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Africa’s Yellow Fever Outbreak is a Glimpse of Our Connected Future

Zika virus has been earning all the headlines, because it is already affecting Americans—including 300 pregnant women, according to a new CDC estimate—and is expected to move into U.S. mosquitoes as the summer bug season starts.

But outside the United States, another mosquito-borne disease is attracting the world’s attention, and it may predict more than Zika does about how epidemics will move around the world in the future. The disease is yellow fever, the epicenter of the outbreak is Angola, and the force that could push it around the globe is Chinese investment in the developing world.

A member of the Angolan military administers a yellow fever vaccine to a child at 'Quilometro 30' market, Luanda, Angola, in February.
A member of the Angolan military administers a yellow fever vaccine to a child at ‘Quilometro 30’ market, Luanda, Angola, in February.

The Angolan outbreak began in December and is large: more than 2,400 cases and 298 deaths, according to the latest report from the World Health Organization. It was originally centered on the capital, Luanda, and has spread through the western half of the country. It has also hopped borders: There are 42 cases in the neighboring Democratic Republic of the Congo and two cases in Kenya (along with an an unrelated outbreak in Uganda, between Kenya and the DRC).

But what has some researchers unusually alarmed is that there are 11 cases in China: workers or families who returned from Angola into an area where yellow fever does not now exist—but the mosquitoes that spread it do.

“Approximately two billion people live in Aedes aegypti-infested countries in Asia,” Sean Wasserman, Paul Anantharajah Tambyah, and Poh Lian Lim, researchers from South Africa and Singapore, say in a paper published online in May in the International Journal of Infectious Diseases. “The prospect of a yellow fever introduction into this unvaccinated population poses a major global health threat,” they write.

Maps of Angola showing month-to-month spread of yellow fever.
Maps of Angola showing month-to-month spread of yellow fever.
Courtesy the World Health Organization.

Yellow fever is a persistent problem in West Africa, where the virus cycles between monkeys and mosquitoes and spills over to humans. That happens first in villages at forest edges, and then in cities as infected people carry the virus to urban mosquitoes. (These happen to be the same kinds of mosquitoes that transmit Zika, and also chikungunya and dengue: voracious day-biters that breed in pools of water as small as a bottle cap, and attack people not only outdoors but inside houses.)

A vaccine prevents yellow fever, but only about 70 percent of Angolans receive it, not enough to create the herd immunity that would prevent an outbreak from taking hold.

That is a serious gap, because unlike the other diseases carried by Aedes mosquitoes—which except for the birth defects of Zika mostly cause mild illnesses—yellow fever can kill. As many as one in four of those who develop symptoms go on to have liver and kidney failure, jaundice (which gives the disease its name) and bleeding, and one in four of those victims die.

Fumigating a Texas town infected with yellow fever, 1873.
Fumigating a Texas town infected with yellow fever, 1873.
Photograph by North Wind Picture Archives, Alamy

Yellow fever has never taken hold in Asia. Lack of familiarity with the disease may explain why the 11 infected people who returned to China were not vaccinated, despite Chinese regulations saying they should have been.

They probably have a lot of company: Angola is one of China’s biggest investment targets in Africa, for cropland and for energy. In 2009, according to the Centre for Chinese Studies in South Africa, China bought almost one-third of Angola’s crude oil. The Chinese expatriate community in Africa is estimated to be 20,000 people, who include not just semi-permanent residents but temporary construction workers who are shipped from job to job.

Because the continents harbor the same mosquito species—Singapore, where Tambyah and Lim work, wages a constant battle against dengue—the researchers suggest that just one unknowing traveler carrying yellow fever virus in their blood could spark a chain of transmission. That could trigger what The Economist warned in an editorial earlier this month would be “a preventable tragedy,” an epidemic as explosive as chikungunya after it arrived in India in 2005, or Zika in the Americas this year.

The authors of the new paper say: “The current scenario of a yellow fever outbreak in Angola, where there is a large community of non-immune foreign nationals, coupled with high volumes of air travel to an environment conducive to transmission in Asia, is unprecedented in history… The growing number of imported cases in China shows how critical it is to recognize this risk now in order to take adequate preventive action so that a global catastrophe can be averted.”

The action that is most needed is vaccination. Monday marked the start of the World Health Assembly, the annual conclave of member states of the World Health Organization. In the opening meeting, director general Dr. Margaret Chan delivered what she called a “stern warning” on failures to vaccinate adequately. (Chan’s term ends in June 2017, so she may have felt safe being blunt—though she did not name names.)

A Rockefeller scientist administers yellow-fever vaccine in Santiago de Guayaquil, Ecuador, in the 1920s.
A Rockefeller scientist administers yellow-fever vaccine in Santiago de Guayaquil, Ecuador, in the 1920s.
Photograph Courtesy of Rockefeller Foundation

“The world failed to use an excellent preventive tool to its full strategic advantage. For more than a decade, WHO has been warning that changes in demography and land use patterns in Africa have created ideal conditions for explosive outbreaks of urban yellow fever,” she said. “Yellow fever vaccines should be and must be used more widely to protect people living in endemic countries.”

Because of the Angolan outbreak, yellow fever vaccines are in short supply worldwide, as Kai Kupferschmidt reported in Science in April. Only four factories, in Russia, Brazil, France and Senegal, make the compounds, and one is about to close. But in May, a WHO emergency committee declined to rank yellow fever as a “public health emergency of international concern.” As global health-law scholars Daniel Lucey and Lawrence Gostin wrote in JAMA two weeks ago, that designation could have given the agency increased leverage to negotiate with vaccine manufacturers. (Following the decision, the committee advised “rapid evaluation” of dividing vaccine doses so that more people can be protected.)

But that may not be enough. In its editorial, The Economist did the vaccine math:

Should yellow fever come to Asia, some experts reckon that over 100m people living in large, well-connected cities would need to be vaccinated. That would rapidly exhaust the world’s supply of vaccine, even if only a fifth of a dose (thought to be enough to confer immunity to adults) were administered to each person who needed it. In the long term, if the disease establishes itself in Asia’s jungles, over 1 billion more people could be at risk…

The world has already failed to thwart yellow fever effectively in Africa. That threatens to put millions more lives at risk.

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Zika Is Likely to Become a Permanent Peril in U.S.

Mosquitos caught for testing in McAllen, Texas, await shipment to a lab. McAllen city workers are catching them in "mosquito traps" and sending them to labs to test for Zika and other mosquito-borne diseases.
Mosquitos caught for testing in McAllen, Texas, await shipment to a lab. Southern states that harbor the species that carries Zika are watching for infected mosquitoes.
Photograph by John Moore/Getty Images

Once Zika virus arrives in the United States, it will be here to stay. Leading experts now predict that the mosquito-borne disease will become a constant low-level threat that Americans will need to be vaccinated against routinely—as we do now for rubella, a virus that, like Zika, causes birth defects.

That is, once there is a vaccine for Zika. The earliest possible deployment of Zika vaccines could be several years away, researchers from around the globe predicted at an Atlanta conference Tuesday, the annual meeting of the Global Virus Network.

Overall, they said, Zika should be understood not as an epidemic wave that will pass over the world and then vanish, but rather as a permanent problem that will wax and wane, as West Nile virus has.

“We don’t know the future course of the epidemic of Zika, but we have to be prepared for the virus to be present for years,” José Esparza of the University of Maryland School of Medicine, current president of the Global Virus Network, said at the conference. “Without a vaccine, we will not be able to control the future course of this epidemic.”

Race for a Vaccine

Everyone reluctantly accepts that vaccines will take some time, while also expecting that infections could reach the United States soon. “The risk of Zika virus beginning to circulate in the United States on the mainland—it’s already in Puerto Rico, of course—is going to be peaking during the next few weeks,” said Scott Weaver, a virologist from the University of Texas Medical Branch.

“The number of travelers coming into the U.S. with Zika is very high, the temperatures are permissive now for mosquito transmission, and populations of mosquitos are growing,” he said.

Delfina Tirado, left, and Chalmers Vasquez of the Miami-Dade County's Mosquito Control Division inspect a pool in Miami, March 17, 2016. The Aedes aegypti mosquito -- the type that is spreading the Zika virus and fear of grave birth defects throughout Latin America and the Caribbean -- is being found in Florida and is expected to soon be buzzing around its usual haunts in the United States.
Workers from the Miami-Dade County’s Mosquito Control Division inspect a pool in Miami. The Aedes aegypti mosquito—the type that is spreading the Zika virus—is being found in Florida and is expected to soon be buzzing around its usual haunts in the United States.
Photograph by Max Reed/The New York Times

A vaccine is most needed to protect women who are pregnant or planning to be, because the virus causes devastating birth defects that seem to appear late in pregnancy, and may also cause more subtle problems as children get older.

“We have no information to believe there are any long-term consequences from infection to healthy adults or healthy children,” Weaver said.

While a small vaccine trial sponsored by the National Institutes of Health could begin as early as next fall, expanding that research into trials with thousands of participants could be complicated by the rapid growth of the epidemic, which is both infecting people and also rendering them immune once they recover.

The first Zika vaccines to be developed probably won’t go to everyone, Weaver predicted. “I think initially there will be some vaccines developed and licensed that are not optimal for vaccinating large populations, that will require multiple doses,” he said. “Those will probably be targeted to girls before they reach childbearing age, or women … if we can determine that they are not immune, if we have the diagnostics to do that.

“And then eventually we should be able to develop a live attenuated vaccine, like the one we have now for yellow fever that has been available for many decades in South America,” Weaver said. Then, he added, doctors can vaccinate children, and the population will develop what we think of as “herd” immunity that protects even the unvaccinated.

MCALLEN, TX - APRIL 14: A health inspector sprays a neighborhood for mosquitos early on April 14, 2016 in McAllen, Texas. Health officials, especially in areas along the Texas-Mexico border, are preparing for the expected arrival of the Zika virus, carried by the aegypti mosquito, which is endemic to the region. The Centers for Disease Control (CDC), announced this week that Zika is the definitive cause of birth defects seen in Brazil and other countries affected by the outbreak. ()
A health inspector sprays a neighborhood for mosquitos in McAllen, Texas. Health officials, especially in areas along the Texas-Mexico border, are preparing for the expected arrival of the Zika virus, which is endemic to the region.
Photograph by John Moore/Getty Images

Introducing a Zika vaccine in that manner would follow the path that rubella vaccine took in the 1960s. Before the vaccine existed, epidemics of rubella (also known as “German measles”) caused only mild illness in adults; but the virus had devastating effects when it infected pregnant women. In 1964-65, the last such epidemic, 11,000 U.S. children were born deaf, 3,500 were born blind, 1,800 were born with developmental abnormalities, and women suffered 2,100 stillbirths—along with more than 11,000 miscarriages and elective abortions.

The vaccine was introduced in 1969 and put on the childhood vaccination schedule that is composed by the Advisory Committee on Immunization Practices, an expert panel that assists the CDC; it is part of the MMR (“measles, mumps, rubella”) shot given at 12-15 months and 4-6 years. Since the vaccine was introduced, there have been only a few cases of rubella in the United States each year.

While the Zika vaccine hunt proceeds, scientists said at the Atlanta conference, it’s imperative to create easy-to-use tests to identify infected people, most of whom show no symptoms. Right now, it is difficult even to ascertain how many people in the Zika zone are already immune, since the current tests for diagnosing Zika infection, which were developed by the Centers for Disease Control and Prevention, are not commercially or widely available.

Zika’s Imminent Arrival

Travelers to the United States, whether visitors or residents returning home, are likely to be the reason that Zika ignites in the U.S. Weaver urged anyone traveling in the Zika zone to be scrupulous with mosquito repellent not just while there, but also for two weeks after they return, to be sure that they do not accidentally transmit the disease to U.S. mosquitos.

“It only takes one infected person to arrive and be bitten and the transmission cycle takes off,” Weaver said.

In the gap before a vaccine can arrive, the researchers said it’s important to achieve antiviral drugs that can work against the virus, and research presented at the conference suggests that combinations of drugs already on the market could be used in the short term.

In Recife, Brazil, Zika virus has been linked to birth defects in babies born to infected mothers. Here, Joao Batista comforts his daughter Alice Vitoria, who has microcephaly.
In Recife, Brazil, Zika virus has been linked to birth defects in babies born to infected mothers. Here, Joao Batista comforts his daughter Alice Vitoria, who has microcephaly.
Photograph by Tomas Munita, National Geographic

“These are drugs that have been used for a long time in people, so the safety issue is not a problem,” said Glaucius Oliva, a structural biologist from the Sao Carlos Institute of Physics at the University of Sao Paulo. “Repurposing drugs could begin in a year or two, whereas new drugs will take longer—10 years, maybe eight.”

Because so much research is needed, scientists sounded especially concerned that funding for Zika work in the U.S. has not yet been authorized. Congress went on recess without approving a White House request for more funds.

“A lot of the scientists in the U.S. are waiting for the floodgates to be opened with funding; a lot of the work that has been done so far has been done with shoestring budgets,” Raymond Schinazi, director of Emory’s Laboratory of Biochemical Pharmacology, said.

“This takes fuel, and the fuel unfortunately is very limited right now.”

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As Zika Advances, Can the U.S. Cope?

The Dallas County Mosquito Lab traps and searches through mosquitos looking for any that carry the Zika virus.
The Dallas County Mosquito Lab traps and searches through mosquitoes looking for any that carry the Zika virus.
Photograph by LM Otero, AP Images

The Zika virus that is advancing on the United States is unlike any other outbreak the country has faced, and countering it will require an effort unlike anything the U.S. and its public health infrastructure has done before.

More than 300 delegates to an emergency summit held at the Centers for Disease Control and Prevention in Atlanta—state, local and tribal officials, members of nonprofits and representatives of private companies—heard that message over and over again Friday. Scientists, political appointees, and public health experts urged them to find a way to pull together groups who seldom have a reason to communicate: health departments, academic physicians, community well-baby clinics, birth-defect surveillance programs, mosquito-control workers, even garbagemen and gardeners.

All of that expertise, they said, will be needed to prevent a disease that is carried by mosquitoes that elude spraying, infects most of its victims silently, damages fetuses in ways that are still not understood, and may not be detected until well after it has arrived.

“Nothing about Zika is going to be easy or quick,” Dr. Thomas R. Frieden, the CDC’s director, said at a press conference halfway through the all-day meeting. “The control of this particular mosquito is hard, and though we are learning a lot quickly, there is still a lot we don’t know. There is an urgent need to learn more.”

CDC Director Dr. Thomas R. Frieden addresses media during the Zika Action Plan Summit in Atlanta, April 1, 2016.
CDC Director Dr. Thomas R. Frieden addresses media during the Zika Action Plan Summit in Atlanta, April 1, 2016.
Photograph by Maryn McKenna.

The meeting, which was standing-room-only in its main sessions and watched by 2,000 people online, revealed a simmering anger over Congress refusing to authorize money to combat the disease. The Obama Administration requested an emergency appropriation of $1.9 billion in February, but no funds have been  approved; Congress recommended the White House use money from last year’s Ebola response instead.

“I understand the polarization of politics in this country; I don’t understand why children are being made the center of it,” Dr. Edward McCabe, the chief medical officer of the March of Dimes, who spoke at the summit, said in a side interview. “We know what needs to be done, and it’s not stealing fron Ebola to fix this disorder. Congress needs to do the right thing.”

The financial stress of anticipating Zika is already hitting some jurisdictions. Daniel Kass, New York City’s deputy commissioner for environmental health services, told the meeting the city has already spent $3 million preparing for Zika, without ever having a case, and expects to spend $5-6 million more. Dr. Umair Shah, executive director of public health and environmental services for Harris County, Texas, which encompasses Houston, said his county expects to spend about half that much but added: “The real challenge is a lot of our daily work has been moved to the side.”

Dr. Georges Benjamin, executive director of the American Public Health Association, said during a break that health departments may struggle because financial support for public health has been so erratic: high just after the World Trade Center attacks and the first advent of West Nile virus, then sliding, only to rise during the 2009 H1N1 flu and then fall again until Ebola arrived. “When the money goes away, the jobs go away, and you’re left without the people you need,” he said. “It’s yo-yo funding, when what we need is to build a consistent approach.”

Zika has barely touched the U.S., compared to the devastation it has wrought in South America. (See “Here’s What we Know Now About Zika and Birth Defects.”) So far, according to the CDC’s most recent numbers, 312 U.S. residents have been infected while traveling in the Zika zone, including 27 pregnant women. No one has contracted Zika from a mosquito in the mainland U.S., but 6 people have caught sexually transmitted Zika from travelers, including two pregnant women, and one person has developed Guillain-Barré paralysis. In US territories—Puerto Rico, American Samoa and the U.S. Virgin Islands—349 people have been infected by local mosquitoes and three while traveling, including 37 pregnant women.

Where Zika cases have been diagnosed in the United States as of March 30, 2016.
Where Zika cases have been diagnosed in the United States as of March 30, 2016.
Map courtesy of the CDC; original here.

Puerto Rico “could have hundreds of thousands of infections and tens of thousands of pregnant women infected,” Frieden said, but he declined to provide projections for the U.S. mainland. “We don’t want to  speculate what may happen,” he said. “We want to maximize our preparedness for what we can prevent.”

Without a vaccine, a disease-specific treatment or even a rapid diagnostic test, preventing Zika will fall on the expertise of mosquito control agencies, and summit attendees were clearly worried about the strain. (See “Disorganized Mosquito Control will Make U.S. Vulnerable to Zika.”) In some jurisdictions, mosquito control is a well-funded part of the health department. In others, personnel are so scarce that “it might be a guy who does water sampling during the day, and at night, it’s Chuck in a truck” spraying for nuisance mosquitoes, Stanton E. Cope, PhD, director of entomology and regulatory services for Terminix and president of the American Mosquito Control Association, told me.

A particular challenge, Cope added, is that existing mosquito control programs were built either to banish nuisance mosquitoes that interfere with tourism or to quell the night-biting mosquitoes that spread West Nile virus—but the Aedes species that transmit Zika bite during the day, breed in minuscule pools of water, lurk inside houses, and require different spraying equipment to dispel them and different traps to catch them so they can be tested to see whether they are carrying virus.

In a piece of irony, the CDC originated from a 1940s agency called the “Office of Malaria Control in War Areas,” and during the summit’s opening session, organizers showed a 70-year-old short movie about its work targeting Aedes aegypti, the mosquito that now spreads Zika. In the intervening decades, that insect slipped off the list of public health priorities, said Dr. Lyle Petersen, director of the CDC’s division of vector-borne diseases.

“It’s an important vector worldwide,” he told me. “It spreads dengue; there are several hundred milion cases of dengue every year. It spreads yellow fever, and right now we are having the first large urban yellow fever outbreak we have had in decades. It also spreads chikungunya. So it’s a bad actor.

“But what happened was, there’s a vaccine for yellow fever. And dengue was confined to the tropical world, and Zika wasn’t even on the horizon yet. So it became a very neglected mosquito, and now we are dealing with it again.”

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Can We Keep Zika Out of the US Blood Supply?

A doctor draw blood from Luana, who was born with microcephaly, at the Oswaldo Cruz Hospital in Recife, Brazil, Thursday, Jan. 28, 2016. Photograph by Felipe Dana, AP
A doctor draw blood from Luana, who was born with microcephaly, at the Oswaldo Cruz Hospital in Recife, Brazil, Thursday, Jan. 28, 2016. Photograph by Felipe Dana, AP

If Zika virus comes to the United States, will the US blood supply be at risk?

Because the disease has demonstrated that it can pass via blood from mother to fetus, and via other bodily fluids between sexual partners, the question lurks in the back of most discussions of Zika’s likely arrival on the US mainland. And because there is not now a test for donated blood, keeping the virus out of the blood supply relies on people adhering to restrictions published by the Food and Drug Administration that ask travelers to defer donating for a period of time—an imprecise deterrent, but currently as good as it gets.

The concern for the blood supply is reasonable. In 2002, when West Nile virus was newly arrived in the United States, transfusions given to a teenage accident victim—who died of her injuries, and became an organ donor—caused that disease to pass to all four recipients of her organs. Dengue, another mosquito-borne illness that is burgeoning in Central and South America and has become established in south Florida, has also passed between blood donors and recipients, though there are only a few cases on record. And Zika virus was identified in 3 percent of donated blood in French Polynesia in late 2013 and early 2014, when the virus first landed in that area.

(See: Pictures Capture Daily Battle Against Zika Mosquitoes)

The concern has been sharpened by a new analysis, published Wednesday in the journal PLoS Currents Outbreaks, that plots the range of the mosquito species known to carry Zika against the numbers of travelers who arrive from the Zika zone. The researchers—from several US government agencies, North Carolina State University and University of Arizona, and Durham University in England—predicted that cities within the mosquito’s range are at highest risk of local transmission of Zika if they have international airports, or airports receiving connecting flights from those hubs. Other cities receiving large numbers of travelers from the Zika transmission zone were at moderate or lower risk if they fell near the edge of the mosquito’s range. So, for instance, Miami, Orlando, Jacksonville, Tallahassee, and New Orleans were at high risk of receiving the disease; New York, Atlanta and Houston were at moderate risk, and Dallas, Denver and Los Angeles at low risk.

A map of cities most at risk for arrival and local transmission of Zika virus.
A map of cities most at risk for arrival and local transmission of Zika virus.
Graphic from Monaghan et al., PLoS Current Outbreaks, March 16, 2016.

What was jaw-dropping in the study, though, were the sheer numbers of people who arrive in US cities from the Zika transmission zone: up to 1 million per month in Miami and New York, 500,000 per month in Atlanta, Houston, New York and Dallas, and millions per month through the ground border crossings of San Diego, El Paso and Laredo.

To prevent Zika contaminating the blood supply, the FDA issued guidelines last month addressing blood donation and this month regarding donated cells and tissues. For blood donation, the agency recommended that blood agencies ask people to defer donation for four weeks after experiencing Zika symptoms, traveling in the Zika transmission zone,  or having sex with a man who either had the symptoms or traveled in the Zika zone. For tissues such as ligaments and corneas, and cells (which include sperm and eggs), the agency extended the deferral to six months. The FDA has not placed any restrictions on donation of solid organs, arguing that because they are both life-saving and in short supply, the benefit outweighs the risk.

Blood donations.
Blood donations.
Photograph by MikeHT, Flickr (CC).

Dr. Matthew Kuehnert, who is director of the office of blood, organ and other tissue safety at the Centers for Disease Control and Prevention, and is serving as the lead for the blood safety team in the CDC’S Zika response, said knowing how far to go to protect the blood supply is challenging because data is so sparse.

“There is little that we know about transfusion transmission of Zika, although I think we should assume it can happen,” he said by phone. “From the data that has been collected on Zika, about 80 percent of people don’t know they are infected. There is a period of viremia”—when virus circulates in the blood—”but we don’t know how long that viremia is. It is thought to be 7-10 days, but as we start to collect more data we may find it is longer than that.”

“It is possible we could get a transfusion or transplant transmission case before we even know local transmission of Zika is occurring.”

A problem, Kuehnert pointed out, is that because symptoms are the signal of an infection, only people who show signs of Zika infection—mostly fever, headache, rash and red eyes—are being interviewed and tested to add to knowledge about the disease. People who do not experience symptoms are not visible to investigators. They also become viremic; but since they are not interviewed or tested, the duration of their viremia, when the virus in their blood could pass into a blood donation, is not being uncovered. And there are early signals that, even after it passes out of the blood, the virus can take shelter in other tissues and fluids. “Zika can be sexually transmitted long after viremia is thought to be gone, so there are likely protected sites where it can hide,” he said. “Thus there might be blips of viremia occurring after symptoms have resolved. So there is a lot of potential for transfusion transmission.”

Those considerations apply in areas where Zika is not yet locally established. Where it is—which in the United States is Puerto Rico (160 cases as of March 9), American Samoa (13 cases) and the Virgin Islands (1 case)—blood is assumed to be a risk, and workarounds are being urgently sought. Because there is no test for Zika in donated blood—an approved test is “weeks to months away,” Kuehnert said—the only alternative is to use what are called “pathogen reduction” treatments, which inactivate viruses. Currently, pathogen reduction can only be used on platelets and plasma; red blood cells can be altered by pathogen reduction, and authorities are urgently searching for better techniques..

In a sign of how quickly an epidemic can upset the balance of blood supplies, Puerto Rico is now receiving outsourced blood from the US mainland, via a joint effort of three blood-collection agencies—the  American Red Cross, Blood Centers of America, and America’s Blood Centers—and the Department of Health and Human Services. The CDC estimates the current need for clean blood and blood products in Puerto Rico is 2,500 units of red blood cells, and an additional 1,000 units of other blood products, every week.

Despite the protections put in place by the FDA, public health authorities are braced for the possibility that transfusion-associated Zika could begin occurring in the United States. “This could happen at any time,” Kuehnert acknowledged.

He added: “It is possible we could get a transfusion or transplant transmission case before we even know local transmission of Zika is occurring,” because the illness that necessitates a transfusion—or the immunosuppressive drugs that transplants recipients take—make them more vulnerable to disease. “We are doing a lot of work to be prepared.”


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Disorganized Mosquito Control Will Make US Vulnerable to Zika

As Zika virus advances in Central and South America, and more US residents (almost 150 so far) return from the area with infections, public health officials are braced for the next likely step: the moment when Zika passes from a traveler bearing the virus in his or her blood, to a local mosquito, and then to another person. That viral traffic has the potential to ignite Zika outbreaks in the United States in the areas where the mosquito species which carry it already flourish, across the South, in the Mid-Atlantic states and as far north as Des Moines, Cleveland and New York.

And though no one is yet talking about it publicly, that presents an enormous problem. In the United States, mosquito control — the tracking, spraying and surveillance that, in the absence of a vaccine, provides the best defense — is conducted by a crazy quilt of local districts that are dependent on cities and counties for funding and personnel. Some belong to local health departments, and others to departments of agriculture, transportation, or parks and recreation; almost none of them answer to the Centers for Disease Control and Prevention, the federal agency that directs US response to new disease threats.

When Zika arrives, that unorganized patchwork could leave the United States vulnerable to a rapidly expanding epidemic. The time that it would take to reorganize mosquito control into a coordinated system may already be running out.

CDC maps of the ranges of two mosquito species that could transmit Zika virus.
CDC maps of the ranges of two mosquito species that could transmit Zika virus.
Graphic from CDC.gov, original here.

“There are more than 700 mosquito-abatement districts in the United States, and it can be very difficult to figure out where they fit into public health,” says Joseph Conlon, a former US Navy entomologist who serves as a spokesman for the American Mosquito Control Association. “Chesapeake, Va. has its own taxing district, nothing to do with the health department. Massachusetts has seven mosquito-control districts, run by the state; so does Delaware. Florida has a government body that establishes policy, but mosquito control is done at the county level; I think they’ve got 66 local abatement districts.”

Some of those bodies, he cautioned, are as well-funded as if they were private industry: “Lee County, Fla., where Fort Myers is, has a budget of $24 million. They have 27 aircraft, more mosquito-control capability than anywhere else in the world. But other places don’t have the budget to do aerial spraying, or the capacity to do mosquito surveillance to drive their control programs. There’s not enough lab capacity, no funding for communication, which is critical.”

Al Hoffer, foreground, with Hoffer Pest Solutions, sprays for mosquitoes as homeowner Bryan Ballejo looks on in Boca Raton, Florida, February 2016. Photograph by Wilfredo Lee, AP
Al Hoffer, foreground, with Hoffer Pest Solutions, sprays for mosquitoes as homeowner Bryan Ballejo looks on in Boca Raton, Florida, February 2016. Photograph by Wilfredo Lee, AP

The uneven status of mosquito defenses is no secret among public health workers, who have been trying for several years to get policy-makers’ attention. Last year, the Association of State and Territorial Health Officials presciently wrote in a report, “Before the Swarm,” assessing vector (that is, not just mosquitoes, but ticks and other insects) control efforts:

The unpredictable nature and severity of vector-borne disease outbreaks demonstrates the urgent need for careful preparation and the incorporation of vector-control emergency-management activities into overall public health preparedness efforts. Since climate change is altering temperature and precipitation patterns across the country, it is critical that public health professionals also prepare for a potential increase in the geographic spread of existing vectors, such as Aedes albopictus or Aedes aegypti, and potentially for new vector-borne diseases.

In 2014, the Council of State and Territorial Epidemiologists examined staffing and budgets for mosquito control in state and large city health departments, comparing levels in 2012 and in 2004, the year that West Nile virus spread to all of the lower 48 states. They found dismaying drops:

  • Overall federal funding down 60 percent, from $24 million to $10 million.
  • Number of staff working at least half-time on West Nile surveillance: down  41 percent.
  • Proportion of states conducting mosquito surveillance: down from 96 percent to 80 percent.
  • States that had reduced mosquito trapping: 58 percent; states that had reduced mosquito testing: 68 percent.
  • States that had reduced testing of human patients suspected of having West Nile: 46 percent.

The group warned that lab capacity in the states, crucial for detecting which of many mosquito- and tick-borne diseases have arrived, and where they are going next, had been deprived of enough money and expertise to be unrecoverable.

Although many state public health laboratories have the capability to test for St. Louis encephalitis (79%), Eastern equine encephalitis (59%), Western equine encephalitis (39%) or LaCrosse (42%) viruses, routine testing for these viruses by state laboratories in meningoencephalitis patient specimens actually occurs much less frequently than for West Nile virus (SLE 73%, EEE 27%, WEE 9%, LaCrosse 8%). In part, this disparity results from inadequate laboratory staffing. Further, only nine state laboratories perform testing for dengue, four for Powassan, and two each for Chikungunya and Colorado tick fever viruses.

“There’s a critical gap of efficiency,” says Dr. E. Oscar Alleyne, a senior advisor at the National Association of County and City Health Officials, who at the start of the West Nile epidemic was the director of epidemiology of Rockland County, NY. “Those that do it obviously try to do it as well as they can, but the reality is, the defunding of many of these vector-borne programs for the sake of other programs, or for the sake of something that’s a little bit more sexy, from a Congressional standpoint, has had an impact on the ability for folks to rapidly mobilize.”

Making things worse, he pointed out, is that whatever mosquito-control capacity still exists was built to respond to West Nile. But Zika is spread by different mosquito species that live in different environmental niches and bite at different times of day; existing lab tests and already-owned mosquito-catching equipment do not match those species. Alleyne said: “You have a defunded system, you have a lessened capacity, and now you have a new threat that, with the equipment that you have, doesn’t provide you with adequate mechanisms to know how to detect them and respond.”

An Aedes aegypti mosquito, the chief vector of Zika virus.
An Aedes aegypti mosquito, the chief vector of Zika virus.
Photograph by James Gathany, CDC

Detecting the Aedes mosquitoes that spread Zika is a particular challenge because those species can breed in very small pools of water: puddles in discarded tires, upturned bottle caps. Anywhere with poor garbage collection, reduced municipal services, or low-quality housing represents prime habitat, and wiping out that habitat requires having enough personnel to scour private properties and go door to door. Dr. Peter Jay Hotez, a noted tropical disease expert who is dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, sees those practically outside his door.

“The Gulf Coast has both species of mosquitoes, and has the second risk factor for Zika, which is extreme poverty,” he told me. “People who live in poverty don’t have access to window screens, don’t have garbage collection;  in many poor neighborhoods, you see plastic containers filled with water, cups discarded, tires lying on the side of the road.”

Without well-funded, well-staffed mosquito surveillance, he said, “We won’t know that Zika’s here until babies start showing up in delivery suites with microcephaly.”

The Obama Administration has asked Congress to authorize a $1.8 billion emergency fund to respond to Zika, with $828 million of that for the CDC. As welcome as that will be, if it is approved, public health experts worry it may not be enough, for two reasons. First, since many mosquito control bodies don’t belong to the public health pyramid—which has the Department of Health and Human Services at the top, then the CDC, then state health departments, then county or city ones—there is no existing mechanism by which money can be funneled to them quickly.

And second, the money—as abundant as it might be—is a one-time emergency appropriation. That means it is likely there will be specific things on which it can and can’t be spent. On the likely list: equipment, assays, physical goods. On the not-likely: ongoing salaries. But those working in the field say that what public health needs most is steady funding to prop up its depleted workforce—and in the past decade, it has been persistently deprived.

“On an annual basis, public health funding continues to be at best fairly flat, and emergency preparedness funding has declined since the bump-up after 9/11,” says Richard Hamburg, interim president and CEO of the nonprofit Trust for America’s Health, which studies public health capacity. “We should be learning that we can’t jump from one emergency funding vehicle to another. We need to maintain a constant higher level of funding to ensure foundational capabilities, no matter what emergency comes through.”

 Update: Via Twitter, Tyler Dukes of WRAL.com in Raleigh, NC points out his colleague Mark Binker’s discovery that North Carolina has already sacrificed its mosquito-control funding to budget cuts.
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An Epidemic 14 Years Ago Shows How Zika Could Unfold in the US

An Aedes albopictus mosquito, which health authorities worry may begin to spread Zika.
An Aedes albopictus mosquito, which health authorities worry may begin to spread Zika.
Photograph by James Gathany, CDC.

If the Zika virus comes to the United States, we could face the threat of the same sort of virgin soil epidemic—an infection arriving in a population that has never been exposed to it before—that has caused more than 1 million known infections, and probably several million asymptomatic ones, in Central and South America. It’s nerve-wracking to wonder what that would be like: How many people would fall ill, how serious the effects would be in adults or in babies, and most important, how good a job we would do of protecting ourselves.

But, in fact, we can guess what it would be like. Because we have a good example, not that long ago, of a novel mosquito-borne threat that caused very serious illness arriving in the United States. And the data since its arrival shows that, despite catching on fairly quickly to what was happening, the U.S. didn’t do that good a job.

This possibility became more real Monday when the Pan American Health Organization released a statement that predicts Zika virus, the mosquito-borne disease that is exploding in South and Central America and seems likely to be causing an epidemic of birth defects especially in Brazil, will spread throughout the Americas. PAHO, which is a regional office of the World Health Organization, said:

There are two main reasons for the virus’s rapid spread (to 21 countries and territories): (1) the population of the Americas had not previously been exposed to Zika and therefore lacks immunity, and (2) Aedes mosquitoes—the main vector for Zika transmission—are present in all the region’s countries except Canada and continental Chile.

PAHO anticipates that Zika virus will continue to spread and will likely reach all countries and territories of the region where Aedes mosquitoes are found.

Those “countries and territories where Aedes mosquitoes are found” include a good portion of the United States, as these maps from the Centers for Disease Control and Prevention demonstrate:

CDC maps of the ranges of two mosquito species that could transmit Zika virus.
CDC maps of the ranges of two mosquito species that could transmit Zika virus.
Graphic from CDC.gov, original here.


The recent history is this: In the summer of 1999, the New York City health department put together reports that had come in from several doctors in the city and realized that an outbreak of encephalitis was moving through the area. Eight people who lived in one neighborhood were ill, four of them so seriously that they had to be put on respirators; five had what their doctors described as “profound muscle weakness.”

Within a month, 37 people had been identified with the perplexing syndrome, which seemed be caused by a virus, and four had died. At the same time, veterinarians at the Bronx Zoo discovered an unusual numbers of dead birds: exotics, like flamingos, and city birds, primarily crows. Their alertness provided the crucial piece for the CDC to realize that a novel disease had landed in the United States: West Nile virus, which was well-known in Europe, but had never been seen in this country before.

West Nile is transmitted by mosquitoes in a complex interplay with birds. It began moving with both birds and bugs down the East Coast and then across the Gulf Coast. As it went, the CDC realized that the neurologic illness that marked the disease’s first arrival had not been a one-time event, but its own looming epidemic within the larger one. “Neuroinvasive” West Nile, which in its worst manifestations caused not transient encephalitis but long-lasting floppy paralysis that resembled polio — and sometimes killed — bloomed in the summer of 2002 east of the Mississippi, and then moved west in the years afterward as the disease exhausted the pool of the vulnerable.

The CDC’s maps showing the emergence of “neuroinvasive” West Nile virus disease from 2001 to 2004; areas in black had the highest incidence.
Graphic by Maryn McKenna using maps by the CDC; originals available here.

So far, so normal, for a newly arrived disease. But here’s where the story gets complicated. By the beginning of this decade, West Nile had become endemic in the lower 48 states. It is not a mysterious new arrival; it is a known, life-altering threat. Its risk waxes and wanes with weather and insect populations, but it has one simple preventative: not allowing yourself to be bitten by a mosquito.

And yet: Here are the CDC’s most recent maps of neuroinvasive West Nile—showing that people are still falling to its most dire complication, 14 years after it was identified.

The CDC's maps for 2011-2014 showing the incidence of "neuroinvasive" West Nile virus disease; areas in black had the highest incidence.
The CDC’s maps for 2011-2014 showing the incidence of “neuroinvasive” West Nile virus disease; areas in black had the highest incidence.
Graphic by Maryn McKenna using maps by the CDC; originals available here.

The point here is not that people are careless or unthinking; in the early years of West Nile, two of the victims were the husband of the CDC’s then director, and the chief of its mosquito-borne diseases division, who would have been well aware of the risks. (Both recovered fully.) The point is that always behaving in a manner that protects you from a mosquito bite—conscientiously, persistently, faultlessly emptying pots and puddles, putting on long sleeves and repellent, choosing when not to go outdoors—is very difficult to maintain.

Zika is not West Nile. Among other things, Zika is spread by many fewer species of mosquitoes — one or possibly two, compared to 65 for West Nile. And West Nile’s non-human hosts, birds, live in closer proximity to more of us than Zika’s, which appear to be non-human primates. But though the rare, deadly complications of West Nile virus infection are different from those of Zika, they are just as serious and life-altering — and yet we failed to protect ourselves from them. As Zika spreads, we can hope that is a lesson we learn in time.

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CDC Recommendations for Pregnant Women Exposed to Zika

An Aedes aegypti mosquito, the chief vector of Zika virus.
An Aedes aegypti mosquito, the chief vector of Zika virus.
Photograph by James Gathany, CDC

(This post has been updated twice.)

The Centers for Disease Control and Prevention has responded to growing alarm over the Zika virus epidemic in Central and South America with quickly published guidelines covering health care and tests for pregnant women who may have been exposed to the virus.

The guidelines come on the heels of the CDC’s recommendation last Friday night that US women who are pregnant, or planning to become pregnant, avoid traveling to the 13 countries where transmission of Zika has occurred, and also to the US territory of Puerto Rico.

Zika, which is transmitted by mosquitoes, arrived in South America in 2014 and ignited a pandemic. Most of the adult cases, which number more than 1 million, have been mild. (It is generally accepted that four out of five people infected with Zika do not develop symptoms; so the true number of those infected is likely more than 5 million.) But in Brazil, there has been an epidemic of a birth defect called microcephaly—smaller than usual brains and heads in newborns— that is associated temporally, and by some lab tests, with Zika infection. So far in Brazil there have been more than 3,500 cases of microcephaly. Zika has come to the United States as well, with local transmission in Puerto Rico and an imported case in the county surrounding Houston, and on Friday, a baby born in Hawaii to a woman who lived in Brazil while she was pregnant was diagnosed with Zika microcephaly. Today, the Illinois Department of Public Health disclosed that it is monitoring two pregnant women who traveled to Zika transmission areas.

(Update, Jan. 20: According to Florida media, that state’s department of health has announced three cases in Florida, all travel-related.)

The CDC’s guidelines today offer advice for pregnant women who traveled to a location where Zika is circulating, whether or not the woman reports symptoms of Zika infection: sudden fever, a rash, conjunctivitis, and joint pain. Broadly, women with a travel history and symptoms should have blood drawn to be tested for Zika infection—the test can be performed only by the CDC and some health departments—and if positive, should have regular ultrasounds to track fetal development and should be seen by one of several specialists. Pregnant women who traveled to a Zika area but did not experience symptoms are recommended to undergo ultrasounds first, and to seek a test to confirm infection if there are abnormalities in the imaging.

The CDC's advice for testing and treating pregnant women exposed to Zika virus, expressed as a flow chart.
The CDC’s advice for testing and treating pregnant women exposed to Zika virus, expressed as a flow chart.
Graphic by the CDC; original here.

Within the text of the recommendations, which were published as an early release from the CDC’s weekly journal Morbidity and Mortality Weekly Report, there are hints of how complex this emerging situation has become. There is no vaccine for Zika, so as prevention the agency can recommend only “wearing long-sleeved shirts and long pants, using U.S. Environmental Protection Agency-registered insect repellents, using permethrin-treated clothing and gear, and staying and sleeping in screened-in or air-conditioned rooms.” There is no specific treatment, so it can recommend only “rest, fluids, and use of analgesics and antipyretics. Fever should be treated with acetaminophen.” (The CDC specifically rules out aspirin, because the mosquito-borne diseases chikungunya and dengue are also circulating in the areas where Zika is, and dengue can lead to hemorrhagic fever—so drugs that can increase bleeding are not recommended.)

The limited options for confirming Zika in a fetus are especially difficult, since amniocentesis—which could yield a sample for testing—also carries a risk of miscarriage. The CDC says:

Zika virus RT-PCR testing can be performed on amniotic fluid. Currently, it is unknown how sensitive or specific this test is for congenital infection. Also, it is unknown if a positive result is predictive of a subsequent fetal abnormality, and if so, what proportion of infants born after infection will have abnormalities. Amniocentesis is associated with an overall 0.1% risk of pregnancy loss when performed at less than 24 weeks of gestation…. early amniocentesis (≤14 weeks of gestation) is not recommended. Health care providers should discuss the risks and benefits of amniocentesis with their patients.

The CDC has also published guidance for health care professionals here, and explanations of how to send samples for testing here.

Update, Jan. 22: The CDC has added Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa to its “don’t travel if pregnant” list.

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For Fear of Zika, CDC Recommends Pregnant Women Not Travel

An Aedes aegypti mosquito, the vector of Zika virus.
An Aedes aegypti mosquito, the vector of Zika virus.
Photograph by James Gathany, CDC.

(This post has been updated with news of the first Zika birth defects case found in the United States.)

In an extraordinary statement likely to launch international controversy, the US Centers for Disease Control and Prevention recommended Friday evening that pregnant women not travel to 14 countries and territories—the commonwealth of Puerto Rico, and Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, and Venezuela—for fear of birth defects associated with infection by mosquito-borne Zika virus.

The recommendation comes in the form of a “Level 2 travel alert,” which in the agency’s lingo represents a warning to “practice enhanced precautions.” In the Zika announcement, the CDC says that pregnant women “should consider postponing travel,” adding, “pregnant women who must travel to one of these areas should talk to their doctor or other healthcare provider first and strictly follow steps to avoid mosquito bites.” Women planning to become pregnant, it says, “should consult with their healthcare provider before traveling to these areas.”

Zika virus has been exploding in South and Central America. In Brazil, where the virus arrived just seven months ago, there have been more than 1 million cases of infection, and more than 3,500 cases of a rare birth defect called microcephaly, babies born with smaller than normal skulls and brains.

The warning follows the CDC’s own analysis of samples from two stillborn children and two who died after birth who suffered microcephaly. The agency said:

“For the two full-term infants, tests showed that Zika virus was present in the brain. Genetic sequence analysis showed that the virus in the four cases was the same as the Zika virus strain currently circulating in Brazil.  All four mothers reported having experienced a fever and rash illness consistent with Zika virus disease during their pregnancies.”

The countries and territories named by the CDC Friday are jurisdictions where Zika virus transmission has been confirmed. (On Friday, one other country not mentioned in the CDC’s list, Guyana, also reported cases, according to Caribbean media.)

The warning not to travel—made, the CDC said, “out of an abundance of caution”— is likely to be controversial. It warns women away from the site of the Olympics, which take place in Rio de Janeiro in August, as well as from most of the beach and tourist economies of Central and South America. In what may be a first, it warns citizens of the United States from entering a part of the United States, the unincorporated territory of Puerto Rico.

Puerto Rico is part of the advisory because Zika infections have occurred there. Zika has also landed in Texas, via a local resident who was infected in Latin America and returned there, but has not been transmitted locally.

How far the risk of imported Zika might be spread by local mosquitoes.
How far the risk of imported Zika might be spread by local mosquitoes.
Graphic from Bogoch et al., The Lancet.

But researchers from several countries said in The Lancet Thursday that infected travelers should also be considered a risk to their home countries, because virus levels in their blood could be high enough to pass Zika back to local mosquitoes when they return.

As a result, they said, some among the 9.9 million travelers who leave from Brazilian airports every year could bring the disease with them and establish it at their destinations. The US receives 2.7 million travelers yearly from Brazil; Italy, 419,000; France, 404,000; and China, 84,000.

The main mosquito species responsible for spreading Zika, Aedes aegypti, flourishes in the far Southern US, and a second species that may transmit the virus, Aedes albopictus, ranges as far north as New York. Thus, the researchers said, if Zika virus came to the United States, 22.7 million people — primarily in Southern California, South Texas and Florida — would be at risk of contracting the disease year-round, and possibly 60 million seasonally if both mosquito species were involved.

Update: Late Friday evening, the CDC also sent out a HAN, a Health Alert Network advisory to health care workers to help them recognize possible cases of Zika. It’s here.

Update 2: Also late Friday, the Hawaii State Department of Health announced that it has identified the first case of Zika-related birth defects in the US, in a baby born on Oahu to a woman who became pregnant while living in Brazil last summer.

“This case further emphasizes the importance of the CDC travel recommendations released today,” state epidemiologist Dr. Sarah Park said in the announcement. “An astute Hawaii physician recognized the possible role of Zika virus infection, immediately notified the Department of Health, and worked with us to confirm the suspected diagnosis.”

So far six Hawaii residents have been found infected with Zika, the announcement said, but all caught the disease outside the state. Hawaii has made Zika a reportable disease, which means physicians who recognize a case are obliged to inform the state department.

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Zika Virus: A New Threat and a New Kind of Pandemic

An Aedes aegypti mosquito, the chief vector of Zika virus.
An Aedes aegypti mosquito, the chief vector of Zika virus.

The leader of infectious disease research in the U.S. government says that the pandemic of Zika virus spreading across the global south, which may be causing an epidemic of birth defects in South America, heralds a new kind of infectious disease threat. It is exploding at the same time and in the same areas as other diseases carried by the same vector, mosquitoes—and thus demonstrates that it is no longer enough to be prepared to counter one disease at a time.

Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, writes in a study released Wednesday in the New England Journal of Medicine with Dr. David Morens of NIAID that Zika arrives in the Americas on the heels of three other mosquito-borne diseases: West Nile virus, in the United States since 1999 and still causing cases; chikungunya, which has invaded the Caribbean and Central America; and dengue, which moved north from the tropics to become re-established in Florida.

“Zika virus forces us to confront a potential new disease-emergence phenomenon: pandemic expansion of multiple, heretofore relatively unimportant arboviruses previously restricted to remote ecologic niches,” they write. “To respond, we urgently need research on these viruses and the ecologic, entomologic, and host determinants of viral maintenance and emergence. Also needed are better public health strategies to control arboviral spread.”

As I reported a month ago, Zika—which is often a mild disease of fever, aches and rash—has spiked extraordinary alarm in Brazil because it is overlaid with, and may be causing, an epidemic of babies being born with unusually small brains and heads. The microcephaly, as it is called, has not been proven to be caused by Zika, but people are so alarmed that, as one commenter here wrote, “People here are very worried about Zika virus, especially pregnant women and the ones trying to get pregnant… In the timespan of two weeks my city has gone from ‘never heard of this virus’ to thousands of infecteds, inclunding myself, my husband, and several relatives and friends of mine.”

At that point, Zika had spread from the shoulder of South America up through Central America and into Mexico. Since then, it has also been found in Puerto Rico, in a person who had not traveled outside the country—putting it on U.S. soil though not in the continental United States—and on Monday, in the vicinity of Houston, though that person was probably infected while traveling.

Zika, dengue and chikungunya are spread by the same mosquito species, A. aegypti, which has adapted to live near humans: It flourishes in small pools and containers of water, like a flower pot or the puddle in a tire. There are limited tests for the diseases—none for Zika, and sparsely distributed ones for the other two —and no treatments for them other than supportive care. Their initial symptoms are similar, but because they have different serious complications—birth defects for Zika, hemorrhagic fever for dengue, reactive arthritis for chikungunya—it is possible to make mistakes in the early stages that can make the late consequences worse.

The researchers argue that all of this adds up to a new responsibility to both prevent diseases, and also confront that prevention is a broader task than has previously been understood. In the case of these mosquito-borne diseases, a “one bug one drug” approach is inadequate, they say. What is needed: broad-spectrum drugs that can address whole classes of viruses, and vaccine “platforms” that can be adjusted as needed to prevent infection with whatever virus arrives on the scene. But more broadly, these diseases provide a lesson, of how rapidly and lethally emerging threats—possibly, multiple threats— will take us by surprise if we do not prepare.

“In our human-dominated world, urban crowding, constant international travel, and other human behaviors combined with human-caused microperturbations in ecologic balance can cause innumerable slumbering infectious agents to emerge unexpectedly,” they write. “We clearly need to up our game with broad and integrated research that expands understanding of the complex ecosystems in which agents of future pandemics are aggressively evolving.”


Previously on Phenomena:

Dec. 2, 2015: Mosquitoes Bring Disease, Maybe Birth Defects, to US Border.





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Raindrops Keep Falling on My Head: A Mosquito’s Lament

This, in case you were wondering, is a mosquito.

Picture of a drawing of a mosquito
Drawing by Robert Krulwich
Drawing by Robert Krulwich

This is a raindrop.

Picture of a drawing of a blue raindrop
Drawing by Robert Krulwich
Drawing by Robert Krulwich

And here’s a puzzle. Raindrops aren’t mosquito friendly. If you’re a mosquito darting about on a rainy day, those drops zinging down at you can be, first of all, as big as you are, and, more dangerously, they’re denser. Water is heavy, so a single raindrop might have 50 times your mass, which means that if one hits you smack where it hurts (between your wings) …

Picture of a mosquito being hit by a drop of water
Photograph by Tim Nowack
Photograph by Tim Nowack

… you should flatten like a pancake. A study says a mosquito being hit by a raindrop is roughly the equivalent of a human being whacked by a school bus, the typical bus being about 50 times the mass of a person. And worse, when it’s raining hard, each mosquito should expect to get smacked, grazed, or shoved by a raindrop every 25 seconds. So rain should be dangerous to a mosquito. And yet (you probably haven’t looked, but trust me), when it’s raining those little pains in the neck are happily darting about in the air, getting banged—and they don’t seem to care. Raindrops, for some reason, don’t bother them.

Picture of a drawing of mosquitos flying through the air, dodging large blue raindrops
Drawing by Robert Krulwich
Drawing by Robert Krulwich

Why not? Why aren’t the mosquitoes getting smooshed?

How Mosquitoes Survive Raindrops

Well, in 2012 David Hu, a professor of mechanical engineering at Georgia Tech, became interested in this problem and decided to pelt some airborne laboratory mosquitoes with water droplets while filming them with a high-speed camera—4,000 to 6,000 frames a second instead of the usual 24. That way he could watch them in super slow motion and figure out what they’re doing when they’re out in the rain. He published his findings in a 2012 paper that I’m going to describe here in “executive summary” form. (His video, by the way, is waiting for you below, so you can see what he saw for yourself.)

What he found is that most of the time anopheles mosquitoes don’t play dodgeball with the raindrops. They do get hit but usually off center, on their long gangly legs, which splay out in six directions. The raindrop can set them rolling and pitching, but they recover quickly—within a hundredth of a second. But even in the worst case, where the mosquito gets slammed right between the wings—a dead-on collision, because the mosquito is so light compared to the heavy raindrop …

Picture of a drawing of a mosquito clinging onto a falling raindrop as it descends through the air
Drawing by Robert Krulwich
Drawing by Robert Krulwich

… it doesn’t offer much resistance, and the raindrop just barrels along with the mosquito suddenly on board as a passenger. Had the raindrop slammed into a bigger, slightly heavier animal, like a dragonfly, the raindrop would “feel” the collision and lose momentum. The raindrop might even break apart because of the impact, and force would transfer from the raindrop to the insect’s exoskeleton, rattling the animal to death.

But because our mosquito is oh-so-light, the raindrop moves on, unimpeded, and hardly any force is transferred. All that happens is that our mosquito is suddenly scooped up by the raindrop and finds itself hurtling toward the ground at a velocity of roughly nine meters per second, an acceleration which can’t be very comfortable, because it puts enormous pressure on the insect’s body, up to 300 gravities worth, says professor Hu.

Picture of a drawing of a mosquito inside a raindrop, falling through the air
Drawing by Robert Krulwich
Drawing by Robert Krulwich

300 Gs is a crazy amount of pressure. Eric Olsen, at his blog at Scientific American, says a jet pilot accelerating out of a loop-de-loop experiences “only about nine gravities (88/m/squared).” One imagines his cheeks all splayed, his face squishy, but hey, that’s a soft-skinned human. We’ve got mosquitoes here. Their heads are harder. They have exoskeletons. Sudden accelerations don’t hurt as much, but what mosquitoes should fear, what they do fear, are crash landings. The ground is a lot harder than a mosquito.

Picture of a drawing of a mosquito being squished by a large blue raindrop
Drawing by Robert Krulwich
Drawing by Robert Krulwich

So what a mosquito has to do is get off that raindrop as quickly as possible. And here comes the best part: In most direct hits, Hu and colleagues write, the insect is carried five to 20 body lengths downward, and then, rather gracefully—maybe helped by a dense layer of wax-coated, water-repellent hairs—gets up and “walks” to the side, then steps off into the air, almost like a schoolchild getting off of a bus (albeit a fast-moving bus hurtling toward its doom). It does this almost matter-of-factly, like it’s no big deal. A mosquito, Hu writes, “is always able to laterally separate itself from the drop and recover its flight.” Always. (Unless the raindrop hits them too close to the ground.) If you want to see this for yourself, take a look at Hu’s video.

Video by David Hu and Andrew Dickerson

The moral here, should we need one, is that if you’re a mosquito on a rainy day, the place to be is high off the ground, and if you’re a human who worries about mosquito safety (not a big group, I know), you can move on. They solved this one roughly 90 million years ago.

Picture of a drawing of a mosquito with its arm around a raindrop, as though they were friends
Drawing by Robert Krulwich
Drawing by Robert Krulwich
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To Beat Malaria, We Need to See It as an Ecological Problem

It’s easy to just think of malaria as a medical problem. It is caused by single-celled parasites—Plasmodium—that are spread through the bites of other parasites—mosquitoes. To beat the disease, we need to neutralise either Plasmodium or its mosquito carriers, using drugs, insecticides, nets, or even genetically-modified competitors.

But malaria is also an ecological problem. Mosquitoes aren’t static, unchanging targets. They move around. They mate. They breed in some areas and not in others. Their populations swell and contract throughout the year. They bite at varying times of day. We need to understand these subtle quirks of mosquito life, because they all have a huge impact on our strategies for fighting malaria.

Consider the Sahel—a belt of land that stretches across Africa’s waist, with the Sahara to the north and savannahs to the south. In this region, half a million people die from malaria every year—which is puzzling. Every year, between December and June, the Sahel goes through an intense dry season. Rain hardly falls. Stagnant pools and puddles, in which mosquitoes lay their eggs, evaporate. The adults ought to die before they can start a new generation. And yet, when the rains return, so do malarial mosquitoes, in huge numbers. How do they survive?

Scientists have puzzled over this ‘dry season paradox’ for more than a century. Some said that the insects persist through the dry spell in a dormant state, while others felt that they migrate over long distances to more habitable climes.

Now, a team of scientists led by Adama Dao from the University of Sciences in Mali, and Tovi Lehmann from the US National Institutes of Health, have finally found that both answers are right. Some species of malarial mosquitoes persist; others travel. And that has big implications for our attempts to stop malaria in this critical region.

The same pond near Thierola village, during the wet and dry seasons. Credit: Drs. Adama Dao, Alpha S. Yaro and Tovi Lehmann
The same pond near Thierola village, during the wet and dry seasons. Credit: Drs. Adama Dao, Alpha S. Yaro and Tovi Lehmann

Under Dao’s leadership, a team of researchers from Mali spent years counting the numbers of malarial mosquitoes in the Malian village of Thierola. They checked for larvae in every puddle, tree hole, or well they could find. They collected adults from every house in the village, and used a variety of traps to capture those flying outside. And they did this on every fourth day or so, for five years.

“How mosquitoes survive the dry season is a deceptively simple question, but it has been very difficult to answer,” says Jason Rasgon from Pennsylvania State University . “It takes the kind of heroic sampling effort that the authors performed to get a handle on this issue.”

The team found different patterns for each of the three different species of malarial mosquitoes in the area. Anopheles coluzzi is the most common of these. Its populations peak in September and October, at the height of the wet season, before plummeting in November as the larval sites dry up. They stay at low levels for most of the dry months, with two exceptions: huge short-lived population spikes in December and April, when numbers suddenly soar by 10 to 90 times. And once it starts properly raining in June, A.coluzzi bounces back almost immediately.

These patterns suggest that the adults somehow wait out the dry season in a dormant state. They can take advantage of any rare bursts of rain, and they’re ready and waiting when the wet season truly begins.

The other two species—Anopheles gambiae and Anopheles arabiensis—showed very different patterns. Neither of them had any peaks during the dry season. Once their populations fell, they stayed that way until the rains returned. Even then, it took a few months for them to bounce back. It seems that these two species survive by migrating to other areas, hundreds of kilometres away.

Credit: Dao et al, 2014. Nature.
Credit: Dao et al, 2014. Nature.

“Any mosquito paper that tries to unravel their complex ecology is a winner in my eyes,” says James Logan from the London School of Hygiene and Tropical Medicine. “There is much about malaria mosquito ecology and biology that we still don’t understand, so studies like this could have large implications in the control of diseases like malaria.”

For example, the team suspects that A.coluzzi’s ability to survive in a dormant state allows it to maintain cycles of malaria transmission that would otherwise break during the dry season. By peaking twice during the drought, it can continuously shuttle Plasmodium between humans at a time when the parasite should face dead-ends. When the wet season begins, A.coluzzi can immediately start ratcheting up these cycles of transmission. And when A.gambiae and A.arabiensis return in September and October, they kick things into even higher gear.

Lehmann’s team are now trying to break these cycles by finding A.coluzzi’s dry-season hide-outs and blitzing them with insecticides. They are testing this approach in a larger number of villages.

It seems counter-intuitive to go after the mosquitoes when they’re at their rarest, but those rare populations are critical—they are the seeds of the next wet season’s boom. “By hitting the late dry-season peak and the early wet-season surge, we think we’ll virtually eliminate the seed population,” says Lehmann. “We think we could potentially cut down transmission in those areas by 75 percent or more, and it would be very cost-effective.”

His results also have implications for other malaria control strategies. For example, some scientists are trying to develop genetically modified mosquitoes that cannot harbour Plasmodium, and that would outcompete local insects. But if these GM-mozzies cannot last through the dry season, their impact would be short-lived. And if A.gambiae and A.arabiensis return in the wet season, flying in from distant parts of the Sahel, they would reintroduce a fresh pot of parasites every year. “The long-term planning of the battle against malaria cannot ignore these phenomena,” says Lehmann.

Unfortunately, that’s exactly what people tend to do. Many historical attempts to control mosquitoes have failed dismally because they were build on shoddy ecological foundations. As Heather Ferguson from the University of Glasgow once wrote: “A lot of the knowledge gaps that hindered previous attempts still remain… We have made substantially more headway in understanding the reproductive biology of species with no direct public health or economic importance, such as Drosophila, fur seals and blue tits, than we have done for this vector that kills millions.”

I wrote about this in a piece for Slate in 2011:

“Crucial ecological research on mosquitoes is trapped in a financial no-man’s land. Organizations that fund basic research into issues like how insects behave assume that biomedical agencies will foot the bill, while these agencies are more likely to prioritize research with more obvious and immediate clinical impact. But the necessary ecological studies would not be expensive. Ferguson estimates that it would take just $500,000 to fund 10 students in the field, an act that “could easily quadruple our knowledge of this area within a few years.”

For example, in 2008, her student Kija Mg’Habi worked in an isolated, malarious part of Tanzania and discovered that among Anopheles gambiae (a species that carries malaria), the medium-sized males get the most sex. You might expect the biggest males to outcompete their smaller rivals, but they were actually six times less successful. This is exactly the type of information you need if you want your modified mosquitoes to outcompete their natural brethren… It may not be as sexy as modifying genes, but ecology is tantamount to knowing your enemy, and that surely is a cornerstone of victory.”

Reference: Dao, Yaro, Diallo, Timbine, Huestis, Kassogue, Traore, Sanogo, Samake & Lehmann. 2014. Signatures of aestivation and migration in Sahelian malaria mosquito populations. Nature http://dx.doi.org/10.1038/nature13987

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The Worst Bit About Feeding Mosquitoes Is The Waiting

The worst thing about feeding hundreds of mosquitoes on your own blood is not the itching – if you do it enough times, your body gets used to the bites. It’s not even the pain, although it is always painful since the mosquitoes will use their snouts to root about your flesh in search of a blood vessel.

It is more that, sometimes, the little suckers take their time.

“They just walk around on your arm. You’re sitting there and thinking, ‘Seriously? I have things to do’,” says Chiara Andolina.

Andolina is an infectious-disease researcher who works at the Shoklo Malaria Research Unit, a world-renowned laboratory nestled in an unassuming town near Thai–Myanmar border. She runs the Unit’s insectory, where mosquitoes are bred, reared, infected with the Plasmodium parasites that cause malaria, and dissected.

There are only five or six such facilities in Thailand, largely because the malarial mosquitoes of South-east Asia are delicate, wilting flowers. In Africa, malaria is transmitted by Anopheles gambiae – a hardy insect with catholic tastes. They will go without food for days. They will endure through tough environmental conditions. They will suck blood from rabbits, cows… basically anything that they can get their proboscis into.

Their Asian cousins, Anopheles dirus, are very different. “You blow on them a little bit and they’re like: ‘No. I’m not mating today. I’m upset.’” They also refuse to eat anything except human blood, which is why Andolina has to feed them herself.

She does this simply by sticking her arm through a muslin sock and into their cages. It takes half an hour and she does it every four days. “They’re very spoiled,” she says.

Andolina fed around 600 mosquitoes yesterday and you wouldn’t be able to tell – her arm is free of any marks because she has built up resistance to the allergens in the mosquito saliva. Her boss, François Nosten, had to fill in for her two weeks ago and his arm is still covered in welts. This is why there is no feeding rota. It’s just Andolina. She has tried to convince her research assistants to help but, for some strange reason, they aren’t keen.

The boxes contain two closely related species of mosquito: Anopheles dirus B and C. The two colonies have to be kept apart. If someone mixes them by mistake, it would be nigh impossible to fix the error. B and C look identical, even under the microscope, and only their genes reveal them to be distinct species. They also transmit very different malarial parasites: B carries Plasmodium falciparum, the main cause of malaria in these parts, while C transmits P. vivax. Andolina once spent a few years on an experiment that just wouldn’t work, because she was trying to infect one of the species with the wrong parasite.

Only female mosquitoes drink blood, and they use proteins in their meals to make the shells of their eggs. But they also need mating partners, and A. dirus are as finicky about sex as they are about food. Andolina used to have to force-mate them.

To begin: decapitate a male, and anaesthetise a female with ether. Next, unite the two by inserting the male’s still-protruding genitals into his unconscious partner. Get it right and the two insects (or one-and-a-half insects) lock together, sperm is transferred, and the female becomes pregnant. Andolina first learned to do this without a microscope. It took steady hands.

The females lay their eggs as little floating rafts. It takes two days for these to hatch into larvae, which hang from the water’s surface, breathing from their rear ends and sweeping up passing debris with brush-like mouthparts. Andolina keeps them in a succession of trays, nourished with tropical fish food. She needs to change the water regularly, or the larvae quickly succumb to all manner of bacterial, viral and fungal infections. They are not the toughest of species.

It takes another two weeks for them to turn into adults. Now, they’re ready for experiments. Typically, this involves infecting them with malaria.

Andolina loads a feeding pump with blood samples from people with malaria. The pump delivers the blood into a grey cylinder, with a membrane stretched across it. She places this on top of a sheet of muslin, draped over an empty noodle cup containing dozens of mosquitoes. The cylinder is like an upside-down feeding trough. The mosquitoes dangle upside-down from the muslin, pierce the adjacent membrane, and suck up the blood.

"Guys, what did you do with my noodlOH MY GOD!"
“Guys, what did you do with my noodlOH MY GOD!”

Once they are infected, security is paramount. The law dictates that there must be four doors between them and the outside world, so they’re kept inside an incubator within one of three adjoining rooms. Andolina counts them every day to make sure that none have escaped. If she ever misses one – and that hasn’t happened yet – she won’t be allowed to leave the lab until she has found and killed it.

“I don’t do it because I love mosquitoes,” says Andolina. Her work creates a ready supply of parasites. She provides these to collaborators in Paris and Singapore, who are trying to develop new drugs that target malarial parasites holding out in a patient’s liver.

More directly, she wants to see if a drug called primaquine can help to break the cycle of malaria transmission. The drug kills malarial parasites in the liver, but there’s a chance that it could also stop the mosquitoes from becoming infected. Andolina wants to see if mosquitoes are less likely to pick up the parasites after feeding on the blood of patients who have taken low doses of primaquine.

At high doses, the drug produces nasty side-effects in some patients. If lower doses are still effective, then primaquine could feature in the Shoklo Unit’s radical campaign to completely eliminate malaria from South-east Asia, by treating as many people as possible with antimalarial drugs.

This post first appeared on Mosaic as part of my feature on drug-resistant malaria.

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Here’s What Happens Inside You When a Mosquito Bites

The video above shows a brown needle that looks like it’s trying to bury itself among some ice-cubes. It is, in fact, the snout of a mosquito, searching for blood vessels in the flesh of a mouse.

This footage was captured by Valerie Choumet and colleagues from the Pasteur Institute in Paris, who watched through a microscope as malarial mosquitoes bit a flap of skin on an anaesthetised mouse. The resulting videos provide an unprecedented look at exactly what happens when a mosquito bites a host and drinks its blood.

For a start, look how flexible the mouthparts are! The tip can almost bend at right angles, and probes between the mouse’s cells in a truly sinister way. This allows the mosquito to search a large area without having to withdraw its mouthparts and start over.

“I was genuinely amazed to see the footage,” says James Logan from the London School of Hygiene and Tropical Medicine, who studies mosquitoes. “I had read that the mouthparts were mobile within the skin, but actually seeing it in real time was superb. What you assume to be a rigid structure, because it has to get into the skin like a needle, is actually flexible and fully controllable. The wonders of the insect body never cease to amaze me!”

From afar, a mosquito’s snout might look like a single tube, but it’s actually a complicated set of tools, encased in a sheath called the labium. You can’t see the labrum at all in the videos; it buckles when the insect bites, allowing the six mouthparts within to slide into the mouse’s skin.

Four of these—a pair of mandibles and a pair of maxillae—are thin filaments that help to pierce the skin. You can see them flaring out to the side in the video. The maxillae end in toothed blades, which grip flesh as they plunge into the host. The mosquito can then push against these to drive the other mouthparts deeper.

The large central needle in the video is actually two parallel tubes—the hypopharynx, which sends saliva down, and the labrum, which pumps blood back up. When a mosquito finds a host, these mouthparts probe around for a blood vessel. They often take several attempts, and a couple of minutes, to find one. And unexpectedly, around half of the ones that Choumet tested failed to do so. While they could all bite, it seemed that many suck at sucking.

The video below shows what happens when a mosquito finally finds and pierces a blood vessel. On average, they drink for around 4 minutes and at higher magnifications, Choumet could actually see red blood cells rushing up their mouthparts. They suck so hard that the blood vessels start to collapse. Some of them rupture, spilling blood into the surrounding spaces. When that happens, the mosquito sometimes goes in for seconds, drinking directly from the blood pool that it had created.

When the mosquitoes were infected with the Plasmodium parasites that cause malaria, they spent more time probing around for blood vessels. It’s not clear why—the parasites could be controlling the insect’s nervous system or changing the activity of genes in its mouthparts. Either way, the infected mosquitoes give up much less readily in their search for blood, which presumably increases the odds that the parasites will enter a new host.

Many hours after a bite, Choumet’s team found Plasmodium in the rodents’ skin, huddled in areas that were also rife with the mosquito’s saliva. The mosquito starts salivating as soon as it probes the mouse’s skin, releasing substances that prevent blood vessels from constricting, stop blood from clotting, and prevent inflammation. Sometimes, Choumet could see the saliva as small bubbles that hung around the tips of the mouthparts. And even after the mosquito stops feeding, pockets of saliva linger in the lower layers of the skin. Plasmodium parasites seem to stay in the same place—perhaps they work together with the salivary chemicals to suppress the mouse’s immune system.

The team also tested “immunised” mice, which were loaded with antibodies that recognise a mosquito’s saliva. “Some people, especially in Africa and Asia, are bitten several times every day, so we wanted to know if mosquitoes behaved differently when they bit animals that were immunised against their saliva,” says Choumet.

She found that the antibodies reacted with the insect’s saliva during a bite, forming noticeable white clumps at the tips of the probing mouthparts. This clogged up smaller blood vessels, which stopped the mosquitoes from drinking from them. But the insects got around this problem by probing around for longer, and by hitting the largest blood vessels.

Beyond the stunning videos, these discoveries are unlikely to lead to new ways of preventing or treating malaria by themselves. However, they do tell us a lot more about the event that kicks off every single malaria case—a mosquito bite. It’s a resource that other researchers will undoubtedly use. “I have submitted  a grant application to investigate  aspects of the interactions between mosquitoes, hosts and parasites,” says Logan. “The techniques and discoveries from this paper are very exciting to me, and will be of value to future activities of my own research group.”

Hat-tip to James Logan for alerting me to the story via Twitter, and inspiring the headline!

Reference: Choumet, Attout, Chartier, Khun, Sautereau, Robbe-Vincent, Brey, Huerre & Bain. 2012. Visualizing Non Infectious and Infectious Anopheles gambiae Blood Feedings in Naive and Saliva-Immunized Mice. PLoS ONE http://dx.doi.org/10.1371/journal.pone.0050464

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Mosquitoes temper severity of malaria

In labs around the world, scientists study malaria by injecting rodents with Plasmodium—the parasites that cause the disease. These experiments are necessary but also artificial. In the wild, the needle that spreads malaria isn’t a hypodermic syringe, but a mosquito’s snout.

Both delivery routes end in infection, but they have very different effects. Philip Spence from the National Institute for Medical Research in London has found that malarial parasites cause less severe disease if they have spent time in a mosquito—that is, they become less virulent. Something in them changes so that when they move into a mammal, they trigger a stronger immune response, grow less well and cause milder symptoms.

A word of caution: This doesn’t mean that mosquitoes are protecting us from malaria. They’re not suddenly our allies. Instead, Spence’s study shows that they can temper the lethality of the disease that they spread. They’re not just a vector but a regulator.

It was in 1897 when Nobel prize-winner Ronald Ross found Plasmodium in the stomach of a mosquito that had bitten a malaria patient, and went on to show the parasite’s full life cycle. Now, 118 years later, “Spence has come full circle by uncovering a new way in which mosquitoes play a central role in malaria—not just by transmitting the disease but by modifying its severity too,” says Sarah Reece from Edinburgh University.

“I don’t remember being as excited about a basic malaria paper for a long time,” says Andrew Read from Pennsylvania State University, who studies the evolution of infectious diseases.

The study

When a malarial mosquito bites a human, Plasmodium travels down its snout into the bloodstream of its new host. Its first stop is the liver, where it reproduces before re-entering the blood and infecting red blood cells. Since the blood-stage is when the parasite causes disease, scientists often bypass the rest of the complicated life-cycle. They just transfer parasites from one animal’s blood to another’s. If you do this repeatedly—a technique called serial blood passage—the parasite seems to become more virulent, although no one knew why.

Jean Langhorne, who led the new research, was originally motivated by criticisms that these mouse experiments weren’t relevant enough for human diseases. “We wanted to make our mouse model as relevant as possible, so we wanted to transmit the parasite as naturally as possible,” she says.

Spence, a postdoc in her lab, worked with Plasmodium chabaudi—a species that causes malaria in rodents but produces similar symptoms to human malaria. When injected directly into a mouse’s blood, P.chabaudi grew rapidly and caused severe chills, weight loss, fatigue and liver damage. But when transmitted by a mosquito, it grew slowly and the mice barely suffered. They became anaemic, but not much else.

The same thing happens to the parasites that cause sleeping sickness after passing through their  tsetse fly vectors. “There was a feeling that this happens in malaria too but this is the first strong evidence for that,” says Read.

The mosquito-borne parasites trigger a very different immune reaction from the mice than those that are injected directly. The rodents marshal a bigger squadron of white blood cells to recognise the invaders and attack them with antibodies. At the same time, these cells produce fewer of the inflammatory molecules that are linked to severe disease.

But it’s not just about the host. Spence found that a spell in a mosquito changes the activity of around 10 percent of the parasite’s genes. These include the majority of the pir genes, which produce proteins that are recognised by the host’s immune system. The upshot is that the mice are better able to control their parasites if delivered by mosquito rather than syringe… but largely due to changes in the parasites themselves.

What does it mean?

Read says that the study reveals two sides to Plasmodium. The parasites have genes that trigger a strong immune response, which leads to mild, long-lasting infections and less collateral damage for their hosts. But they must also have genes that trigger a stronger short-term infection—that’s what you see if you inject them directly into the blood.

“Within its genome, the parasite has the capacity to produce two very different infection profiles,” Read says. Short, strong infections are a good strategy in an epidemic, when hosts are plentiful. But in long dry seasons, when there might not be any mosquitoes for months, “natural selection will produce infections that grumble on for a long time without making the host very sick. There won’t be just one type of malaria.”

But Margaret Mackinnon, who studies malaria at the KEMRI-Wellcome Research Programme in Kenya, cautions against thinking that the “parasite uses the vector to modify its virulence in order to stop itself from killing the host”. To her, it’s more that the  mosquito puts a natural brake on the parasite. Serial blood passages remove that brake and things go hay-wire. “But don’t worry, because this can never happen in nature,” says Mackinnon.

Indeed, some scientists say that the mosquito results only stand out because they use parasites that have already gone through several serial blood passages. “Blood passage is totally abnormal,” says William Collins from the Center of Disease Control. He praises the paper but disagrees that a stay in a mosquito reduces the parasites’ virulence. “Rather, mosquito transmission restores it to near that of the original level,” he says.

Sure, blood passage artificially inflates the parasite’s powers and in the wild, mosquitoes might reduce virulence to a much lesser extent. But “if the effects are smaller in a natural situation, it doesn’t mean that they aren’t important,” says Mackinnon. “Natural selection operates on small as well as large differences.”

Regardless of the interpretation, it’s clear that the study raises more questions than it answers. “There’s no question that it’s a very cool paper, but it feels like it’s a start of something,” says Read. For example, we only know that the parasite activates genes that affect the host’s immune system. But when? In the mosquito? In the liver? In the blood? And Reece wants to know if these genes interact with the mosquito’s own immune system, rather than just the mammal’s.

And, perhaps most importantly, how does the mosquito modify the parasite? Mackinnon puts forward three possibilities. It could be that a small (and genetically narrow) force of parasites makes it out of the mosquito, and they’re more easily handled by the immune system. Alternatively, virulent mutants might get weeded out during the infection because they’re harder to transmit. Or maybe the mosquitoes could trigger “epigenetic” changes that alter how the parasite’s genes are used without changing the sequences of the underlying DNA. Langhorne strongly suspects that the epigenetic explanation is right, and she’s planning to test it.

Reference: Spence, Jarra, Levy, Reid, Chappell, Brugat, Sanders, Berriman & Langhorne. 2013. Vector transmission regulates immune control of Plasmodium virulence. Nature http://dx.doi.org/10.1038/nature12231

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Engineering mosquito gut bacteria to fight malaria

A malarial mosquito is a flying factory for Plasmodium – a parasite that fills its guts, and storms the blood of every person it bites. By hosting and spreading these parasites, mosquitoes kill 1.2 million people every year.

But Plasmodium isn’t the only thing living inside a mosquito’s guts. Just as our bowels are home to trillions of bacteria, mosquitoes also carry their own microscopic menageries. Now, Sibao Wang from Johns Hopkins Bloomberg School of Public Health has transformed one of these bacterial associates into the latest recruit in our war against malaria. By loading it with genes that destroy malarial parasites, Wang has turned the friend of our enemy into our friend.

Many groups of scientists have tried to beat malaria by genetically modifying the species of mosquito that carries it – Anopheles gambiae. Marcelo Jacobs-Lorena, who led Wang’s new study, has been at the forefront of these efforts. In 2002, his team loaded mosquitoes with a modified gene so that their guts produce a substance that kills off Plasmodium.