Study of H7N9 cases shows extent of severe disease

May 22, 2013 (CIDRAP News) – Researchers from China today published a detailed clinical analysis of 111 patients sickened in the country's H7N9 influenza outbreak that showed how severe patients' illnesses have been, with 77% admitted to intensive care units (ICUs).

The team reviewed the medical charts of 111 patients whose cases were lab-confirmed through May 10, publishing their analysis in the New England Journal of Medicine (NEJM). Their latest work expands on an epidemiologic analysis of 82 confirmed H7N9 cases that appeared in the same journal on Apr 24.

So far the new virus has sickened at least 131 people, 36 of them fatally. One of the cases was reported from Taiwan, a man who had traveled for business to China's outbreak area.

Some of the findings echoed those from the earlier study. For example, 42% were 65 years old or older, males outnumbered females two to one, and many patients—in this case, 61%—had underlying medical conditions.

Fever and cough were the most common symptoms, and though conjunctivitis has been a hallmark in people infected with other H7 strains, none of the study patients had the symptom. As with other patients with avian influenza, those with H7N9 illnesses didn't report sore throat or runny nose.

Infection with H7N9 went on to cause severe illness, including pneumonia in 108 patients (97%) and acute respiratory distress syndrome (ARDS) in 79 (71%). Eighty-five patients (77%) were admitted to ICUs.

Of the patients with ARDS, 65 required mechanical ventilation and, of those, 20 received extracorporeal membrane oxygenation. Other complications included shock, kidney injury, and rhabdomyolysis.

Among the patients included in the review, 30 (27%) died, 49 have been discharged after a median stay of 3 weeks, and 30 remained hospitalized as of May 10. The median time from illness onset to death was 14 days, and all of the patients who died had pneumonia and ARDS.

One of the two pregnant women in the group has been discharged, and the other is still hospitalized in stable condition. Only 2 of the 111 patients were not hospitalized; 1 died 7 days after becoming sick, and the other has fully recovered.

Researchers were able to calculate incubation period based on data from 62 patients who had a definite date of exposure to live poultry. The team estimated an incubation period of 5 days.

The investigators wrote that the age distribution of hospitalized H7N9 patients is similar to that for seasonal flu, but different from the young adult profile seen in patients hospitalized with H5N1 and 2009 H1N1 infections. They suggested that the high number of older patients could reflect that retired people have more time to shop at live-animal markets or that they are more likely to have underlying health issues, which may make them more susceptible to the disease.

Clinical features, however, in H7N9 hospitalized patients were similar to those with severe H5N1 or 2009 H1N1 infections, the group wrote. When compared with seasonal influenza A, those with H7N9 infections were more likely to have severe symptoms. For example, only about 16% of hospitalized adults with seasonal flu require ICU admission, compared with the 77% figure in the current study.

Lab profiles for H7N9 patients were similar to those infected with H5N1 or 2009 H1N1 flu, including, for example, leukopenia, lymphocytopenia, and thrombocytopenia.

The investigators found that antiviral treatment was started at a median of 7 days after illness onset, and those with moderate-to-severe ARDS were less likely to have been treated within 5 days. The group urged clinicians to start early antiviral treatment for H7N9 patients, as recommended by the World Health Organization for H5N1 and 2009 H1N1.

The authors cautioned that their study could represent the severe spectrum of the disease, but they also said the deaths they reported could be an underestimate, because many of the patients are still hospitalized.

Poultry exposure
In a separate NEJM report today, another research group from China compared an H7N9 isolate from a woman who worked as a poultry slaughterer in Jiangsu province to H7N9 viruses they found in poultry areas near her market stall.

They collected samples from a wholesale market that sourced the birds, where they found mixed avian influenza nucleic acids from one feces sample. The 45-year-old woman from the city of Nanjing had no contact with other animals or people with fevers.

Researchers found that theH7N9 virus genomes from the woman and a poultry cage specimen from a neighboring stall were 98.9% to 100% similar. Both isolates had markers of adaptation to mammals, which they said suggested that the new virus had been evolving and, with a few changes, might adapt to humans.

Their phylogenetic analysis of the M genes of the two isolates revealed a unique sublineage compared with other H7N9 viruses that are derived from H9N2 and other viruses, which they said could suggest that the novel H7N9 has varied origins, with possible ongoing reassortment in poultry.

They said their findings suggest that the new virus was probably transmitted from the wholesale market to the live-animal market and then to the patient, lending further support to an epidemiologic link between poultry in live-animal markets and humans.

Gao HN, Lu HZ, Cao B, et al. Clinical findings of 111 cases of influenza A (H7N9) virus infection. N Engl J Med 2013 May 22 [Full text]

Bao CJ, Cui LB, Zhou MH. Live-animal markets and influenza A (H7N9) virus infection. (Letter) N Engl J Med 2013 May 22 [Full text]

See also:

Apr 24 CIDRAP News story "Report: Most H7N9 patients had underlying conditions, animal exposure"

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