H5N1

The forgotten virus: Zika families and researchers struggle for support

Via The New York Times, Stephanie Nolen writes: The Forgotten Virus: Zika Families and Researchers Struggle for Support.

RECIFE, Brazil — A procession of mothers pushed children in bulky wheelchairs down a long corridor at a health center in this northeastern Brazilian city, passing patients who glanced at the children, looked away, then looked back, quickly and uneasily.  

The children were smartly turned out in Disney T-shirts, striped socks, plastic sandals. Girls had ponytails tied with big bows; many wore brightly colored glasses. And all were profoundly disabled, their limbs rigid, their mouths slack, many with foreheads that sloped sharply back above their dark eyes.  

Most Brazilians know as soon as they see them: These are Zika babies, whose mothers were infected with the virus while pregnant during a virulent outbreak of the mosquito-borne illness in 2015 and 2016. The chief signifier at birth was microcephaly, unusually small heads that hinted at the devastating brain damage the virus caused while they were still in utero.

Seven years later, they are now children, many of them nearly as big as their mothers. The sight of them visibly startles people who have not thought about them for years. After the Zika epidemic did not turn into a pandemic that swept the globe, Brazil and the rest of the world moved on.  

That has left families in this scrappy corner of Brazil, where the epidemic originated, struggling, mostly alone, to get help for their children, whose mysterious condition presents new challenges constantly. Many rely on charity, such as free physical therapy at the private foundation where they come each week in the procession of wheelchairs. Many of the women pushing the chairs wear T-shirts that say “Fight like a Mother” in Portuguese.  

It has also left scientists unable to answer basic questions about the virus and the danger it could pose.  

The virus is still circulating at a low level in Brazil and elsewhere in Latin America, as well as in South and Southeast Asia. But attention and funding dried up after the global concerns faded, said Dr. Diana Rojas Alvarez, who leads the Zika work by the World Health Organization. 

“This is what happens when you have a public health emergency that affects tropical countries and that doesn’t have the global impact Covid had,” she said. “Initially, there was a lot of interest in developing good treatments and diagnostic tests — I remember being in a meeting where there were 40 vaccine candidates in development. But since 2017, everything went quiet.”

A hat-tip to the World Mosquito Program

While the pandemic has taken up most of our time, we really need to pay some attention to other global health problems as well. Mosquito-borne diseases are as urgent as ever.From the website of the World Mosquito Program:

The World Mosquito Program uses safe and natural bacteria called Wolbachia to prevent the transmission of mosquito-borne viral diseases such as dengue, Zika, chikungunya and yellow fever.  

Since releasing the first Wolbachia mosquitoes in 2011, evidence from international pilot studies shows that we can use Wolbachia more broadly to decrease the risk of Aedes aegypti mosquitoes transmitting viruses. Multiple trials in various locations demonstrate that our method is a safe and effective way to help prevent the spread of diseases across entire cities and regions.  

We continue to rapidly expand our operations by building partnerships with local governments and communities around the world who are embracing our Wolbachia method.  

 The World Mosquito Program currently has two regional hubs – our Asia hub in Ho Chi Minh City, Vietnam and our Oceania hub, based at Monash University in Melbourne, Australia. We are in the process of establishing our third Americas hub in Panama. These hubs support projects in their respective regions and contribute to core global operations. 

We have projects operating in 12 countries and our Wolbachia-carrying mosquitoes have reached 5 million people as at December 2019. 

In areas where Wolbachia is self-sustaining at a high level, monitoring shows that virus transmission is greatly reduced. Our measured impact is consistent with local elimination of disease. We are committed to improving health conditions and strengthening the capacity of local communities around the world to help reduce the threat of mosquito-borne diseases.  

Through collaboration and innovation, we can make a difference to millions of lives.

The Program has asked me to get the word out about a Twitter event on October 12 at which Professor Scott O'Neill, director of the Program, will answer questions. I'm happy to oblige. You can post your questions ahead of time at #Releasing Hope.

Lessons unlearned: Four years before the CDC fumbled COVID-19 testing, the agency made some of the same mistakes with Zika

Via The Washington Post: Lessons unlearned: Four years before the CDC fumbled coronavirus testing, the agency made some of the same mistakes with Zika. Excerpt:

Four years before the federal Centers for Disease Control and Prevention fumbled the nation’s chance to begin effective early testing for the novel coronavirus, the agency similarly mishandled its efforts to detect another dreaded pathogen. 

Amid a feared outbreak of the newly emerged Zika virus, senior CDC officials in 2016 sidelined an effective test for it — and instead directed public health laboratories nationwide to use a more complicated test that failed about one-third of the time.  

The agency’s response to Zika now stands as an unheeded prequel for how the CDC stumbled this year as it confronted the coronavirus pandemic, which has claimed more than 125,000 lives nationwide. 

Both Zika and the coronavirus originated overseas and became American health emergencies that have challenged the CDC’s ability to carry out its fundamental mission to rapidly identify and contain newly arrived pathogens.  

In both emergencies, the CDC pressured the public health labs to shelve the effective tests and to use less reliable test kits manufactured by the agency that sought to detect multiple pathogens. The agency stood behind the troubled test kits despite internal data indicating they were flawed. Ultimately, the CDC notified the public lab officials that they could switch to more effective tests. 

With Zika, the CDC took nearly a year to change course. With the coronavirus, the agency took more than a month, delaying a nationwide rollout of effective testing as the malady it causes, covid-19, erupted into the nation’s most deadly infectious disease in a century. Clinicians and public health officials believe the delay caused additional deaths, although the total number is uncertain.  

The component of the CDC’s coronavirus test kits that was designed to detect strains other than SARS-CoV-2 became contaminated during manufacturing at the agency in January, causing false-positive results at 24 of 26 labs that first tried out the kits, The Washington Post revealed in April. The CDC waited until Feb. 28 before dropping the problematic “pan-coronavirus’’ segment from the kit — while the public labs were blocked from using an effective test made available in mid-January by the World Health Organization.  

The parallels in how the CDC responded to the two health crises emerge from a Washington Post examination of federal investigative and regulatory records, congressional testimony, CDC emails and documents, and interviews with scientists and other technical experts.  

“It’s painful to watch the same challenges again and again,’’ said Timothy M. Persons, who has reviewed the efforts to counter Zika and the coronavirus as chief scientist of the U.S. Government Accountability Office. “As I think we saw with Zika, we need to apply lessons learned to definitely try and respond better.” 

An audit that Persons led three years ago for the government faulted CDC leaders for not being more rigorous in evaluating the troubled test for Zika. Reliable early testing “is a critical piece of the overall preparedness and response system,” Persons said in an interview.

The first local cases of Zika virus in Europe

A letter in The Lancet: The first local cases of Zika virus in Europe. Excerpt:

In October, 2019, the first mosquito-transmitted, locally acquired cases of Zika virus were reported in Europe. This outbreak event has implications far beyond the three people affected and represents a new phase in the global Zika threat. 

When Zika virus first emerged in the Pacific in 2007, then spread to the Americas and the Caribbean in 2015–17, the global community treated Zika virus as an epidemic disease. The Zika virus was expected to spread to Asia, but when surveillance began, not only were outbreaks in Asia found to be due to indigenous strains of Zika virus, but the virus was found to have been circulating silently for decades. The source of this latest European outbreak is unknown at present, but the world is clearly moving into an era of more unpredictable circulation of the Zika virus. 

The arrival of Zika virus in Europe is part of a wider pattern of accelerating arboviral risk on the continent (figure). The arrival also confirms the mosquito species Aedes albopictus as capable of supporting Zika virus transmission. This expands considerably the number of countries and territories where this unpredictable disease can occur to 177, putting 4·6 billion people potentially at risk.

Although the European Centre for Disease Prevention and Control describes the individual risk of infection in many of these areas as very low, advice for pregnant women living in or visiting these areas is wanting. These introductions also challenge the view that Zika is a tropical disease best dealt with by reactive outbreak response and containment. Zika is an increasingly cosmopolitan and more unpredictable threat than ever before. The Zika virus and other arboviruses continue their global expansion.

The arrival of Zika virus in Europe should signal a re-evaluation of the broader field of arboviral diseases. In an increasingly globalised world, Europeans need to care as much about outbreaks in Manila, Manaus, or Majuro as they do about outbreaks in Marseille. Investments in arbovirus research and surveillance systems worldwide are needed to monitor the new and emerging threats posed by this increasingly high-profile group of viruses. The global emergence of dengue virus, chikungunya virus, and Zika virus should be a wake-up call to shift the strategy from emergency response to increased vigilance and prevention measures. We should not have to wait for the next global arbovirus to arrive on the shores of Europe or the USA before we act on this.

Mosquito sterilization offers new opportunity to control chikungunya, dengue, and Zika

WHO has published Mosquito sterilization offers new opportunity to control chikungunya, dengue, and Zika. Excerpt:

A technique that sterilizes male mosquitoes using radiation will soon be tested as part of global health efforts to control diseases such as chikungunya, dengue, and Zika.  

The Sterile Insect Technique (SIT) is a form of insect birth control.  The process involves rearing large quantities of sterilized male mosquitoes in dedicated facilities, and then releasing them to mate with females in the wild. As they do not produce any offspring, the insect population declines over time. 

The Special Programme for Research and Training in Tropical Diseases (TDR) and the International Atomic Energy Agency (IAEA), in partnership with the Food and Agriculture Organization of the United Nations (FAO), and WHO have developed a guidance document for countries that have expressed interest in testing the Sterile Insect Technique (SIT) for Aedes mosquitoes.  

Half the world at risk of dengue 

“Half the world’s population is now at risk of dengue,” said Dr Soumya Swaminathan, WHO Chief Scientist. “And despite our best efforts, current efforts to control it are falling short. We desperately need new approaches and this initiative is both promising and exciting.”  

In recent decades, the incidence of dengue has increased dramatically due to environmental changes, unregulated urbanization, transport and travel, and insufficient sustainable vector control tools and their application.   

Dengue outbreaks are currently occurring in several countries, notably on the Indian sub-continent. Bangladesh is facing the worst outbreak of dengue since its first recorded epidemic in 2000. The South Asian nation has seen the number of cases rise to over 92,000 since January 2019, with daily admissions peaking at more than 1,500 new dengue patients in hospitals in recent weeks and is one of the countries to express interest in the Sterile Insect Technique. 

Diseases transmitted by mosquitoes such as malaria, dengue, Zika, chikungunya, and yellow fever account for about 17% of all infectious diseases globally, claiming more than 700,000 lives each year, and inflicting suffering on many more. The 2015 outbreak of Zika in Brazil was linked to an increase in the number of babies being born with microcephaly. 

Vector-borne transmission of Zika virus in Europe, southern France, August 2019

A rapid communication in Eurosurveillance: Vector-borne transmission of Zika virus in Europe, southern France, August 2019. The abstract: 

On 1 October 2019, a locally-acquired Zika virus disease case was laboratory confirmed in Hyères, Var department. Active case finding identified two additional locally-acquired cases living within 90 m, with symptom onset 8 days before the index case. Extensive patient interviews did not yield information supporting transmission through sexual contact or substances of human origin. Vector-borne transmission by local Aedes albopictus mosquitoes is the most likely mode of transmission. Here we describe the public health response.

Experiment with genetically modified mosquitos backfires in Brazil

Via brazzil.com, a September 21 report: Experiment with Genetically-Modified Mosquitoes Backfires in Brazil. Excerpt:

An attempt to contain the populations of the yellow fever mosquito Aedes aegypti in Brazil may have failed. It appears that gene mutations have been transferred to the local population. 

The British company Oxitec had released about 450,000 male mosquitoes every week in the city of Jacobina in the Bahia region with official permission over a period of 27 weeks. The experiment was designed to control the infectious diseases dengue, Zika and yellow fever. 

The gene modification called OX513A in the mosquitoes was designed in such a way that the first descendant generation of the mosquitoes, known as F1, would not reach the adult stage and thus not be able to reproduce. 

The hope of the Ministry of Health was to reduce mosquito populations by 90 percent. And this worked well during the field trial. About 18 months after the end of the experiment, the mosquito population returned to what it had been before. 

The gene modification of the released mosquitoes also produced a fluorescent protein that made it possible to distinguish the first F1 generation from other mosquitoes.  

Researchers at Yale University have examined the mosquitoes found in the region for their genetic alterations one year after the release, as well as 27 to 30 months after the release.  

They came to the conclusion that parts of the gene alteration had unexpectedly migrated into the target population of local mosquitoes. 

Gene Modification Passed On 

In the different samples, between 10 and 60 percent of the mosquitoes carried corresponding changes in the genome. The study was published in Nature: Scientific Reports on September 10.  

If the field trial had taken place as originally predicted, the gene modification would not have been allowed to migrate into the mosquito populations because the offspring of the mosquitoes originally released would not have been able to reproduce. 

However, it was already known from previous laboratory experiments that a small proportion of about three to four percent of OX513A descendants can reach adulthood; the scientists had assumed that those would be too weak to reproduce.  

The authors of the study found that the GM mosquitoes were equally suitable as carriers of infectious diseases as the mosquitos were before the experiment. 

Critics Take the Floor  

The Yale research team around Jeffrey Powell warns that the newly formed mosquito population could possibly be more robust than the mosquitoes were before.  

The authors conclude: “These results demonstrate the importance of having in place a genetic monitoring program during releases of transgenic organisms to detect unanticipated consequences”. 

Biologists critical of genetic engineering go one step further with their criticism, among them the Brazilian biologist José Maria Gusman Ferraz: “The release of the mosquitos was carried out hastily without any points having been clarified,” Ferraz told the newspaper Folha de S. Paulo.

ECDC rapid risk assessment: Zika virus disease in Var department, France

ECDC has published Rapid risk assessment: Zika virus disease in Var department, France. The executive summary:

On 1 October 2019, a case of locally acquired Zika virus (ZIKV) disease in France (Hyères city, Var department) was laboratory confirmed. The case had symptoms compatible with ZIKV disease during the first half of August 2019. The case did not report any history of travel to countries with historical ZIKV transmission. No evidence of sexual transmission was retrieved during the investigation. No imported ZIKV disease cases were reported in the area in 2019. 

Further epidemiological investigations are ongoing to define the most probable mode of transmission. At this stage, vector-borne ZIKV transmission is the hypothesis that forms the basis for this ECDC risk assessment. If this hypothesis turned out to be correct, this event would mark the first case of autochtonous vectorborne transmission of ZIKV in Europe.  

Vector control measures are being implemented near the residence of the case. To date, investigations have not managed to identify additional cases, but further cases may be detected through ongoing active case finding.   

Ae. albopictus is widely established in southern Europe (see Ae. albopictus , current known distribution, August 2019) and a competent vector for ZIKV. However, it is considered a less competent vector than the tropical and subtropical vector Ae. aegypti. The occurrence of sporadic cases or clusters of locally acquired vector-borne ZIKV cases is possible, notably in the Mediterranean region of Europe when environmental conditions during summer and early autumn can support vector abundance and arbovirus replication at a level that is sufficient for autochthonous transmission of ZIKV. The report of a locally acquired ZIKV disease case in the southern part of France is thus not unexpected.  

To date, and based on ECDC’s epidemiological assessment, the probability of ongoing vector-borne local transmission in Hyères (and surrounding areas) is considered very low because current evidence does not indicate the existence of a more extensive cluster of ZIKV cases. As temperatures are progressively decreasing during autumn, the environmental conditions are currently not favourable for sustained transmission. The current risk posed to the population, including pregnant women and their unborn children, is very low. If autochthonous, vector-borne cases could be documented, for example by detecting additional locally acquired cases in the immediate vicinity of the case, the risk for pregnant women and unborn children would be low instead of very low. 

It is possible that the ongoing investigation will retrospectively identify locally acquired cases because Ae. albopictus abundance at the time the case had symptoms would have allowed vector-borne transmission. Currently, however, there is a very low likelihood that travellers to this area will become infected, introduce the virus, and initiate further local transmission in their EU/EEA country of residence.  

Substantial uncertainty regarding possible local transmission at the time of publication remains. The level of risk should be re-assessed when significant new facts become available. For options for response, please refer to the section of that name below. 

How mosquitos shaped humanity

The Tyee has published my review of Timothy C. Winegard's new book The Mosquito: A Human History of Our Deadliest Predator: How Mosquitos Shaped Humanity. Excerpt:

The mosquito, Timothy Winegard argues, has killed half of all humans who ever lived — 52 billion of us.  

Add all the other mammals and birds it preys upon, and it is clearly the planet’s apex predator. After millions of years in that role, however, the mosquito could be overthrown by its human victims’ ingenuity. 

Winegard’s research makes this an important book for anyone concerned with mosquito-borne diseases. As his subtitle suggests, he focuses on how mosquitos have shaped human history. And they have even shaped us genetically. Humans evolved in an Africa where mosquitos had prospered for millions of years. They preyed on our ancestral species, and by the time modern humans emerged we had even evolved sickle-cell anemia as a defensive measure against malaria.  

Modern humans who left Africa took malaria and other mosquito-borne diseases with them, infecting the mosquito populations they encountered. Migration and settlement must have come at a terrible price in deaths and sickness. The survivors, after repeated infections, might become “seasoned” — able to recover from malaria relatively easily. But if they moved into a new region, an unfamiliar strain of malaria might still finish them off.

Zika was soaring across Cuba. Few outside the country knew

Via The New York Times: Zika Was Soaring Across Cuba. Few Outside the Country Knew. Excerpt and then a comment:

A previously unknown outbreak of the Zika virus swept across Cuba in 2017, a year after the global health emergency was declared over, scientists reported on Thursday.  

Until now, the Pan American Health Organization had no record of any Zika infection in Cuba in 2017, much less an outbreak. Following inquiries by The New York Times about the new study, published in the journal Cell, officials acknowledged that they had failed to tally 1,384 cases reported by Cuban officials that year.

That figure is a sharp increase over the 187 cases confirmed in 2016 and is “in line with the estimates for 2017 from our own study,” said Kristian Andersen, an infectious disease researcher at Scripps Research Translational Institute in La Jolla, Calif., and a co-author of the new study. 

Because most cases of Zika go unconfirmed, Dr. Andersen added, the outbreak actually may have comprised tens of thousands of infections.

 Cuba saw record tourism in 2017, raising the possibility that many travelers were unknowingly exposed. Some 4.7 million foreign visitors arrived that year, an increase of 16 percent over 2016. More than one million were Canadians.  

“If we want to stay ahead of communicable diseases, we need to know where they are and how many cases are occurring,” said Jennifer Gardy of the Bill & Melinda Gates Foundation in Seattle. “For some diseases in some settings, this is pretty straightforward. For others, like Zika, it isn’t.” 

Officials at P.A.H.O., an arm of the World Health Organization, blamed the failure to publish timely data on the Cuba outbreak on a “technical glitch.” The information was held in a database, they said, but not visible on the website. By Thursday afternoon, the website had been updated.

"Technical glitch" indeed. I blogged about this outbreak last December, when the Cell study appeared on bioRxiv. It's a very quiet scandal, reminiscent of PAHO/WHO's refusal to identify the source of Haiti's disastrous cholera outbreak in 2010 and thereafter. (And the Cubans were also very quiet about the cholera imported from Haiti by their own returning healthcare workers.)