Uganda: Hundreds Stuck At Busia Over Yellow Fever, April 2016

The population of stranded travellers without yellow fever vaccination certificates continues to soar at the Busia border post in eastern Uganda as Kenyan and Uganda authorities continue to turn away people without proof of vaccination.

Scores have been reportedly camped at the immigration office on the Ugandan and Kenyan side for the last one week waiting to be vaccinated.

Dr Maurice Siminyu, the Busia county executive in charge of health and sanitation, said the Kenyan government had dispatched 2,000 doses of yellow fever vaccines from Nairobi to Busia border to help address the crisis.

However, he added that even after vaccination, travellers have to wait for up to 10 days before they are allowed to cross the border. Ten days is the grace period for the body to develop immunity against yellow fever.

Dr Jane Aceng, the director general of Health Services, has since rushed to the Busia border post. She has held meetings with immigration officials from both countries.

She said government is set to roll out mass yellow fever vaccinations in areas where the outbreak has been confirmed.

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Yellow fever vaccine shortage prompts call for a lower dose, April 2016

by Eric Sagonowsky | 

Apr 26, 2016 4:21pm

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With the death toll for the Angola yellow fever outbreak above 250 people and the WHO fighting a global vaccine shortage, some experts are calling on the health authority to employ a novel strategy in its efforts against the epidemic: cut vaccine doses by 90%.

That’s the recommendation from retired virologist Jack Woodall and colleagues, who argue in a Lancet article that the WHO should consider invoking an emergency protocol to allow for the use of a lower dose to stretch supplies fivefold. According to previous clinical trials, a one-tenth dose is as effective as the full dose in rapidly stimulating immunity, the team said.

The WHO contends, however, that more research is needed in children and on the duration of protection from a lower dose, Reuters reported. The availability of syringes could hinder a move to follow the suggestion, a WHO spokesperson added.

The proposal comes as the international health authority is grappling with depleted yellow fever vaccine stockpiles and as cases have been reported in the Democratic Republic of Congo, Kenya and China. The WHO says the cases in those countries--imported from Angola--demonstrate that the virus “constitutes a potential threat for the entire world.”

Spread by the same mosquitoes that transmit Zika and dengue, yellow fever can kill at least half of severely affected patients who don't receive treatment within 10 to 14 days. In Angola, the WHO’s nationwide vaccination drive has reached 7 million people.

Sanofi Pasteur, the Institut Pasteur Foundation in Dakar, Brazil’s Bio-Manguinhos/Fiocruz and a state-owned manufacturer are makers of yellow fever vaccines, according to WHO listings. In February, the Institut Pasteur Foundation in Dakar announced a plan to build a $25 million yellow fever vaccine plant there, though that facility isn’t expected to be ready until 2019.

Woodall and colleagues note that annual production of yellow fever vaccines is about 80 million doses, with the global supply sitting at about 5 million doses.

- here’s the Lancet article
- get more from Reuters

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Why a yellow fever outbreak in Angola is a "potential threat for the entire world"

Yellow fever, a much-feared mosquito-borne virus, has sickened thousands of people and killed hundreds in Angola over the past five months.

A cluster of cases first appeared in Angola's capital, Luanda, in December, and the virus has now sickened people in 16 of the country’s 18 provinces. People infected in Angola have already taken the virus to China, Kenya, Mauritania, and the Democratic Republic of the Congo (where at least 21 people have died), a pattern that has the World Health Organization very worried.

"This outbreak," the agency said this week, "constitutes a potential threat for the entire world."

A leading researcher of mosquito-borne diseases, Duane Gubler at Duke-NUS Medical School, is gravely concerned about the outbreak too. "We're sitting on a time bomb waiting for it to blow," he said, "and we're really not doing anything about it."

As scientists try to get a grip on the outbreak in Angola, one fact is already clear: Many other countries are at risk because they're not adequately prepared. Yellow fever is part of an uptick in mosquito-borne diseases all over the world that are suddenly threatening global heath in new and scary ways.

We've had a yellow fever vaccine since 1936, but the global stockpile is running low

BSIP / Getty

The vaccine for yellow fever. (BSIP/Getty)

Unlike Zika, a virus that until recently was little understood and hardly bothered humans, yellow fever has plagued humanity for centuries.

The virus is carried by infected mosquitoes, most commonly the Aedes aegypti, the same type that carries Zika and dengue. But yellow fever is a much deadlier disease. Symptoms in most people are mild and flu-like: muscle pain, fever, headache, nausea, vomiting, and fatigue. But 15 percent of patients go on to experience a much more severe second phase of illness: high fever, yellowing of the skin and eyes, internal bleeding, and organ failure. Of those, up to half die within two weeks.

The first epidemic was reported in 1648, according to JAMA. In 1793, a yellow fever outbreak wiped out 10 percent of the population of Philadelphia (then the capital of the United States), "causing 17,000 people, including President Washington and other members of the federal government, to flee to the countryside," according to one history of the disease. In 1878, an epidemic "destroyed" Memphis, Tennessee, killing 5,000.

There's no cure for yellow fever, but a vaccine was developed in 1936, and it's highly effective. Within three or four weeks after receiving the shot, nearly all people are protected from the virus. But in order for the vaccine to really prevent outbreaks, many people need to be immunized.

That's not happening in many parts of Africa, including Angola, where the virus is endemic. Starting in 2006, the World Health Organization, with support from Gavi (an international organization focused on improving vaccine access), ramped up efforts to make sure at-risk communities get vaccinated. But many countries on the continent still have vaccine coverage rates that are much too low to make the vaccine effective.

Take Nigeria. According to Gavi, yellow fever immunization coverage stood at just 49 percent in 2014. There, an outbreak that started in 1986 eventually infected 116,000 people and killed 24,000.

To stop the outbreak, more people in and around Angola will need to be immunized. But there's a big problem with this strategy: Vaccine stockpiles are running low. "We have a vaccine," said Seth Berkley, head of Gavi, "but we don't have adequate supplies."

Since the Angolan outbreak sparked late last year, the WHO has given more than 6 million doses to people in the country of more than 21 million. That push quickly depleted the international emergency stockpile.

"We don't use [the vaccine] for prevention — we use it for emergency response," said Gubler.

Berkley noted that when the outbreak started to spread in Angola, the systems in place to scale vaccine production couldn't meet the rapid uptick in demand. 

Globally, there are six manufacturers of yellow fever vaccine. But supply is usually low because there have been few outbreaks in recent years, and the disease hasn't been as much of a priority for global health groups relative to other diseases.

Researchers fear spread beyond Angola

CDC

Areas with risk of yellow fever virus transmission in Africa.

Health officials are now urging authorities to rapidly increase vaccine production in the event that the virus continues to spread in Angola and beyond. For now, all the cases outside Angola originated in Angola, which means the virus isn't transmitting anywhere else.

The parts of the world at greatest immediate risk are highly urbanized areas in sub-Saharan Africa and South America, where a combination of a warm climate, weak health systems, a ready mosquito vector, and densely packed populations with unvaccinated people is particularly worrisome, according to Gubler. (Much of South America is already currently battling outbreaks of dengue and Zika, again both related to yellow fever and carried by the same mosquito.)

But there's a real worry that it could spread to countries in Asia, including China, where immunization rates are practically nonexistent. Already, six unvaccinated guest workers from China returned from Angola with the virus. And infectious disease experts there foresee a potential public health emergency. 

"With growing migration and an increasing density of Aedes aegypti [mosquitoes] in Asia, there is an increased risk of yellow fever outbreaks in Asia," researchers fromShanghai Public Health Clinical Center wrote in a recent paper. "If no action is taken, it may spread in Southern China."

The probability of large outbreaks in the US is low, Gubler said, for the same reasons public health officials believe Zika wouldn't spread very far here: Many people live in air-conditioned homes that aren't hospitable to mosquitoes. We also have much stronger health systems to prepare and respond to outbreaks.

But in a PLOS post, tropical medicine experts Peter Hotez and Kristy Murray from Baylor College of Medicine asked the question, "Could Yellow Fever Return to the United States?" Their answer was a resounding yes.

Berkley agreed that if the outbreak isn't contained and spreads in the regions most at risk, it will inevitably reach the US. "If you want to protect the US from yellow fever," he said, "you have to have those countries that have yellow fever now vaccinated."

Why yellow fever started to spread in Angola is still a mystery

Wiki Commons

The Aedes aegypti mosquito that spreads yellow fever also carries the Zika and dengue viruses.

It's not clear why, after decades of only sporadic outbreaks in Africa, yellow fever suddenly got nasty in Angola. But the outbreak is a reminder of what can happen when our short-term planning for epidemics collides with the rapid globalization of tropical diseases.

Yellow fever is related to the Zika, dengue, and chikungunya viruses, all spread byAedes aegypti and all seen outbreaks in new regions of the world lately.

African cities have also grown extensively, said Gubler, and the Aedes aegypti mosquito lives very comfortably in urban areas, feeding off the densely packed humans.

Heidi Brown, a professor of epidemiology at the University of Arizona, explained there are at least three factors that help viruses like these spread: the number of mosquitoes out there, the number that are biting humans infected with the virus, and the number that are surviving long enough to infect other humans.

"The survival of the mosquito is driven a lot by temperature," she added — it also needs moisture to thrive. "So people go to the idea of global warming — that climate change and changes in precipitation patterns and temperature are helping mosquitoes survive in different areas." In other words, warming is helping expand the range of places that are habitable to mosquitoes.

There are other factors that may be driving the trend, too: People are traveling more than ever, bringing diseases to new locales. And with more people living in crowded cities, it's easy for viruses to jump from person to person and for mosquitoes to find large concentrations of humans to feast on.

It also doesn't help that the mosquito control programs that started after the Second World War have also been victims of their own success. 

"Health authorities couldn't see any sense in continuing to spend a lot of money to control diseases that weren't occurring, so the programs were disbanded," explained Gubler. "At the same time, many countries disbanded their public health infrastructure to deal with vector-borne diseases." That's why some countries may be woefully unprepared if yellow fever comes surging in.

Researchers will need to study Angola's yellow fever outbreak to better understand precisely why the disease is back and whether the virus has mutated to spread more effectively among humans. For now, though, Gubler wants to see fast mobilization to prevent the Angola outbreak from getting worse. He thinks vector control and a scaling up of vaccine production so more people in at-risk communities can be immunized will help.

"We live in a crisis-oriented society," he said. "We're always chasing the fire instead of preventing it. With dengue, Zika, chikungunya, you can get away with that. But yellow fever has a high fatality rate, and it could create chaos in the world."

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Fears rise over yellow fever’s next move - Can India be next target ?

Joost De Raeymaeker/EPA

Locals wait in line for vaccinations in the Angolan capital Luanda after an outbreak of yellow fever.

As the largest outbreak of yellow fever in almost 30 years continues to spread in Angola, scientists are warning that the world is ill-prepared for what would be a public-health calamity: the re-emergence of urban epidemics of the deadly infection, which could overwhelm vaccine stockpiles.

Yellow fever virus caused devastating outbreaks in cities in the past, but by the 1970s its mosquito carrier in urban areas — Aedes aegypti — had been wiped from large swathes of the globe; vaccination programmes also helped to confine the virus to the jungle. But now, as a result of the scaling-back of control efforts, Aedes mosquitoes have re-emerged in densely populated tropical and subtropical cities where many people are unvaccinated — and the Angolan situation has renewed fears that the virus might be poised to break out from the jungle.

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Worst of all would be if yellow fever gains a foothold in Asia — where, mysteriously, it has never become established despite apparently ideal ecological conditions. “We don’t know if this will happen, but if it does it would be a public-health disaster,” says Duane Gubler, a researcher in mosquito-borne diseases at Duke-NUS Medical School in Singapore.

Yellow fever, which is endemic in parts of South America and Africa, causes at least 60,000 deaths each year. Many people who become infected recover quickly (there are 84,000–170,000 annual infections, more than 90% of them in Africa), but some develop jaundice, bleed from their orifices and sustain fatal organ damage.

A 2006 initiative led by the World Health Organization (WHO) upped mass vaccinations and introduced routine immunization of children in many high-risk countries in Africa, but vaccination rates remain too low. The Angolan outbreak points to the continued risk posed by yellow fever: it began last December in the capital Luanda and has since spread to 6 of the country’s 18 provinces. Officially, some 490 people have been infected and 198 have died, although the true figures are probably much higher.

The immediate concern is that the virus might spread to larger African urban centres, as happened in the biggest previous outbreak, which began in 1986 in Nigeria and ultimately infected 116,000 people and killed 24,000 (see ‘Where might yellow fever go next?’).

Sources: M. U. G. Kraemer et al. eLife 4, e08347; 2015 (Mosquito distribution); www.cdc.gov/yellowfever/maps (transmission risk areas)

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Africa’s urban populations are now much larger than they were in the 1980s, notes Thomas Monath, a yellow fever and vaccine specialist who is chief scientific officer of NewLink Genetics in Ames, Iowa. People who contracted the infection in Angola have already carried it to Kenya, Mauritania and the Democratic Republic of the Congo, although this hasn’t yet sparked new outbreaks.

From jungle to city

As long as the virus is confined mainly to small outbreaks in Africa, the world’s vaccine production — just over 40 million doses annually — should be sufficient to replenish emergency stockpiles and contain outbreaks, says William Perea, who coordinates the WHO’s Control of Epidemic Diseases Unit in Geneva, Switzerland.

But the fear is that yellow fever could follow the same path as other less-severe mosquito-borne diseases, such as dengue, chikungunya and Zika, which have already seen major urban epidemics tied to the resurgence of Aedes mosquitoes.

Scientists are struggling to assess that risk, in part because there is little research on the virus. In South America, for instance, despite endemic jungle yellow fever and A. aegypti-infested cities, urban outbreaks are almost unheard of. This may be because populations of monkeys and jungle mosquitoes (the reservoirs for the virus) are smaller than in Africa, and because of relatively high vaccination rates among people living in or near the jungle.

Yellow fever also seems to spread less easily by Aedes mosquitoes than do other viruses such as dengue, says Pedro Fernando da Costa Vasconcelos, an infectious-disease researcher who is director of the Evandro Chagas Institute in Ananindeua, Brazil.

Nevertheless, the WHO estimates that South America is now “at greater risk of urban epidemics than at any time in the past 50 years”. Vaccination is officially recommended only in areas where the virus is endemic, because the vaccine can have serious — sometimes fatal — side effects in around 1 in 100,000 people. This means that few people are vaccinated on the densely populated eastern seaboard of Brazil, for example, because the region is the only part of the country where the virus is not endemic.

In Asia, the absence of yellow fever is an enigma: the continent has the monkeys, mosquitoes and climate in its warm regions that seem ideal conditions for the virus to thrive. Furthermore, infected travellers from elsewhere have introduced the virus to the region many times, and Asian populations don’t have any specific resistance to yellow fever.

One hypothesis, says Gubler, is that strains of dengue and other related flaviviruses have for centuries been so prevalent that they offer cross-protection against yellow fever — and so viral loads are reduced to levels below those required to sustain mosquito-borne cycles of disease. But with the recent unbridled growth of large cities and mosquito-infested slums, Asia’s past freedom from yellow fever may be no guide to its future, Gubler cautions.

The Angolan outbreak has also heightened concerns because hundreds of thousands of people from China and other Asian countries now work in Angola and in other at-risk parts of Africa, and many are unvaccinated, says Monath. Several unvaccinated individuals have fallen ill with yellow fever after returning from Angola to southern China.

Vaccine stocks

Many specialists want authorities to increase international vaccine stockpiles and to accelerate vaccination campaigns in endemic areas. But that would require boosting funding commitments to guarantee a market for manufacturers of the vaccine, Pereas says. Currently, there are only four suppliers worldwide, and supply is falling short of demand. (In a crisis, the WHO could dilute vaccines tenfold to boost its stocks without negating the vaccines’ effectiveness. But the process would require a specific kind of single-use, small-volume syringe, which is not commercially available, Pereas adds.)

Gubler argues that vaccination should be considered in A. aegypti-infested cities close to endemic regions in Africa and South America. In Asia, the risk is too uncertain to recommend vaccination now, he says, but health-care workers there need to be trained to identify cases so that any outbreaks can be nipped in the bud. Renewed efforts to curb A. aegypti mosquitoes globally are also essential, he adds.

For now, the area of most immediate concern is Africa — where some countries, such as Nigeria, have less than 50% yellow fever vaccination coverage. The availability of vaccines has led to ill-founded complacency about the threat posed by yellow fever, warns Perea. “It’s a neglected and forgotten disease.”

Nature

 

532,

 

155–156

 

(14 April 2016)

 

doi:10.1038/532155a

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Yellow fever vaccine shortage as outbreak in Angola spreads

By Debra Goldschmidt, CNN

Updated 2306 GMT (0706 HKT) March 25, 2016

Angolan military administers a yellow fever vaccine to a child at 'Quilometro 30' market, Luanda, Angola.

(CNN)More than 1,100 people have been diagnosed with yellow fever in Angola since December, according to the World Health Organization, and at least 178 have died. It's the worst outbreak of yellow fever in the country in three decades, and the supply of vaccines is running low.

The outbreak began in the capital of Luanda but has now spread to at least 10 of the 18 provinces in the country.

"With the majority of cases reported in ... Luanda, the situation is more dangerous and difficult to contain because the disease can spread easily from one person to another. We are already seeing cases spread to a number of provinces outside Luanda," Dr. Sergio Yactayo, WHO expert on epidemic diseases, said in a WHO publication.

Of greater concern to health officials is that China, the Democratic Republic of Congo and Kenya have reported cases they suspect were imported from Angola. Namibia and Zambia, which border Angola, also are on high alert, the WHO said.

"The worry is that this could result in a widespread outbreak of yellow fever in Angola, Asia and other areas," Dr. Tom Frieden, director of the U.S. Centers for Disease Control and Prevention, told CNN.

Yellow fever outbreak kills dozens in Angola

According to WHO, there are between 84,000 and 170,000 cases of yellow fever a year and as many as 60,000 of those cases are fatal. Yellow fever is a mosquito-borne disease transmitted by two types of mosquitoes. One is Aedes aegypti, the same type of mosquito that transmits Zika virus and dengue fever.

Yellow fever is a viral hemorrhagic illness. It's transmitted to people after a mosquito becomes infected from biting an infected monkey and then the infected mosquito bites a person and infects him or her.

Symptoms usually begin three to six days after a bite from an infected mosquito and last for about three or four days. They include fever, muscle pain, nausea, vomiting and loss of appetite. Yellow fever can be confused as dengue fever, malaria or other illnesses. Fifteen percent of infected individuals experience a second phase of illness within 24 hours of when they first become sick. This can include jaundice and bleeding from the eyes, nose, mouth, stomach and, eventually, bloody vomit and feces.

There is no treatment for yellow fever. Those who are sick are given supportive care, which can include fluids, pain management and monitoring. Fifty percent of patients who experience this second phase of illness die within 10 to 14 days.

There is a vaccine that protects against the virus. Health officials launched a mass vaccination program in February to try to contain this outbreak. Officials in Angola developed a plan to vaccinate nearly 6.5 million people in Luanda and so far 87% of those targeted have been vaccinated. The WHO considers this a success. But supply isn't meeting the demand for the vaccine because big outbreaks of yellow fever are unusual.

"We have to keep going and vaccinate all the people in Luanda and the affected provinces to end this outbreak. This is an enormous job which is exhausting supplies of vaccines," Yactayo said.

The emergency stockpile of the vaccine has been exhausted, the WHO said. Another 1.5 million doses are needed for residents of Luanda alone. In the meantime, shipments designated for the national routine vaccination there are being redirected to help control the outbreak.

"It's possible we could run out of vaccine," Frieden said.

Vaccine manufacturers are doing their part to increase vaccine production but the process takes some time, he said.

Travelers to the country, and any country where yellow fever circulates, including 33 other African countries, are advised to be vaccinated before traveling. Many of those countries require proof of vaccination upon arrival.

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Chinese medical team vaccinte exptriates against yellow fever in Angola

Mar 29,2016

LUANDA, March 28 (Xinhua) -- A 10-member Chinese medical team started epidemic research and vaccinated over 120 chinese nationals working in Angola as part of the bilateral cooperation between the two countries to combat an on-going out-break of yellow fever in the African country.

The team, sent by China's State General Administration for Quality Supervision and Inspection and Quarantine, conducted physical checks over 200 Chinese in the clinic under the Group 14 of the China's Railway Construction Company in southern Luanda, and diagnosed one Chinese woman as a new victim of yellow fever which had killed at least eight Chinese working in the African country.

The team was expected to vaccinate Chinese against yellow fever and conduct education and prevention campaigns for Chinese companies working in Angola, and to carry out epidemic studies and evaluation of the impact of the disease in the country, said Jin Xia, a leading epidemic expert in the team.

At least 189 Angolans, in the capital city of Luanda alone, were killed by yellow fever, a disease transmitted by mosquitoes, since the first cases were reported in Luanda since the end of 2015. The disease is highly preventable by vaccination.

The Angolan government has ordered some 5.7 million doses of vaccine and vaccinated over 75 percent of the population in Luanda against yellow fever, while vaccination campaigns were conducted in other provinces, according to local press reports.

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