May 3, 2013 (CIDRAP News) – Although no new H7N9 influenza cases or deaths were announced in China today, a team that treated severely ill patients in Shanghai raised questions about the benefits of oseltamivir (Tamiflu), and health groups issued updates on preparedness steps.
Hong Kong's Centre for Health Protection (CHP) said no new human cases were reported on the mainland today, keeping the outbreak total at 128 infections and 27 deaths.
A team from Shanghai Public Health Clinical Center (SPHCC) today described the first four severely ill H7N9 patients that were transferred to the facility on Apr 6 and Apr 7 after their infections were diagnosed at other hospitals. The group published its findings in Emerging Infectious Diseases.
All of the patients were men ages 58 to 73 who lived in Shanghai. Three had underlying medical conditions. One raised chickens in his home and although the three others didn't have close contact with poultry, they all had visited markets that sold live poultry.
The men had cold-like symptoms and fatigue before their flu symptoms began, and they had fever and a productive cough for 6 or 7 days before they were transferred to SPHCC.
The hospital formed an emergency team to care for the H7N9 patients and followed a protocol for treating them. All four patients received antibiotics and oseltamivir at the hospital, but they received the treatment at different stages of their illness, with one started on treatment 16 days after his symptoms began.
One of the patients died from respiratory failure 11 days after his symptoms began and 2 hours after he was intubated and placed on a mechanical ventilator. Two patients improved and were discharged, 18 and 21 days after illness onset, respectively.
The fourth patient was still in critical condition on Apr 21. His condition deteriorated after he was admitted to SPHCC, and he was first put on a ventilator and then treated with extracorporeal membrane oxygenation (ECMO).
The authors said the clinical course is consistent with those of other patients infected with H7N9. Two of the patients had more severe disease that included rapidly progressing acute respiratory distress syndrome and acute kidney injury.
Earlier higher doses of oseltamivir might improve patient outcomes, the group wrote, adding that they now use 150 mg of the drug twice a day for severely ill patients, while monitoring them for toxicity. They questioned, however, the benefits of oseltamivir treatment for H7N9 patients, because two of the men tested positive for the virus after 9 and 11 days of drug therapy.
They wrote that the drug's ineffectiveness may have contributed to treatment failure in two of the patients, and the drug may not have been well absorbed in severely ill patients. The next crucial steps are to determine if the virus has developed resistance to oseltamivir or patients might benefit from an intravenous or parenteral version of the drug, if one were available, they wrote.
An early genetic analysis of some of the first human H7N9 isolates found that one had a marker for neuraminidase inhibitor resistance. However, sensitivity tests on one of the isolates that China sent to the US Centers for Disease Control and Prevention (CDC) found that it was sensitive to oseltamivir and zanamivir, according to a previous report. The CDC has said it will do further testing on more isolates it receives.
The patient who died is the one who had close contact with chickens, and it's not clear if that factor played a role in his rapid disease progression, they wrote. No close contacts of the four patients had symptoms of infection.
In preparedness developments, the World Health Organization (WHO) yesterday posted an update on the development of an H7N9 candidate vaccine virus.
It said H7N9 viruses have been shipped from China to WHO collaborating centers and essential regulatory laboratories in the Global Influenza Surveillance and Response System (GISRS) for candidate vaccine virus development and other preparedness efforts, such as the development of diagnostic tests and risk assessment.
The WHO noted that the candidates have also been developed for other flu viruses that have pandemic potential, including H5N1 and H9N2.
Labs are using classical reassortment and reverse genetics to develop high-growth reassortants that would be useful for H7N9 vaccine development and production. It said it will regularly provide status updates. The viruses are typically released to manufacturers after characterization and safety tests have been completed, but the release can be expedited in certain situations.
The European Centre for Disease Prevention and Control (ECDC) today released an interim case definition for H7N9 infections, along with an algorithm for reporting cases. It said the tools are for surveillance purposes only and will be adjusted as the outbreak develops.
May 3 CHP statement
May 3 Emerg Infect Dis report
May 2 WHO candidate vaccine virus update
May 3 ECDC statement