# 7961
With the specter of the possible return of the H7N9 virus looming large this fall and winter, we’ve a study today that looks at 6 early cases hospitalized between February and March of this year at Fifth People’s Hospital of Shanghai, providing us with both epidemiological and clinical details.
Today’s report, when coupled with others we’ve examined in recent months (see Study: Hematological & Biochemical Abnormalities In H7N9 Patients & EID Journal: Clinical Course & Treatment Of Four Early H7N9 Cases) paint a picture of an emerging virus that may be difficult to catch, but once acquired, can produce profound (often fatal) illness in humans.
A link to the open-access study and some extended excerpts follow, although I would recommend reading it in its entirety. When you return, I’ll have a bit more.
Jindong Shi equal contributor, Juan Xie equal contributor, Zebao He equal contributor, Yunwen Hu, Yanchao He, Qihui Huang, Beizheng Leng, Wei He, Ying Sheng, Fangming Li, Yuanlin Song, Chunxue Bai, Yong Gu mail, Zhijun Jie mail
hi J, Xie J, He Z, Hu Y, He Y, et al. (2013) A Detailed Epidemiological and Clinical Description of 6 Human Cases of Avian-Origin Influenza A (H7N9) Virus Infection in Shanghai. PLoS ONE 8(10): e77651. doi:10.1371/journal.pone.0077651
Abstract
Background
The world’s first reported patient infected with avian influenza H7N9 was treated at the Fifth People’s Hospital of Shanghai. Shortly thereafter, several other cases emerged in the local area. Here, we describe the detailed epidemiological and clinical data of 6 cases of avian influenza H7N9.
Methods and Findings
We analyzed the epidemiologic and clinical data from clustered patients infected with H7N9 in the Minhang District of Shanghai during a 2-week period. Of the 6 patients, 2 were from a single family. In addition, 3 patients had a history of contact with poultry; however, all 6 patients lived in the proximity of 2 food markets where the H7N9 virus was detected in chickens and pigeons. The main symptoms were fever, cough, and hemoptysis. At onset, a decreased lymphocyte count and elevated creatine kinase, lactate dehydrogenase, procalcitonin, and C-reactive protein levels were observed. As the disease progressed, most patients developed dyspnea and hypoxemia. Imaging studies revealed lung consolidation and multiple ground-glass opacities in the early stage, rapidly extending bilaterally. All patients were treated with oseltamivir tablets beginning on days 3–8 after onset. The main complications were as follows: acute respiratory distress syndrome (ARDS; 83.3%), secondary bacterial infection (66.7%), pleural effusion (50%), left ventricular failure (33.3%), neuropsychiatric symptoms (33.3%), and rhabdomyolysis (16.7%). Of the 6 patients, 4 died of ARDS, with 2 patients recovering from the infection.
Conclusions
An outbreak of H7N9 infection occurred in the Minhang District of Shanghai that easily progressed to acute respiratory distress syndrome. Two cases showed family aggregation, which led us to identify the H7N9 virus and indicated that human transmission may be involved in the spread of this infection.
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Demographic characteristics
All 6 patents were male, Han nationality, aged from 27 to 87 years old, 4 were retired individuals, 1 in-service worker, and 1 pork peddler. Four patients had history of tobacco, 1 had history of drinking, and 5 had at least 1 of the following underlying diseases: chronic obstructive pulmonary diseases, hypertension, dextrocardia, diabetes, coronary heart disease, hepatitis B, and/or gastric ulcer. (Table 1)
History of exposure to birds and residence state
Among the 6 patients, 5 were residents of the Minhang District of Shanghai and had not left Shanghai prior to the onset of illness. One patient, who was a pork seller at a market in the Minhang District, was originally from the Jingsu province and had been a resident of Minhang District for 9 months at the time of disease onset. All 6 patients lived in the proximity of 2 food markets where poultry were traded and H7N9 virus carrier birds had been discovered. Trading of poultry was banned in the markets on April 4. Two patients had a history of exposure to live birds and 1 had a history of suspected exposure.
The time course of case identification, treatment, and diagnosis
Disease onset in the 6 cases occurred within a 2-week period from 19 February and 5 March 2013. The time range from onset to hospitalization was 3–7 days (mean, 4.6 days). Cases 3 and 4 were admitted to the intensive care unit (ICU) because of disease progression on the first and second day of hospitalization, respectively. The length of hospital stay was 3–15 days (mean, 8 days). H7N9 was confirmed by RT-PCR and virus isolation in 4 cases and by elevated (4× that of normal) levels of specific antibodies to H7N9 in the acute phase and recovery stage in 2 cases. Case 2 was the son of case 1, whose other son (age, 55 years) developed severe pneumonia on February 11 and died on February 28. However, the H7N9 virus was not detected in respiratory specimens from the deceased son by RT-PCR or viral isolation. (Table 2)
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Treatment, complications, and outcome
Oseltamivir (tablet, 75 mg bid) therapy was initiated 3–8 days after disease onset in all patients. One recovering patient was treated with a combination of oseltamivir (tablet, 75 mg bid) and amantadine (tablet, 0.2, bid). Broad-spectrum antibiotics against Gram-positive and Gram-negative bacteria and atypical pathogens, such as penicillium, carbon alkene, and fluoroquinolone, were administered to all patients. Except for the recovering patient, all patients were treated with intravenous glucocorticoid as an anti-inflammatory at a dose of 80–240 mg/d. Intravenous immunoglobulin was administered in 4 patients, and thymosin was administered in 2 patients.
In terms of complications, 4 patients developed ARDS between days 3 and 9 (mean, day 6) after disease onset. Three patients had secondary bacterial infections, 3 had pleural effusion, 2 had left heart functional failure, 2 had neuropsychiatric symptoms, and 1 had rhabdomyolysis. Among the 2 recovering patients, 1 patient had no complications, while the other developed secondary bacterial infections. (Table 5).
The extraordinary CFR of these first 6 cases (66%) was thankfully halved in the weeks and months that followed, as hospitals and doctors began to better understand what they were dealing with. The actual identification of the H7N9 virus came several weeks after these six cases were hospitalized and treated.
Unlike what we’ve seen with the H5N1 avian virus – which has a history of infecting younger, generally healthier people –hospitalized H7N9 cases have tended to be older, and often suffering from pre-existing medical conditions. H7N9 infections – for reasons not yet understood – have also been skewed heavily towards males (71% of cases).
With only 137 cases reported, and literally thousands of their close contacts monitored for illness with no additional illnesses reported, this virus doesn’t appear to have acquired the ability to transmit efficiently between humans. Unknown, of course, is whether some of these close contacts may have experienced asymptomatic or subclinical infections.
Some researchers have estimated that the true number of cases in China last spring really ran into the thousands (see Lancet: Clinical Severity Of Human H7N9 Infection). Their estimate? Between 1500 and 27,000 symptomatic infections.
So we really don’t know just how big of the tip of this iceberg these 137 cases really represents.
Of additional concern, patient reports and laboratory testing have revealed this virus is unusually well-adapted to mammalian physiology (see mBio: H7N9 Naturally Adapted For Efficient Growth in Human Lung Tissue), and we’ve seen some early signs of spontaneous antiviral resistance in patients (see mBio: Antiviral Resistance In H7N9).
Returning again to the PLoS One study, the authors conclude by writing:
In conclusion, the first ever patient infected with H7N9 was treated at the Fifth People’s Hospital of Shanghai in February 2013. Within a 2-week period, several other cases of H7N9 infection emerged around 2 markets near the hospital. Fever, cough, sputum with blood, low lymphocyte counts, elevated CK and LDH levels, and pulmonary exudative lesions are significant characteristics of H7N9 infection, which easily progresses to ARDS. Among the cases, there was family clustering, which led to a high suspicion of contagious respiratory virus infection. In the early stage, human infection with H7N9 can be diagnosed by RT-PCR and viral isolation from respiratory specimens. Smoking, drinking, underlying diseases, dyspnea, low platelet counts, elevated CK levels, hypoxemia, and complications may be related to poor prognosis. However, diagnosis and treatment may be delayed because of the limited experience with this infection and small number of cases, which were among the first cases of H7N9 infection to be identified. Future studies are needed to elucidate the pathogenicity, transmissibility, and clinical features of H7N9 infection. In addition, techniques for early diagnosis to enable early administration of antiviral therapy and determination of the the factors affecting prognosis require further investigation.
