May 2, 2013 (CIDRAP News) – Three more people in China have died from severe respiratory infections from the H7N9 virus, pushing the number of deaths so far to 27, according to official and media reports today.

No provinces or cities reported new infections today, according to an update from Hong Kong's Centre for Health Protection (CHP). The total number of cases remains at 128, according to the latest update today from the World Health Organization (WHO).

The WHO's update includes confirmation of two deaths in previously confirmed patients. Also, local officials in Hunan province reported the death of an earlier reported 55-year-old man who was a resident of Jiangxi province but hospitalized in neighboring Hunan province, according to Xinhua, China's state news agency. He was transferred to that facility on Apr 26, about 11 days after his symptoms began.

It's not clear if the drop-off in cases today reflects a decrease in H7N9 activity or is related to May Day holidays in China and surrounding areas.

In a separate update, the WHO's Western Pacific Region Office (WPRO) added that 26 patients with H7N9 infections have been discharged from the hospital. It said questions still remain on the source, reservoir, and mode of infection, as well as the best way to control the outbreak in animals.

So far there is no evidence of sustained human-to-human transmission, and there have been no reports of animal H7N9 infections outside of China, the WHO said.

Experts discuss animal reservoir puzzle

One dip in cases that appears to be real, though, are those from Shanghai, according to two influenza experts who took part in a live video chat today hosted by Jon Cohen from the journal Science.

The experts are Yuelong Shu, PhD, a virologist at the National Influenza Center in Beijing and the Chinese Center for Disease Control and Prevention (China CDC), and Marion Koopmans, DVM, PhD, a virologist at the National Institute for Public Health and the Environment in the Netherlands and a professor at Erasmus University.

The first two H7N9 cases in the outbreak surfaced in Shanghai, and the city has reported 33 cases so far, but it hasn't reported a new infection since about Apr 20. The city closed its poultry markets early in the outbreak when testing found the virus in small numbers of poultry and investigations of some human cases pointed to exposure in markets.

Both Shu and Koopmans said infections reported from Shanghai seem to have ebbed since officials closed the markets. Shu said residents and visitors to China can minimize their exposure to the virus by staying out of live-poultry markets. Koopmans said the link between the virus and market poultry begs the question of where the virus come from in the markets.

She noted that so far testing hasn't turned up the virus on any poultry farms. "Where are chickens getting the virus from? That is more than likely the root of the question."

Shu said Chinese researchers are working on more-sensitive tests to detect exposure to the virus in animals as well as people. He noted that opportunities for avian influenza reassortment can occur in southern China were wild birds, including ducks, winter in areas where and times when heavy poultry production takes place.

Koopmans said one lesson learned during an H7N7 outbreak 10 years ago in the Netherlands is that the virus needs to be monitored very closely. She noted that Dutch researchers who studied the genetic sequences saw several lineages, including some that had mutations, evolve in poultry over just a few months.

She also said throat swabs weren't always useful for detecting H7N7 infections, because, as with some other H7 viruses that have infected humans, conjunctivitis was one of the mild symptoms that characterized the illness. For H7N9, the possible involvement of conjunctivitis and eye swabs should be looked at closely, Koopmans said.

Shu said so far Chinese health officials haven't seen a pattern with conjunctivitis and that most patients have had respiratory symptoms and pneumonia.

More evidence is needed to determine if other animal species are reservoirs of the H7N9 virus and are playing a role in the spread of the virus to people, he said.

In an update today, the World Organization for Animal Health (OIE) said so far tests on pigs by Chinese authorities in areas where human infections have been reported have been negative for H7N9, though further testing is under way.

Avian-to-swine H7 virus transmission has been rarely reported before, with no onward transmission to pigs or to other hosts, including people, according to the OIE. Though the H7N9 is causing sporadic infections in humans, it's not clear if it can infect and transmit in pigs. The OIE urged swine producers to take standard precautions for any type of flu, such as avoiding contact with potentially infected birds, humans, or fomites.

More on H7N9 clinical cases

In other developments, two Chinese research teams published clinical case reports yesterday, one on five patients from Shanghai and the other describing an infection in a Zhejiang province man and virus findings in poultry from the market booths where he shopped.

The team that described the Shanghai patients reported their findings in an early online edition of Emerging Infectious Diseases. The patients included two adults who died, two adults who were critically ill but recovered, and a 3-year-old boy.

The child had a fever and mild rhinorrhea for 3 days before he was hospitalized on Apr 1 and treated with oseltamivir. His condition improved and he was discharged 11 days after his symptoms began.

All four of the adults had severe pneumonia with shortness of breath and hypoxia. The time span between illness onset and severe disease was 5 to 7 days. A 52-year-old woman and a 49-year-old man died from acute respiratory distress and multiple organ failure. The two other adults improved, tested negative 4 and 6 days after antiviral treatment, and have been discharged.

The authors noted that the two patients who died received methylprednisolone and that one who survived received a low dose of the drug, and they warned clinicians about the possible adverse effects of using the drug.

They concluded that H7N9 doesn't seem to be as virulent as H5N1, but the new virus appears to cause more severe disease than other H7 subgroups.

Meanwhile, the team familiar with the Zhejiang province patient published their findings in Emerging Microbes and Infections. The 64-year-old man they described had a history of smoking-related chronic respiratory illness and had shopped at live-poultry markets before he got sick with H7N9 and died from the infection.

The researchers described the man's illness and characterized the genetic characteristics of his H7N9 isolate and H7N9 viruses found in a poultry market where the man shopped.

The man had a low- and fever for a few days before his condition worsened and he was admitted to the hospital with dyspnea. Four days later he died from acute respiratory distress and multiple organ failure.

He had visited two poultry booths before he got sick, and health officials collected samples from avian feces, waste, and sewage at the booths and at the wholesale market that supplied the booths. Of 39 samples, 11 were positive for H7N9: 5 from one poultry booth and 6 from the wholesale market.

Tests on two poultry vendors and 55 of the man's close contacts were negative for the virus.

Phylogenetic analysis of the hemagglutinin (HA) and neuraminidase genes from the H7N9 viruses from the patient and poultry booth found a close relationship, suggesting that the patient may have been exposed by infected poultry. The researchers also found five variations in the HA receptor-binding site that are associated with the ability to infect humans.

The team also suggested that some mechanisms, such as underlying health condition, may influence susceptibility to H7N9 infection.

See also:

May 2 CHP statement

May 2 WHO statement

May 2 Xinhua story

May 2 WHO WPRO update

May 1 Science live chat link

May 1 OIE FAQ update

May 1 Emerg Infect Dis report

May 1 Emerg Microb Infect report