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On May 22 2009, the Centre for Disease Control (CDC) published its weekly report in which it discussed the characteristics of the first 30 patients with swine flu who had been hospitalised up to May 17 in California.

This report provides a helpful snapshot of the nature of the illness in a sample of patients hospitalised with swine flu.

 

Key points

• The majority of the 30 swine flu patients hospitalised in California up to May 17 were discharged after 30 days.
• Those who experienced severe disease and prolonged hospitalisation commonly had underlying conditions that were probably contributing to the severity of their illness.
• The CDC says that more information is needed on which populations are at greatest risk of hospitalisation.

 

Where was the article published?

This is a Morbidity and Mortality Weekly Report (MMWR) published by the CDC in Atlanta on May 22 2009. These reports are prepared each week based on provisional data from state health departments in the US and are published for doctors, public health practitioners, epidemiologists, nurses and other interested parties.

 

What kind of study was this?

In this particular report, the CDC discusses the features of the 30 swine flu patients that had been hospitalised in California as of May 17 2009. At this time, there were 553 cases of novel H1N1 influenza reported across California and no fatalities. Of these 553 cases, 333 were confirmed cases, with the remaining 220 being ‘probable cases’ (diagnosed with influenza type A, but waiting for confirmation on whether it was type H1 or H3).

The report summarises the characteristics of these 30 patients and describes four of them in detail. The four case studies illustrate ‘the spectrum of illness severity and underlying risk factors’.

 

What does the research say?

These are the notable characteristics of the 30 hospitalised patients:

• Twenty-six of the hospitalised cases were confirmed H1N1 infections; four were ‘probable H1N1’.
• Patient ages ranged from 27 days old to 89 years, with an average age of 27.5 years.
• Females outnumbered males and comprised 70% of the cases.
• No patients reported that they had been exposed to pigs or to a known confirmed case of influenza H1N1; four patients had travelled to Mexico in the week before they experienced symptoms.
• Patients were most commonly admitted to hospital with pneumonia and dehydration.
• Nineteen of the cases had underlying medical conditions, of which the most common were chronic lung disease (asthma, COPD), heart disease, obesity, diabetes or conditions that might cause immunosuppression.
• Fever, cough, vomiting and shortness of breath were the most common presenting symptoms and on examination, 15 patients had probable pneumonia.
• Five of the patients were pregnant; two of whom developed complications, one with spontaneous abortion at 13-weeks gestation and the second with premature rupture of membranes at 35 weeks gestation (the outcome of this pregnancy was not reported).
• Half of the patients were treated with oseltamivir (Tamiflu) and for five of them treatment was given within 48 hours of symptoms developing.
• Six of the hospitalised patients had received seasonal influenza vaccination.
• Those who were discharged by May 17 (23 patients) had stayed in hospital for an average of four days (ranging from one to ten days). Those still in hospital on May 17 had stayed an average of 15 days (ranging from four to 167 days). This long hospitalisation was in a five-month-old child, who was born prematurely and had growth retardation, congenital heart disease and lung disease.

 

Detailed case reports

Selected by CDC to demonstrate patient history and the range of severity.

A five-month-old girl born prematurely with several underlying medical problems including congenital heart disease, lung problems and growth retardation who had been hospitalised since her birth. On her 150th day in hospital, she developed a fever, a cough and had evidence of a lung infection when X-rayed. Tests revealed she was infected with the H1N1 virus. It was unclear how she was infected or if she received antivirals and antibiotics. She was still hospitalised by the time this report was written.

A previously healthy 29-year-old woman who was 28-weeks pregnant when she presented with fever, a productive cough and shortness of breath. She was admitted to hospital and received antibiotics but did not receive antivirals. She gradually improved and was discharged after nine days.

An 87-year-old woman with many comorbidities, including diabetes mellitus, high blood pressure, obesity, coronary artery disease and kidney problems, was admitted following presentation at an emergency department after being found unconscious. She had reported fever, cough and weakness prior to her admission. She was admitted with a diagnosis of heart attack, pneumonia, heart failure and presumed sepsis. Further testing revealed lung masses and she tested positive for H1N1. At the time of the report, she remained hospitalised in critical condition.

A 32-year-old man with a history of obstructive sleep apnoea presented with history of fever, chills and a cough. He had an elevated temperature and some evidence of lung infection on X-ray. He was already taking antibiotics for sinusitis. He was admitted and treated with broad-spectrum antibiotics. Initial tests for flu were negative, but he started antiviral treatment on day two in hospital and a repeat test confirmed H1N1 infection. He was discharged after 10 days in hospital.

 

Hospitalisations in the UK

The July 16th weekly pandemic flu update by the Health Protection Agency reported that 652 swine flu patients have been hospitalised in England since the pandemic began. Of these, the majority (354 cases) were in the 16 to 64 year-old-age group. The highest hospitalisation rate was in the under-fives.

Health Protection Scotland report that a large proportion (40%) of the 44 patients hospitalised to date in Scotland were known to have underlying comorbidities including chronic respiratory disease, diabetes or immunosuppression.

The government has predicted that for every 100 people infected with swine flu, two will require hospitalisation.

 

What is the implication and importance of this?

The cases described by the CDC’s May 22 report illustrate the range of severity of hospitalised cases. The majority of hospitalised patients are discharged after a short hospital stay. Two of five pregnant women who were admitted had serious complications, but the CDC says it is not clear what role the H1N1 infection played in this.

While this report is from the relatively early stages of the pandemic, it provides some details about the characteristics of hospitalised H1N1 patients. For those who remain hospitalised and need prolonged intensive care, extremes in age and multiple comorbidities may contribute to the severity of their illnesses.

Links To Science

Hospitalized Patients with Novel Influenza A (H1N1) Virus Infection, California, April-May, 2009 MMWR Morb Mortal Wkly Rep. May 22, 2009; 58: 536-541

Weekly pandemic flu update. HPA, July 16 2009

Weekly Situation Report Influenza A H1N1. HPS, July 15 2009

“Scientists have made a breakthrough which could reduce the risk of children suffering serious allergic reactions to peanuts and other food,” BBC News reported. It said that researchers have identified a new chemical that plays a key part in the development of anaphylaxis, a severe, potentially life-threatening allergic reaction.

These experiments in mice demonstrated the key role of IL-33, a newly discovered chemical (called a cytokine) involved in immune responses, in causing an anaphylactic reaction. These important findings suggest that this cytokine could be a potential target for the future treatment of anaphylaxis. It is important to note, however, that these are animal experiments, which means a human application may be some time away.

 

Where did the story come from?

The study was carried out by Dr Peter Pushparaj and colleagues from the University of Glasgow, the National University of Singapore and the Medical Research Council Laboratory of Molecular Biology in Cambridge. The research was funded by grants from the Wellcome Trust and the Medical Research Council. It was published in the peer-reviewed medical journal: PNAS (Proceedings of the National Academy of Sciences).

 

What kind of scientific study was this?

This study investigated the role of a cytokine, called cytokine interleukin-33 (IL-33), in allergic reactions. Cytokines are chemicals that play a role in the functioning of the immune system. The researchers examined levels of IL-33 in serum and tissue from patients having anaphylactic and allergic responses. Their findings from these observations in humans led them to test their theories in experiments on mice.

Very simply, parts of the immune system are activated by the presence of an antigen (a substance that provokes an immune response), which stimulates the production of an antibody to that antigen. An important antibody that is elevated in the blood of people with allergies is the IgE antibody. This antibody is specific to whatever type of antigen induced its release and it acts to remember the exposure so that future exposures result in a strong allergic response to that challenge.

In their animal experiments, the researchers sensitised some mice with IgE antibody, with the aim of inducing a response to a particular antigen called dinitrophenyl-human serum albumin (DNP-HSA). A day later, the mice were exposed intravenously to several different antigens, including DNP-HSA, IL-33 (the new cytokine) or IL-33 plus DNP-HSA. The level of vascular permeability was then compared between the mice in the different exposure groups. Vascular permeability is a measure of the level of small molecules (e.g. nutrients, water and blood cells) that can pass through small blood vessels. During an allergic response, vessels become more permeable. Further experiments were undertaken to determine which immune cells were involved in the immune response.

 

What were the results of the study?

The researchers observed that people who developed anaphylactic shock in the operating theatre had higher levels of several chemicals associated with allergy, including IgE and IL-33, compared to healthy people and to those with allergies, but who had not developed anaphylaxis. Higher levels of IL-33 were also evident in the skin lesions of people with atopic dermatitis (a type of eczema) compared with non-inflamed skin samples.

Sensitised mice that were exposed to DNP-HSA (an allergen) showed expectedly raised levels of vascular permeability, while those who were not sensitised showed no response to any of the three allergens. However, sensitised mice exposed to IL-33 showed a similar increase in vascular permeability and this effect was more extreme when the sensitised mice were exposed to both IL-33 and DNP-HSA. IL-33 triggered anaphylactic shock in these mice, leading to a rapid drop in body temperature, increased histamine levels and inflammation in the lungs.

Importantly, further detailed experiments revealed that IL-33 may be responsible for ‘tipping the balance’ of the mast cells (which play a key role in inflammation) from ‘helpful’ to ‘harmful’ allergic responses and may therefore represent a potential target for treatment of anaphylactic shock.

 

What interpretations did the researchers draw from these results?

Observations in humans suggest that IL-33 is raised in allergic patients during an allergic-inflammatory response. Furthermore, IL-33 can trigger anaphylactic responses in mice that are IgE sensitised, demonstrating the key role that this cytokine plays in allergies. IL-33 may be a potential target for treating allergic shock.

 

What does the NHS Knowledge Service make of this study?

These animal experiments further the understanding of the workings of complex immune systems in the body. Their direct relevance to allergic reaction in humans is unclear as the studies are in mice. However, observations in humans with allergies or in humans who were experiencing anaphylactic shock support the theory that IL-33 plays a key role in severe allergic responses.

The researchers say that it is not possible from their observational human data to know whether IL-33 was produced in response to the allergic reaction or whether it caused it. They also note that they only reviewed data from allergic patients who developed anaphylactic shock during surgery, and while they say that IL-33 may indeed be elevated in other inflammatory conditions such as peanut or drug-induced anaphylactic shock, this is currently being investigated.

Overall, the findings from this study will be of particular interest to scientists who are trying to understand how the immune system functions. It may one day lead to novel ways to treat allergic conditions, but these are still some time in the future.

Links To The Headlines

Find ‘could cut allergy deaths’. BBC News, July 20 2009

Links To Science

Peter N, Pushparaj PN, Tay H-K, H’ng S-C et al. The cytokine interleukin-33 mediates anaphylactic shock. PNAS 2009, published online before print June 8