Thursday, May 05, 2016

WHO: Zika Sitrep - May 5th


The World Health Organization has posted its weekly Sitrep on Zika, Microcephaly and Guillain-Barré syndrome. I've only posted the summary, follow the link to download and read the full 6-page PDF report. 

Zika situation report

5 May 2016

Zika virus, Microcephaly and Guillain-Barré syndrome

  • Mosquito-borne transmission:
    • 44 countries are experiencing a first outbreak of Zika virus since 2015, with no previous evidence of circulation, and with ongoing transmission by mosquitoes.
    • 13 countries reported evidence of Zika virus transmission between 2007 and 2014, with ongoing transmission.
    • Four countries or territories have reported an outbreak since 2015 that is now over: Cook Islands, French Polynesia, ISLA DE PASCUA – Chile and YAP (Federated States of Micronesia).
  • Person-to-person transmission:
    • Nine countries have reported evidence of person-to-person transmission of Zika virus, probably via a sexual route.
  • In the week to 4 May 2016, Peru and Saint Barthélemy are the latest country and territory to report mosquito-borne Zika virus transmission.
  • Microcephaly and other fetal malformations potentially associated with Zika virus infection or suggestive of congenital infection have been reported in six countries or territories. Two cases, each linked to a stay in Brazil, were detected in Slovenia and the United States of America. One additional case, linked to a brief stay in Mexico, Guatemala and Belize, was detected in a pregnant woman in the United States of America. A case in Marshall Islands was also recently reported and is awaiting confirmation.
  • In the context of Zika virus circulation, 13 countries and territories worldwide have reported an increased incidence of Guillain-Barré syndrome (GBS) and/or laboratory confirmation of a Zika virus infection among GBS cases.
  • Based on research to date, there is scientific consensus that Zika virus is a cause of microcephaly and GBS.
  • The global prevention and control strategy launched by the World Health Organization (WHO) as a Strategic Response Framework encompasses surveillance, response activities and research. Key interventions are being undertaken jointly by WHO and international, regional and national partners in response to this public health emergency.
  • Incident managers from the six WHO Regional Offices and headquarters, as well as relevant technical and support staff, are meeting in Washington D.C., USA on 4 and 5 May 2016 to review past and ongoing activities, to discuss key lessons and to develop a strategy for future action to ensure that the response collaboration continues to work effectively.
  • WHO has developed new advice and information on diverse topics in the context of Zika virus. WHO’s latest information materials, news and resources to support risk communication, and community engagement are available online.

Eurosurveillance: Susceptibility of Italian Aedes Albopictus To Zika Virus



The Aedes aegypti mosquito is believed to be the primary vector of the Zika virus, but other Aedes species - including the Aedes albopictus - are believed to have some transmission potential as well.  While laboratory experiments have shown the albopictus can be infected with the Zika virus, its competence as a vector remains unknown.

This is important to both North America and Europe since the Ae. albopictus is far better distributed than the Ae. aegypti  (see map above). 

Today the ECDC Journal Eurosurveillance has a report that looks at the competency of Italian Aedes albopictus mosquitoes compared to the Aedes aegypti mosquito in carrying the Zika virus.

They also looked at the potential for transovarial  or vertical transmission of the Zika virus - where the female lays infected eggs -  allowing new generations of mosquitoes to be born already carrying the disease.

While they determined the Italian Aedes albopictus was a competent vector for Zika, they found it far less so than the Aedes aegypti.  They also found no indication of transovarial transmission by either species.

While encouraging news, It is always possible that Aedes albopictus mosquitoes from other parts of the world could be a more competent vector than the Italian variety. We also don't know just how efficient a vector needs to be in order to sustain an epidemic in a target rich urban environment. 

The authors caution:

However, the epidemic potential and the capacity to cause long chains of transmission depends on a series of factors such as the abundance of the mosquito population, the density of the human population, feeding host preferences, biting rates and environmental conditions. High mosquito density, day-biting activity, opportunistic feeding behaviour and climatic and environmental adaptability can affect the efficiency of Ae. albopictus as a vector, favouring its primary role in epidemics, also in the presence of a limited vector competence [15].

The full Rapid Communication is worth reading, so follow the link.  I've only posted some excerpts below:

Eurosurveillance, Volume 21, Issue 18, 05 May 2016

Rapid communication 

Citation style for this article: Di Luca M, Severini F, Toma L, Boccolini D, Romi R, Remoli ME, Sabbatucci M, Rizzo C, Venturi G, RezzaG, Fortuna C. Experimental studies of susceptibility of Italian Aedes albopictus to Zika virus. Euro Surveill. 2016;21(18):pii=30223. DOI:

Received:22 April 2016; Accepted:04 May 2016

Saudi MOH Announces 1 Asymptomatic MERS Case In Riyadh

# 11,344

Although sporadic asymptomatic MERS cases have been detected via contact tracing and prospective testing during outbreaks, we really don't have a good handle on their incidence in the larger community.

Like most viral infections, MERS-CoV can produce a wide range of symptomology, and many mild cases likely go undiagnosed.

In April we saw two asymptomatic cases announced by the Saudi MOH, while in March they reported three.   Today the MOH reports a new asymptomatic case - a household contact of a symptomatic case - in Riyadh.

For the vast majority of community acquired cases, the source of infection remains a mystery.  Asymptomatic carriage and transmission offers one plausible, if not proven, explanation (see Study: Possible Transmission From Asymptomatic MERS-CoV Case).

Last November's EID Journal: Risk Factors For Primary MERS-CoV Infection, Saudi Arabia found that camel exposure was a significant factor for infection, but that many community cases had no obvious exposure risk.  They wrote:

Other potential explanations of MERS-CoV illness in primary case-patients who did not have direct contact with dromedaries include unrecognized community exposure to patients with mild or subclinical MERS-CoV infection or exposure to other sources of primary MERS-CoV infection not ascertained in our study.

The World Health Organization interim guidance on the Management of asymptomatic persons who are RTPCR positive for Middle East respiratory syndrome coronavirus (MERS-CoV) Interim Guidance, calls for asymptomatic PCR-positive MERS cases to be isolated, and for their contacts be monitored as well.
But up until last fall, and contrary to WHO advice, the Saudi MOH didn't treat PCR positive MERS-CoV cases as `real cases’ unless they were symptomatic.

Now that the Saudis are taking asymptomatic cases more seriously, we have a better chance of discovering what role they may play.  For more on the possibility of there being some limited `stealth’ transmission of the virus in the community see The Community Transmission Mystery.

Brazilian MOH: Weekly Microcephaly Report - May 4th


The Brazilian MOH Microcephaly report is out, albeit about 24 hours later than usual, and this week we see the number of new cases placed under investigation has increased by 115 after hitting a low of only 78 in the last report.
Both numbers are a fraction of the numbers we were seeing added only a couple of months ago. While the cause of this drop is unknown, a few possible factors include:
  • In March Brazil adopted a more stringent definition for microcephaly 
  • Much of Brazil was still in their winter dry season (Aug-Dec) - with presumably fewer mosquitoes - when this week's birth cohort were in their 1st & early 2nd trimester
  • Brazil's mosquito control efforts and mosquito protection awareness efforts were starting to ramp up during that time period as well

Meanwhile, upon further investigation, another 172 have been discarded as not meeting the criteria for microcephaly, while 73 were confirmed. The total remaining under investigation sits at 3,580.
While microcephaly is the most visibly apparent congenital defect, we've been warned by CDC, NIH, and WHO that maternal Zika infection may produce other, less obvious neurological deficits in developing fetuses.  

Meaning it may be months or even years before we know whether any of these `discarded' cases will go on to display other congenital defects

Registration Date: 05/04/2016 16:05:18 the amended 05/04/2016 16:05:18 the
The new epidemiological bulletin of the Ministry of Health disclosed on Wednesday (4), points out that, until 30 April, were confirmed 1,271 cases of microcefaliae other nervous system disorders, suggestive of congenital infection in all país. No total of 7,343 suspected cases have been reported since the start of the investigation in October 2015, and 2,492 were discarded. Other 3,580 are under investigation. The report meets weekly information submitted by state health departments.
Of the confirmed cases, 203 had laboratory confirmation to the Zika virus. However, the Ministry of Health points out that this figure does not represent adequately the total number of cases related to the virus. That is, the folder considers that there was infection Zika most of the mothers who had babies with a final diagnosis of microcephaly. In Brazil, the 1,271 confirmed cases occurred in 470 municipalities located in 25 states of the federation.
Microcephaly was confirmed in the states of Alagoas, Bahia, Ceará, Maranhão, Paraíba, Pernambuco, Piauí, Rio Grande do Norte, Sergipe, Espírito Santo, Minas Gerais, Rio de Janeiro, Amapá, Amazonas, Pará, Rondônia, Roraima, Tocantins, Distrito Federal, Goiás, Mato Grosso, Mato Grosso do Sul, Parana, Rio Grande do Sul, and Sao Paulo which recorded eight cases of the disease to the Health Ministry, one with laboratory confirmation for Zika.
In the same period, there were 267 microcephaly suspicious deaths and / or alteration of the central nervous system after birth or during pregnancy (miscarriage or stillbirth) in the country. Of these, 57 were confirmed to microcephaly and / or alteration of the central nervous system. Other 178 are still under investigation and 32 were discarded.
Already 2,492 cases were discarded because of normal examinations or submit microcefalias and / or changes in the central nervous system by an infectious causes. It should be noted that the Ministry of Health is investigating all cases of microcephaly and other disorders of the central nervous system, informed the states, and the possible relationship with the Zika virus and other congenital infections. Microcephaly may be caused by , various infectious agents beyond Zika as Syphilis, Toxoplasmosis, Other Infectious Agents, Rubella, Cytomegalovirus and Herpes Viral.
The Ministry of Health advises pregnant women to adopt measures to reduce the presence of the mosquito Aedes aegypti , with the elimination of breeding sites , and protect themselves from mosquito exposure, keeping doors and closed or screened windows, wear pants and long sleeved shirts and use repellents allowed to pregnant women.

Video: PAHO Zika Briefing (May 3rd)


On Monday I mentioned an Upcoming PAHO Zika Briefing (May 3rd) with Dr. Anthony Fauci and Dr. Sylvain Aldighieri to be held on Tuesday afternoon. Together they discussed vaccine development and the epidemiology of the Zika virus, and took about 20 minutes of questions.

Late yesterday the video for that 35 minute presser was posted on the PAHO TV Youtube Channel, and you can watch it at the following link: 

Wednesday, May 04, 2016

EID Journal: Novel Reassortant H5N6 Viruses In Humans, Guangdong China

# 11,341

In April of 2014 a new, highly pathogenic H5N6 virus emerged in Sichuan China, infecting a local poultry flock and killing one man. This was actually the second new HPAI H5 virus to emerge in the first half of 2014, with Korea's H5N8 starting 3 months earlier.

Over the next 18 months China would report three more H5N6 human infections, and a number of outbreaks in poultry.  Laos and Vietnam also reported poultry outbreaks, but no human cases (see FAO Warns On H5N6).

While human cases have  been rare, last December and January we saw 5 cases reported from Guangdong province, followed by another in March. In April Hebei and Hunnan province each reported cases, and just yesterday Anhui province reported their first case.

Although these cases have all been widely scattered, and we've seen no evidence of clustering, or human-to-human transmission, this is a noticable uptick in cases.

Like all influenza viruses, H5N6 is constantly changing.  This evolution is driven by two different processes. Antigenic drift & Antigenic Shift (reassortment).

  • Antigenic drift causes small, incremental changes in the virus over time. Drift is the standard evolutionary process of influenza viruses, and often come about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).
  • Shift occurs when one virus swap out chunks of their genetic code with gene segments from another virus. This is known as reassortment. While far less common than drift, shift can sometimes produce abrupt, dramatic changes to the virus (see NIAID Video: How Influenza Pandemics Occur).

With only four human samples availble for analysis until last December's upsurge, we haven't seen much data on how the H5N6 virus is evolving, although reports last summer (see H5N6 Rising: Infecting Birds, Humans, & Even Cats) raised some red flags.

Today, a letter in the EID Journal finds while H5N6's  HA (H5 clade and NA (N6) genes have remained fairly stable, its internal genes have changed since 2014. 

The viruses sequenced last December show that H5N6 has reassorted with other avian flu viruses (both H9N2 and H6N6), and suggest there may be other - as yet undetected - H5N6 reassortants in the wild and others may yet emerge.

Two of the three 2015 isolates also appear to have picked up genes for amantadine (an older antiviral) resistance, that were not present in 2014.

None of this means that H5N6 is ready for prime time, or even that it is poised to become the next big avian flu threat. But its high morbidity and mortality in humans, along with its rapid spread and increasing genetic diversity, make H5N6 a virus worthy of our attention.

I've only included some excerpts from the letter, so follow the link to read it - and the supporting material - in their entirety.

Volume 22, Number 8—August 2016


Novel Reassortant Avian Influenza A(H5N6) Viruses in Humans, Guangdong, China, 2015
To the Editor: Avian influenza A(H5N6) influenza viruses have circulated among poultry in southern (Jiangxi, Guangdong) and western (Sichuan) provinces of China since 2013 (1,2). In 2014, outbreaks of H5N6 virus infection occurred among poultry in China, Laos, and Vietnam (1). In April 2014, the first case of highly pathogenic H5N6 infection among humans was detected in Sichuan Province (3); the second case was detected on December 3, 2014, in Guangdong Province (4). In December 2015, 4 humans in Guangdong Province were infected with H5N6 influenza (5,6).

To study the genetic basis of continuing human infections with this avian influenza subtype, we sequenced the complete genomes of 2 of the 4 human H5N6 isolates obtained in December 2015 in Guangdong Province. We compared these sequences with those of 1 H6N6 and 8 H5N6 influenza viruses isolated from birds in live poultry markets in this region during 2013–2015 (Technical Appendix[PDF - 1.63 MB - 12 pages]) and other published genomes of H5, H6N6, and H9N2 avian influenza viruses (Technical Appendix[PDF - 1.63 MB - 12 pages]).

In summary, we isolated 2 novel reassortant H5N6 viruses from 2 patients in Guangdong Province, China. The internal genes of these strains are different from those found in the first wave of H5N6 infections in 2014. The PB2 of 2 human isolate A/Guangdong/ZQ874/2015 (H5N6) appears to have been derived from a duck H6N6 virus, and all other genes of this virus originated in circulating H5N6 viruses. 

In contrast, the 6 internal genes of the other human isolate, A/Guangdong/SZ872/2015 (H5N6), were derived from enzootic H9N2 viruses. Although human infection has been sporadic, the co-circulation and reassortment of this virus with other enzootic low pathogenicity influenza viruses has resulted in new reassortant viruses. Further surveillance of birds is needed to monitor the spread of this novel virus.

Yong-Yi Shen1, Chang-Wen Ke1, Qian Li1, Run-Yu Yuan, Dan Xiang, Wei-Xin Jia, Yun-Di Yu, Lu Liu, Can Huang, Wen-Bao Qi, Reina Sikkema, Jie Wu, Marion Koopmans, and Ming LiaoComments to Author