Tag Archives: pandemic

Risk factors for severe hand foot mouth disease in Singapore: a case control study

Hand foot mouth disease (HFMD) is a common childhood infection that can potentially lead to serious complications. The aim of this study is to identify risk factors of acquiring severe HFMD in our population.
We performed a case control study using patients admitted to our hospital from August 2004 to July 2014. Cases were patients with severe HFMD disease while controls were age-matched patients obtained from the same year, in a 2:1 ratio. Data comprising demographic characteristics, clinical symptoms and signs, and lab findings were collected. Conditional univariable logistic regression was performed to determine risk factors for severe disease.
A total of 24 cases of severe HFMD were identified and matched with 48 controls. Seventeen (70.8 %) cases had central nervous system complications. Seven (29.2 %) had cardiovascular complications without evidence of myocarditis. One patient died of encephalitis. The overall mortality of severe disease is 4 %. Evidence of hypoperfusion, seizure, altered mentation, meningeal irritation, tachycardia, tachypnea, raised absolute neutrophil count and EV-A71 (Enterovirus A71) positivity were significantly associated with a severe course of HFMD.
In managing children with HFMD, physicians should consider these factors to help identify patients at risk for severe disease.

Study shows immune response from H1N1 flu vaccine is short-lived

Scientists from the Hong Kong Polytechnic University recently conducted a study that demonstrated that people who receive the H1N1 flu vaccine have a strong immune response for just two years.

Health professionals first identified

H1N1, or swine flu, in 2009 as the virus rapidly spread and killed countless people around the world. Now, it is one of the flus that spreads every season.

Scientists previously thought that people with the H1N1 flu vaccine had strong immune responses against the virus for approximately 10 years.

The researchers, divided into teams in Australia, China and the U.S., applied a mathematical model to show a map of how the various flu strains spread from 2006 to 2015. The results showed that H1N1 followed a “skip and resurgence” pattern in both Eastern Asia and Europe. For example, the virus was estimated to strike in 2011 and 2012, but there was no outbreak until the next flu season.

The pattern is made clear with fundamental epidemiological theories. When a population has sustained immunity to the virus after the initial infection, the virus cannot outbreak like before, so it spreads elsewhere. When the immunity declines after two years, people become vulnerable to the virus again. 

WHO sends oral cholera vaccine to Iraq

The World Health Organization (WHO) recently sent 510,000 doses of the oral cholera vaccine to Iraq to help maintain the upper hand over the cholera outbreak.

Approximately 250,000 displaced persons are the target for the new oral cholera vaccine campaign. They live throughout 62 camps dedicated to internally displaced persons and refugees. The goal is to stabilize and maintain control over the cholera outbreak. Active herd immunity requires that all family members older than 1-year old receive their vaccinations.

There are now 14 governorates involved in the campaign, which is almost finished in its preparation phase. The first round of vaccines will take place through Saturday. At a minimum interval of 14 days, there will be a second round of doses which ends the vaccine campaign.

The campaign will only be successful if both doses are received. Campaign logistics, targeted social mobilization, and health education are also important parts of the strategy for success with the campaign. The supplies will be sent mostly to areas that are considered at the highest risk for the disease. These efforts are part of a strategy to stop the outbreak before it becomes large-scale.

MERS in bats..what have we actually found so far?

Only 1 MERS-CoV sequence. In 1 bat.

That’s the short answer.

Researchers found a Middle East respiratory syndrome (MERS) coronavirus (CoV) sequence in a bat. They’ve found lots of other coronavirus sequences in bats before and after that. Heaps of them. But from different CoVs. I’m not even sure how many dromedary camels (DCs) have tested positive for viral RNA or MERS-CoV-specific (as far as we know) antibodies.

One bat.

I’m deviating from the camel literature reviews for this post to go back to the paper that describes that one sequence found in that one bat. I had asked for a little more info on the paper from the authors but they are busy and I have little patience so I’ll update this post if that information comes my way. Worthy of note is that some of the specifics about which CoV came from what sample and whether that was from a live bat or old dried faecal pellets can be a bit hard to decipher.

Oh, and I have posted on this paper before by the way:

  1. MERS-CoV genetic sequences found in Taphozous perforatus bat.(22AUG2013; [6])
  2. Taphozous perforatus – The Egyptian Tomb Bat.(22AUG2013; [4])
  3. MERS-CoVs: South African bats vs Saudi Arabian bats.(23AUG2013; [3])
  4. T.perforatus MERS-CoV strain sequence, and others, online…(26AUG2013; [7])
  5. A model of MERS-CoV acquisition (ver1).(30AUG2013; [7])
  6. Is there a better smoking bat or camel?(01SEPT2013; [5])

On to this post. The paper in question comes from Professors Memish, Lipkin and crew. Good pedigree. Sadly, not an ongoing collaboration.[1] The paper, in Emerging Infectious Diseases’ November 2013 edition was entitled Middle East Respiratory Syndrome Coronavirus in Bats, Saudi Arabia.

The samples were tested by eight different PCR methods:

  1. A nested pan-CoV reverse-transcription polymerase chain reaction (RT-PCR; “pan”meaning an assay that theoretically detects all known and perhaps as-yet-undiscovered CoVs; assay called ‘PLQ’) targeting the RNA dependent RNA polymerase (RdRp)
  2. A nested pan-CoV RT-PCR assay (called WT-CoV) targeting RdRp region
  3. A semi-nested MERS-CoV RT-PCR assay (called EMC-SeqRdRp) targeting RdRp region
  4. A semi-nested MERS-CoV RT-PCR assay (called EMC-SeqN) targeting the nucleocapsid (N) region
  5. A nested pan-CoV RT-PCR assay (called NM-CoV) targeting the helicase region
  6. A nested MERS RT-PCR assay (called NM-HCOV) targeting RdRp region
  7. A semi-nested MERS RT-PCR assay (called NM-NSeq) targeting the N region
  8. A real-time RT-PCR (RT-rtPCR) assay (called upE [7]) targeting upstream of the E region
  9. An RT-rtPCR assay (called ORF1b) targeting the ORF 1b region.[7]

Samples included those from a known number of bats (some with multiple samples taken) and also samples of opportunity – bat faecal pellets that could not be matched to a bat so bat numbers could not be estimated. Samples were collected in two rounds (whether a MERS-CoV sequence or any other fragment of CoV RNA genome was identified, is indicated within brackets):

  1. The first in October 2012, shortly after the first human MERS case was identified in Bisha (the MERS-CoV variant represented by Human betacoronavirus 2c EMC/2012, complete genome, on GenBank as JX869059 [8]; 96 bats) 
  • 314 samples from which 8 (2.5% of samples; from 8 distinct bats I think) were positive for a CoV, 1 of which was MERS-CoV
  • 96 bats were tested encompassing 7 species…
    • Rhinopoma hardwickii (CoVs detected)
    • Rhinopoma microphyllum
    • Taphozous perforatus (MERS-CoV & other CoVs detected)
    • Pipistrellus kuhlii (CoVs detected)
    • Eptesicus bottae
    • Eidolon helvum (CoVs detected)
    • Rosettus aegyptiacus
    • From 29 T.perforatus bats in Bisha ruins…
      • 29 yielded throat swabs
      • 25 yielded faecal pellets (2 CoV positives; 1 yielded  a MERS-CoV sequence)
      • 8 yielded urine samples
      • 22 yielded sera
      • 10 yielded roost faeces samples (1 CoV positive)
    • From 25 E.helvum bats in Bisha town centre
      • 25 yielded throat swabs
      • 25 yielded faecal pellets (5 CoV positives)
      • 13 yielded urine samples
      • 19 yielded sera
    • From 3 R.aegypticus bats in Bisha town centre
      • 3 yielded throat swabs
      • 3 yielded faecal pellets
      • 1 yielded urine sample
      • 2 yielded sera
    • From 36 R.hardwickii bats in Naqi and Old Naqi
      • 36 yielded throat swabs
      • 35 yielded faecal pellets
      • 4 yielded urine samples
      • 15 yielded roost faeces samples
    • From 1 R.microphyllum bat in Old Naqi
      • 1 yielded a throat swab
      • 1 yielded a faecal pellet
    • From 1 E.bottae bat in Bisha ruins
      • 1 yielded throat swab
      • 1 yielded faecal pellets
      • 1 yielded urine sample
      • 32 yielded roost faces samples
    • From 1 P.kuhlii bat in Bisha ruins
      • 1 yielded throat swab
      • 1 yielded faecal pellets

The second in April  2013 (mostly faecal pellets and samples; 14  bats)

  • 689 samples, 219 (31.8% of samples) positive for a CoV
  • 14 bats and a lot of faeces not associated with bats, were tested..
    • From R.hardwickii bats in Greater Bisha area
      • 209 yielded roost faeces samples (93 CoV positives)
    • From T.perforatus bats in Bisha ruins
      • 203 yielded roost faeces samples
    • From 9 P.kuhlii bats in Greater Unaizah area
      • 9 yielded throat swabs
    • From 5 P.kuhlii bats in Greater Riyadh area
      • 5 yielded throat swabs
    • Also from P.kuhlii bats in Greater Unaizah area
      • 263 yielded roost faeces samples (126 CoV positives)

So in total, 1,003 samples were tested and 1 MERS-CoV hit was returned while 226 other coronaviruses were confirmed by sequencing. The authors attribute the big difference between finding 8 CoVs in the October 2012 bat sampling (2.5% of samples) and 219 in the April 2013 sampling (31.8% of samples) to a cold chain failure after the arrival of samples back to the United States for testing. There were also fewer roost faeces samples in the October 2012 vs. April 2013 batch (52 vs. 472). No April 2013 T.perforatus bats, from which the October 2012 MERS-CoV sequence was obtained, yielded any CoV sequences. 

And what of that 1 MERS-CoV sequence? We don’t know precisely which of the 8 PCR assays amplified it though (probably #3 or #6 above). We do know it’s very short and that it could not be confirmed by other PCR assays. 

We know that to date there is no other bat CoV, anywhere, that has a sequence that is 100% identical to a MERS-CoV variant’s sequence, except for the T.perfortaus faecal pellet sequence; not Neoromicia/PML-PHE1/RSA/2011, not Bat HKU4, Bat HKU5, Bat HKU9, and not Bat HKU10…just human and camel MERS-CoV variants. 

But it is of interest that two of these camel variants are called NRCE-HKU205 and NRCE-HKU270 from camels in Egypt. The sequence of these MERS-CoV variants in other places across the genome is relatively different from the majority of MERS-CoV variants from humans and camels. This may provide support for the existence of other different MERS-CoV variants out there, that look like the MERS-CoV we know in small parts of their genomes, but are otherwise quite distinct. And perhaps they reside in other camels outside the Arabian peninsula, or in bats. 

The T.perforatus faecal pellet sequence is a diagnostic sequence as far as we know. It most likely came from a MERS-CoV virus or a variant or ancestor we have not yet met. Or…a contaminant from someone or something else with a MERS-CoV infection of course. 

So, to all the people who continue to insist that bats are a current player in human cases of MERS, I suggest you organize some funding and do some collaborative bat testing because so far there is very limited evidence of there being a bat host for MERS-CoV. 

Just 1 MERS-CoV sequence. 

From 1 bat.


  1. http://bitly.com/1SjH1dIl
  2. Middle East Respiratory Syndrome Coronavirus in Bats, Saudi Arabia
    Memish ZA, Mishra N, Olival KJ, Fagbo SF, Kapoor V, Epstein JH, Alhakeem R, Durosinloun A, Al Asmari M, Islam A, Kapoor A, Briese T, Daszak P, Al Rabeeah AA, Lipkin WI.
  3. http://bitly.com/1SjH1dK
  4. http://bitly.com/1Q6viA1
  5. http://bitly.com/1SjGYhW
  6. http://bitly.com/1Q6viA2
  7. http://bitly.com/1SjH1dN
  8. http://1.usa.gov/1Q6vjUp
© 2013-2015 Ian M. Mackay. PhD.
This content was originally published at http://bitly.com/1Kas2vY

Health workers say turning down flu vaccines costs lives

Health professionals recently reported that when people say no to influenza vaccines, it costs others their lives.

The medical industry recommends that all people who are older than 65, are pregnant, have an underlying health problem, or work as a health care worker receive their vaccines each year.

“Every year up to 500 000 people around the globe die because of influenza complications,” Caroline Brown, World Health Organization Europe’s program manager for influenza and other respiratory pathogens, said. “About 10% of these deaths are in Europe. Many of these lives could have been saved with a simple action: getting the influenza shot. Annually, at least 30 million people in the WHO European Region decide to get vaccinated against influenza. Everyone who is over 65, has an underlying health problem, is pregnant or is a health care worker should be one of them.”

Typically, people only have mild influenza symptoms, and some people who have underlying health concerns or other health situations die from influenza.

“Far too many over 65s and people with underlying health conditions are not aware of how flu can affect their health; they are complacent and do not bother about getting vaccinated,” Brown said. “Thinking of influenza as a harmless disease is misguided, especially for these people. By getting the flu shot they could reduce the risk of complications, and this has to be done every year, not just once, as influenza viruses change.”

New vaccine provides full protection against malaria

Aduro Biotech Inc. and Protein Potential LLC recently announced that representatives will present details with pre-clinical data about a new vaccine that offers 100 percent protection against malaria in models.

The vaccine showed that the two-component vaccine regimen provided mice with 100


 protection against malaria when they were infected with a rodent malaria parasite. The success is attributed to the vaccine provoking an immune response that isolates the circumsporozoite protein antigen in Plasmodium falciparum, which is the parasite that causes the majority of malaria deaths.

“The Plasmodium falciparum parasite is able to adapt to the human host and evade its immune response very effectively and to date, the most effective subunit, recombinant vaccine prevents infection by malaria parasites in only 30 to 50 percent of those immunized,” B. Kim Lee Sim,  president and chief scientific officer of Protein Potential, said. “In order to be broadly adopted by travelers and the military, a vaccine must provide more than 80

percent protection against infection for at least six months. There is a significant need for more effective vaccines for malaria and we believe the data shared today represent a very positive first step. We look forward to IND-enabling studies and clinical testing in humans.”

The data was presented Wednesday in Philadelphia at the 64th Annual Meeting of the American Society for Tropical Medicine and Hygiene Meeting under Post Session C, or Abstract No. 1647.

Annual tuberculosis deaths drop by nearly half in 25 years

Health officials recently announced the global death rate for tuberculosis (TB) in 2015 is almost half compared to the figure from 1990.

Since 2000, the year officials established the Millennium Development Goals, an estimated 43 million lives have been saved by better diagnosis and treatment.

Despite the encouraging news,

TB is still one of the leading causes of death around the world, and 1.5 million people died from the disease in 2014. According to the


Global TB report, which was released by the World Health Organization (WHO), many of these deaths were avoidable.

To further reduce the overall burden of TB, gaps in detection and treatment need to be closed. There also needs to be novel diagnostics and better funding, new vaccines and innovative drugs.

“The report shows that TB control has had a tremendous impact in terms of lives saved and patients cured,”

WHO Director-General

Margaret Chan said. “These advances are heartening, but if the world is to end this epidemic, it needs to scale up services and, critically, invest in research.”

Superspreaders & The Korean MERS Epidemiological Report


Transmission Map – Credit Korean CDC MERS Study


# 10,659


Although it was published last month in the Korean CDC’s official journal Osong Public Health and Research Perspectives, this overview of the their large cluster of MERS cases hasn’t really garnered much attention until today, when it was detailed at length in a Korea Herald article called 83% of Korean MERS cases stemmed from 5 patients.


While the media reports focuses on the role of handful of superspreaders driving this outbreak, the Korean CDC report goes to some length to acknowledge the unique conditions common to the Korean healthcare system that appear to have amplified these chains of infection.  They list:


Prolonged duration of exposure before diagnosis and proper isolation, practice of seeking care at multiple healthcare facilities, frequent interhospital transfer, significant numbers of paid caregivers, and large numbers of contacts in large crowded tertiary referral hospitals might have contributed to multiple spreading events.

Moreover, the custom of family members and friends to accompany or visit patients, and to provide care with staying in the same hospital rooms (mostly multibed rooms) or in the crowded emergency rooms, may have also contributed to the increased number of contacts.


The full open access report, which contains a great deal of epidemiological detail on patients and chains of transmission, can be read at the link below.   After which, I’ll return with a bit more on the superspreader phenomenon.


Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015

Korea Centers for Disease Control and Prevention

Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea

Correspondence.E-mail: korea.cdc.mers@gmail.com.

Open Access DOI: http://bitly.com/1GqgPg5




The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the Republic of Korea started from the index case who developed fever after returning from the Middle East. He infected 26 cases in Hospital C, and consecutive nosocomial transmission proceeded throughout the nation. We provide an epidemiologic description of the outbreak, as of July 2015.


Epidemiological research was performed by direct interview of the confirmed patients and reviewing medical records. We also analyzed the incubation period, serial interval, the characteristics of superspreaders, and factors associated with mortality. Full genome sequence was obtained from sputum specimens of the index patient.


A total of 186 confirmed patients with MERS-CoV infection across 16 hospitals were identified in the Republic of Korea. Some 44.1% of the cases were patients exposed in hospitals, 32.8% were caregivers, and 13.4% were healthcare personnel. The most common presenting symptom was fever and chills. The estimated incubation period was 6.83 days and the serial interval was 12.5 days. A total of 83.2% of the transmission events were epidemiologically linked to five superspreaders, all of whom had pneumonia at presentation and contacted hundreds of people. Older age [odds ratio (OR) = 4.86, 95% confidence interval (CI) 1.90–12.45] and underlying respiratory disease (OR = 4.90, 95% CI 1.64–14.65) were significantly associated with mortality. Phylogenetic analysis showed that the MERS-CoV of the index case clustered closest with a recent virus from Riyadh, Saudi Arabia.


A single imported MERS-CoV infection case imposed a huge threat to public health and safety. This highlights the importance of robust preparedness and optimal infection prevention control. The lessons learned from the current outbreak will contribute to more up-to-date guidelines and global health security.

(Continue . . . )


During the SARS outbreak of 2003 – which is generally considered to have been more infectious than MERS – studies found most patients would typically only infect 1 or perhaps 2 additional people, and often none at all. 

But a small percentage of patients proved unusually efficient at spreading the disease, with some responsible for 10 or more secondary infections (see MMWR Severe Acute Respiratory Syndrome — Singapore, 2003).

By contrast, one of the Korean MERS patients (#14) is believed to have infected as many as 85 people, while two others (#1 & #16) appear to have infected more than 50 others between them.


While impressive totals, it seems unlikely that absent the crowded conditions and lax infection control procedures present in Korean hospitals, these three would have been nearly so successful in spreading the virus. 


According to Stein’s excellent 2011 review Super-spreaders in infectious diseases:


Super-spreading events are shaped by host, pathogen, and environmental factors. Often, more than one factor may be implicated in the same outbreak.


The SARS super spreader phenomenon gave rise to the 20/80 rule, that 20% of the cases were responsible for 80% of the transmission of the virus (see 2011 IJID study).  Super spreading events aren’t  limited to SARS, they have been documented with measles, HIV, TB, S. aureus, Ebola, and various STDs . . .among others (cite)


In January of 2013, in Influenza Transmission, PPEs & `Super Emitters’ we looked at research that found a five patients (19 percent) in their study  were “super-emitters” who emitted up to 32 times more flu virus than did the rest. Patients who emitted a higher concentration of influenza virus also reported greater severity of illness. 


While the host and the pathogen are important parts to the equation, environment and opportunity also play a pivotal role in exacerbating these super spreader events.


The experience has been, once the threat is recognized and rigid infection control procedures are put into place, these outbreaks can be halted.  The challenge, however, is finding ways to prevent these outbreaks, not just stop them.



Hepatitis E virus antibody prevalence in hunters from a district in Central Germany, 2013: a cross-sectional study providing evidence for the benefit of protective gloves during disembowelling of wild boars


In Germany, 17 % of the general human population have antibodies to hepatitis E virus (HEV) (recomLine HEV-IgG/IgM immunoassay [Mikrogen GmbH]). Wild boars represent an animal reservoir for HEV genotype 3, which is the common genotype in Germany. We estimated the seroprevalence among hunters with contact to wild boars to identify factors that may be associated with past or present HEV infection.
In 2013, the local veterinarian authority in a district in Central Germany attended meetings of hunters who provided blood specimens and completed a questionnaire collecting information on age, sex, hunting-related activities and consumption of wild boar meat. Specimens of wild boars were taken during drive hunts in this district during the season 2012/2013. All specimens were tested for HEV RNA and anti-HEV IgM and IgG antibodies. Log-binomial regression was used to estimate prevalence ratios (PR) for the hunters.
Of 126 hunters (median age 55; 94 % male) 21 % tested positive for anti-HEV IgG antibodies (95 % confidence interval [CI] 13–28 %) (recomWell HEV IgG assay [Mikrogen GmbH]). Anti-HEV prevalence was highest in the age group of the 70–79-year-olds (67 %; 95 % CI 39–95 %). Wild boars showed an average anti-HEV prevalence of 41 %. HEV RNA was detected in 4/22 (18 %) liver specimens and in 1/22 (4.5 %) muscle specimens. Most wild boars were tested positive for HEV RNA (3/10; 30 %) and HEV-specific antibodies (7/15; 47 %) in the southwestern part of the district. Hunters preferring this hunting ground had a lower anti-HEV prevalence when gloves were frequently used during disembowelling of wild boars compared to hunters using gloves never or infrequently (age-adjusted PR 0.12; 95 % CI 0.02–0.86).
Hunters may benefit from wearing gloves when in contact with blood or body fluids of HEV animal reservoirs. Anti-HEV prevalence among the hunters of this study did not significantly differ from that of the general population suggesting that other factors play a major role in the epidemiology of HEV in Germany.