WHO MERS Update - Oman

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Earlier this week in Oman: MOH Announces 7th MERS Case, we learned of a new Coronavirus infection, but few details were provided. Today the World Health Organization has posted an update which provides the onset dates (Dec 25th), hospitalization date (Jan 1st), and possible exposure (camels) on this 44 year old male patient. 

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

Disease outbreak news
7 January 2016

 
On 3 January 2016, the National IHR Focal Point of Oman notified WHO of 1 additional case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

Details of the case

A 44-year-old male from the North Batinah Governorate developed symptoms on 25 December and, on 1 January, was admitted to hospital. On 3 January, the patient, who has no comorbidities, tested positive for MERS-CoV. Currently, he is in stable condition in a negative pressure isolation room on a ward. The patient has a history of exposure to dromedary camels in the 14 days prior to the onset of symptoms. He has no history of exposure to other known risk factors in the 14 days prior to the onset of symptoms. Contact tracing of household contacts is ongoing for the case. Investigation of camels is also ongoing.

Globally, since September 2012, WHO has been notified of 1,626 laboratory-confirmed cases of infection with MERS-CoV, including at least 586 related deaths.

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French MOA: 67th HPAI Outbreak Across 7 Departments

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Although the number of new outbreaks continues at a much reduced rate over last month, the French MOA continues to identify sporadic new HPAI outbreaks across the nation's southwest.  

While the impacts have been relatively small, they involve five new strains of avian flu, all said to be of `European lineage', and not descended from the more dangerous Asian H5N1 virus.

Details on these viruses (HPAI H5N1, H5N2, H5N9 and LPAI H5N2, H5N3), and how they all emerged more or less simultaneously in France, have been slow to emerge.  The last DEFRA Update On France's HPAI Outbreak (Dec 24th) cited this lack of information as hampering their ability to produce a full threats analysis.

The most recent outbreak comes from the Pyrénées Atlantiques, and is the first reported there since December 20th.

- An outbreak was declared on Jan. 6, 2016 on a farm of 10,000 chickens and 4,000 ducks in the town of Gabat

Here is the latest (translated) update from the French MOA. 

What is the current situation in France? (updated on 01/07/2016 at 15h)

In total, to date, 67 of highly pathogenic avian influenza outbreaks in poultry were detected in 7 southwestern departments of France.

ANSES gave its opinion delivered on 14 December 2015, on the potential danger to humans from the avian influenza strain identified, including the results of the complete sequencing of the H5N1 strain detected in the first home in the Dordogne. She confirmed the absence for this dangerous H5N1 strain of the key markers for human.

Find below the details of homes by department below:

In the Dordogne, 13 homes

In the Landes, 28 homes

In Haute-Vienne, a home

In Gers, 10 homes

In the Pyrénées Atlantiques, 11 homes

In the Hautes-Pyrénées, 3 fireplaces

In the Lot: a home

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HK CHP: 3rd H5N6 Case In Guangdong Province In Last 2 Weeks

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The H5N6 virus was first reported 20 months ago in Southern China, and during the first 19 months China reported a total of four human infections.  While the virus has been sporadically reported in poultry in both Vietnam and Laos, no human infections have been reported outside of China.

Two weeks ago, Guangdong Province reported a human infection (see Hong Kong Notification: Fatal H7N9 Case In Guangdong Province), followed just last week with Guangdong Province Reports 2nd H5N6 Case In A Week. 

Today Hong Kong's CHP is reporting a 3rd case in neighboring Guangdong Province.  While three cases does not an epidemic make, this sudden increase in reported cases is certainly something to watch.

CHP notified of additional human case of avian influenza A(H5N6) in Guangdong

 
The Centre for Health Protection (CHP) of the Department of Health (DH) was notified of an additional human case of avian influenza A (H5N6) by the Health and Family Planning Commission of Guangdong Province today (January 7), and again urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.

It involves a man aged 25 in Longgang, Shenzhen, currently hospitalised for treatment in serious condition.?

From 2014 to date, a total of seven human cases of avian influenza A(H5N6) have been reported by the Mainland health authorities.

(Continue . . .)

It is worth noting that a couple of days ago Hong Kong announced H5N6 Detected In Dead Egret, making the 4th such detection in wild or migratory birds in the new territories.

H5N6 is one of the new reassortant viruses to come out of China since 2013, a list that includes H7N9, H5N8 (and its reassortants), and H5N6.

Of these, H7N9 has infected the most humans (roughly 700), while H5N8 - which has not infected humans - has spread the furthest afield (making it to Europe, Taiwan, Japan, and North America). 


Of these three, H5N6 is the biggest unknown, having been studied the least.  That, of course, could start to change if this virus begins to pose a serious public health threat.  For some previous studies, you may wish to revisit:

FAO-EMPRES Report On The Emergence And Threat Of H5N6

H5N6 Rising: Infecting Birds, Humans, & Even Cats

EID Journal: Influenza A(H5N6) Virus Reassortant, Southern China, 2014

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EID Journal: Accuracy Of Dengue Reporting By National Surveillance System, Brazil

Credit CDC

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When we talk about the number of dengue, malaria, tuberculosis, MERS, or avian flu cases - or of any other disease - the understanding is that the numbers we have are almost certainly incomplete, and nearly always a major under count.


As an example, during the first wave of H7N9 in China in the spring of 2013, 133 cases were identified by Chinese authorities, but estimates (see Lancet: Clinical Severity Of Human H7N9 Infection) ranged from 12 to 200 times that number. 

Our estimate that between 1500 and 27 000 symptomatic infections with avian influenza A H7N9 virus might have occurred as of May 28, 2013, is much larger than the number of laboratory-confirmed cases.

Similarly, in CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012), during a time when only 13 cases were registered by the CDC, researchers estimated there were as many as 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections.


Saudi Arabia has reported 1280 MERS infections to date, yet a seroprevalence study published last April in the Lancet (see Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study  by Drosten & Memish et al.,  projected 44 951 (95% CI 26 971–71 922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia.

The list goes on.  For every West Nile infection reported in the United States there are likely 100 that go unreported. And this is true for one of the most advanced public health systems in the world.

Imagine the disease data `gap' from countries where surveillance and reporting capabilities are far less robust or where the political will to report these types of findings is lacking. For many countries there is little `up side' to reporting diseases like MERS or avian flu, and so they simply look the other way. 

The lack of reported MERS cases in sub-Saharan Africa, or relatively low numbers of human cases in bird flu endemic regions, yields far less reassurance when you consider those factors.

All of which brings us to a new report in the EID journal that takes retrospective look at the testing and diagnosis of suspected dengue cases in Brazil (where reporting is mandatory) over a  2 year period - and finds that even among those hospitalized and tested - the number of cases is badly under reported. 

You can read the methods, materials, and math below, but the bottom line is they found that official counts likely captures less than 10% of the actual number of cases.  

Since this study period, two new mosquito-borne viruses - Chikungunya and Zika - have been introduced into the region, have already likely produced millions of additional illnesses, and will further complicate the process of diagnosis and treatment going forward.

Volume 22, Number 2—February 2016

Letter

Accuracy of Dengue Reporting by National Surveillance System, Brazil

To the Editor: Dengue is an underreported disease globally. In 2010, the World Health Organization recorded 2.2 million dengue cases (1), but models projected that the number of symptomatic dengue cases might have been as high as 96 million (2). Brazil reports more cases of dengue than any other country (1); however, the degree of dengue underreporting in Brazil is unknown. We conducted a study to evaluate dengue underreporting by Brazil’s Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação [SINAN]). 

From January 1, 2009, through December 31, 2011, we performed enhanced surveillance for acute febrile illness (AFI) in a public emergency unit in Salvador, Brazil. The surveillance team enrolled outpatients >5 years of age with measured (>37.8°C) or reported fever. Patients or their legal guardians provided written consent. The study was approved by the Oswaldo Cruz Foundation Ethics Committee, Brazil’s National Council for Ethics in Research, and the Yale Institutional Review Board.

(BIG SNIP)

We estimated that overall, there were 12 dengue cases per reported case in the community, but in months of low dengue transmission, this ratio was >17:1 (Table). Comparable results have been observed in Nicaragua, Thailand, and Cambodia (6–8). By applying the estimated multiplication factor to the study period’s mean annual incidence of 303.8 reported dengue cases/100,000 Salvador residents (9), we estimated that the actual mean annual dengue incidence for Salvador was 3,645.7 cases/100,000 residents.

We showed that dengue surveillance substantially underestimated disease burden in Brazil, especially in what are considered low-transmission periods. Dengue underreporting has been attributed to passive case detection, which fails to identify persons with dengue who do not seek health care (1). We also showed that surveillance failed to detect dengue cases among symptomatic patients seeking health care.

Novel surveillance tools, such as active syndromic surveillance and point-of-care testing, should be applied to improve estimates of dengue incidence. Furthermore, given the recent emergence of chikungunya and Zika virus in Brazil (10), improved surveillance and laboratory diagnostics are needed to avert misclassification and mismanagement of cases.

Monaise M.O. Silva, Moreno S. Rodrigues, Igor A.D. Paploski, Mariana Kikuti, Amelia M. Kasper, Jaqueline S. Cruz, Tássia L. Queiroz, Aline S. Tavares, Perla M. Santana, Josélio M.G. Araújo, Albert I. Ko, Mitermayer Galvão Reis, and Guilherme S. Ribeiro 

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NEJM: Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

Credit Wikipedia

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Over the years we've looked at a number of attempts to use convalescent plasma - donated by survivors of H5N1, H1N1, H7N9, SARS and most recently MERS and  Ebola - to treat infected patients.

Results have been mixed, but they’ve reported some success along the way.

Although in limited use today, human and animal serum therapy was used extensively during the first half of the 20th century to treat a variety of infectious diseases, including anthrax, scarlet fever, measles, tularemia, diphtheria and rabies.

While often effective, a relatively high percentage of adverse reactions (serum sickness) along with the development of effective antibiotics and drugs, has seen its use decline.

But with a new crop of deadly infectious diseases - with few, if any therapeutic options - convalescent serum is getting a new life.


Earlier this summer we saw Korea Trying Convalescent Serum Treatment For MERS  and,  while in 2011 we saw a study (see CID Journal: Convalescent Plasma Therapy For Severe H1N1) that found a substantial drop in mortality among  hospitalized patients in Hong Kong who received the treatment.


Over the past year there have been several small clinical trials using convalescent plasma conducted in Western Africa for treating Ebola and several Ebola patients in the United States received convalescent blood products as well.


While hopes have run high for this type of treatment, late yesterday the NEJM published the results of the first clinical trial of convalescent plasma therapy from the West African Ebola outbreak, and the results are disappointing:

Of 84 patients treated in this clinical trial, no statistically significant improvement in survival was noted over the control group.

There were limitations to this study, not the least of which was an inability to determine the level of antibodies in the donor plasma due to a lack of a BSL-4 lab in West Africa.  It may well be that a serum containing a higher level of antibodies would produce a better result. 


First a link to the NEJM report, then a link to Lisa Schnirring's excellent review on CIDRAP News. 

Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

Johan van Griensven, M.D., Ph.D., Tansy Edwards, M.Sc., Xavier de Lamballerie, M.D., Ph.D., Malcolm G. Semple, M.D., Ph.D., Pierre Gallian, Ph.D., Sylvain Baize, Ph.D., Peter W. Horby, M.D., Ph.D., Hervé Raoul, Ph.D., N’Faly Magassouba, Ph.D., Annick Antierens, M.D., Carolyn Lomas, M.D., Ousmane Faye, Ph.D., Amadou A. Sall, Ph.D., Katrien Fransen, M.Sc., Jozefien Buyze, Ph.D., Raffaella Ravinetto, Pharm.D., Pierre Tiberghien, M.D., Ph.D., Yves Claeys, M.Sc., Maaike De Crop, M.Sc., Lutgarde Lynen, M.D., Ph.D., Elhadj Ibrahima Bah, M.D., Peter G. Smith, D.Sc., Alexandre Delamou, M.D., Anja De Weggheleire, M.D., and Nyankoye Haba, M.Sc. for the Ebola-Tx Consortium

N Engl J Med 2016; 374:33-42January 7, 2016DOI: 10.1056/NEJMoa1511812

Abstract
Results

A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, −7 percentage points; 95% confidence interval [CI], −18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, −3 percentage points; 95% CI, −13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.

From CIDRAP News:

Ebola studies pan convalescent plasma, find hope for malaria regimen

Lisa Schnirring | News Editor | CIDRAP News
 | Jan 06, 2016

In a pair of new studies on Ebola treatment, a trial of convalescent plasma at a treatment center in Guinea didn't find a significant survival benefit, while patients at a Liberian treatment unit unexpectedly seemed to benefit from a malaria drug combo clinicians gave in response to a drug shortage.


Both studies were published today in the latest online edition of the New England Journal of Medicine (NEJM), alongside a shorter report on gender differences during the Ebola outbreak, such as higher survival rates in female patients.

(Continue . . . )

While this particular trial did not produce the desired results, the idea of using convalescent serum to treat emerging infectious diseases like MERS, avian flu, and Ebola is far from dead. For some earlier blogs on the use of convalescent therapy, you may wish to revisit:

Int J Infect Dis: Convalescent Plasma Treatment Of An H7N9 Patient In China

JVI: Investigating Dromedary Immune Serum As MERS-CoV Treatment

MERS-CoV: The Long Road To A Pharmacological Solution

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RESEP KETAN SUSU TANSU KEJU COKLAT

Resep Ketan Susu (Tansu) - Kita banyak mengenal beragam penganan tradisional dari olahan beras ketan, baik dibuat tepung sebagai bahan aneka kue atau diolah menjadi ketan serundeng, srikaya maupun kinca durian hingga jajanan yang lagi hits saat ini adalah ketan susu biasa disingkat dengan tansu.

Tansu sendiri juga terdapat variasi dalam cara menghidangkannya, mulai disiram susu hingga aneka topping yang membuatnya menarik perhatian, bahkan bisa disajikan dengan parutan es untuk sensasi dingin yang menyegarkan.

Ketan kukus yang pulen bersama legitnya susu kental manis ternyata menjadi perpaduan cita rasa enak yang bikin ketagihan, apalagi ditambah aneka topping seperti keju dan coklat. Cara membuat tansu yang mudah dan praktis bisa kita olah sendiri di rumah dengan variasi topping sesuai dengan yang diinginkan.

Persiapan Bahan Membuat Ketan Susu

• 500 gram beras ketan direndam minimal 2 jam
• 300 ml santan kental dari 1 butir kelapa parut
• 1 sdt garam
• 2 lembar daun pandan

Aneka topping :

• susu kental manis
• keju cheddar diparut
• coklat batang diparut atau dilelehkan
• meses coklat dan warna-warni
• kelapa parut atau aneka topping lainnya

Cara Membuat Ketan Susu

1. Rendam beras ketan minimal selama 2 jam, kemudian kukus beras ketan bersama 2 lembar daun pandan selama 15 menit. Sementara itu, masak santan dan garam sambil terus diaduk hingga mendidih.
2. Angkat ketan dan masukkan dalam sebuah wadah lalu tuangkan juga santan kental yang sudah dididihkan tadi, aduk rata hingga santan menyerap ke dalam ketan (gunakan sendok kayu agar tidak panas).
3. Apabila sudah rata dan menyerap, kukus kembali ketan tersebut selama 20 menit lalu matikan api dan biarkan hangat.
4. Bentuk ketan menggunakan cetakan atau bisa langsung dituang dalam mangkuk/piring saji, sirami dengan susu kental manis, kemudian beri aneka topping sesuai selera serta siap untuk disajikan.

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HK CHP Notified Of 1 H7N9 Case In Jieyang, Guangdong Province

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Hong Kong's CHP has been notified by adjacent Guangdong province authorities of another H7N9 case, this time in Jieyang.   Details are scant, with no indication of her likely exposure, although the vast majority of cases reported thus far are believed to have contracted the virus through direct contact with infected birds.


Over the course of the past four winters in China, H7N9 cases generally begin to rise in January and peak between February and April.

CHP closely monitors additional human case of avian influenza A(H7N9) in Mainland

The Centre for Health Protection (CHP) of the Department of Health (DH) is today (January 6) closely monitoring an additional human case of avian influenza A(H7N9) in the Mainland, and again urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.

According to the Health and Family Planning Commission of Guangdong Province, the patient is a 58-year-old woman in Jieyang. She is now hospitalised for treatment and in critical condition.

From 2013 to date, 667 human cases of avian influenza A(H7N9) have been reported by the Mainland health authorities.

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