CDC MMWR Early Release: Zika Spread & Possible Association With Microcephaly

Credit MMWR

#10,922


Coming off a 2pm embargo, the CDC has published two Early Release MMWR reports on the rapidly emerging Zika virus; one on the potential link between Zika and Microcephalic birth defects and the other on the rapid spread of the virus to new regions around the world.

Due to their combined length, I've only presented the link, a short description, and the summary for each MMWR report.  

Follow the link to read each in its entirety.

Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015

JANUARY 22, 2016

An outbreak of Zika virus infection was first recognized in northeastern Brazil in early 2015. By September, a sharp increase in microcephaly cases was reported from affected areas. The Brazil Ministry of Health developed a case definition for Zika virus–related microcephaly, and established a task force and a registry to investigate Zika virus–related cases of microcephaly and to describe the clinical characteristics of cases.

Summary

What is already known about this topic?

 An outbreak of Zika virus infection, a flavivirus transmitted by Aedes mosquitoes, was first recognized in northeastern Brazil in early 2015. In September, a sharp increase in the number of reported cases of microcephaly was reported in areas affected by the outbreak.

What is added by this report?
The Brazil Ministry of Health developed a case definition for Zika virus–related microcephaly (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth). A task force and registry were established to investigate Zika virus–related cases of microcephaly and to describe the clinical characteristics of cases. Among the first 35 cases of microcephaly reported to the registry, 74% of mothers reported a rash illness during pregnancy, 71% of infants had severe microcephaly (>3 SD below the mean), approximately half had at least one neurologic abnormality, and among 27 who had neuroimaging studies, all were abnormal. Cerebrospinal fluid from all infants is being tested for Zika virus; results are not currently available.

What are the implications for public health practice?
The increased occurrence of microcephaly associated with cerebral damage characteristically seen in congenital infections in Zika virus-affected areas is suggestive of a possible relationship. Additional studies are warranted to confirm the association and to more fully characterize the phenotype. In addition to removing potential breeding areas for mosquitoes, pregnant women in Zika-affected areas should wear protective clothing, apply a U.S. Environmental Protection Agency (EPA)-approved insect repellent, and sleep in a screened room or under a mosquito net.

Zika Virus Spreads to New Areas — Region of the Americas, May 2015–January 2016
 
JANUARY 22, 2016
 
In May 2015, the World Health Organization reported the first local transmission of Zika virus in the Americas, with autochthonous cases identified in Brazil. In December, the Ministry of Health estimated that 440,000–1,300,000 suspected cases of Zika virus disease had occurred in Brazil in 2015

Summary

What is already known on this topic?

Zika virus is a mosquito-borne flavivirus transmitted primarily by Aedes aegypti mosquitoes. Most infections are asymptomatic, and symptomatic disease generally is mild. In May 2015, the first local transmission of Zika virus in the Region of the Americas was reported in Brazil. Following the spread of Zika virus in Brazil, there has been a marked reported increase in the number of infants born with microcephaly; it is not known how many of these cases are associated with Zika virus infection.

What is added by this report?

By mid-January 2016, local Zika virus transmission had been reported to the Pan American Health Organization from 20 countries or territories in the Region of the Americas; spread to other countries in the region is likely. Although local transmission of Zika virus has not been documented in the continental United States, infections have been reported among travelers visiting or returning to the United States, and  these likely will increase. Imported cases might result in local transmission in limited areas of the continental United States.

What are the implications for public health practice?

The best way to prevent Zika virus infection is to avoid mosquito bites by avoiding exposure and eliminating mosquito breeding areas. Until more is known, pregnant women should consider postponing travel to any area with ongoing Zika virus transmission. Health care providers should contact their state or local health department about testing patients with symptoms of Zika virus infection and a compatible travel history.

Read More

CDC Expands Zika Travel Advisory Country List

Credit PAHO - Epi Wk 2

#10,921


Seven days ago the CDC issued a Level-II travel advisory for 14 countries and territories over the Zika Virus threat, and warned that list would likely grow. Two days ago, in PAHO: Zika Marches On, we looked at an updated list of affected countries from the Pan American Health Organization, which had increased to 20 nations and territories.

Today the CDC has released a statement adding Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa to the list. 

Given the speed with which this virus is spreading, it seems likely this list will continue to expand in the weeks ahead.

CDC adds countries to interim travel guidance related to Zika virus

Media Statement

For Immediate Release: Friday, January 22, 2016Contact: Media Relations, (404) 639-3286

CDC is working with other public health officials to monitor for ongoing Zika virus‎ transmission. Today, CDC added the following destinations to the Zika virus travel alerts:  Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa.  On January 15, CDC issued a travel alert (Level 2-Practice Enhanced Precautions) for people traveling to regions and certain countries where Zika virus transmission is ongoing: the Commonwealth of Puerto Rico, a U.S. territory; Brazil; Colombia; El Salvador; French Guiana; Guatemala; Haiti; Honduras; Martinique; Mexico; Panama; Paraguay; Suriname; and Venezuela. 

Specific areas where Zika virus transmission is ongoing are often difficult to determine and are likely to continue to change over time.

As more information becomes available, CDC travel alerts will be updated. Travelers to areas where cases of Zika virus infection have been recently confirmed are at risk of being infected with the Zika virus. Travelers to these areas may also be at risk of being infected with dengue or chikungunya viruses. Mosquitoes that spread Zika, chikungunya, and dengue are aggressive daytime biters, prefer to bite people, and live indoors and outdoors near people. 
There is no vaccine or medicine available for Zika virus. The best way to avoid Zika virus infection is to prevent mosquito bites.

Some travelers to areas with ongoing Zika virus transmission will become infected while traveling but will not become sick until they return home. Symptoms include fever, rash, joint pain, and red eyes. Other commonly reported symptoms include muscle pain, headache, and pain behind the eyes. The illness is usually mild with symptoms lasting from several days to a week. Severe disease requiring hospitalization is uncommon and case fatality is low. 

Travelers to these areas should monitor for symptoms or illness upon return. If they become ill, they should tell their healthcare professional where they have traveled and when.

Until more is known, and out of an abundance of caution, CDC continues to recommend that pregnant women and women trying to become pregnant take the following precautions:

• Pregnant women in any trimester should consider postponing travel to the areas where Zika virus transmission is ongoing. Pregnant women who must travel to one of these areas should talk to their doctor or other healthcare professional first and strictly follow steps to avoid mosquito bites during the trip.
• Women trying to become pregnant should consult with their healthcare professional before traveling to these areas and strictly follow steps to prevent mosquito bites during the trip. 

Guillain-Barré syndrome (GBS) has been reported in patients with probable Zika virus infection in French Polynesia and Brazil. Research efforts will also examine the link between Zika and GBS.

Read More

MMWR: Dengue Outbreak In Hawaii

#10,920


Although Florida and Texas have both seen minor outbreaks of dengue fever over the past few years, Hawaii is presently seeing the largest outbreak to date, with 230 cases reported on the Big Island over the past few months.

The following is the latest update from the Hawaiian State Department of Health.

Dengue Fever – Hawaii Island Outbreak

The Hawaii Department of Health (HDOH) is investigating a cluster of locally-acquired cases of dengue fever on Hawaii Island (the Big Island). Dengue is not endemic to Hawaii. However, it is intermittently imported from endemic areas by infected travelers. This is the first cluster of locally-acquired dengue fever since the 2011 outbreak on Oahu.  The Big Island and the rest of Hawaii remain safe destinations for visitors and residents.

As of January 21, 2016*:


Since the last update, HDOH has identified 6 new cases of dengue fever.  Currently, as many as 3 of the confirmed cases to date are potentially infectious to mosquitoes. All others are no longer infectious.

Of the confirmed cases, 208 are Hawaii Island residents and 22 are visitors.

188 cases have been adults; 42 have been children. Onset of illness has ranged between 9/11/15 – 1/16/16.

As of today, a total of 962 reported potential cases have been excluded based on test results and/or not meeting case criteria.

Yesterday the CDC's MMWR published a Notes From The Field report on this outbreak, which covers the opening six weeks of this outbreak.  At that time 117 Dengue infections had been identified.

Notes from the Field: Outbreak of Locally Acquired Cases of Dengue Fever — Hawaii, 2015

Weekly / January 22, 2016 / 65(2);34–35

David Johnston, MPH¹; Melissa Viray, MD¹; Jenny Ushiroda¹; A. Christian Whelen, PhD¹; Rebecca Sciulli¹; Remedios Gose¹; Roland Lee¹; Eric Honda¹; Sarah Y. Park, MD¹ (View author affiliations)

On October 21, 2015, the Hawaii Department of Health (HDOH) was notified of a positive dengue immunoglobulin M (IgM) antibody result in a woman residing on Hawaii Island (also known as the Big Island). The patient had no history of travel off the island, and other family members reported having similar signs and symptoms, which consisted of fever, headache, myalgias and arthralgias, and a generalized erythematous rash. HDOH initiated an investigation to identify any additional cases and potential exposure sources. On October 24, HDOH received report of a group of mainland U.S. visitors who had traveled together on Hawaii Island, including several who had developed a febrile illness. Additionally, on October 27, HDOH was notified of an unrelated person, also on Hawaii Island, with a positive dengue IgM result. As of November 26, 2015, HDOH had identified 107 laboratory-confirmed cases of dengue fever (1), with dates of onset ranging from September 11 to November 18, 2015 (Figure).

(SNIP)

All travelers, whether visitors to the state of Hawaii or returning residents, should consult with and advise their health care providers regarding their recent travel if they develop illness within 2 weeks of their return home. All health care providers, especially those in Hawaii, should be familiar with and alert for signs and symptoms of dengue fever, as well as for other more common infections such as leptospirosis, which sometimes mimics dengue infection. 

Additionally, health care providers should know the warning signs and management of potential severe dengue (i.e., dengue hemorrhagic fever) (1). It is important for all persons, and especially for state of Hawaii residents and those on Hawaii Island, to avoid exposure to mosquitoes, eliminate potential mosquito breeding locations from their property, and protect themselves from mosquito bites.

The arrival of Dengue to Hawaii undoubtedly occurred in much the same way that Zika arrived in Brazil, Chikungunya arrived in the Caribbean, and Dengue turned up in South Florida. 

Carried in (unknowingly) by an infected traveler - one who may very well have been asymptomatic or only mildly ill.

Although humans are usually only viremic for a week or 10 days - during this window they are capable of infecting local mosquitoes who partake in a blood meal, even if they aren't symptomatic (see PNAS: Asymptomatic Humans Transmit Dengue Virus To Mosquitoes).

It takes the confluence of a several conditions - a viremic visitor, a competent vector like the Aedes mosquito, the right weather/climatic conditions, and usually a dense population - but when the conditions are right, sustained local transmission (albeit sometimes only temporarily) can occur.

With Zika, Chikungunya, and Dengue making substantial inroads into the Americas, Southeast Asia, and the Pacific - all areas with a substantial tourist trade - the ability for these viruses to hop a plane and turn up in Europe, North America, and other regions where they are not currently active continues to grow.

Read More

Saudi MOH Announces 2 MERS Cases

10,919


We've seen a very quiet December and January with regards to MERS reports from Saudi Arabia, but today the MOH announces two new cases, both supposedly having had (1 direct and 1 indirect) camel contact.

Although there is no overriding `season' for MERS, late winter and spring are viewed as times of heightened concern, primarily because of so many young - virologically naive - camels born over the winter.

While camel contact no doubt contributes to the `reseeding' of the virus into the human population, by far most people are infected by contact with infected individuals, often in hospital or health care settings. 

For the majority of `primary' cases (those that occur in the community when there is no known exposure to a healthcare facility or to a known human case), the risk exposure remains unknown.

Read More

ECDC Rapid Risk Assessment On Zika Virus Epidemic

Credit ECDC

#10,918


The ECDC has published a 20 page, data-rich, overview and analysis on the Zika virus called  Rapid Risk Assessment: Zika virus disease epidemic: potential association with microcephaly and Guillain-Barré syndrome (first update).

As we've come to expect from the ECDC, it is comprehensive, well documented, and makes an invaluable reference.  

You'll want to download to read and keep this PDF file handy, as it is simply too large to excerpt the full  gist here.


You'll find sections devoted to genetic lineage and possible changes to the Zika virus (see AFD Blog Paper: Zika Adaptations To Humans Helped Spark Global Spread), the risks from blood transfusion, advice to international travelers and their doctors, and of course the two big (and as yet, unanswered) $64 questions:

Risk of microcephaly and other congenital central nervous system malformations

To date, health authorities have reported eight adverse pregnancy outcomes and/or other congenital CNS malformations with laboratory confirmation of Zika virus in amniotic fluid, placenta or foetal tissues. In addition, information on six cases of Zika virus detection in newborns from the Paraíba State with partly severe congenital malformations has been recently published. All fourteen reported cases have history of exposure in Brazil.

After performing a retrospective analysis following the alert from Brazil, the health authorities of French Polynesia reported an increase from an average of one case annually to 17 cases of CNS malformations in foetuses and infants during 2014–2015, following a Zika virus outbreak in 2013–2014.

No cases of microcephaly or other CNS malformations potentially related to Zika virus have been reported from other countries of Americas and Caribbean affected by Zika virus outbreaks. However, autochthonous transmission of Zika virus did presumably not start before the last trimester of 2015 in most of these countries, and the prospective monitoring of congenital malformations will support the evaluation of the association with Zika virus infections.


In summary, the evidence regarding a causal link between Zika virus infections during pregnancy and congenital CNS malformations is growing, although the available information is not yet sufficient to confirm it. The definitions of suspected cases applied in the epidemiological surveillance protocol for Brazil are broad and will capture many healthy children who are within the normal variation as well as children with medical conditions that are unrelated to Zika virus infections. The cases identified with the surveillance protocol will need to be further investigated and assessed, and many will have to be followed over time. It is expected that many of the suspected cases will be reclassified and discarded. So far, no results have been made public from the epidemiological studies that reportedly are ongoing and may substantiate or disprove the association between intra-uterine Zika virus infections and congenital lesions in CNS.

Risk of Guillain–Barré syndrome
 

No new scientific evidence about the association of GBS and Zika virus infection has been published since the ECDC RRA published on 10 December 2015. Two new countries, El Salvador and Venezuela (according to media), have reported an unusual increase above the baseline, concomitant with the development of Zika outbreaks in the country. This observation supports a temporal and spatial association as that seen in French Polynesia.

The bottom line is, despite a growing body of evidence, there is not yet conclusive proof that microcephalic births or the rise in GBS are due to Zika virus infection.  For now, however, it remains the most likely culprit.

With no vaccine, no specific treatment, and far too many unanswered questions - the immediate focus is on prevention. 

Better mosquito control, limiting personal exposure to mosquitoes, and taking steps (using repellents, wearing long sleeved shirts, etc.) to prevent mosquito bites will be the best way to limit the spread of Zika, along with Dengue and Chikungunya.

Read More

Macquarie Scholarship Interview session

 Macquarie Scholarship Interview session 

JM EDUCATION GROUP, Penang will be organising 

the Macquarie University Scholarship Opportunities Info Session in our office at  441-1-4, Pulau Tikus Plaza, Burmah Road, 

10350 Penang

 on 27^thJanuary 2016, Wednesday, 2pm-3.30pm.  

Please bring along your recent academic results for offer letters. For further details, please call 04-2277376

Read More

EID Journal: H5N1 In Egypt

#10,917



Despite the overly reassuring (and quite possibly fanciful) statements coming out of Egypt's MOH this year (see Egyptian MOH Statement: No Bird Flu Cases Since Last Summer)  the expectation is many - perhaps even most - human avian flu infections go undetected. 


It's a phenomenon we've seen repeated in China with H7N9, where estimates (see Lancet: Clinical Severity Of Human H7N9 Infection) ran from 12 to 200 times the official number of cases, to the United States where Swine variant flu infections in 2012 (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012)) were estimated 200 times greater than reported.

Similarly, Saudi Arabia has reported 1285 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.

None of these are actual head counts, yet based on the limited serological studies that have been done and some calculations way above my pay grade, the numbers are probably reasonable extrapolations.  


Last year Egypt reported roughly 160 H5N1 cases, four time more than in any twelve month period before.  These represented only those sick enough to be hospitalized, and lucky enough to be tested. Presumably some number were only mildly ill, were misdiagnosed,  or otherwise lost in the shuffle.

Last year we also saw evidence that the H5N1 virus in Egypt - which has been poorly controlled for a decade - had developed some `mammalian' mutations (see Eurosurveillance: Emergence Of A Novel Cluster of H5N1 Clade 2.2.1.2) that might have made it easier for the virus to jump to humans. 

Over the years we've seen several analyses indicating that most of the poultry vaccines in use have been ineffective (see A Paltry Poultry Vaccine) and may only have hidden signs of infection in poultry, allowing viruses to spread and mutate. 


All of which brings us to an EID Journal study, published today, that suggests there may have been tens (perhaps, hundreds) of thousands of human H5N1 infections in Egypt over the past decade.

If true, it would dramatically lower the CFR (Case Fatality Rate) for the virus (a good thing), but it would aslo indicate the virus is more human adapted than previously thought (a not-so good thing).

The authors base this assumption on a limited serological study that found antibodies for H5 in roughly 2% of the people tested.  Even more remarkably, this study found 5.6% to 7.5% seroprevlance of antibodies to H9N2, an even less commonly reported human infection.


I've only excerpted the abstract, along with a few choice selections from this lengthy, data-rich, and fascinating report. It is well worth reading in its entirety.

Avian Influenza A(H5N1) Virus in Egypt

Ghazi Kayali , Ahmed Kandeil, Rabeh El-Shesheny, Ahmed S. Kayed, Asmaa M. Maatouq, Zhipeng Cai, Pamela P. McKenzie, Richard J. Webby, Samir El Refaey, Amr Kandeel, and Mohamed A. Ali 

Abstract

In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt.

An unprecedented increase in the number of human infections with the highly pathogenic avian influenza A(H5N1) virus was observed in Egypt during the 2014–15 winter season. The World Health Organization reported that 31 cases were confirmed in 2014, of which 27 were in persons infected as of September (1). The Ministry of Health and Population in Egypt confirmed 31 cases in 2014 and 88 in January and February 2015. Thus, the official number of cases during September 2014–February 2015 was 114, including 36 deaths. Furthermore, in February 2015, the first human case of subtype H9N2 virus infection in Egypt was reported. These events compelled national and international authorities to examine the reasons behind the increase in human infections and implement control measures.

(SNIP)

Extent of Avian Influenza Infection in Egypt

In Egypt, the number of reported human cases of avian influenza infection appears to be underestimated. An underestimation might result in an overestimation of the case-fatality rate, but it would certainly underestimate the extent of human infection with avian influenza viruses. Results from a controlled, serologic cohort study of persons in Egypt exposed and not exposed to poultry estimated the seroprevalence of antibodies against H5N1 (titers >80) at 2% (19).

If this seroprevalence were to be extrapolated to the entire poultry-exposed population in Egypt, the true number of infections would amount to several hundred thousand. These figures are even more striking when it comes to human infection with H9N2 viruses. The seroprevalence of H9N2 antibodies detected in the same cohort study (19) ranged from 5.6% to 7.5%, whereas just 1 case of H9N2 infection was reported.

H5N1 viruses elicit a poor humoral immune response, providing low antibody titers that typically fade over a short period (20,21). Thus, relying on serologic testing to detect prevalence or incidence of infection can yield underestimated results. 

(SNIP)

Conclusions

Egypt is one of the few countries where H5N1 virus has become enzootic and is the only country with a high number of H5N1 outbreaks among poultry and cases among human. During the 2014–15 winter season, a sudden and substantial increase in human infection with H5N1 viruses was observed. There is no obvious or confirmed reason for this increase, but data indicate the following:

1) H9N2 virus is co-circulating and co-infecting with H5N1 viruses,

2) H5N1 viruses causing the infections possess some mutations that were rarely seen in the past, and

3) the poultry vaccination program is failing.

However, our perspective was limited to the data available through our surveillance program, which might not be representative of the epizootiology of avian influenza virus in Egypt. Regardless of the causes of the recent increase in human H5N1 cases, this situation evolved because of the ineffective control strategy that was implemented. Controlling the situation requires a One Health approach, but certainly the greater share of responsibility now lies with the veterinary side.

Dr. Kayali is a staff scientist at the St. Jude Children’s Research Hospital, Memphis, TN. His research interests are the epidemiology of influenza and viral zoonotic diseases.

Read More