[Source: Chinese Medical Journal, full page: (LINK). Edited.]


Clinical practice

Discovery process, clinical characteristics, and treatment of patients infected with avian influenza virus (H7N9) in Shanghai

Sun Yang, Shen Yinzhong and Lu Hongzhou

Keywords: discovery process; avian influenza virus; H7N9; clinical characteristics; treatment
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During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread in Shanghai. On May 9, 2013, 33 lab-confirmed cases (2 children and 31 adults) have been reported, among whom 13 died.

Among the 31 adult cases of H7N9 avian influenza A virus infections in humans, 80.6% (25/31) were older men (average age 65 years). Clear history of poultry exposure was found in eight patients (8/33, 24.3%) and the remaining 21 cases had been suspected poultry exposure. Clustered cases were found in two families (two cases from a father and his son, and the other two cases from a wife and her husband). However, no evidence of human-to-human transmission had been identified. Avian influenza is one of the most dangerous contagions in poultry worldwide, and avian influenza A virus is the major pathogen responsible.

Transmission from poultry to humans has now been proven. Some gene segments of the strain have mutated, and further mutations might result in human-to-human transmission.1,2 Discovery process: On February 25, 2013, physicians on duty found clusters (three cases) of unexplained pneumonia in Emergency Department of Shanghai Fifth People?s Hospital.

The hospital disposed these cases immediately in accordance with the national unexplained pneumonia screening work plan and organized experts from the Municipal Public Health Clinical Center and Center for Disease Control and Prevention, Shanghai. After careful consultation, experts (Prof Lu Hongzhou arrived at Shanghai Fifth People?s Hospital at noon of February 26) considered that the novel virus infection may be original ominous and suggested an immediate oseltamivir treatment (150 mg bid). Meanwhile, throat swab samplings from all patients were collected and sent to Shanghai Public Health Clinical Center (SPHCC) and District Disease Control Center for detection. On March 2, the testing result was confirmed positive by using universal primers for influenza A virus. A hint is a helpful piece of advice usually about how to do something. The inspection report suggested that experimenters of SPHCC continued to test the specimen after considering patients infected with avian influenza A virus (H7N9). In the meantime, specimens were sent to National CDC and were confirmed to be infected with H7N9. National Health Development Planning Commission verified new cases of human infection with the H7N9 virus on March 30 and declared that this is the first discovery of new cases of human infection with H7N9 avian influenza A virus in the world.


Epidemiologic characteristics:

From March 1 to May 30, H7N9 cases have risen to 33 in Shanghai and still had a tendency to increase. We described the clinical characteristics of the patients with H7N9 virus infection. Of the 30 patients, one is a 3-year-old boy; the rest are all adults, male (constituting 82.8% (24/29) of patients); most of them are old people; eight patients had clear poultry exposure history (constituting 24.3% (8/33) of patients), among them three are from poultry-related work and 2 had exposure to disease for 4 days and 15 days, respectively; two had exposure to agglomeration disease; and one of the three patients had parent-child relationship and another had spousal relationship. The first two patients were suffering from illness and were waiting to see doctor: the time intervals were between 4 and 5 days, 26 and 33 days from seeing the doctor to the diagnosis, and 2 and 3 days from seeing the doctor to receiving Tamiflu (Roche, USA) therapy.


Clinical characteristics:

Major clinical manifestations were fever (100%), cough (79.3%), tachypnea (44.8%), fatigue (13.8%), muscle ache (10.3%), diarrhea (6.9%), and consciousness disorders (3.4%). Basic diseases such as hypertension (41.4%), diabetes (17.2%), chronic obstructive pulmonary disease (10.3%), and mild ground-glass opacity could be observed.

Substantial bilateral ground-glass opacity and consolidation can be seen after computed tomographic scan of the chest. Coronary heart disease accounted for 6.9% of cases. Hematopoietic system disease (thrombocytopenia, anemia, and leukopenia) accounted for about 24.1% of cases. The digestive system lesions were observed. Alanine aminotransferase (ALT) level increased to 53.3% and the aspartate aminotransferase (AST) level increased to 73.3%. In the endocrine metabolic system, elevated blood sugar level was 46.7% and hypokalemia was seen in 33.3% of cases. Elevated C-reactive protein accounted for 93.3%.


Clinical treatment:

Twenty-two patients received antiviral therapy and routine dose of 75 mg bid; five people were treated with 150 mg bid, 48 hours after onset; proportion of patients treated with oseltamivir (4.5%) accounted for 21.7%; administration of oxygen inhalation through nasal catheter oxygen mask accounted for 13.0%; noninvasive ventilator users accounted for 47.8%; endotracheal intubation was performed in 21.7% of cases; and 8.7% of lung samples had cells in vitro. Hormone users accounted for 65.5%. Dosing regimen comprised 40 mg qd?120 mg methyl-prednisolone bid. Patients using antibiotics accounted for 75.9%.


Clinical outcomes:

Of the 33 cases, 13 cases died, 18 cases were discharged from rehabilitation hospitals, and the remaining two cases were under quarantine treatment. Among 13 patients who died, one was female and 12 were male; the time interval from onset to death averaged 10.4 days and the time interval from diagnosis to death averaged 2.9 days.

H7N9 cases were found and reported in Shanghai, but people need to spend large amount of time for clarification. Currently, severe lower respiratory tract infection has been clinically diagnosed; the upper respiratory tract symptoms were found to be lighter involving multiple body systems and organs; and elderly people and men with many basic diseases were considered as vulnerable groups. Since most patients had no clear exposure to poultry, there was no evidence of human-to-human transmission. The time interval from onset to diagnosis was longer, and more longer was the time interval from onset to receiving antiviral treatment in patients with H7N9 infection.

Despite the use of oseltamivir treatment, clinical curative effect seemed to be very limited.3,4 Respiratory failure and multiple organ failure are main causes of death. In 13 deceased cases, four cases died before lab confirmation of this new kind of disease. So, the four patients were diagnosed only after death. Elderly patients are mainly susceptible to this disease and in those patients in whom a variety of basic diseases often merge, the treatment became increasingly difficult. The above-mentioned factors may be the main reason for early death in patients. Therefore, we must continue to adhere to the principle of ?detecting early, reporting early, diagnosing early, and treating early? and strengthen the treatment of serious illness case with H7N9 infection paying equal attention to therapy of traditional Chinese medicine and Western medicine, which is the key step to reduce high mortality.

The situation of increasing number of new cases and high mortality due to infections caused by the novel avianorigin influenza A (H7N9) viruses in Shanghai has raised global concerns.5 However, information on the clinical characteristics of illness and risk factors for severity among persons who were hospitalized for the treatment of H7N9 influenza virus is still lacking.

WHO has been concerned about the transmission of the avian influenza virus from animals to humans because humans were reportedly infected with the avian influenza virus in Hong Kong (China) in 1997. The avian influenza virus is highly speciesspecific, but it has crossed the species barrier to cause infection in human beings. The emerging human infections caused by the novel H7N9 virus have been associated with high mortality and fear of human-to-human transmission has been reported. This report provides information about the discovery process, epidemiologic characteristics, clinical characteristics, and treatment of Shanghai patients infected with H7N9.


REFERENCES
  1. Shanghai Joint Defense and Control H7N9 Spreading Comprehensive Coordination Office. No new cases of people infected with H7N9 avian influenza confirmed cases today, 1 patient had rehabilitation and hospital discharge. Epidemic information report of Shanghai people H7N9 infection prevention and control of avian influenza. May 6, 2013.
  2. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 2013; 368: 1888-1897.
  3. Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterization of viral genome. Lancet 2013; 381: 1916-1925.
  4. Lu S, Xi X, Zheng Y, Cao Y, Liu X, Lu H. Analysis of the clinical characteristics and treatment of two patients with avian influenza virus (H7N9). Biosci Trends 2013; 7: 109-112.
  5. Uyeki TM, Cox NJ. Global concerns regarding novel influenza A (H7N9) virus infections. N Engl J Med 2013; 368: 1862-1864. (Received May 10, 2013)

Edited by Sun Jing
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DOI: 10.3760/cma.j.issn.0366-6999.20131240

Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China (Sun Y, Shen YZ and Lu HZ) Institute of Medicine Science, Shanghai Tongji Hospital, Shanghai Tongji University School of Medicine, Shanghai 200065, China (Sun Y)

Correspondence to: Dr. Lu Hongzhou, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China (Tel: 86-21-57248758. Fax: 86-21-57248758. Email: luhongzhou@fudan.edu.cn)

This work was supported by Multidisciplinary Comprehensive Early Detection and Cure and Innovative Application for Patients with H7N9 Avian Influenza Virus in General Hospital Grant (No. 2013QLG005).


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