Thursday, August 25, 2016

EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016

Credit CDC


One of the realities of disease surveillance is that the number of cases `officially' reported by public health agencies is assumed to represent only a fraction of the total number of cases in a populaton.

Factors affecting undercounts can include the percentage of mild cases (unlikely to be tested), the availability and quality of local medical care, the sensitivity of lab tests, the amount of background noise from similar diseases, and whether public health is actively `looking' for a specific disease. 

It is probably fair to say a novel flu infection is far more likely to be detected (and reported) by Hong Kong authorities than by those from rural Mainland China, Cambodia, or Central Africa.

We've looked at these challenges before, and while they may be more pronounced in low resource regions of the world, even our own CDC can't tell us how many people get the flu, or Lyme Disease, or West Nile Fever each year in the United States. 

Trying to get a handle on the burden and spread of emerging infectious diseases - particularly those with some pandemic potential - is always a priority, and in recent years the MERS Coronavirus has been very near the top of that list.

We've previously looked at estimates that have suggested the number of MERS cases far exceeds the numbers reported by countries on the Arabian Peninsula.   

The expectation is that many of these `uncounted' cases were mild, and were therefore never hospitalized or tested. Complicating matters, the persistence of antibodies in `mild' MERS-CoV infections appears limited, so the sensitivity of seroprevalence studies may be limited as well.

We've a new study, published today in the EID Journal, that makes another attempt to estimate the number of severe MERS-CoV cases in the Middle East since 2012, based on a small number of infected travelers from the region.

The authors estimate 3,250 (95% CI 1,300–6,600) severe MERS cases have occurred since 2012 on the Arabian peninsula.  

In other words, their estimate of severe cases is 2.3-times higher than the total number of all laboratory-confirmed cases combined (including mild and asymptomatic) cases in the region.

Granted, their results are based on a small (n=11) number of infected travelers, extrapolated out across the population of the region. Still, their multipliers are actually fairly low, compared to others we've seen for MERS and novel influenzas.

I've included the abstract and excerpts from the discussion, but follow the link below to read the report in its entirety.

Estimation of Severe Middle East Respiratory Syndrome Cases in the Middle East, 2012–2016 

Justin J. O’Hagan Comments to Author , Cristina Carias, Jessica M. Rudd, Huong T. Pham, Yonat Haber, Nicki Pesik, Martin S. Cetron, Manoj Gambhir, Susan I. Gerber, and David L. Swerdlow


Most Middle East respiratory syndrome cases have been recorded in the Middle East. Using data from travelers to this region, we estimated 3,250 (95% CI 1,300–6,600) severe MERS cases occurred in the Middle East during September 2012–January 2016, which is 2.3-fold higher than the number of laboratory-confirmed cases recorded in these countries.

Middle East respiratory syndrome (MERS), caused by MERS coronavirus (MERS-CoV), was first recognized in September 2012 (1). From that time until January 2016, >1,600 cases were laboratory-confirmed, and ≈600 deaths have been attributed to the virus (2). Cases have been detected among persons who traveled from the Middle East to 16 countries, and a MERS-CoV outbreak in South Korea introduced by a traveler caused >100 cases (3).

Estimates of the epidemic size in the Middle East are required to understand the level of MERS-CoV circulation and the likelihood of MERS-CoV exportations. However, these estimates have not been calculated for >2 years, during which time the number of recorded cases has increased by >15 times (2,4). We used data from travelers to this region to update estimates of severe MERS cases in the Middle East.

Our estimates were based on a small sample size (11 travel-associated cases) and assumed that travelers and residents of the Middle East had similar infection risks. Our sensitivity analyses demonstrated that results are sensitive to travelers’ estimated lengths of stay and also showed that estimates of the epidemic size that incorporated data from lower-income countries were 60% lower than estimates obtained by using data from high-income countries alone. This finding implies different levels of case detection across travelers’ home countries or different MERS-CoV exposure between visitors of different nationalities. Additional data (e.g., larger sample size; travel volume; and lengths of stay stratified by age and immigration status, frequencies of testing and contact with camels) could provide further estimates.

Public health officials are concerned about MERS-CoV, both in the source countries and from exported cases in persons who can seed outbreaks elsewhere (9,11). By better estimating the epidemic size in the Middle East, our results can help guide public health preparedness efforts in source countries and contribute to projections of the number of cases that could occur among travelers (9,11–13).
Dr. O’Hagan is an epidemiologist and transmission modeler at Centers for Disease Control and Prevention. His interests include the combined use of mathematical modeling and epidemiologic studies to better understand the effect of infectious disease risk factors and interventions.

NEJM: Prolonged Shedding of Zika Virus Associated with Congenital Infection


Late yesterday the NEJM published a correspondence from doctors at Santa Casa de Misericordia and researchers from the University of São Paulo describing a child born last January - without visible neurological defects - but carrying an active Zika infection, who went on to develop severe neurological symptoms by six months of age.

The Zika virus infection continued to be detected in the child's system for two months post delivery.  Despite that finding, doctors described him at 54 days of age as having `no obvious illness or evidence of any immunocompromising condition'.

By six months, however, his condition had deteriorated, developing neuropsychomotor developmental delay, global hypertonia, and spastic hemiplegia.

This correspondence raises serious questions for which there are currently few good answers.  It is unknown whether this child's neurological damage occurred while still in the womb, or after the child was born.

This also raises concerns that infants - whose brains continue to develop in the months following delivery - might be at risk of neurological damage if infected shortly after birth. 

And this also raises questions about the true status of some of the `discarded' cases reported by Brazil's MOH as not meeting the requirement for microcephaly at birth.

Of note, Brazil's MOH doesn't appear to have updated those numbers since late-July.

Two links.   First, to the NEJM correspondence, and then a link to the press release from the University of Sao Paulo Scientific Outreach Unit.


Prolonged Shedding of Zika Virus Associated with Congenital Infection
August 24, 2016DOI: 10.1056/NEJMc1607583

    To the Editor:

    The presence of Zika virus (ZIKV) infection has been associated with microcephaly in multiple studies,1-3 although little is known about ZIKV shedding in congenitally infected infants. We report a case of a newborn who had continued viremia with ZIKV for at least 67 days after birth.

    On January 2, 2016, a male child was born with microcephaly in São Paulo, Brazil, at 40 weeks of gestation to a mother who had reported having symptoms associated with ZIKV infection during the 26th week of pregnancy. At birth, the weight was 3095 g, the length 48 cm, and the head circumference 32.5 cm. The neurologic abnormality was not detected during an initial physical examination.

(Continue . . . )
 Public Release: 

Zika virus detected in newborn until 2 months after birth

The case is reported by researchers from the University of São Paulo and the Santa Casa de São Paulo hospital on the website of The New England Journal of Medicine on Wednesday, July 24

University of Sao Paulo Scientific Outreach Unit

Physicians at the Santa Casa de Misericordia and researchers from the Institute of Biomedical Sciences at University of São Paulo describe the case of a baby born with Zika infection in January 2016, who remained infected by the virus even two months and one week after birth. 

This is the first reported case of prolonged Zika infection in newborns. 

The baby was born with 3 kg, 48 cm in length and the head perimeter of 32.5 cm, slightly smaller than the 33cm recommended by WHO. At first, doctors did not detect signs of any neurological abnormality: the analysis of the cerebrospinal fluid and the exams of the eyes and the ears showed normal results. Images taken by MRI, though, showed a reduced brain parenchyma, foci of calcification in the subcortical area and compensatory dilation of the supraventricular system. These results and the fact that the mother's symptoms of Zika infection appeared in the seventh month of pregnancy - when it is thought that the damage to the fetus is less severe than when the infection occurs earlier in pregnancy - led to a first diagnosis of mild microcephaly. 

After 54 days of life, the baby showed no illness or neurological impairment. However, at six months, doctors noticed delayed psychomotor development, with an abnormal increase in the muscle tone and reduced muscle stretchability. Also, spastic hemiplegia (cerebral palsy) was detected. These characteristics imply a more serious condition than diagnosed before.

The baby's father traveled to the Northeast of Brazil and showed symptoms of Zika before his wife. It may indicate that the virus could have been sexually transmitted. Serological tests confirmed the infection in both parents.

(Continue . . . )

Wednesday, August 24, 2016

J. Ag. Biotech: Characteristics of Two Avian H3N8 Viruses - China


Although we keep watch on a large number of influenza subtypes in the wild, the H3N8 virus gets extra attention because it is believed to have sparked human pandemic at the turn of the last century, variants of it have become endemic in horses and dogs over the past few decades, and it persists in the wild as an avian virus.

It doesn't preclude seeing our seeing an H7N9 or H5N1 pandemic, but over the past 130 years we've only seen human influenza epidemics caused by H1, H2, and H3 subtypes, leading some scientists to wonder:

Are Influenza Pandemic Viruses Members Of An Exclusive Club?

While the jury is still out on that, it is worth noting that H3N8 has also been detected in camels and in November of 2011, we saw a die off of seals in New England that was eventually determined to be due to a Mammalian Adapted avian H3N8 virus.

Just last month we saw PLoS One: Evidence of Subtype H3N8 Influenza Virus Infection among Pet Dogs in China, although it wasn't clear whether North American canine H3N8 had been imported into China, or if avian (or possibly equine) H3N8 jumped species there, as we saw with avian H3N2 virus in Korea a decade ago.

Since we don't get a lot of surveillance data out of China, the following report in the Journal of Agricultural Biotechnology where researchers characterized two H3N8 viruses collected from ducks in Guizhou province, is of interest.

First the abstract, then I'll return with a bit more.

Biological Characteristic of Two H3N8 Subtype Avian influenza viruses(AIV)

CUI Peng-Fei;LU Kun-Peng;CHEN Si;XIAO Li;GUAN Li-Zheng;DENG Guo-Hua;CHEN Hua-Lan;

H3N8 influenza viruses have a broad host range, which are commonly found in wild birds and domestic poultry, and have been isolated from some mammals. Moreover, H3N8 influenza viruses have the ability to occasionally infect and transmit among other species.

In recent years, avian influenza surveillance data indicates that the number of isolated H3N8 subtype Avian influenza virus(AIV) has a tendency to increase year by year.
To understand the biological characteristics of the H3N8 AIV, two H3N8 viruses(A/duck/Guizhou/S1092/2013(H3N8)(DK/GZ/S1092/2013) and A/duck/Guizhou/S1145/2013(H3N8)(DK/GZ/S1145/2013)) were isolated from Guizhou province at 2013 for phylogenetic analysis, infectious experiment in mice (Mus musculus) and receptor-binding specificity analysis.

The phylogenetic analysis results indicated that the 2 viruses displayed obviously genetic diversity, and all genome of the viruses had different origins except for hemagglutinin(HA) gene.
The mice study suggested that the 2 viruses could effectively replicate in the lung and nasal turbinate of mice without pre-adaptation. The virus titers of DK/GZ/S1092/2013 in lung and nasal turbinate were 4.00 and 5.50 log10EID50/m L(EID50: Fifty percent embryo infection doses), respectively, and the virus titers of DK/GZ/S1145/2013 in lung and nasal turbinate were 4.25 and 3.58 log10EID50/m L, respectively.

In addition, the 2 H3N8 influenza viruses displayed low virulence to mice, and mice did not display obvious clinical symptoms after infection with the viruses.
In the observation period, DK/GZ/S1092/2013 only caused1.8% bodyweight loss and DK/GZ/S1145/2013 only caused 0.8% bodyweight loss. The receptor- binding specificity analysis demonstrated that the 2 viruses had the ability to bind both sialic acid(SA) α2,3- Gal receptor from poultry and SA α2,6- Gal receptor from human, which indicated that the 2 H3N8 subtype AIV posed potential threat to infect human.

In conclusion, this study systematically researched the biological characteristic of the 2 H3N8 subtype AIV, and the results indicated that the H3N8 influenza viruses posed potential risk to infect mammals. This study plays an important role in the prevention and control of H3N8 subtype AIV.

While both viruses replicated (with only low virulence) in mice, they also showed the ability to bind to both avian (α2,3) and mammalian (α2,6) receptor cells.

This is significant because purely Avian adapted flu viruses bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds.

The ability to bind to human α2-6 receptor cells - which line the human upper respiratory tract - is considered the single biggest obstacle that an avian flu virus must overcome in order to successfully jump to humans.

But it isn’t the only one. 

Avian viruses also typically replicate at the higher temperatures found in birds, and would need to adapt to the lower (roughly 33C) temps found in the upper human respiratory tract.

There are undoubtedly other obstacles – some we know about, others we don’t – that must come in proper sync to allow an avian virus to become a `humanized' virus. 

Today's report suggests that the avian H3N8 viruses these researchers examined have gained at least one of the traits that could someday make them a potential human health risk.

Sci Rpts: Characterization of Avian H7N2 in Wild Birds and Pikas in Qinghai-Tibet Plateau Area

Credit Wikipedia


While avian influenza is primarily a disease of birds, and only occasionally spills over into humans, the role played by small mammals in its ecology and evolution remains only partially explored. 

Last May, in Report: Skunks and Rabbits Can Catch And Shed Avian Flu, we looked at research by Dr. Jeffrey root on infection and shedding of avian flu by peridomestic animals. 

And last year, in Taking HPAI To The Bank (Vole), we looked at research showing voles were not only susceptible to two types of avian flu viruses (H5N1 & H7N1), were able to carry the virus asymptomatically, shed the virus in copious amounts, and could pass on the virus to naïve co-housed sentinel voles.

Small mammals are frequently found roaming around live bird markets, on poultry farms, and drinking from the same water sources in the wild as migratory birds. All places where they could conceivably either pick up - or spread - avian flu viruses.

Asymptomatic carriage by small mammals could also allow these avian viruses to pick up additional mammalian adaptations, which could increase their host range and potentially, their threat to public health.

One species that keeps coming up in the literature is the plateau pika - a small burrowing rabbit-like mammal - found in Tibet and China.

In 2009 a study in the Journal of Virology found that Wild Pikas were Natural Hosts of H5N1 Avian Influenza Virus in Qinghai, China.  While in 2014 LPAI H9N2 was found in Pikas at Qinghai Lake, China.

Qinghai lake is somewhat famous as the site of several major avian flu reassortments and large die offs of birds. In 2005 H5N1 clade 2.2 appeared there, followed four years later by clade 2.3.2 (see 2011 EID Journal New Avian Influenza Virus (H5N1) in Wild Birds, Qinghai, China).

All of which brings us to a new report in Nature which finds  phylogenetically similar avian H7N2 viruses in wild birds and pikas in the Qinghai lake region, further suggesting a role of pikas in the ecology of avian influenza viruses. 

Shuo Su, Gang Xing, Junhua Wang, Zengkui Li, Jinyan Gu, Liping Yan, Jing Lei, Senlin Ji, Boli Hu, Gregory C. Gray, Yan Yan & Jiyong Zhou


Qinghai Lake is a major migrating bird breeding site that has experienced several recent highly pathogenic avian influenza virus (HPAIV) epizootics. From 2006 to 2009 we studied Qinghai’s wild birds and pikas for evidence of AIV infections. 

We sampled 941 healthy wild animals and isolated seventeen H7N2 viruses (eight from pikas and nine from wild birds). The H7N2 viruses were phylogenetically closely related to each other and to viruses isolated in Hong Kong in the 1970s. We determined the pathogenicity of the H7N2 viruses by infecting chickens and mice. 

Our results suggest that pikas might play an important role in the ecology of AIVs, acting as intermediate hosts in which viruses become more adapted to mammals. Our findings of AI infection in pikas are consistent with previous observations and raise the possibility that pikas might play a previously unrecognized role in the ecology of AIVs peridomestic aquatic environments.
Su, S. et al. Characterization of H7N2 Avian Influenza Virus in Wild Birds and Pikas in Qinghai-Tibet Plateau Area. Sci. Rep. 6, 30974; doi: 10.1038/srep30974 (2016).

These H7N2 viruses were LPAI, and not related to the H7N9 viruses that emerged in China in 2013. 

As the authors point out, it is a bit of a mystery how these H7N2 viruses could have become enzootic in this region yet we've seen no reports of their detection in domestic poultry.

They write:
Perhaps this is due to limited AIV surveillance among poultry in this area. It seems logical that if AIVs are enzootic among the many wild birds in the Qinghai-Tibet plateau area, especially around the Qinghai Lake area, infections in other wild and domestic animals are likely occurring but unrecognized. More extensive AIV surveillance among Qinghai Lakes migrating birds, wild mammals, and domestic animals seems imperative.

More evidence to suggest that what we don't know about avian flu could still fill volumes.

Strong Quake & Aftershocks Hit Italy



A  very shallow, strong M6.2 earthquake struck central Italy overnight, heavily damaging several small towns, and was felt (see map above) widely across the region.   The initial quake has been followed by more than 100 aftershocks, with several of them in the 5.0-5.5 magnitude range.

MagnitudeMw 6.2
Date time2016-08-24 01:36:32.3 UTC
Location42.71 N ; 13.22 E
Depth4 km
Distances109 km NE of Roma, Italy / pop: 2,563,241 / local time: 03:36:32.3 2016-08-24
43 km N of L’Aquila, Italy / pop: 68,503 / local time: 03:36:32.3 2016-08-24
14 km E of Maltignano, Italy / pop: 2,514 / local time: 03:36:32.3 2016-08-24

Rescue efforts are underway, with reportedly many people trapped in the rubble.  CNN is reporting at least 21 deaths, although that number could certainly go higher.

While we tend to think of the Pacific's ring of fire and central  Asia when it comes to seismic activity, much of Europe is vulnerable as well.  Below you’ll find the 2013 SHARE (Seismic Hazard Harmonization in Europe) seismic hazard map.

In 2011, in A Look At Europe’s Seismic Risks, we took a look at some of the most devastating earthquakes to strike Europe over the past 700 years, including the quake that leveled the Swiss town of Basel in 1356 and the horrific earthquake and tsunami that struck Portugal in 1755 on November 1st (All Saint’s Day).

Also in 2011 (see UNDP: Supercities At Seismic Risk) we saw a report that stated that half of the world’s supercities (urban areas with 2 million – 15 million inhabitants) are at high risk for seismic activity.

In January of 2012 (see UN Agency Warns On Global Seismic Risks), the United Nations International Strategy For Disaster Reduction (UNIDSR.Org) issued a cautionary warning about ignoring seismic threats.
Last night's tragedy comes just hours before Germany is expected to announce what role their citizens should play in preparing for disasters (natural or otherwise).  

Three days ago, in German Govt. Contemplates Mandating Personal Preparedness, we looked at a proposal that all German households have 10 days worth of emergency supplies in the event of a national emergency.

Last night’s temblor is a reminder that disasters can strike anytime, and anywhere, and preparedness isn’t just for those who live on major fault lines or in the historic path of hurricanes and typhoons. 

Every home should have no less than a 72-hour supply of emergency food and water, a good first aid kit, emergency lighting (not candles!), a battery operated radio, and a disaster plan.
And three days should be considered a minimum.  Ten days is a far better goal. 

Starting next week FEMA and will spend the month of September promoting National Preparedness Month through community events, drills, and exercises.

Because in any emergency, the advantage goes to those who were prepared.

Tuesday, August 23, 2016

Fla Governor's Office: One Non-Travel Related Zika Case In Pinellas County


For those unfamiliar with the geography, Pinellas county is located on the west coast of Florida, makes up the western shore of Tampa Bay, and is the home of St. Petersburg, Clearwater, and Largo.
It is roughly 200 miles to the North and West of Miami-Dade county, where local Zika transmission has been reported for the past month.

Additionally, four more non-travel related cases are reported from the Wynwood area in Miami.   This from the Governor's office:


On August 23, 2016, in News Releases, by Staff

CLEARWATER, Fla. – Today, Governor Rick Scott announced that the Florida Department of Health (DOH) is investigating five new non-travel related cases of Zika. One of these cases is in Pinellas County and four cases are in the impacted area in Wynwood. DOH has begun door-to-door outreach and sampling in Pinellas County and mosquito abatement and reduction activities are also taking place. DOH still believes ongoing active transmission is only taking place within the small identified areas in Wynwood and Miami Beach in Miami-Dade County. More details will be announced when the Pinellas County investigation concludes.

Governor Scott also announced that following further testing and no evidence of continued active transmission, DOH is able to clear nearly the entire perimeter of the area in Wynwood. The total area that DOH has cleared in Wynwood is now 76 blocks (see maps below). This makes the impacted area in Wynwood now approximately 0.5 square mile. The total number of local transmissions of Zika in Florida is 42.

Governor Rick Scott said, “Today, we learned that the Florida Department of Health is investigating one new individual with non-travel related Zika in Pinellas County. While this investigation is ongoing, DOH still believes that ongoing active transmissions are only occurring in the two previously identified areas in Wynwood and Miami Beach. As we’ve seen in Wynwood, our aggressive mosquito control and public education efforts are working which is why DOH was able to clear a significant area in Wynwood today, bringing the total cleared area to 76 blocks. This means that we have now cleared half of the area in Wynwood where we believe ongoing active transmission of Zika is occurring. This is great news and we hope to continue reducing this area.

“In Pinellas County, the Department of Health and Pinellas County Mosquito Control are already working together and have begun aggressive spraying and mosquito abatement efforts. Any pregnant woman who would like to receive a free Zika test or a Zika prevention kit should contact the Florida Department of Health in Pinellas County. We remain fully committed to ensuring that every county has all of the resources they need to combat this virus and stand ready to assist residents and visitors in the impacted communities.”

Any Pinellas County resident who would like to request mosquito control services for their residence or business should contact Pinellas County Mosquito Control HERE.

Click HERE to see a detailed timeline of actions taken by Governor Scott to combat the Zika virus in Florida.