How a vaccine made of mosquito spit could help stop the next epidemic

By Clare Baldwin

(Reuters) – Five years ago, in an office complex with a giant sculpture of a mosquito just northwest of Phnom Penh, Jessica Manning struck on a novel idea. Rather than spend more years in what felt like a futile search for a malaria vaccine, she would take on all mosquito-borne pathogens at once.

Her idea revolved around mosquito spit.

A lab technician Nhek Sreynik works with mosquitoes, at a lab in Kompong Speu Province, in Cambodia, June 11, 2020. REUTERS/Chantha Lach

Building on the work of colleagues and other scientists, Manning, a clinical researcher for the U.S. National Institute of Allergy and Infectious Diseases, believed she could use pieces of mosquito saliva protein to build a universal vaccine.

The vaccine, if it pans out, would protect against all of the pathogens the insects inject into humans – malaria, dengue, chikungunya, Zika, yellow fever, West Nile, Mayaro viruses and anything else that may emerge.

“We need more innovative tools,” said Manning. A vaccine like this would be “the Holy Grail.”

On Thursday, The Lancet published the initial results of this work with her colleagues: the first-ever clinical trial of a mosquito spit vaccine in humans.

The trial showed that an Anopheles mosquito-based vaccine was safe and that it triggered antibody and cellular responses.

Michael McCracken, a researcher not involved in the study, called the initial results “foundational.”

“This is big, important work,” said McCracken, who studies immune responses to mosquito-borne viruses at the Walter Reed Army Institute of Research in Maryland. “Mosquitoes are arguably the deadliest animal on Earth.”

A boy sits in the pediatrics ward at Kampong Speu District Referral Hospital, at the beginning of a dengue, also called ‘breakbone fever’, epidemic in Krong Chbar Mon, Cambodia April 2019. Jessica Manning/Handout

Malaria alone kills more than 400,000 people each year, according to the World Health Organization. Those deaths occur mostly in poor countries that do not receive as much vaccine research and funding. Because of global warming, however, those mosquitoes that thrive in the tropics are moving into more countries each year.

The global disruption of the COVID-19 pandemic has brought a sharp focus to infectious diseases and vaccine research. One of the key areas of concern are pathogens transmitted by mosquitoes.

The novel coronavirus, believed to have originated in bats, has so far infected more than 7.4 million people and killed nearly 420,000 worldwide. The Asian Development Bank estimates the pandemic could cost the global economy as much as $8.8 trillion.

TARGETING THE CARRIER

Manning’s research is specific to mosquitoes but is an example of how scientists are broadening their thinking about how to tackle infectious diseases, and the new types of tools they are developing.

What Manning is looking for is called a vector-based vaccine. A vector is the living organism – like a mosquito – that transmits a pathogen such as malaria – between humans, or from animals to humans.

All existing vaccines for humans target a pathogen. Manning’s goes after the vector.

The idea is to train the body’s immune system to recognize the saliva proteins and mount a response that would weaken or prevent an infection.

Scientists have known for decades that mosquito spit helps establish mosquito-borne infections and enhance their severity. Just recently, scientists have begun to exploit this.

A study of macaque monkeys published in 2015 showed vaccination with sand fly saliva reduced leishmaniasis lesion size and parasite load. A study of mice published in 2018 showed immunization with Anopheles mosquito spit protected against malaria. Another mouse study published last year showed immunization with Aedes mosquito saliva improved survival against the Zika virus.

The study published in The Lancet was conducted in 2017.

The Phase I trial conducted at the National Institutes of Health Clinical Center in Bethesda, Maryland, tested for safety and side effects in 49 healthy volunteers.

Participants were randomly assigned to receive one of two versions of the vaccine or a placebo. After a few weeks, hungry mosquitoes were placed on the arms of study participants. The study measured immune response to the mosquito spit proteins but did not involve pathogens.

More trials are needed to determine the effect the mosquito spit vaccine would have against actual pathogens.

No systemic safety concerns were identified. One participant developed an 8-centimeter (3.15 inches) reddened area around the injection site and was treated with steroids and antihistamines.

“I’m not as worried about redness as I would be about something more systemic like fever, headache, muscle aches, nausea or vomiting,” said Stephen Thomas, an infectious disease expert at SUNY Upstate Medical University who was not involved with the study.

Thomas has previously worked on dengue vaccine programs for the U.S. Department of Defense and helped manage its response to Ebola and the Zika virus.

Another scientist at the University of Maryland is running a follow-up trial with more mosquito spit proteins and a different vaccine formulation.

Meanwhile, Manning has returned to Cambodia and is running a field study to identify vaccine-candidate spit proteins in Aedes mosquitoes. She also has a separate project sequencing the genomes of all pathogens found in Aedes and Culex mosquitoes, some of which can infect humans.

One worrying discovery so far? “They carry a ton of different viruses that we are only just discovering.”

(Reporting by Clare Baldwin; Editing by Elyse Tanouye and Bill Berkrot)

‘Dengue kills too’ – Latin America faces two epidemics at once

By Oliver Griffin

BOGOTA (Reuters) – As the coronavirus kills thousands and dominates government attention across Latin America, another deadly viral infection is quietly stalking the region.

Dengue – colloquially called breakbone fever for the severe joint pain it causes – is endemic in much of Latin America, but COVID-19’s arrival has pulled crucial attention and resources away from the fight against it, doctors and officials say.

The Pan-American Health Organization (PAHO) expects 2020 to be marked by high rates of dengue, which can fill intensive care units and kill patients even absent the pressures of COVID-19, the respiratory disease caused by the novel coronavirus.

Around the world, COVID-19 has affected other diseases in different ways. Though in Europe measures to stop the coronavirus have banished seasonal flu, in Africa border closures have stopped transportation of measles vaccines and other supplies.

In Latin America, a dengue epidemic that started in late 2018 is still being felt. Dengue infections in the Americas surged to an all-time high of 3.1 million in 2019, with over 1,500 deaths in Latin America and the Caribbean, according to the PAHO.

Cases of the disease should begin to decline in the second half of the year, the organization said.

Spread by mosquitoes, dengue outbreaks typically occur three to five years after the previous epidemic.

And with four strains of dengue in circulation, people may catch it more than once, with second cases more likely to be severe.

“COVID is the star right now, so all of the attention is being put on COVID, but there are still problems with dengue,” said Doctor Jaime Gomez, who works at a hospital in Floridablanca, in Colombia’s Santander province.

Although dengue is not usually fatal and can be treated with painkillers, some sufferers deal with persistent symptoms like fatigue, weight loss, and depression that affect their ability to work. Severe dengue is treated with intravenous fluids and those who do not get tested are at risk of dangerous complications.

Such medical intervention cannot be given if patients stay home, worried about contracting the coronavirus, or if overcrowded hospitals have to turn them away.

With relatively few cases of COVID-19 in the province where he works, Gomez said his clinic had seen hospitalizations fall by half, as people were fearful of venturing outdoors.

‘SYSTEM HAS COLLAPSED’

Paraguayan lawyer Sonia Fernandez avoided seeking care when she and her two daughters, ages 11 and 8, got sick with dengue at the beginning of April.

“All three of us had dengue, we had all the symptoms, the pain, the rash, but we didn’t go to a clinic or a health center so as not to expose ourselves (to COVID-19),” Fernandez said.

All three have since recovered.

Dengue cases in Paraguay have exploded this year. In the first 18 weeks of 2020, the country reported 42,710 confirmed cases and 64 deaths, compared to 384 confirmed cases and six deaths in the year-earlier period.

In Ecuador, where the coronavirus outbreak has hit hard and hospitals in the largest city of Guayaquil been overwhelmed, an apparent fall in the number of dengue cases could mask other issues.

According to Ecuador’s health ministry, dengue cases peaked at 888 in the week ending March 14, two weeks after the country confirmed its first case of COVID-19. For the week of April 4, they fell to 257.

“Very clearly dengue is being under-reported,” said Esteban Ortiz, global health researcher at Quito’s University of the Americas.

“Cases haven’t decreased, the diagnosis of cases has decreased, which confirms the system has totally collapsed,” he added.

Ecuador’s health ministry said in a statement that the country was no more exposed to the double impact of COVID-19 and dengue than any other in the region, adding it has sufficient supplies to treat cases of the mosquito-borne disease.

Dengue has also spiked sharply in Central America. Cases in Costa Rica nearly tripled through May 1 compared with a year ago, to over 2,000.

“We are going through a difficult moment dealing with COVID-19 but unfortunately other diseases continue their cycle,” Rodrigo Marin, director of Costa Rica’s health surveillance agency, recently told journalists.

In Panama, where dengue has caused at least two deaths this year, Panama City health official Yamileth Lopez also sounded the alarm in an interview with Reuters.

“Dengue kills too,” she said.

(Reporting by Oliver Griffin; additional reporting by Daniela Desantis in Asuncion, Alexandra Valencia in Quito, Alvaro Murillo in San Jose and Elida Moreno in Panama City; Editing by Julia Symmes Cobb and Rosalba O’Brien)

Philippines orders probe into Sanofi dengue vaccine for 730,000 children

Concepcion Yusop, a national immunization program manager, shows an anti-dengue vaccine Dengvaxia inside a vaccine storage room in Sta. Cruz city, Metro Manila, Philippines December 4, 2017.

By Manolo Serapio Jr and Neil Jerome Morales

MANILA (Reuters) – The Philippines ordered an investigation on Monday into the immunization of more than 730,000 children with a vaccine for dengue that has been suspended following an announcement by French drug company Sanofi  that it could worsen the disease in some cases.

The World Health Organization said it hoped to conduct a full review by year-end of data on the vaccine, commercially known as Dengvaxia. In the meantime, the WHO recommended that it only be used in people who had a prior infection with dengue.

The government of Brazil, where dengue is a significant health challenge, confirmed it already had recommended restricted use of the vaccine but had not suspended it entirely.

Amid mounting public concern, Sanofi explained its “new findings” at a news conference in Manila but did not say why action was not taken after a WHO report in mid-2016 that identified the risk it was now flagging.

A non-governmental organization (NGO) said it had received information that three children who were vaccinated with Dengvaxia in the Philippines had died and a senator said he was aware of two cases.

However, Department of Health Undersecretary Gerardo Bayugo told Reuters the three referred to by the NGO died due to causes not related to the vaccine and Sanofi said no deaths had been reported as a result of the program.

“As far as we know, as far as we are made aware, there are no reported deaths that are related to dengue vaccination,” said Ruby Dizon, medical director at Sanofi Pasteur Philippines.

Last week, the Philippines Department of Health halted the use of Dengvaxia after Sanofi said it must be strictly limited due to evidence it can worsen the disease in people not previously exposed to the infection.

In a statement, Sanofi said the long-term safety evaluation of the vaccines showed significantly fewer hospitalizations due to dengue in vaccinated people over 9 years old compared with those who had not been vaccinated.

Nearly 734,000 children aged 9 and over in the Philippines have received one dose of the vaccine as part of a program that cost 3.5 billion pesos ($69.54 million).

The Department of Justice on Monday ordered the National Bureau of Investigation to look into “the alleged danger to public health … and if evidence so warrants, to file appropriate charges thereon.”

There was no indication that Philippines health officials knew of any risks when they administered the vaccination.

However, the WHO said in a July 2016 research paper that “vaccination may be ineffective or may theoretically even increase the future risk of hospitalized or severe dengue illness in those who are seronegative at the time of first vaccination regardless of age.”

Singapore’s Health Sciences Authority said last week that it flagged risks when Dengvaxia was approved there in October 2016, and was working with Sanofi to strengthen risk warnings on the drug’s packaging.

According to Sanofi in Manila, 19 licences were granted for Dengvaxia, and it was launched in 11 countries, two of which – the Philippines and Brazil – had public vaccination programs.

Brazil’s healthcare regulator Anvisa said in a statement that it now recommends that people who have never been infected with dengue not take the vaccine, which was approved for use in Brazil at the end of 2015.

It was not known whether many people have taken the vaccine, if it was part of any government immunization program or if any illnesses or deaths linked to the drug have been reported to the government.

Anvisa did not immediately respond to a request for comment, nor did the Health Ministry.

A spokesman for Sanofi in Paris was not immediately available for comment. “A SHAMELESS SCAM” A spokesman for Philippines President Rodrigo Duterte said on Sunday the government would hold to account those responsible for the program.

Former Health Secretary Janette Garin, who implemented the program under the administration of then-President Benigno Aquino, said she welcomed the investigation.

“In the event that there will be authorities who will point culpability to me, I am ready to face the consequences,” she told ANC TV. “We implemented it in accordance with WHO guidance and recommendations.”

Presidential spokesman Harry Roque said there had been no reported case of severe dengue infection since the vaccine was administered and urged the public “not to spread information that may cause undue alarm.”

Volunteers Against Crime and Corruption, an NGO, said it was checking a report that three children on the northern island of Luzon had died since being vaccinated in April 2016 but the Department of Health said the deaths were not due to Dengvaxia.

“When we evaluated the clinical records, it was not related to the dengue vaccination,” Bayugo said.

A prominent senator, Richard Gordon, told Reuters he was aware of two deaths – but gave no details – and said approval and procurement for the program was done with “undue haste.”

Dengue is a mosquito-borne tropical disease. Although it is not as serious as malaria, it is spreading rapidly in many parts of the world, killing about 20,000 people a year and infecting hundreds of millions.

While Sanofi’s Dengvaxia is the first-ever approved vaccine for dengue, scientists already recognized it was not perfect and did not protect equally against the four different types of the virus in clinical tests.

A new analysis from six years of clinical data showed Dengvaxia vaccine provides persistent protective benefit against dengue fever in those who had prior infection.

But for those not previously infected by the virus, more cases of severe disease could occur in the long term following vaccination, Sanofi said.

 

(Additional reporting by Karen Lema in Manila, John Geddie in Singapore and Brad Brooks in Sao Paulo and Anthony Boadle in Brasilia; Writing by John Chalmers; Editing by Raju Gopalakrishnan and Bill Trott)

 

Dengue outbreak kills 300 in Sri Lanka, hospitals at limit

A mosquito landing on a person. Courtesy of Pixabay

COLOMBO (Reuters) – An outbreak of dengue virus has killed around 300 people so far this year in Sri Lanka and hospitals are stretched to capacity, health officials said on Monday.

They blamed recent monsoon rains and floods that have left pools of stagnant water and rotting rain-soaked trash — ideal breeding sites for mosquitoes that carry the virus.

The International Federation of Red Cross and Red Crescent Societies is scaling up emergency assistance to Sri Lanka with the Sri Lanka Red Cross to help contain the outbreak.

“Dengue patients are streaming into overcrowded hospitals that are stretched beyond capacity and struggling to cope, particularly in the country’s hardest hit western province,” Red Cross/Red Crescent said in a statement.

According to the World Health Organization, dengue is one of the world’s fastest growing diseases, endemic in 100 countries, with as many as 390 million infections annually. Early detection and treatment save lives when infections are severe, particularly for young children.

The Sri Lankan government is struggling to control the virus, which causes flu-like symptoms and can develop into the deadly hemorrhagic dengue fever.

The ministry of health said the number of dengue infections has climbed above 100,000 since the start of 2017, with 296 deaths.

“Ongoing downpours and worsening sanitation conditions raise concerns the disease will continue to spread,” Red Cross/Red Crescent said.

Its assistance comes a week after Australia announced programs to help control dengue fever in Sri Lanka.

“Dengue is endemic here, but one reason for the dramatic rise in cases is that the virus currently spreading has evolved and people lack the immunity to fight off the new strain,” Novil Wijesekara, head of health at the Sri Lanka Red Cross said in a statement.

(Reporting by Ranga Sirilal and Shihar Aneez Editing by Jeremy Gaunt.)

Fijian islands still cut off after cyclone, fear of Zika and Dengue outbreaks

SYDNEY (Reuters) – Fiji sent boats on Tuesday carrying desperately needed aid to remote islands and coastal villages devastated by a powerful cyclone which killed at least 29 people, as aid workers warned of possible outbreaks of Zika and Dengue viruses.

There are fears the death toll could rise in the nation of 900,000 people when communication resumes with the smaller islands hit by Cyclone Winston on Saturday.

Aerial footage of outlying islands taken by the Royal New Zealand Air Force, and posted on the Fiji government’s official website, showed whole villages flattened and flooded after Winston’s destructive winds, up to 200 mph, tore through the archipelago of 300 islands. Thousands of Fijians live in tin or wooden shacks in low-lying coastal areas.

Authorities have warned of “catastrophic” damage to Koro Island, Fiji’s seventh-largest island, and more than 8,000 people continue to shelter in evacuation centers across the country.

Prime Minister Frank Bainimarama reassured Fijians that the government was doing all it could amid growing criticism of the slow emergency response in some parts of the country.

“We realize the desperate position that you are in,” Bainimarama said in a statement after visiting an evacuation center. “We will not rest until we have reached you and given you the helping hand you so badly need and deserve.”

“Unfortunately the recovery process will take time, perhaps a long time,” he added. “Almost no part of our nation has been left unscarred.”

Aid workers warned of potential outbreaks of the Zika and Dengue viruses, both carried by mosquitoes which will breed in the stagnant water left by the storm.

“The threat of dengue and Zika in the coming days in Fiji is real,” said Chris Hagarty, senior health program manager at Plan International Australia.

“The period immediately following a disaster of this scale can be a particularly dangerous one.”

The World Health Organization declared a Zika outbreak in South America an international health emergency on Feb. 1, citing a “strongly suspected” relationship between Zika infection in pregnancy and microcephaly, a condition marked by unusually small heads that can result in developmental problems.

Much remains unknown about Zika, including whether the virus actually causes microcephaly. Brazil has confirmed more than 500 cases of microcephaly, and considers most of them related to Zika infections in mothers. Brazil is investigating more than 3,900 additional suspected cases of microcephaly.

Fiji’s international airport at Nadi has reopened and an aeromedical evacuation team was being sent to outer islands on Tuesday to provide urgent support and supplies, including water and hygiene kits, medicines and access to shelter.

(Editing by Michael Perry)

Hawaii Reports Additional Cases of Dengue Fever

The number of people infected with dengue fever in Hawaii is climbing, officials said Monday.

The Hawaii Department of Health reported that it was investigating 167 total cases of the mosquito-borne illness, which can lead to fatal consequences in extreme cases. There were 122 confirmed dengue cases as of Dec. 2, signifying 45 additional infections in about three weeks.

State health officials said only three of the 167 cases are currently infectious. The other people got sick between Sept. 11 and Dec. 10, so they are no longer at risk of transmitting the disease.

The health department also reported there were 659 additional potential dengue infections that had been ruled out, either through test results or the illnesses failing to meet the case criteria.

Dengue isn’t endemic (regularly found) in Hawaii, though health officials said it can occasionally be brought in from travelers who got infected in endemic regions. But this latest outbreak on the Big Island is unique because it’s the first cluster of locally acquired cases since 2011, when Centers for Disease Control and Prevention (CDC) records indicate five people got sick in Oahu.

According to the World Health Organization (WHO), an arm of the United Nations, dengue is transmitted when an infected mosquito bites a human. The infection generates a flu-like illness — from which most people usually recover within a week — though it sometimes progresses to severe dengue. In those instances, people can suffer organ impairment and severe bleeding.

The WHO estimates severe dengue hospitalizes about 500,000 people per year, and about 2.5 percent of them die. Dengue is much more common, with some estimates indicating as many as 136 million people falling ill every year, but non-severe cases of the disease are rarely ever fatal. Symptoms can include severe headaches, swollen glands, joint and muscle pain and a high fever.

The Hawaii outbreak reflects a global trend in which dengue is spreading to new locales.

The WHO reports the disease was traditionally found in the tropics and subtropics, but it’s now endemic in more than 100 countries and about half the world’s population is at risk of infection. Still, early detection and access to good medical care keeps the mortality rate below 1 percent. Without those, the WHO says severe dengue can be fatal in more than 20 percent of cases.

Hawaii health officials say it’s still safe to visit the island. The department encourages travelers to use insect repellant and wear long sleeves and pants to help prevent mosquitos from biting.