Zika virus kills cells that form key brain tissue: report

In what may be the first lab evidence of the potency of the Zika virus, researchers in the United States have found that it severely damages a type of neural stem cell that gives rise to the brain’s cerebral cortex.

The findings are significant given that the World Health Organisation (WHO) is set to decide, within the next few months, whether the Zika virus — historically known to be relatively benign — is indeed wholly responsible for the outbreak of microcephaly, or deformed skulls, in newborns in Brazil and other parts of South America.

The team of researchers, led by Guo-li Ming and Hongjun Song of the Johns Hopkins University School of Medicine and Hengli Tang of Florida State University report in the current edition of the journal Cell Stem Cell that they saw the virus’ destruction, on neuronal cells derived from human induced pluripotent stem cells.

“This is a first step, and there’s a lot more that needs to be done,” said Mr. Song, a neuroscientist and stem cell biologist. “What we show is that the Zika virus infects neuronal cells in dish that are counterparts to those that form the cortex during human brain development. We still don’t know at all what is happening in the developing foetus. These findings may correlate with disrupted brain development, but direct evidence for a link between Zika virus and microcephaly is more likely to come from clinical studies,” the statement added.

Several other questions however remain. For instance, why are the symptoms in adults so mild? How is the virus entering the nervous system of the developing foetus?

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Moving in for the kill

An estimated 390 million dengue infections occurring each year across 150-odd countries is proof that the current mosquito control measures are grossly inadequate to keep the Aedes species, the vector that transmits dengue, chikungunya and Zika, under check. In Brazil, more than 1.5 million people were affected by Zika last year. That the virus has now spread to more than 20 countries in Latin America and the Caribbean only serves to augment the failure on the Aedes front.

In spite of several challenges, insecticide-treated bed nets have helped in cutting down the number of malaria cases in Africa. But they are of little use in keeping the Aedes mosquito species, which are aggressive daytime biters, at bay. Urbanisation has allowed the Aedes aegypti mosquitoes, found in tropical and sub-tropical countries, to breed in diverse waterbodies and even indoors in nearly any sort of water-filled container.

A major constraint in the fight against Aedes aegypti has been the vector’s resistance to widely used insecticides such as organophosphates and pyrethroids. Developing an effective vaccine against Zika may take years but there’s hope in the case of dengue: Sanofi has recently launched the first-ever vaccine against it. It, however, has several limitations as of now, including lower efficacy against the DENV-2 serotype (dengue has four serotypes in all) that is prevalent in India and vaccine-generated antibodies that facilitate the entry of the dengue virus into human cells. Even when a cheap, safe and effective vaccine against dengue becomes available, the compulsion to reduce the mosquito population will remain a top priority as A. aegypti transmits Zika and chikungunya as well.

Novel strategies
Two novel strategies have shown promise in recent years. One involves the use of genetically modified male Aedes aegypti mosquitoes that carry a dominant lethal gene. The gene is passed down to offspring when they mate with wild female mosquitoes that are not genetically altered. The lethal gene in the offspring produces a protein that stops their cells from functioning normally by producing more of itself and prevents other genes essential for survival from turning on. This prevents the mosquito larvae from growing properly and causes them to die before adulthood, essentially breaking the insect’s life cycle. The dominant lethal gene is kept under check while breeding in labs by using tetracycline drug. But due to the absence of tetracycline in sufficient quantities in nature, the larvae end up dying due to overproduction of the protein. As male mosquitoes do not bite humans, the release of genetically modified males will not increase the risk of dengue.

The biggest advantage of using this technique is its species-specificity; mutant Aedes aegypti released into the wild will not breed with another species of Aedes. Also, field studies carried out in West Panama have shown that short-term suppression of Aedes aegypti population did not lead to abundance of Aedes albopictus (Asian tiger mosquito), notes a paper published in September 2015 in the journal Pest Management Science. But more data may be needed to confirm this.

Since the modified insects disperse and actively seek wild female unaltered mosquitoes for mating, targeting the difficult-to-reach pest populations like Aedes aegypti becomes easier and more efficient than conventional control measures.

To be effective, genetically altered male mosquitoes need to be released in large quantities at regular intervals so they compete with the wild normal male insects for mating. Since the offspring do not live long enough to reproduce and the release can be stopped at any time, the Release of Insects carrying Dominant Lethal genes (RIDL) is a “self-limiting approach (the genetic modifications are not perpetuated in wild populations)”, notes a piece in The Lancet (February 1, 2016).

The first open field trial carried out in 2010 in the Caribbean island of Grand Cayman without much publicity by Oxitec, a British company founded and part-owned by the University of Oxford, was reported to be a success. An 80 per cent reduction in adult dengue-causing mosquitoes was registered in a 16-hectare plot.

The key performance parameters for genetically modified male mosquitoes released into the wild are longevity, dispersal capacity and mating competitiveness. According to an August 2012 paper in PLOS ONE, a field study done between 2010 and 2011 in an uninhabited forested area of Pahang, Malaysia showed that longevity of released males was similar to the wild ones but the mean distance travelled by the genetically sterile males was lower (52 m against 100 m for wild mosquitoes).

Similar trials have been carried out in several countries including Brazil (Itaberaba suburb of the city of Juazeiro, Bahia) with great success. The release of sterile male mosquitoes led to 80-95 per cent suppression of the target wild population in Brazil (PLOS Neglected Tropical Diseases, July 2015).

Radiation too can produce sterile males and has been successfully used for controlling certain agricultural pests. But in the case of mosquitoes, several field trials carried out using radiation- or chemically-sterilised mosquitoes have been hit by “poor performance of irradiated mosquitoes”.

Blocking dengue transmission
Another novel approach successfully tested in the northern Australian city of Cairns is to block dengue transmission to humans by greatly reducing the replication of the dengue virus and its spread inside the body of the mosquito. This is achieved by introducing a life-shortening Wolbachia (a diverse group of intracellular bacteria) bacteria strain into male and female Aedes aegypti mosquitoes. While embryos from uninfected wild females fertilised by sperm from Wolbachia-infected males fail to develop, embryos from infected females fertilised by infected or uninfected wild males survive. Since Wolbachia is maternally inherited, infected females pass on the bacteria to offspring immaterial of which male mosquito it mated with. As a result, when male and female mosquitoes carrying Wolbachia are released spatially apart to breed with wild mosquitoes in an area, the bacteria spreads rapidly in the mosquito population there.

Unlike in the case of mosquitoes carrying the dominant lethal gene, the release of even a single female mosquito infected with Wolbachia bacteria could “potentially lead to the alien Wolbachia spreading in the target population”, warns a paper published in June 2013 in the journal Pathogens and Global Health. “This is likely to be seen as an undesirable outcome and therefore a significant risk, unless species-wide invasion is the intent of the release.”

The release of Wolbachia-infected Aedes aegypti mosquitoes is “ongoing in dengue-endemic countries such as Indonesia, Vietnam and Brazil”, The Lancet paper notes.

As the field trials showed, the ability of wild Aedes aegypti’s ability to spread dengue virus can be greatly reduced, if not eliminated, as it tends to be a population-replacement approach. Though Wolbachia’s ability to cut Zika transmission is not known, studies have indicated that it can be effective against chikungunya, yellow fever and West Nile disease transmitted by the Aedes aegypti mosquito.

None of these novel approaches should be looked upon as silver bullets. Only an integrated pest management programme can help reduce the mosquito population and sustain the gains. Even a less effective vaccine can then become a great complementary tool.

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AP photographer reflects on 'bucket baby' in Brazil

The first time I met Solange Ferreira was in December. She was at a hospital, waiting to hear from a doctor whether her baby boy had what so many in her village were talking about microcephaly, or an abnormally small head that is a sign of severe disabilities and a truncated life-expectancy.

I had no doubt that little Jose, born in September, had the condition that many experts believe is linked to the Zika virus. His head was notably small, his skull practically flat.

“Everybody says he has a small head, but I don’t know what’s going on,” Ferreira, a 38-year-old maid, told me while she waited in Caruaru, a city in northeast Brazil near Recife, where the Zika virus has hit hardest.

Like so many other mothers I have interviewed and photographed, Ferreira asked me what I thought. I said nothing. I didn’t want to be the one to dash her hopes that Jose would be fine.

When she emerged from the doctor’s office, she told me the news. She had come alone to the hospital with Jose, and it was clear she needed to talk to somebody. She didn’t cry, but her sadness was palpable, and she seemed in shock. I asked for her phone number, and she agreed to let me photograph her and Jose the next day.

In her small house in Poco Fundo, about a three-hour drive from Recife, I saw a mother struggling. The boy would scream uncontrollably for long stretches, getting red in the face and tightening his already stiff limbs. He also struggled to feed, something I had learned was common in children with neurological disorders.

When his screaming got so bad that nobody in the house could take it, Ferreira would put Jose in a bucket. A nurse at the hospital had suggested the technique, and it seemed to calm the child.

“We were lucky to learn about the bucket,” said Ferreira.

Editing my pictures that night was hard. I realised that so many captured Jose suffering, but I didn’t want to just show him in that light.

The pictures of Jose in the bucket would have a large impact on me and on readers around the world. So this week I decided to visit the family again.

Ferreira had moved a few hours away to a town called Bonito while her husband remained in their old village. She said she wanted to be closer to Recife, where Jose can get therapy, and to get away from an area infested with mosquitoes.

“If we had not been there, this wouldn’t have happened,” she said.

In reality, Bonito is no different than Poco Fundo in terms of mosquitoes and the viruses they transmit, such as Zika, dengue and chikungunya.

Jose looked worse. Not only did he scream uncontrollably, but one of his eyes convulsed. Ferreira told me that she fears Jose could end up paralyzed and blind. He had lost weight, from 7 to 5 kilograms (15 to 11 pounds), a huge drop for a baby who should be growing. Depending on the severity, some children with microcephaly fail to thrive and thus die before becoming adults.

Ferreira cried when she said she had realised that Jose may never run and play like her two older children. I realised then that the full weight of what Ferreira was up against had hit her. This wasn’t a temporary problem, a challenge that would eventually be overcome. Jose would need extreme care for the rest of his life.

As I was leaving, a neighbour with an infant about the same age as Jose came over for a visit.

Ferreira looked at the baby and smiled.

“Now I have started believing that it is actually the other babies that have heads that are too big,” she said, in a tone both playful and sad. “Jose is my new normal.”

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Indian firm files patent for Zika vaccine candidates

Hyderabad-based Bharat Biotech has filed for global patent of two vaccine candidates - a recombination vaccine and an inactivated vaccine - for Zika virus.

The company announced that it could make available the inactivated vaccine in two years if the Indian Government fast-tracked the regulatory approvals once the pre-clinical trials proved to be successful.

Addressing a press conference here on Wednesday, Krishna Ella, Chairman and Managing Director of the company, said that Bharat Biotech was probably the first in the world to file for global patent for the two promising Zikavac vaccine candidates.

While the recombination vaccine might take time, the pre-clinical testing of the inactivated vaccine in animals would be completed in five months.

He said that the company had invested over $ 150 million since its inception to build its portfolio of vaccines, which included Rotovac (rotavirus vaccine) and Typbar TCV, typhoid conjugate vaccine. He said that a patent was also filed for Chikungunya vaccine, which would be entering Phase-1 trials shortly.

Bharat Biotech Director R & D Sumathy said that work on Zika vaccine project was started in 2014 and the patent was filed in July 2015. She said that Zika fever was an unmet healthcare need in India and other countries and the potential for Zika virus epidemic was high.

Mr. Krishna Ella said the normal process for a vaccine to get commercialized would take seven years, including the clinical trials.

However, he said that the Zikavac vaccine could be made available if the Indian Government declares national emergency and moves aggressively in regulatory approvals. He said that women would be the prime target group for the vaccine, followed by adults of both the genders since the virus causes Guillain-Barre syndrome in them.

A Bharat Biotech press release said that the WHO just announced a disease linked to the Zika virus in Latin America poses a global public health emergency requiring a united response.

Zika is now present in 23 countries. Brazil, the hardest-hit country, has reported around 3,500 cases of the devastating birth defect called microcephaly. The Zika virus is spread by mosquitoes of the Aedes genus, which can breed in a pool of water as small as a bottle cap and usually bite during the day.

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Sexually transmitted Zika case confirmed in Texas

A person in Texas has been infected with the Zika virus — the first case of the virus being transmitted in the U.S. during the current outbreak of Zika which has been linked to birth defects in the Americas.

“It’s very rare but this is not new, we always looked at the point that this could be transmitted sexually,” said Zachary Thompson, director of the Dallas County Health and Human Services, told WFAA-TV.

The Zika virus is usually spread through mosquito bites, but investigators have been exploring the possibility of the virus spreading through sexual contact.

“That gives you the plausibility of spread, but the science is clear to date that Zika virus is primarily transmitted to people through the bite of an infected mosquito,” Dr. Anne Schuchat of the Centers for Disease Control (CDC) said during a recent news conference.

The CDC says it will issue guidance in the coming days on prevention of sexual transmission of Zika virus, focusing on the male sexual partners of women who are or may be pregnant. The CDC has already recommended that pregnant women postpone trips to more than two dozen countries with Zika outbreaks, mostly in Latin America and the Caribbean, including Venezuela. It also said other visitors should use insect repellent and take other precautions to prevent mosquito bites.

'80% of infected never experience symptoms'

The World Health Organization (WHO) on Monday declared a global emergency over the rapidly spreading Zika virus, saying it is an “extraordinary event” that poses a threat to the rest of the world. The declaration was made after an emergency meeting of independent experts called in response to a spike in babies born with brain defects and abnormally small heads in Brazil since the virus was first found there last year.

WHO officials say it could be six to nine months before science proves or disproves any connection between the virus and babies born with abnormally small heads.

Zika was first identified in 1947 in Uganda. It wasn’t believed to cause any serious effects until last year; about 80 per cent of infected people never experience symptoms.

The most common symptoms are fever, rash, joint pain and red eyes. The illness is usually mild with symptoms lasting several days to a week. Symptoms usually start two days to a week after being bitten by an infected mosquito.

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More than 2,100 Colombian women infected with Zika virus

More than 2,100 pregnant Colombian women are infected with the mosquito-borne Zika virus, the country’s national health institute said on Saturday, as the disease continues its spread across the Americas.

The virus has been linked to the devastating birth defect microcephaly, which prevents foetus’ brains from developing properly. There is no vaccine.

There are 20,297 confirmed cases of the disease in Colombia, the national health institute said in a epidemiology bulletin, among them 2,116 pregnant women. There are so far no reported cases of microcephaly or deaths from the virus in Colombia.

The institute said 37.2 per cent of pregnant women with Zika live in Norte de Santander province, along the eastern border with Venezuela.

Zika cases have been confirmed in 23 countries and territories in the Americas and scientists are racing to develop a vaccine for the virus.

The health ministry has said Zika infection falls within the health requirements women must meet to get abortions in the country, which restricts the procedure unless patients are victims of rape, have significant medical problems or the foetus is fatally deformed.

Many women, especially those living far from large cities, struggle to find abortion providers even when they meet the legal requirements and illegal abortions are widespread.

The government has urged women to delay pregnancy for six to eight months to avoid potential infection. Officials expect up to 700,000 cases.

Brazil is the country hit hardest by the disease. It has reported around 3,700 cases of microcephaly strongly suspected to be related to Zika.

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Zika could infect 4 mn people: WHO

The World Health Organization (WHO) expects the Zika virus, which is spreading through the Americas, to affect between three million and four million people, a disease expert said on Thursday.

The WHO’s director-general said the spread of the mosquito-borne disease had gone from a mild threat to one of alarming proportions.

Marcos Espinal, an infectious disease expert at the WHO’s Americas regional office, said: “We can expect 3 to 4 million cases of Zika virus disease”. He gave no time frame. There is no vaccine or treatment for Zika, which is a close cousin of dengue and chikungunya and causes mild fever, rash and red eyes. An estimated 80 per cent of people infected have no symptoms, making it difficult for pregnant women to know whether they have been infected.

WHO Director-General Margaret Chan said the organisation will convene an emergency committee on Monday to help determine the level of the international response to the outbreak of the virus spreading from Brazil that is believed to be linked to severe birth defects. “The level of alarm is extremely high,” Ms. Chan told WHO executive board members at a meeting in Geneva. “As of today, cases have been reported in 23 countries and territories in the [Americas] region.”

Brazil’s Health Ministry said in November 2015 that Zika was linked to a foetal deformation known as microcephaly, in which infants are born with abnormally small heads. Brazil has reported 3,893 suspected cases of microcephaly, the WHO said last week, more than 30 times more than in any year since 2010 and equivalent to 1-2 per cent of all newborns in the state of Pernambuco, one of the worst-hit areas.

Ms. Chan said that while a direct causal relationship between Zika virus infection and birth malformations has not yet been established, it is “strongly suspected”.

“The possible links, only recently suspected, have rapidly changed the risk profile of Zika from a mild threat to one of alarming proportions,

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New Year, new public health threat

An obscure mosquito-borne virus, Zika, is on the prowl and has already caused an “unprecedent[ed] situation” in the world of scientific research. It stems from a huge surge in babies being born with microscopically, a rare, incurable condition in which their heads are abnormally small. The disease is currently sweeping through Northeastern Brazil, with officials reporting at least 2,782 cases in 2015, as against 147 in 2014 and 167 in 2013. At least 40 infants have died so far.

What is Zika virus?

The virus gets its name from the Zika forest in Uganda, Africa, where it was first identified in rhesus monkeys in 1947. It was reported in humans in 1952 but was unknown in the Americas until last year. The virus is transmitted by the Aedes aegypti mosquito, which is also responsible for the spread of dengue and chikungunya.

In the last few years, confirmed cases have been reported from Brazil, Colombia, the Dominican Republic, El Salvador, Guatemala, Mexico, Panama, Paraguay, Suriname and Venezuela.

Why is this outbreak alarming?

The Zika virus was considered benign until recently when scientists, for the first time in November 2015, linked it to a surge in babies born with microcephaly — an incurable birth defect, they are born with abnormally small heads. According to Brazilian authorities, by the end of the year, Zika could infect over 1.5 million people. Further, the disease is spreading fast and experts believe it could spread to other countries in the Southern hemisphere. Puerto Rico reported its first case of Zika on Friday.

Outbreaks have also occurred in parts of Africa, Southeast Asia and the Pacific Islands. Because the Aedes species mosquitoes that spread Zika virus are found throughout the world, it is likely that outbreaks will spread to new countries.

The Centers for Disease Control and Prevention (CDC) in the United States, and the Canadian government have issued travel advisories, warning tourists to protect themselves from mosquito bites. Further, the Brazilian government is advising women to delay pregnancies till the outbreak is under control.

What are the symptoms?

The most common symptoms are fever, rash, joint pain, or conjunctivitis (red eyes). Other symptoms include experiencing muscle pain, headache, pain behind the eyes, and vomiting. The virus causes a painful but temporary rash in adults. The illness is usually mild with symptoms lasting for several days to a week but 1 in 5 people infected with the Zika virus become ill

How is it Zika treated?

There is no medicine as yet to treat Zika. According to the CDC, the condition can be managed and symptoms treated with patients being put on bed rest, increasing fluid intake and having fever medication.

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