza vaccines which are designed to provide protection against pandemic as well as seasonal influenza viruses.”

Influenza A (H7N9) and the Importance of Digital Epidemiology.

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On March 31, 2013, Chinese health officials notified the World Health Organization of three cases of human infection with novel influenza A (H7N9). Since then, 132 people have been infected, 37 of them fatally , To date, there is no evidence of ongoing human-to-human transmission. However, a number of characteristics of this virus are cause for heightened attention.

First, the human population has not been exposed on a large scale to hemagglutinin 7 (H7) and neuraminidase 9 (N9) antigens in recent times and therefore most likely lacks immunity against this strain. Second, initial analyses of viral genome sequences suggest signs of adaptation to mammals — such as the ability to attach to respiratory tissue and to replicate at mammalian body temperatures1 — which could facilitate human-to-human transmission. Third, because the virus has low pathogenicity in birds, its presence is difficult to detect in bird flocks by symptomatic surveillance alone. Testing of more than 20,000 people with influenza-like illness in China revealed only six cases of H7N9 infection, suggesting that there are not widespread mild cases of H7N9.2

Public health officials on the ground continue to focus substantial resources on assessing and mitigating the pandemic potential of this virus strain. Although these efforts are critical for understanding the evolving public health situation, since there are limited resources available, intelligence for assessing the threat must come from a wide range of data sources. Though relatively new, digital disease surveillance is an increasingly powerful tool that complements traditional approaches.3

In this and other outbreaks, digital disease surveillance has supplemented the critical laboratory studies and work in the trenches by public health officials and epidemiologists, by leveraging widespread use of the Internet, mobile phones, and social media.3 Many of these added insights come from the general population, whose access to technology enables rapid information flow. In 2013, there are 6.8 billion cell-phone subscribers; 2.7 billion people are online; and by the end of the year, there will be more than 2 billion mobile broadband subscriptions worldwide. A large percentage of the online population publicly shares information on social media services: in both the United States and China, for example, more than half the population with access to the Internet uses social media services.

Digital data can be used in at least four ways for studying infectious-disease dynamics. First, they can be used for early detection of disease outbreaks. This capacity was illustrated most recently in China, when a hospital employee uploaded an image of the medical record of a patient with H7N9 infection to Sina Weibo, a popular Chinese social network similar to Twitter. The post was promptly deleted, but it appears to have accelerated the government’s acknowledgment of four new cases (see figure, Panel B). More generally, because digital surveillance is not limited by the hierarchies of traditional public health infrastructure, geographic communication barriers, and geopolitical obstacles, it has improved the timeliness of outbreak detection substantially in recent years.4

Second, these data can be used to continuously monitor disease levels. With proper filtering by automated systems (see the Journal‘s H7N9 HealthMap tracking system [http://healthmap.org/h7n9]), analyst-driven systems (e.g., the Global Public Health Intelligence Network of Canada), vigilant journalists on Twitter (e.g., Crawford Kilian [@Crof] and Helen Branswell [@HelenBranswell]), and crowd-sourced systems (e.g., FluTrackers and ProMED-mail), informal data sources such as news media, e-mail lists, blogs, and social media can complement formal public health surveillance by offering real-time clues to disease dynamics. Internet-based surveillance systems provided important early epidemic intelligence during the 2003 outbreak of severe acute respiratory syndrome (SARS) and the 2009 H1N1 influenza pandemic, enhancing transparency by rapidly publicizing outbreak information.3

Third, Internet-based data from social media can be used to assess disease-relevant health-related behaviors and sentiments relevant to disease control. During the H1N1 pandemic, sentiments about vaccination extracted from Twitter were shown to correlate well geographically with subsequent vaccination coverage throughout the United States.5 Such analyses could provide important information to aid in planning and in the distribution of limited resources, as well as improving public health communications efforts.

Fourth, these data provide researchers with an additional method for examining the period before an outbreak came to light. Despite international agreement that transparency is critical during an outbreak, accusations of delayed reporting are common and can be difficult to dispel. Time-series analysis of the volume of influenza-related searches on the Chinese Web search engine Baidu shows a low level of activity in the months leading up to the first announced H7N9 cases, which suggests that widespread unreported outbreaks were not festering before the announcement.

Though digital epidemiology as an enabler of disease surveillance across political, cultural, and linguistic borders carries many advantages, it’s not without its challenges. The dynamics of information spread are inherently different from the dynamics of disease spread. In the days immediately following the first reports of a few cases of a new disease, the volume of news reports and social media posts typically spikes dramatically (see figure, Panel A), because during that period most information is new and potentially relevant and therefore of high interest to the public. After some time, information saturation sets in, and public interest wanes, even as the number of new cases continues to rise. For newly emerging diseases with initially few cases, the social media data are typically dominated by news reports rather than first-person accounts of symptoms by sick individuals — a situation that differs markedly from that during recurring epidemics such as seasonal influenza. In the early phase of an outbreak, this effect makes it challenging for digital epidemiology to provide intelligence for early detection of cases of disease. Both human assessment and computational algorithmic intelligence are required to meet the challenge of extracting information from data sets that are both extremely large and noisy.

In addition, information retrieval itself can be difficult. Consider Sina Weibo, which can be a particularly challenging platform for harvesting information. Posts are censored at a reportedly rapid rate, with 5% of deletions happening within 8 minutes, and 30% within 30 minutes. Because of concerns about censors, some Sina Weibo users rely on metaphors (seehttp://chinadigitaltimes.net/space/Introduction_to_the_Grass-Mud_Horse_Lexicon for an interesting glossary of terms used in the past), making it challenging for outsiders to follow what they’re talking about. For example, in Chinese, the eponymous “grass-mud horse” sounds like an obscene phrase and indirectly references the Communist party. The phrase has evolved to mean an Internet-savvy person who dislikes and seeks to circumvent government censorship.

Despite these challenges, the recent outbreaks of H7N9 influenza and the Middle East respiratory syndrome coronavirus (MERS-CoV) infections illustrate the strengths of digital disease surveillance. In the case of H7N9, such surveillance has enhanced transparency and helped public health officials to understand the outbreak more fully. Although information was sparse in the MERS-CoV outbreak, digital disease surveillance proved its usefulness: the initial MERS-CoV case reports came to light through ProMED-mail (www.promedmail.org/direct.php?id=20120920.1302733). Since the SARS outbreak, the world has seen substantial progress in transparency and rapid reporting. The extent of these advancements varies, but overall, digital disease surveillance is providing the global health community with tools supporting faster response and deeper understanding of emerging public health threats.

Health officials are aware of the catastrophic potential of pandemics. The potential for widespread infections with MERS-CoV outside of Saudi Arabia and the potential reemergence of H7N9 during next year’s influenza season demand that digital disease surveillance be a part of the response.

 

Source: NEJM

158 cases of new swine flu strain from pigs.

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 Don’t pet the pigs.

That’s the message state and county fair visitors got Thursday from health officials who reported a five-fold increase of cases of a new strain of swine flu that spreads from pigs to people. Most of the cases are linked to the fairs, where visitors are in close contact with infected pigs.

This flu has mild symptoms and it’s not really spreading from person to person.

“This is not a pandemic situation,” said Dr. Joseph Bresee of the Centers for Disease Control and Prevention.

But any flu can be a risk for some people, and people should be cautious when they can, he added.

The case count jumped from 29 a week ago to 158 this week, thanks to a wave of new cases in Indiana and Ohio, said Bresee, the agency’s chief of influenza epidemiology.

Most of the infected patients are children — probably because many were working closely with raising, displaying and visiting pigs at the agricultural fairs, Bresee said.

The recent cases include at least 113 in Indiana, 30 in Ohio, one in Hawaii and one in Illinois, Bresee said in a conference call with reporters.

The count is changing rapidly. Indiana health officials on Thursday afternoon said they had seven more confirmed cases than Bresee noted. That would raise the grand total to 165 so far.

Also, diagnosis of cases has become quicker in the last week. CDC no longer must confirm a case with its own lab. Now states are using CDC test kits to confirm cases on their own on, speeding the process along. The newly reported cases were likely infected a week or two ago.

The CDC has been tracking cases since last summer. A concern: The new strain has a gene from the 2009 pandemic strain that might let it spread more easily than pig viruses normally do.

The good news is the flu does not seem to be unusually dangerous. Almost all the illnesses have been mild and no one has died. Two of the recent cases were hospitalized, but both recovered and were discharged, Bresee said.

More good news is that all of the recent cases appear to have spread from pigs to humans, meaning it’s not very contagious, at least between people. But there probably will be more cases in the weeks ahead, and it won’t be surprising if at least a few of them involve person-to-person transmission, Bresee said.

Pigs spread flu virus just like people do, with coughing, sneezing and runny noses, so people can get it by touching pigs or being near them.

Health officials don’t think it’s necessary to cancel swine shows, but are urging people to take precautions.

Fairgoers should wash their hands and avoid taking food and drinks into livestock barns, officials said, while pregnant women, young children, the elderly and people with weakened immune systems should be particularly careful.

Source: Yahoo news.

 

 

Pandemic (H1N1) 2009: a clinical spectrum in the general paediatric population.

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This retrospective case series describes the clinical spectrum of 43 children with pandemic (H1N1) 2009 admitted to a single hospital in Australia during the peak winter flu season. Clinical features, diagnoses, length of hospitalisation and complications were reviewed in children up to 17 years of age with proven pandemic (H1N1) 2009 by RT-PCR. The median age was 6 years, 42% had a pre-existing medical condition. The most common presentation was fever and cough, and 88% of patients met our criteria for flu-like illness. Consolidation on chest x ray was the most common diagnosis (n=20, 46%), followed by dehydration (n=13, 30%). Three (7%) had encephalopathy and two (5%) had diabetic ketoacidosis. There were two intensive care admissions and no deaths. Pandemic (H1N1) 2009 flu has a wide range of presentation in the paediatric population. The diagnosis should be considered during the current pandemic in any child with fever, or who is unwell.

Introduction

Since being identified in Mexico in April 2009, human influenza A (H1N1) virus has spread across the world and has widespread community transmission in many countries. The World Health Organization escalated the pandemic to alert phase 6 in early June 2009.1 The outbreak coincided with Australia’s flu season resulting in 35 579 confirmed cases of pandemic (H1N1) 2009 and 161 deaths, in Australia as of 7 September 2009.2 An early report of 18 hospitalised patients of the initial outbreak in Mexico showed that the pandemic (H1N1) 2009 virus caused severe illness and death in previously healthy young to middle-aged persons.3 Despite this, it has been found that the majority of patients continue to experience mild illness.

The purpose of this study was to describe the clinical spectrum of pandemic (H1N1) 2009 virus in the general paediatric population. The Gold Coast Hospital serves a population of over 455 000 people. Our case series describes the epidemiological characteristics, clinical features, range of diagnoses and length of hospitalisation in 43 children positive for pandemic (H1N1) 2009 admitted to the Gold Coast Hospital.

Methods

This retrospective study was conducted by review of medical charts, laboratory and radiological findings of all children admitted to the Gold Coast Hospital with confirmed pandemic (H1N1) 2009. The study period was from the 25 May 2009 to the 16 August 2009, coinciding with Australia’s flu season. During this period, all children admitted into hospital with a febrile or respiratory illness were tested for pandemic (H1N1) 2009 by two Taqman based real-time RT-PCR methods, designed locally in Australia. The two assays, H1-PCR and N1-PCR, were designed targeting the pandemic (H1N1) 2009 virus haemagglutinin and neuraminidase genes, respectively. These RT-PCR methods are found to be sensitive and specific for pandemic (H1N1) 2009 RNA.4 The tests were done at the closest tertiary centre 1 h away and took 2 h to complete. In the peak of the pandemic, due to the overwhelming number of samples, it took 48 h for results to return. Specimens were collected from nasal pharyngeal aspirates or nasal pharyngeal swabs. These specimens were also tested with a multiplex PCR assay for a select respiratory viral panel including influenza A, influenza B, respiratory syncytial virus, parainfluenza types 1, 2 and 3, adenovirus and human metapneumovirus.

Epidemiological characteristics observed were age, gender and pre-existing medical conditions. Pre-existing medical conditions were obtained from the initial history and chart review. These were then categorised according to physiological system. Asthmatic patients were included if they were, at the time of admission, on preventive treatment for asthma. Due to variable documentation of obesity or indigenous background in the medical charts, these factors were not examined in our study.

Clinical features were obtained from findings documented by the treating physician. Based on Queensland Health’s pandemic (H1N1) 2009 case definition, children had flu-like illness if they presented with a fever of at least 38°C, or a history of fever, with one symptom of cough, sore throat or rhinorrhoea.5

Diagnosis was based on history and examination findings documented by the admitting physician, laboratory and radiological findings. In our study, respiratory diagnoses were divided into three groups namely, asthma, bronchiolitis and consolidation on chest x ray. Asthma was defined as the presence of wheezing and/or chest retraction in those with a past history of asthma, without evidence of consolidation on chest x ray. Bronchiolitis was defined as the presence of wheezing and/or chest retraction in those <1 year of age without evidence of consolidation on chest x ray. Due to the difficulty in differentiating consolidation caused by pneumonia or asthma, those with bilateral or unilateral consolidation on chest x ray were analysed in one group called consolidation. Febrile convulsion was defined as a seizure associated with a fever, or history of recent fever, with no previous history of afebrile seizures or evidence of central nervous infection or metabolic abnormality. Dehydration was defined according to the admitting physician’s initial assessment based on history of fluid loss, or poor oral intake, clinical signs including tachycardia, dry mucous membranes, poor central capillary refill, poor urine output and laboratory findings. Encephalopathy was defined as altered mental status lasting greater than 24 h. Diabetic ketoacidosis was defined by biochemical criteria of a blood glucose greater than 11 mmol/litre and evidence of metabolic acidosis (venous pH <7.3 and/or plasma bicarbonate <15 mmol/litre).

Patients were treated with the antiviral, oseltamivir, at the discretion of the admitting physician. Factors considered when commencing treatment were based on the joint position statement published by the Australasian Society for Infectious Diseases (ASID) and the Thoracic Society of Australia and New Zealand (TSANZ).6 These recommendations included treatment for children with risk factors for severe disease, particularly children <5 years of age, those with immunosuppression or chronic disease like asthma, cardiorespiratory disease, diabetes and renal failure. In children with no risk factors for severe disease, oseltamivir was recommended in those who presented within 48 h of onset of symptoms. Oseltamivir was not recommended in those <1 year of age due to limited safety data. Oseltamivir was given to those hospitalised with severe flu infection even after 48 h of symptom onset.

Results

In the period from the end of May to mid-August 2009, a total of 683 children were admitted to hospital. Of these 130 children were screened, via nasopharyngeal swab or aspirate, for pandemic (H1N1) 2009 influenza virus and other common respiratory viruses on our respiratory viral PCR panel. Forty-three children were proven to have pandemic (H1N1) 2009. The characteristics of the patients with pandemic (H1N1) 2009 are listed in table 1.

Fever was the most common presenting symptom (n=41, 95%) followed by cough (n=40, 93%). Other common symptoms were vomiting (n=21, 49%), rhinorrhoea (n=19, 44%) and respiratory distress (n=16, 37%). Headache, myalgia, sore throat, lethargy, abdominal pain, diarrhoea, confusion and seizures were other symptoms reported at presentation. Two (5%) patients did not have a fever or history of fever. Both had pre-existing medical conditions. Thirty-eight (88%) patients fulfilled our criteria for flu-like illness.

The most common diagnosis was consolidation on chest x-ray, with a total of 20 (46%) patients. Thirteen (30%) patients were clinically dehydrated, and four (9%) patients had an exacerbation of asthma. Encephalopathy was diagnosed in three (7%) patients and two (5%) were admitted with diabetic ketoacidosis. Febrile convulsion, bronchiolitis and abdominal pain each occurred in one (2%) patient.

Overall, the median length of stay was 2 days. Those with consolidation had a median length of stay of 2 days while asthma, bronchiolitis, clinical dehydration and febrile convulsion had a median length of 1 day. Patients with encephalopathy and diabetic ketoacidosis had a median length of stay of 4 and 5 days, respectively. Those who were previously healthy had a median stay of 1 day while those who had a pre-existing medical condition had a median stay of 2 days. Twenty-nine (67.4%) patients were treated with oseltamivir.

Of the 43 patients, there were no deaths. Two patients (4.6%) required intensive care; both had pre-existing disorders. One patient had severe bilateral pneumonia and respiratory distress requiring non-invasive ventilation with a background of Retts syndrome. The other patient was admitted to intensive care in severe diabetic ketoacidosis. Five patients (11.6%) were readmitted with complications, including secondary pneumonia, ongoing confusion and exacerbation of asthma. Three of these patients had been treated initially with oseltamivir.

Discussion

Our case series of 43 paediatric patients with proven pandemic (H1N1) 2009 admitted to hospital during the peak of Australia’s flu season demonstrates the wide range of presentations in the paediatric population. All paediatric age groups were affected and almost half of those admitted had an underlying medical problem.

During this study period, there was a low clinical threshold to obtain pandemic (H1N1) 2009 identification. It became apparent that children were being admitted with a wide range of presentations. Fever and cough were present in almost all our cases. Screening only with our criteria for flu-like illness would have missed 12% of children with pandemic (H1N1) 2009 in contrast to a similar report in the UK which found it would have missed 40% of cases using their case definition which required fever and two other symptoms.7 This same report found that 19% of cases did not have a temperature of at least 38ºC or history of fever in contrast to our study which found only 5%. A full screening study of all admissions may be warranted in the future. This was unable to be done due to the significant impact it would have on the testing laboratory during a pandemic.

Consolidation on chest x ray was the most common diagnosis followed by clinical dehydration requiring rehydration in hospital. Interestingly three patients had encephalopathy. Similar neurological complications have been documented in patients with pandemic (H1N1) 2009 in Dallas, Texas as well as in other seasonal flu epidemics.8 In one case, a 16-year-old boy with no previous medical or psychological disorder, had hallucinations and paranoid delusions for 7 days. The other two cases, 2 and 9 years of age, had seizures and altered mental status. Two patients were admitted with diabetic ketoacidosis, one with known diabetes and the other their first presentation.

Conclusion

Pandemic (H1N1) 2009 in the general paediatric population can have a wide range of presentation. Respiratory illness was the most common presentation, there were however, less typical presentations like encephalopathy and diabetic ketoacidosis. There were no deaths and two admissions to intensive care in which both patients had pre-existing medical conditions. Pandemic (H1N1) 2009 should be considered as a diagnosis in any child with fever or who is unwell, even without fever.

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Source: BMJ.