MMWR: MERS Epidemiological Update & Guidance

Coronavirus – Credit CDC PHIL

 

# 9645

 

While all eyes right now are on our current flu season, and the merry band of novel flu viruses harassing people and poultry operations on four continents (Africa, Asia, Europe, North America) - if last year is any indication - in a few months the MERS coronavirus will be making headlines as well.

 

As the chart below from today’s MMWR illustrates, MERS seems to blossom in the spring, although exactly why is still up for grabs.  The most popular theory involves the winter calving of camels. Young camel are the most susceptible to the virus, and are believed a likely conduit to pass it on to humans.

FIGURE. Number of cases of Middle East respiratory syndrome coronavirus infection reported by the World Health Organization,* by month of illness onset — worldwide, 2012–2015

 

As both a `head’s up’ and an overview, today the MMWR has published a brief epidemiological review of the MERS coronavirus.

Update on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection, and Guidance for the Public, Clinicians, and Public Health Authorities — January 2015

Weekly

January 30, 2015 / 64(03);61-62

Brian Rha, MD1, Jessica Rudd, MPH1, Daniel Feikin, MD1, John Watson, MD1, Aaron T. Curns, MPH1, David L. Swerdlow, MD2, Mark A. Pallansch, PhD1, Susan I. Gerber, MD1 (Author affiliations at end of text)

CDC continues to work with the World Health Organization (WHO) and other partners to closely monitor Middle East respiratory syndrome coronavirus (MERS-CoV) infections globally and to better understand the risks to public health. The purpose of this report is to provide a brief update on MERS-CoV epidemiology and to notify health care providers, public health officials, and others to maintain awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula.*

MERS-CoV was first identified and reported to WHO in September 2012 (1). As of January 23, 2015, WHO has confirmed 956 laboratory-confirmed† cases of MERS-CoV infection, which include at least 351 deaths. All reported cases have been directly or indirectly linked through travel or residence to nine countries: Saudi Arabia, the United Arab Emirates, Qatar, Jordan, Oman, Kuwait, Yemen, Lebanon, and Iran. In the United States, two patients tested positive for MERS-CoV in May 2014, each of whom had a history of fever and one or more respiratory symptoms after recent travel from Saudi Arabia (2). No further cases have been reported in the United States despite nationwide surveillance and the testing of 514 patients from 45 states to date.

The majority (504) of the 956 MERS cases were reported to have occurred during March–May 2014 (Figure). However, WHO continues to receive reports of MERS cases, mostly from Saudi Arabia.§ From August 1, 2014, through January 23, 2015, WHO confirmed 102 cases, 97 of which occurred in persons with residence in Saudi Arabia, including three travel-associated cases reported by Austria, Turkey, and Jordan; of the remaining cases, two cases were in persons from Qatar, and three cases were in persons from Oman.

CDC continues to recommend that U.S. travelers to countries in or near the Arabian Peninsula protect themselves from respiratory diseases, including MERS, by washing their hands often and avoiding contact with persons who are ill. If travelers to the region have onset of fever and symptoms of respiratory illness during their trip or within 14 days of returning to the United States, they should seek medical care. They should call ahead to inform their health care provider of their recent travel so that appropriate isolation measures can be taken in health care settings. Health care providers and health departments throughout the United States should continue to consider a diagnosis of MERS-CoV infection in persons who develop fever and respiratory symptoms within 14 days after traveling from countries in or near the Arabian Peninsula, and be prepared to detect and manage cases of MERS.

Recommendations might change and be updated as additional data become available. More detailed travel recommendations related to MERS, including general precautions posted by WHO for anyone visiting farms, markets, barns, or other places where animals are present, are available at http://wwwnc.cdc.gov/travel/notices/alert/coronavirus-arabian-peninsula.

The website also lists more specific WHO recommendations for persons with diabetes, kidney failure, or chronic lung disease, and immunocompromised persons, that include avoiding contact with camels.¶ Guidance on the evaluation of patients for MERS-CoV infection, infection control, home care and isolation, and clinical specimen collection and testing is available on the CDC MERS website at http://www.cdc.gov/coronavirus/mers/index.html.

Treatment is supportive; no specific treatment for MERS-CoV infection is available. WHO has posted guidance for clinical management of MERS patients at

http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf?ua=1.

1Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC; 2Office of the Director, National Center for Immunization and Respiratory Diseases, CDC (Corresponding author: Brian Rha, wif8@cdc.gov, 404-639-3972)

References

1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012;367:1814–20.
2. Bialek SR, Allen D, Alvarado-Ramy F, et al. First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities—May 2014. MMWR Morb Mortal Wkly Rep 2014;63:431–6.

* Countries considered in the Arabian Peninsula and neighboring include: Bahrain; Iraq; Iran; Israel, the West Bank and Gaza; Jordan; Kuwait; Lebanon; Oman; Qatar; Saudi Arabia; Syria; the United Arab Emirates; and Yemen.

† Confirmatory laboratory testing requires a positive polymerase chain reaction test result on at least two specific genomic targets for MERS-CoV or a single positive target with sequencing on a second.

§ Additional information available at http://www.who.int/csr/don/archive/disease/coronavirus_infections/en.

¶ Additional information available at http://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_RA_20140613.pdf?ua=1.

ECDC: MERS-CoV Epidemiological Update & Risk Assessment

 

Credit ECDC

 

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As part of their larger overall weekly Communicable Disease Threats report, the ECDC today has updated their assessment of the MERS outbreak in the Middle East. 

 

Middle East respiratory syndrome- coronavirus (MERS CoV) – Multistate

Opening date: 24 September 2012 Latest update: 17 April 2014

Epidemiological summary

Since April 2012 and as of 18 April 2014, 275 laboratory-confirmed cases of MERS-CoV have been reported by local health authorities worldwide, including 98 deaths and 64 healthcare workers. The following countries have reported MERS-CoV cases:

Saudi Arabia: 212 cases / 72 deaths
United Arab Emirates: 33 cases / 9 deaths
Qatar: 7 cases / 4 deaths
Jordan: 4 cases / 3 deaths
Oman: 2 cases / 2 deaths
Kuwait: 3 cases / 1 death
UK: 4 cases / 3 deaths
Germany: 2 cases / 1 death
France: 2 cases / 1 death
Italy: 1 case / 0 death
Tunisia: 3 cases / 1 death
Malaysia: 1 case / 1 death
Philippines: 1 case / 0 death

Fourteen cases have been reported from outside the Middle East: the UK (4), France (2), Tunisia (3), Germany (2), Italy (1), Malaysia (1) and Philippines (1). In France, Tunisia and the UK, there has been local transmission among patients who had not been to the Middle East, but had been in close contact with laboratory-confirmed or probable cases. Person-to-person transmission has occurred both among close contacts and in healthcare facilities.

In the first 18 days of April 2014, 57 cases (21% of total cases) have been reported, 29 of whom are healthcare workers (51%) and 21 are asymptomatic cases. In the United Arab Emirates, a cluster of 14 healthcare workers (including one case exposed in UAE and reported by the Philippines) has been reported during the past week. They all had had contact with a previously reported case, who died on 10 April 2014. Eight of the cases had mild symptoms and six were asymptomatic.

In Saudi Arabia, during the past week, 30 cases have all occurred in Jeddah, including 11 healthcare workers; five cases were fatal and eight were asymptomatic.

The first cases reported in Asia have occurred in people returning from the Middle East:

• The case from the Philippines is an asymptomatic healthcare worker returning from the United Arab Emirates.
• The case in Malaysia was in a 54-year-old man who returned from Saudi Arabia after Umrah on 29 March 2014. He developed symptoms (fever, coughing) around 8 April 2014. On 10 April 2014, he was admitted to hospital and died on 13 April 2014. The Malaysian health authorities are conducting prevention and control activities including monitoring close contacts of the case.

ECDC assessment

The source of MERS-CoV infection and the mode of transmission have not been identified, but the continued detection of cases in the Middle East indicates that there is an ongoing source of infection in the region. Dromedary camels are likely an important host species for the virus, and many of the primary cases in clusters have reported direct or indirect camel exposures. Almost all of the recently reported secondary cases, many of whom are asymptomatic or have only mild symptoms, have been acquired in healthcare settings. There is therefore a continued risk of cases presenting in Europe following exposure in the Middle East and international surveillance for MERS-CoV cases is essential. An international case-control study has been designed and proposed by WHO. Results of this or similar epidemiological studies to determine the initial exposures and risk behaviours among the primary cases are urgently needed.

The risk of secondary transmission in the EU remains low and can be reduced further through screening for exposure among patients presenting with respiratory symptoms and their contacts, and strict implementation of infection prevention and control measures for patients under investigation. The case detected in Malaysia last week had participated in the muslim pilgrimage Umrah. However, more details are needed on possible and suspected exposure events and it is possible that these cases were also infected when visiting healthcare facilities in the region.

The Malaysian authorities have asked all passengers travelling on the flights with the case detected in Malaysia on 29 March to be screened for health complaints.

The Philippines authorities have asked all passengers travelling with the Filipino case detected on 15 April to be screened for signs and symptoms of MERS-CoV infection, while the department of health is also actively contact tracing passengers.

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CIDRAP: NEJM H7N9 Epidemiology Study & Yesterday’s Case Summary

Credit CDC

 

 

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Yesterday the NEJM published a lengthy study that looked at the epidemiology of the first 139 human H7N9 cases (and nearly 2,700 contacts), that reaffirms what the World Health Organization, China’s CDC, and our own CDC have repeatedly said regarding this virus;  while there is a lot we don’t know, so far there is no evidence of sustained human-to-human spread.

Last night Robert Roos summarized this report on CIDRAP NEWS, which you can read at the link below:

 

Study reaffirms that H7N9 rarely spreads person to person

Robert Roos | News Editor | CIDRAP News

A Chinese study suggests that H7N9 may spread person to person only with prolonged close contact, if at all.

Feb 05, 2014

 A detailed epidemiologic study of the first 9 months of the H7N9 avian flu outbreak in China reinforces the image of the illness as one that rarely spreads from person to person but may possibly do so when there is prolonged, close contact between the sick and the healthy.

The lengthy report, released today by The New England Journal of Medicine, covers 139 human H7N9 cases recorded through November of 2013. All but 2 of the patients were hospitalized, and 47 (34%) died. More than 80% of the patients were exposed to animals, mostly poultry, before they got sick.

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As we saw in 2009 with the pandemic H1N1 virus, once an influenza virus manages to achieve efficient transmission, it doesn’t take long for it to become painfully obvious.  The fact that we haven’t seen hundreds of H7N9 cases show up in London, New York, Sydney, and Paris is a pretty good indicator that as a pandemic virus, H7N9 isn’t ready for prime time.

 

While reassuring news, influenza viruses have a history of changing over time. And so while this virus isn’t currently spreading efficiently, there are no guarantees about its behavior tomorrow or next week.

 

As Lisa Schnirring wrote last night, also on CIDRAP News, the daily parade of new human cases from Easter China continues, as do concerns over the geographic spread of the virus.

 

No H7N9 letup as Guangxi detections prompt warning

Lisa Schnirring | Staff Writer | CIDRAP News

Feb 05, 2014

China reported nine new H7N9 influenza cases today, including the third from Guangxi province, signaling a rise in disease activity in a region that borders Vietnam along with the first reports of poultry market detections there, according to a warning today from an animal health group.

 

The other eight new cases are from two provinces—Guangdong and Zhejiang—that are reporting the largest portion of cases in the second wave, which has now eclipsed the first wave by a growing margin. So far 174 cases have been reported in the outbreak's second wave, compared to 136 recorded during the first spike in disease activity last spring.

(Continue . . . )

 

Hong Kong: CHP Update On 2nd H7N9 Case Investigation

Credit CHP

 

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Hong Kong’s CHP has issued another lengthy update this morning (late evening, Dec 8th their time) on their ongoing epidemiological investigation into the second H7N9 case in that city in a week. 

 

While no new H7N9 infections (or other major revelations) are to be found in this announcement, it does present us with a progress report on the investigation, and shows just how willing Hong Kong’s public health agencies are to provide updates – even late on a Sunday evening.

 

A commendable policy that one can only hope rubs off on some of the other, less forthcoming, public health agencies around the world.

 

Epidemiological investigation and follow-up actions by CHP on second confirmed human case of avian influenza A(H7N9)

Sunday, December 8, 2013
Issued at HKT 21:07

The Centre for Health Protection (CHP) of the Department of Health (DH) today (December 8) provided an update on the second confirmed human case of avian influenza A(H7N9) in Hong Kong.

"The epidemiological investigation, enhanced disease surveillance, port health measures and health education are proceeding," a spokesman for the DH remarked.

The 80-year-old male patient lives in Fu Yong Xin He District in Shenzhen. As of 4pm today, no additional close contacts have been identified. The number of close contacts remains at 19 while there are over 140 other contacts. Details are as follows:

(A) The 19 close contacts remain under quarantine for 10 days since their last contact with the patient. Their specimens all tested negative for the avian influenza A(H7N9) virus upon preliminary laboratory testing by the Public Health Laboratory Services Branch of the CHP. They were prescribed with the antiviral Tamiflu prophylaxis. During isolation, if their health conditions change, further testing and surveillance will be conducted. They include:

1. Thirteen patients who had stayed in the same cubicle with the confirmed patient in Tuen Mun Hospital (TMH). One of them has newly developed fever and another specimen collected from the patient today tested negative for the avian influenza A(H7N9) virus;

2. His five family members; and

3. The taxi driver who had taken the patient and his family members from Shenzhen Bay Port Border Control Point (SBP BCP) to TMH on December 3.

(B) Over 140 other contacts, including other relatives of the patient, health-care workers (HCWs) of TMH and the ambulance service, relevant hospital visitors as well as an immigration control officer at SBP BCP, have been put under medical surveillance and offered Tamiflu prophylaxis. Among them, one HCW of TMH newly developed non-specific symptoms whose specimen collected today has been tested negative for the avian influenza A(H7N9) virus.

Regarding the first confirmed case affecting the 36-year-old female patient, as of 4pm today, no additional close contacts of this case have been identified. The number of close contacts remains at 17 while there are now 230 other contacts under medical surveillance. Of the 17 close contacts, 11 have completed quarantine and will continue to be put under medical surveillance for 10 more days. The remaining six close contacts remain under quarantine for 10 days since their last contact with the patient. During isolation, if their health conditions change, further testing and surveillance will be conducted.

The Lady MacLehose Holiday Village in Sai Kung under the Leisure and Cultural Services Department has been converted as quarantine centre. Currently, seven asymptomatic close contacts of the second case are under quarantine in the centre.

The epidemiological investigation into the two cases by the CHP, including contact tracing and tracing the source of infection, is ongoing.

Locally, enhanced surveillance over suspected cases in public and private hospitals is under way. The CHP will continue to maintain liaison with the World Health Organization (WHO), the Mainland and overseas health authorities to monitor the latest developments and obtain timely and accurate information. Local surveillance activities will be modified according to the WHO's recommendations.

"All border control points (BCPs) have implemented disease prevention and control measures. Thermal imaging systems are in place at BCPs for body temperature checks of inbound travellers. The DH has liaised with the Auxiliary Medical Service and the Civil Aid Service to deploy additional manpower at BCPs to conduct random temperature checks using handheld devices. Suspected cases will be immediately referred to public hospitals for follow-up investigation," the spokesman said.

Regarding health education for travellers at BCPs, the distribution of health education pamphlets, display of posters on avian influenza A(H7N9) in departure and arrival halls, in-flight public announcements, environmental health inspection and the provision of regular updates to travel industries via meetings and correspondence have all been escalated. The DH will keep a close eye on the latest developments and adopt corresponding port health measures.

"We have enhanced our publicity and health education on the prevention of avian influenza. The CHP has also sent letters to government departments and related organisations to reinforce our health advice on the prevention of avian influenza," the spokesman added.

The CHP hotline (2125 1111) has been set up for public enquiries. As of 4pm today, 72 calls had been received.

"Travellers, especially those returning from avian influenza A(H7N9)-affected areas and provinces, with fever or respiratory symptoms are reminded to immediately wear facial masks, seek medical attention and reveal their travel history to doctors. Health-care professionals should also pay special attention to patients who might have had contact with birds, poultry or their droppings in affected areas and provinces," the spokesman advised.

The spokesman also urged travellers not to visit live poultry markets in the affected areas and provinces and avoid direct contact with poultry, birds and their droppings. If contact has been made, they should thoroughly wash their hands with soap and water.

Members of the public should remain vigilant and are reminded to take heed of the following preventive advice against avian influenza:

• Poultry and eggs should be thoroughly cooked before eating;
• Wash hands frequently with soap, especially before touching the mouth, nose or eyes, handling food or eating; after going to the toilet or touching public installations or equipment such as escalator handrails, elevator control panels or door knobs; or when hands are dirtied by respiratory secretions after coughing or sneezing;
• Cover the nose and mouth while sneezing or coughing, and hold the spit with a tissue and put it into a covered dustbin;
• Avoid crowded places and contact with fever patients; and
• Wear a mask when respiratory symptoms develop or when taking care of fever patients.

HK CHP: Epidemiological Investigation & Response To H7N9 Case

 

# 8037

 

This morning  Hong Kong’s CHP has published a detailed accounting of their epidemiological tracing, and follow up, of contacts of their H7N9 patient this morning, with additional details on their quarantine plans that I blogged about earlier today (see HK: H7N9 Contact Tracing, Testing, Isolation & Quarantine). Among the revelations:

 

The patient’s traveling companion has now been located (see Video: HK Officials Seeking Traveling Companion Of H7N9 Patient), has tested negative, and remains asymptomatic.

At this point more than 200 people with potential exposure have been offered Tamiflu ® prophylaxis, most of whom are medical staff or hospital employees (see H7N9: CDC Guidance On Antiviral Chemoprophylaxis  for additional background).

The CHP is undertaking a massive public awareness campaign on H7N9 prevention.

 

All of which illustrates the seriousness with which Hong Kong’s public health authority is treating this single case.

3 December 2013

Epidemiological investigation and follow-up actions by CHP on confirmed human case of avian influenza A(H7N9) 

A spokesman for the Centre for Health Protection (CHP) of the Department of Health (DH) today (December 3) provided an update on the first confirmed human case of avian influenza A(H7N9) in Hong Kong affecting a woman aged 36.

 

"The Serious Response Level under the Government's Preparedness Plan for Influenza Pandemic has been activated while the CHP's epidemiological investigation and follow-up actions are currently in full swing," the spokesman remarked.

 

As of 2pm today, contact tracing conducted by the CHP has located 17 close contacts and over 200 other contacts. Details are as follows:

 

(A) 17 close contacts of the patient have been quarantined and prescribed with Tamiflu prophylaxis, including:

1. All ten home contacts, including four with non-specific symptoms, have been quarantined in Princess Margaret Hospital (PMH). Their specimens all tested negative for the avian influenza A(H7) virus upon preliminary laboratory testing by the Public Health Laboratory Services Branch (PHLSB) of the CHP;

2. The female travel collateral aged 33 who visited Shenzhen with the patient has been located and has remained asymptomatic. Her specimen tested negative for the avian influenza A(H7) virus upon preliminary laboratory testing by the PHLSB and she was transferred to PMH for quarantine; and

3. Six patients who stayed in the same cubicle with the confirmed patient in Tuen Mun Hospital (TMH) are currently under quarantine in hospital pending laboratory testing.

    The Lady MacLehose Holiday Village in Sai Kung under the Leisure and Cultural Services Department has been converted as quarantine centre and asymptomatic close contacts will be transferred there.

(B) Over 200 other contacts of the patient have been put under medical surveillance and offered with Tamiflu prophylaxis, including:

1. The two private doctors, Dr Simon Wong Siu-shan (Shop 17, G/F, Kai Hei Land Building, 385 Castle Peak Road) and Dr Wong Chun-yan (Shop 102A-103, G/F, Kam Wah Shopping Arcade, Tuen Lung Street), practising in Tuen Mun whom the patient respectively consulted at about 11am on November 25 and around 8.30pm on November 26 have been located. Both doctors, their staff, patients and accompanying relatives (over 30 persons) have all remained asymptomatic; and

2. Over 170 healthcare workers (HCWs) in TMH and QMH and the ambulance officers involved in patient transfer between the two hospitals have been identified. Seven of the HCWs who presented with non-specific symptoms have been tested negative for the avian influenza A(H7) virus.

    Contact tracing by the CHP is ongoing.

    "The CHP has also enhanced surveillance over suspected cases in public and private hospitals starting from today," the spokesman added.

    The CHP has issued letters to doctors and hospitals, kindergartens, child care centres, primary and secondary schools, as well as residential care homes for the elderly and disabled to keep them abreast of the latest situation.

    "The confirmed case has been notified to the World Health Organization, the National Health and Family Planning Commission, the General Administration of Quality Supervision, Inspection and Quarantine of the Mainland as well as health and quarantine authorities of Guangdong, Zhuhai and Macau," the spokesman said.

    "All border control points (BCPs) have implemented disease prevention and control measures. Body temperature checks and health surveillance have been enhanced. The Port Health Office of the DH has maintained liaison with the Shenzhen Entry-Exit Inspection and Quarantine Bureau in paying attention to travellers, and also cross-boundary students, who present with fever or are symptomatic. Suspected cases will be immediately referred to public hospitals for follow-up investigation," the spokesman remarked.

    Regarding health education to travellers at BCPs, distribution of health education pamphlets, the display of posters on avian influenza A(H7N9) in departure and arrival halls, in-flight public announcements, environmental health inspection, and the provision of regular updates to the travel industry via meetings and correspondence have all been escalated.

    The DH will keep a close eye on the latest development and adopt corresponding port health measures.

    The CHP's hotline (2125 1111) has been set up for public enquiries which will operate from 9am to 6pm. As of 4pm today, 13 enquiries were received.

    "Travellers, especially those returning from avian influenza A(H7N9)-affected areas, with fever or respiratory symptoms are reminded to immediately wear facial masks, seek medical attention, and reveal their travel history to doctors. Healthcare professionals should also pay special attention to patients who might have had contact with birds, poultry or their droppings in affected areas," the spokesman advised.

    The spokesman also urged travellers not to visit wet markets with live poultry in the affected areas and to avoid direct contact with poultry, birds and their droppings. If contact has been made, they should thoroughly wash their hands with soap and water.

    Members of the public should remain vigilant and are reminded to take heed of the following preventive advice against avian influenza:

• Poultry and eggs should be thoroughly cooked before eating;
• Wash hands frequently with soap, especially before touching the mouth, nose or eyes, handling food or eating; after going to the toilet or touching public installations or equipment such as escalator handrails, elevator control panels or door knobs; or when hands are dirtied by respiratory secretions after coughing or sneezing;
• Cover the nose and mouth while sneezing or coughing, and hold the spit with a tissue and put it into a covered dustbin;
• Avoid crowded places and contact with fever patients; and
• Wear a mask when respiratory symptoms develop or when taking care of fever patients.

    The public may visit the CHP's avian influenza page (www.chp.gov.hk/en/view_content/24244.html) and its website (www.chp.gov.hk/files/pdf/global_statistics_avian_influenza_e.pdf) for more information on avian influenza-affected are

PLoS One: Epidemiological & Clinical Description Of 6 H7N9 Cases - Shanghai

 

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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.

 

A Detailed Epidemiological and Clinical Description of 6 Human Cases of Avian-Origin Influenza A (H7N9) Virus Infection in Shanghai

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.

<SNIP>

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)

<SNIP>

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).

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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.