Wednesday, January 11, 2017

What is happening with H7N9 in China?



Based on illness onset dates from January through the end of November 2016, China officially reported about 115 human cases H7N9 infection. Over the course of several days in early January 2017, China notified the World Health Organization of more than 100 additional human cases of H7N9 presumably having been infected in December 2016. It appears that almost as many people were infected in December as all of the preceding months in 2016.

The graph below shows the distribution of H7N9 cases by onset date where available and then by reporting date. The graph clearly shows the large increases in the number of infected individual reported recently. Should this increase be a cause for alarm?


Increases in human cases of avian influenza always increase the risk for sustained human to human transmission of the disease. Reviewing the minimal data that is available for the 107 recent cases reported by China, some observations can be made. About 36% of these new cases are female and 67% are male. This gender ratio is similar to the earlier cases in 2016. The age range of these cases is 23 to 91 years with a median age of 54 years old, also similar to the age distribution of earlier cases in 2016. There is no evidence from these recent cases that different age groups are being disproportionately infected.

Finally, the case fatality risk (CFR) for these recent cases is about .31. This is higher than the CFR for earlier cases in 2016 and the overall CFR for all cases since the initial outbreak in 2013. Many of the nonfatal cases are reported to have severe pneumonia, which suggests that more of these individuals may not recover.

There is nothing in the publicly available reports of these cases which would indicate the extent of human to human transmission, if any. The best indirect way to assess the potential for human to human transmission is to evaluate human clusters. In the available data, there is no information about relationships among various infected individuals, nor are onset dates available to assess chains of transmission.

 The only information we currently have available to interpret potential clusters is the geographic distribution of cases. The map below plots the geographic distribution of human cases recently reported by China compared with all of the H7N9 cases with onset dates or reported dates since January 1, 2016. About half of these newly reported cases are spread out among various provinces in eastern China and probably represented isolated sporadic infections. 


However, the remaining 50+ cases were reported from just four cities. The map below shows the four cities with 9 or more H7N9 cases reported in the January announcements, Suzhou, 21 cases, Wuxi 11 cases, and Changzhou 10 cases, all in Jiangsu Province. The fourth city is Hangzhou in Zhejiang Province with 9 cases. All of these cities are large population centers, so we will need more case details to determine if there is human to human transmission in these areas.

Information on contact tracing would be useful as well. None of the reported cases appears to be asymptomatic. Less 10 cases since the initial human H7N9 outbreak have been reported as asymptomatic. Are mild cases being overlooked?

If the number of reported H7N9 cases continues to grow dramatically over the next several weeks, it may signal a local H7N9 epidemic in China. We need to be watching H7N9 in China very closely.

Monday, January 2, 2017

A Review of Human Influenza A(H7N9) Infections in 2016

Note: Between January 1 and January 9 2017, China officially reported  to WHO at least another 107 human cases of H7N9 most with onset dates in 2016. The information presented below relates to  the first 125 cases reported with onset dates in 2016.  updated January 11, 2017


The first officially reported human case of infection from a reassortant avian influenza A(H7N9) virus was from the People’s Republic of China (China) in March of 2013, although human H7N9 infection may have occurred in or near Hong Kong as early as 2007 (FAO ID event 220957). Since 2013 the World Health Organization (WHO) has officially reported 808 human cases of H7N9 as of December 23, 2016. In the past few days, an additional 13 H7N9 cases have been reported by public health officials in China but have not yet been published by the WHO. Of these 821 cases, 696 have onset or reporting dates prior to December 31, 2015. The total number of reported H7N9 cases in 2016 is 125.

Geographic Distribution 

All 125 human cases of H7N9 in 2016 were reported from China. These cases have been reported from 18 provinces and special administrative regions. More specific geographic location information was available for 117 of these cases, the remaining 8 cases were only reported from a specific province; Anhui 2, Hebei 2, Fujian 1, Hubei 1, Shandong 1, and Zhejiang 1. The map below depicts the provinces and special administrative regions with reported 2016 cases. Dots indicate the locations of individual or multiple cases reported in 2016. In 2016, these cases all occurred in the Western portion of China.

Table: Comparison of the frequencies of human H7N9 infections reported in China between 2013-2015 and 2016 by province/special administrative regions.

Map: Geographic distribution of human H7N9 cases in China in 2016.

Age Statistics 

From 2013 to 2015, the median age of H7N9 infected males was 57.5 years with ages ranging from 1 to 91 years old. For females during that period the median age was 54.5 with ages ranging from less than year to 85 years old. The age distributions by gender for 2016 is similar. The chart below compares age categories for 2013-2015 and 2016. In 2016, infected individuals were somewhat younger than previous years.

Graph: Comparison of the frequencies of human H7N9 cases by age categories.

Gender

Between 2013 and 2015, 471 of the reported cases were male (68%) and 220 of the reported cases were female (32%). The genders of the remaining cases were not published. Among the 125 cases reported in 2016, 72% (85) were male and 28% (33) were female. Seven cases do not have a reported gender.

It seems that males are far more likely to contract H7N9 infections than females. Because almost all cases are associated with exposure to infected poultry, it is possible that different gender roles expose males more frequently to affected poultry than females. 

Fatalities

Between 2013 and 2015, 143 of the 696 reported H7N9 cases were reported as fatal. These data would suggest a minimum case fatality risk (CFR) of .21.

The CFR, as defined here, is the conditional probability of death from an H7N9 infection, a ratio between H7N9-caused deaths and recoveries/asymptomatic cases. Because follow-up reporting is lacking in many of these cases, the actual number of deaths versus the number of recoveries is uncertain. Very few of the cases in the period from 2013 to 2015 were officially reported as recovered (only 133).

In 2016, 29 of the 125 cases were reported as fatal. At face value, the CFR for 2016 is .23 but it is likely to be higher since many of the recently reported cases are currently being treated.

H7N9 Clusters

Most of the reported human H7N9 infections in 2016 result from zoonotic transmission of the virus from domestic poultry. Public health reports in 2016 rarely indicate the possibility of human-to-human transmission among confirmed H7N9 cases which would signal a cluster of cases. A human cluster of cases is generally defined by WHO as two or more cases of confirmed, probable, or suspected infections with onset of illness occurring within the same two-week period and who are in the same geographical area and/or are epidemiologically link.

Based on family ties or restricted geographic area, potential human H7N9 clusters in 2016 include the following. In February 2016 infected individuals in several locations may represent multiple clusters, two siblings in Suzhou Jiangsu, several family members in Wuxi Jiangsu, and several unrelated individuals in Fuzhou Fujian. Several family members from Tahie Jiangxi were reported as H7N9 cases in April. Two cases from Hebei in July of 2016 may represent a cluster. Recently, two infected individuals from Kunshan Jiangsu were reported in November and three cases in Hefei Anhui in December, with no other details are available.

Discussion

Most of the human H7N9 case reported in 2016 are sporadic infections. As noted above, a few clusters of cases suggest that human-to-human transmission may have occurred but did not result in sustained human-to-human transmission. H7N9 cases seems to occur on an annual cyclical basis that follows the pattern of season human influenza infections. As depicted in the chart below, H7N9 cases were frequent from week numbers 1-23 and started increasing again in week number 46. The seasonal fluctuation in human infections indicates that more H7N9 cases can be expected in the coming months. While the number of H7N9 cases declined in 2016 compared to earlier years, the potential for a deadly epidemic or a possible H7N9 pandemic continues to exist.


 

 Chart: Epidemic curve of human H7N9 cases in 2016.


Note: The information presented and discussed here is based on a compilation of publicly available data sources including WHO, Food and Agriculture Organization of the United Nations, and various public health agencies supplemented by media reports as available.

Sunday, April 3, 2016

MERS is Widespread in Saudi Arabia



Middle East Respiratory Syndrome (MERS) has infected at least 1370 individuals (including asymptomatic cases) in Saudi Arabia since 2012 (e.g. ProMED link). Since mid-February 2016, Buraidah in Al Qassim region in Saudia Arabia has been experiencing a local MERS outbreak with 23 cases reported through March 16, 2016 (link). As of April 3, 2016 there have been an additional 11 cases reported, bringing the total cases reported from Buraidah by Saudi Arabia Ministry of Health to 34.  Many of these cases are a result of nosocomial infection, but perhaps as many as eight of these cases were community acquired infections with some individuals having contact with animals. Among these 34 cases, 17 have been reported as deaths so far. (see note)

While the Buraidah MERS outbreak has raised concerns, the 34 cases from Buraidah represented about 40% of all MERS cases reported from Saudi Arabia since January 1, 2016. The majority of MERS cases since January 1, 2016, about 49 cases, have been reported from numerous other locations around Saudi Arabia as shown in the map below. 



Since January 1, 2016, human MERS cases have been reported from at least 23 populated places scattered across Saudi Arabia. The widespread geographic distribution of these cases suggests that MERS has now become endemic in Saudi Arabia.

 Note: The total cases from Buraidah include a 60 year-old male who experienced symptom onset in Hail and was treated in the Buraidah hospital where he died (Case No 3. DON March 21,  2016)

Wednesday, March 16, 2016

The MERS Outbreak in Buraidah, Saudi Arabia, February - March 2016


Since late February, a Middle East Respiratory Syndrome (MERS) outbreak has been occurring in northcentral Saudi Arabia in Buraidah in the Al Qassim region. Through March 16, 2016, there have been 23 MERS cases reported from Buraidah by the Saudi Arabia Ministry of Health (SAMOH), include 6 females and 17 males, ranging in age from 22 to 84 years. Six of the cases are healthcare workers. Based on reports by the SAMOH, 11 of these individuals have died. Only five individuals have been reported to have recovered.

Constructing a preliminary timeline of Buraidah outbreak

Details are only available from the World Health Organization (WHO) for 18 of these cases prior to March 10, 2016. (link, link)

At least five of the cases reported by WHO appear to be community-acquired infections which suggest that MERS may be wide-spread in the Buraidah community. These individuals include a 40 year-old male (WHO 1670) who experienced symptoms on February 22 and was hospitalized the same day. It is not clear how this individual became infected. At least four other community-acquired infections also occurred. The first is a 42-year-old male (WHO 1658) who had symptoms on February 26 and was hospitalized on March 4 and is reported to have contact with animals. A 67-year-old female (WHO 1668) developed symptoms on February 28 and was hospitalized two days later on March 1. Investigations of exposure to known risk factors for this case are continuing. A 68 year-old female (WHO 1655) experienced symptom onset on March 2 and was hospitalized on March 5. Investigations of exposure to known risk factors prior to symptom onset is currently ongoing for this individual as well. The fifth individual is a 50-year-old male (WHO 1684) who experienced symptom onset on March 1 and was hospitalized the same day. He is reported by the SAMOH to have died.

Thirteen of the remaining WHO-reported MERS cases, including three healthcare workers, appear to be associated with the nosocomial outbreak at a hospital in Buraidah. The first healthcare worker developed symptoms on February 28 and the second on March 3. The third healthcare worker developed symptoms on March 6. This indicates that the coronavirus was present in the hospital prior to February 28.

According to the WHO report, eight of the confirmed cases were being hospitalized or treated in the Buraidah hospital starting as early as February 4 (seven had comorbidities and were possibly being treated for these conditions) and continuing through the start of the hospital outbreak. Three of these hospitalized cases initially tested negative for MERS; one on February 20, and two on February 24. Later all three of these individuals tested positive on March 4, indicating that these cases may have been infected after February 20.

This suggests that the possible index case for the hospital outbreak is the 40-year-old male (WHO 1670) who was experiencing symptoms on February 22 and was hospitalized on same day. He died on March 4. The other four community-acquired cases discussed above were hospitalized between March 1 and March 4, too late to have infected the first health care worker and some of the other hospitalized cases.

Between March 11 and March 16, the SAMOH identified five additional MERS cases from Buraidah. The WHO has not yet reported the details of these cases, but all least two or three of these cases appear to be part of the nosocomial outbreak.

Discussion

Although the details are unclear, community-acquired MERS infections are occurring in Buraidah  along with a nosocomial outbreak that originated after February 20 in a local hospital. In the Buraidah outbreak almost half of all of the reported fatalities (5 out of 11) are under 35 years in age. This is a high percentage. Of the previously reported MERS fatalities from Saudi Arabia only about 10% are under the age of 35.

It is not clear if the nosocomial MERS outbreak in Buraidah has been contained.

Wednesday, January 20, 2016

The Geography of MERS




Since 2012, the World Health Organization (WHO) has been notified of 1626 laboratory-confirmed cases of Middle East Respiratory Virus Syndrome (MERS) as of January 7, 2016 (link). These cases have been reported from 26 countries as shown on the map and table below. Cases have been reported from most continents: North America, Africa, Europe, and Asia. No cases have been yet been reported from South America, Australia, or the sparsely inhabited Antarctica. More than 75% of these cases have been reported from Saudi Arabia. 

Countries Reporting MERS infections to WHO
 
Worldwide count of MERS cases  


The earliest cases of MERS in 2012 were geographically associated with countries in the Middle East. Numerous cases in Saudi Arabia are reported as “primary cases”, autochthonous cases, which have been infected from local animal hosts. Current research indicates that camel populations on the Arabian Peninsula are a reservoir for this coronavirus, although there may be other intermediate animal hosts as well. 

The map above only shows countries that have officially reported MERS cases to WHO, not the countries where the individual cases were initially infected. A review of the published case reports indicates local infections from animal sources has only occurred in countries on or adjacent to the Arabian Peninsula as shown in the map below. Although the MERS jump from animals to human appears to be occurring only in a small geographic region in the Middle East, this coronavirus is very infectious. Many infections on the Arabian Peninsula and elsewhere are reported to have occurred from human-to-human contact or by transmission within a healthcare facility. 

Secondary cases of infections have occurred in health care facilities in Saudi Arabia, South Korea, and other countries. The large number of MERS infections among healthcare workers, healthcare facility patients, and patient visitors is a strong indication of the infectious nature of this coronavirus. According to published information, at least 240 reported MERS cases were healthcare workers.

Last year in South Korea, 185 cases of MERS were sparked by a single infected individual who traveled to South Korea from the Middle East. The infections spread primarily though hospitals. The nature of infectious transmission in health care settings is not clear. Human-to-human airborne transmission has been proposed for pneumonia-infected “superspreaders” in South Korea (link), but human-to- fomite-to-human transmission seems to occur frequently as well. 

Because of the nature of international travel and the infectious nature of this coronavirus MERS, cases have been reported from 26 countries around the world in less than four years. We can expect more MERS cases to be infected in the Middle East and to be reported from more countries in the future. 

Countries on the Arabian Peninsula reporting autochthonous cases of MERS