Groups take next H7N9 vaccine step amid questions about summer spread

May 10, 2013 (CIDRAP News) – The steep decline in H7N9 cases in China has influenza experts wondering if poultry market closures have slowed the disease or if the new virus is showing a summerlike decline that other avian flu viruses show, according to the latest assessments today.

Despite uncertainty about what the virus will do next, the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) have taken another step toward developing a vaccine by making H7N9 candidate vaccine viruses available to pharmaceutical companies and labs that plan on developing and testing a vaccine targeted to the novel virus.

A summer lull for H7N9 activity?
The WHO today issued its second H7N9 outbreak risk assessment, a follow-up of the initial analysis it made on Apr 13. Though many questions remain about how the virus circulates and how humans are exposed to it, the WHO said four factors point to live poultry and contaminated environments as the source: human, bird, and environmental samples are genetically similar, many infected patients were exposed to chickens, the virus has been detected in live bird markets, and in the number of cases has dropped following market closures.

Though the risk hasn't changed since the first update, the WHO said that understanding of H7N9 epidemiology is limited and the next question is whether the virus will follow the pattern of a drop in human cases in the summer that has been seen with other avian influenza viruses such as H5N1.

The virus bears close monitoring in the months ahead, especially given genetic clues that H7N9 may have adapted to mammals, including humans, and that it can cause severe disease. "Should sustained human-to-human transmission occur with an increased number of clinically severe cases, health systems are likely to be strained," the WHO stated.

The CDC, in an H7N9 outbreak and response update today, said the current drop in cases could reflect the impact of market closures, of the changing season, or both. If H7N9 follows the pattern of seasonal flu and H5N1, infections in birds and humans could pick up again when the weather cools.

The risk to the United States is low, but the CDC is still monitoring the virus closely because of its pandemic potential and is taking readiness steps in case the virus becomes more transmissible among humans.

Vaccine development takes next early step
The WHO today announced the availability of two candidate vaccine viruses. Labs at the CDC and the United Kingdom's National Institute for Biological Standards and Control (NIBSC) have used reverse genetics to produce candidate vaccine viruses based on influenza A/Shanghai/2/2013. The NIBSC also produced a candidate vaccine virus using a different H7N9 isolate, influenza A Anhui/1/2013.

With its announcement, the WHO emphasized that the viruses are potential candidates for vaccines, that full characterization and safety testing are still under way, and that the viruses must be handled under biosafety level 3 (BSL-3) containment.

The WHO and its lab network routinely make candidate vaccine viruses for flu strains that have pandemic potential, including H5N1 and H9N2. The labs use classic reassortment and reverse-genetics techniques to produce high-growth reassortants that can be used to develop and produce vaccines. The organization usually doesn't release the candidate vaccine viruses until characterization and safety tests have been completed, but it is expediting the process to advance H7N9 preparedness.

In a separate announcement today, the CDC said it is working on candidate vaccine viruses using both isolates. It noted that candidate vaccine viruses are picked on the basis of how similar they are to the viruses that are infecting people and how easily they grow in chicken eggs. The CDC said it can be very difficult to make a vaccine against a new flu virus without a high-yield candidate vaccine virus.

Manufacturers that have received the candidate viruses make a seed strain that they adapt to use with their own vaccine platforms and production systems to make large quantities of vaccine.

The CDC said on May 1 that it began shipping potential candidate vaccine viruses to qualified labs with BSL-3 facilities that want to get a head start on making the seed strain. It said neither the WHO nor the US Food and Drug Administration (FDA) have recommended which candidate vaccine virus to use for making H7N9 vaccine.

The US government has not decided to launch an H7N9 vaccine program, but it is taking initial preparedness steps in case one is needed. The CDC said vaccine production is complex and unpredictable and delays at any of the stages could delay the availability of the vaccine, which takes about 6 months to produce in large quantities.

Also today the CDC updated the status of its H7N9 diagnostic kit shipments, which began Apr 25. As of today, the CDC has shipped 122 test kits—95 to domestic recipients and 27 to international requestors. The kits have been sent to 47 states and the District of Columbia, allowing jurisdictions to more quickly to identify the virus directly, rather than having to wait on further testing of unsubtypeable results.

So far, of 54 people with flulike illness after travel to China, none have tested positive, the CDC said. An H7N9 case detected in the United States would not signal an increase in the nation's risk unless the virus changed to become more transmissible in humans, the CDC said. So far the new virus doesn't appear to spread easily from person to person.

In other preparedness developments today, the WHO also issued two new guidance documents, interim surveillance recommendations, and interim lab biorisk management recommendations. Its surveillance guidance emphasizes increased awareness among clinicians, especially when treating patients who have unexplained severe acute respiratory infections. The WHO's lab biorisk guidance, aimed at facilities that handle H7N9 clinical specimens, recommends higher levels of biocontainment for virus isolation procedures.

Chinese experts air concerns about farms, poultry transport
In other developments, scientists from China and Hong Kong today aired some of their observations and concerns in medical literature reports today. In a letter to The Lancet, one group examined all media reports of officially reported cases and noted that 25 of the infections were linked to farm exposure, though no positive H7N9 samples so far have been detected in poultry in farm settings.

Aside from the pattern of common market exposures in Shanghai, reports of H7N9 infections in other parts of China suggest the virus is transmitting over a large area that includes several provinces and cities, the group wrote.

The threat to farms and the country's vital poultry industry points to a need to control poultry at the farm level through large-scale poultry vaccination. Urban outbreaks could be stemmed by banning imports and providing for centralized slaughtering sites.

In separate letter to The Lancet, another group compared the timing of H7N9 case detections with live poultry market closures in Shanghai and Hangzhou. They observed that most of the cases reported after the ban involved patients already infected before the closures went into effect and that the measure has helped reduce the number of infections.

However, they said that shuttering live bird markets probably won't be enough to control the disease. The group wrote that the number of infected cities has increased, each with only a few patients, which is alarming. Curbing the transport of live birds carrying the virus is the only way to reduce the number of cities with cases and limit the geographic spread of the disease, the researchers said.

See also:

May 10 WHO H7N9 candidate vaccine virus announcement

May 10 WHO H7N9 risk assessment update

May 10 WHO interim H7N9 surveillance recommendations

May 10 WHO interim guidance for H7N9 lab biorisk management

May 10 CDC H7N9 situation and response update

May 10 Lancet letter on H7N9 farm threat

May 10 Lancet letter on reducing H7N9 exposure

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