A Family’s Perspective – “The Brutality of Sepsis will Haunt Us for the Rest of Our Lives”

Skin May Play A Hidden Role In Ebola Infection

Ebola, a severe hemorrhagic disease caused by a virus endemic in parts of East-Central and West Africa, is generally known to spread through contact with bodily fluids from individuals who have the infection. 

Ebola virus on the skin surface

More recent outbreaks, such as the 2013-2016 Ebola epidemic in West Africa, have shown that infectious Ebola virus (EBOV) is also found on the surface of the skin of those who have succumbed to infection or at late times during infection. 

Although this suggests that the virus can be transmitted from skin contact with someone in the later stages of the disease, researchers have not yet fully understood how the virus exits the body and appears on the skin's surface.

In a recent study, scientists at University of Iowa Health Care, working with colleagues at Texas Biomedical Research Institute and Boston University, have uncovered a cellular route that EBOV uses to traverse the inner and outer layers of skin and emerge onto the surface. 

The researchers identified new cell types within the skin that are targeted by EBOV during infection and confirms that human skin tissues actively sustain EBOV infection. 

Possible route of Ebola infection

The results, published in the journal Science Advances, suggest that the skin's surface may be one possible route of person-to-person transmission.

"The skin is the largest organ in the human body yet is woefully understudied compared to most other organs. Interactions of EBOV with skin cells have not previously been extensively examined," said study senior author Wendy Maury, a professor of microbiology and immunology at the University of Iowa. 

"Our work provides evidence for one mechanistic avenue that EBOV uses to exit from the human body. A comprehensive understanding of which cells are targeted during virus infection is critical for rational development of antiviral approaches."

Human skin model for tracking Ebola

The research team, guided by Maury and Kelly Messingham, a research professor of dermatology at the University of Iowa, designed a new method for discovering which skin cells are infected by Ebola virus. 

They constructed a human skin explant system using full-thickness biopsies from healthy individuals, preserving both the deeper (dermal) and surface (epidermal) layers of skin.

Next, the team placed these explants dermal side down in culture media, adding virus particles to simulate how EBOV would move from the bloodstream outward toward the skin's exterior. 

This setup let the researchers use specialized tracing and labeling techniques to observe how the virus progressed from one layer of skin to the next, tracking which cells became infected as time passed.

Skin cells prone to Ebola infection

Prior clinical and animal studies indicated that skin cells could become infected with EBOV, yet they did not identify the particular cells involved. 

In this work, the authors showed that EBOV infects several cell types in the skin explant, including macrophages, endothelial cells, fibroblasts, and keratinocytes. 

Some of these cells are also infected by EBOV in other tissues, but keratinocytes – particular to skin – had not been previously recognized as an EBOV replication site.

Notably, the virus appeared to replicate more actively in the epidermal layer than in the dermal layer when compared on a per-gram basis. Within three days, infectious virus was detected at the epidermal surface, underscoring the virus's ability to rapidly move through skin to the surface.

In addition to mapping how the virus travels through the skin, the scientists demonstrated that human skin explants offer a realistic, three-dimensional model for examining potential antiviral treatments against EBOV. This model could be an economical and valuable tool for exploring new therapies.

"This study explores the role of the skin as a potential route of Ebola virus infection and identifies, for the first time, several cell types in the skin that are permissive to infection," Messingham said. 

"In total, these findings elucidate a mechanism by which EBOV traffics to the skin's surface and may explain person-to-person transmission via skin contact."

New insights into Ebola infection 

Beyond its discoveries about the skin, the research also zoomed in on interactions between the Ebola virus and two particular skin cell types, fibroblasts and keratinocytes. 

The team found specific receptors on these cells that facilitate the virus's entry, adding further clarity on how EBOV infects skin on a molecular level.

By clarifying one route the virus may take to exit the body, these findings expand our knowledge of Ebola's spread and highlight why skin-to-skin contact in advanced cases of infection can pose such a risk. 

Ongoing public health concern

Understanding these pathways, and identifying the cell types that the virus relies on, can influence future efforts to develop effective treatments and prevention measures.

This work also sets the stage for further investigations into how EBOV might exploit other organs or tissues and suggests potential ways to block the virus's path at the skin level. 

With Ebola remaining an ongoing global health concern, insights like these can help scientists target the virus more effectively and better protect those at risk of infection.

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What Is Ebola And Why Is Uganda's Outbreak So Serious?

Health workers are at risk from treating Ebola patients

An outbreak of Ebola in Uganda is proving more difficult to deal with than more recent epidemics, with its recent spread to the capital city, Kampala, causing particular concern.

So far 75 cases have been confirmed in four provinces, though it is feared that there could be many more which were not detected before the victims were buried.

What is Ebola?

It is a deadly virus with initial symptoms which can include a sudden fever, intense weakness, muscle pain and a sore throat.

Subsequent stages can include vomiting, diarrhoea and - in some cases - both internal and external bleeding, known as haemorrhaging.

The incubation period can last from two days to three weeks. Symptoms of Ebola can sometimes be confused with other illnesses such as malaria and typhoid.

Why is this outbreak so serious?

The virus has been circulating in rural parts of Uganda since September but an outbreak in an urban area - like Kampala - is much more complex to deal with.

The population density and ease of mobility, including internationally, means the virus can easily travel through an infected but asymptomatic patient within a short period of time.

However an asymptomatic person cannot transmit the virus. Speed is of the essence when tracing contacts of known cases, isolating and monitoring them for at least the 21-day incubation period of the virus.

The cooperation of such contacts with response teams is also crucial. The infection in Kampala has been traced to a contact of a confirmed case who reportedly travelled to the capital under a disguised identity.

He tried to seek help from a traditional healer before turning to a hospital where he was admitted, but later succumbed to the illness.

Seven members of one family he had come into contact with got infected.

Ebola spreads between humans by direct contact with bodily fluids and contaminated items or environments. Funerals can be a particular risk if mourners have direct contact with the body.

The Health Ministry says there were 18 deaths, linked to confirmed cases, where the bodies were buried before they could be tested.

There is a discrepancy between the numbers of deaths given by Uganda's government and WHO figures, because the latter is counting the 18 probable Ebola deaths, whereas Kampala is only including deaths where Ebola has been confirmed.

The World Health Organization (WHO) estimates the fatality rate is between 41% and 100%.

Is there a vaccine?

Another concern is that this is the Sudan strain of Ebola, for which there is no approved vaccine, unlike the more common Zaire strain.

The Health Ministry has said three candidate vaccines from Oxford, Sabin and Merck will be trialled for efficacy "in coming weeks". Several treatment options are also being tested, said Health Minister Jane Ruth Aceng.

Ebola vaccines developed in the last few years have not been tested on the Sudan strain

The Zaire strain was responsible for the largest ever outbreak of Ebola, in West Africa from December 2013 to 2016. More than 11,000 people died.

With more than 28,000 cases in Guinea, Liberia and Sierra Leone, scientists carried out intensive research into Ebola vaccines.

Two years after that epidemic ended, the then unlicensed Ervebo vaccine, developed by Merck, was used during an outbreak of the Zaire strain in the west of the Democratic Republic of Congo.

It was granted clearance by the WHO, which said it had limited infections and saved lives.

A second vaccine by Johnson & Johnson has since been approved for use by the European Medicines Agency.

But neither of these vaccines has been tested against the Sudan strain.

Nonetheless Uganda's President Yoweri Museveni had previously said his government was exploring whether it was worth trying them.

How is Uganda dealing with the outbreak?

The focus is on contact tracing - finding those who have been in close proximity with patients, especially those who attended the community funerals.

Treatment and isolation facilities have been set up in the affected districts. Their capacity is being ramped up as the virus spreads.

Mobile laboratories were also deployed, so that people would not have to travel for tests and risk spreading the virus.

Medics have expressed concern about the lack of adequate personal protective equipment (PPE) such as gloves and masks. They have also called for stricter measures including more lockdowns of areas with confirmed cases.

President Museveni initially ruled out such restrictions, saying: "Ebola is not spread like corona[virus]" as it is not an airborne disease.

He said markets, schools and places of worship would remain open, but urged people to observe personal hygiene and avoid close contact.

The government later relented and placed the two districts at the centre of the outbreak under lockdown.

"We believe transmission may have been disrupted," said the Health Ministry as there had been no secondary cases of infection since the lockdown. However, no such restrictions have been imposed in Kampala.

How does Ebola spread?

Ebola jumps to humans from infected animals, such as chimpanzees, fruit bats and forest antelope.

Bushmeat - wild forest animals hunted for human consumption - is thought to be the natural reservoir of the virus.

It then spreads between humans by direct contact with contaminated bodily fluids - blood, saliva, vomit, semen, vaginal discharge, urine, faeces and sweat.

Men who have recovered from Ebola have also been found to harbour the virus in their semen for a period after recovery.

What precautions can be taken?

To prevent infection, health professionals advise avoiding contact with cases, including stopping shaking hands, washing hands with soap and water and cleaning surfaces with chlorinated water.

It is also important to isolate cases and their contacts. Countries usually set up holding centres for suspected cases and treatment centres for laboratory-confirmed cases.

Quarantines have been ruled out

In eastern DR Congo, which borders Uganda, survivors of Ebola played a key role in providing care for infected patients as it has been established that they cannot be re-infected.

However, medical teams must wear full PPE when attending to cases to prevent infection.

Bodies, in a body bag, must be buried by those wearing proper PPE. More recent innovations have included having body bags with clear covers around the face to enable families to view the body safely before burial.

Why Ebola keeps coming back

The virus detective who discovered Ebola

Ebola: The Hopeless Struggle In A Liberian Slum Where Two Young Girls Await Their Fate

The two girls had nursed their mother as she died, cleaning up her vomit and curling up against her feverish body on the family's only mattress. They braided her hair until a truck came for the corpse. 

Now, as Ebola leapt from house to house in this sprawling slum, it seemed inevitable that Princess, 13, and Georgina, 12, would soon come down with the disease themselves. Unless someone intervened, they would be the next links in an endless chain of transmission that was destroying New Kru Town.

It was Bobby Pomney's job to intervene.

Pomney is a "contact tracer" for the Liberian government. When he arrived on a sweltering morning earlier this month, Mary Nyanford's body was being driven away. Princess was screaming for her mother. Tears were running down Georgina's cheeks.

"These girls need to be isolated," said Pomney, a slim, bald man, sweat beading on his forehead.

Impossible task

There may be only one way to halt the worst Ebola outbreak in history: find the disease's victims, strictly quarantine them and monitor everyone with whom they interacted.

When Thomas Eric Duncan tested positive for Ebola in Dallas, US authorities sent a team to identify everyone with whom he might have made physical contact. In a few days, they created a list of more than 120 people. Another team found 142 people who had contact with Amber Vinson, a nurse who became infected. Those measures appear to have kept Ebola from spreading in the United States.

But doing contact tracing and enforcing quarantines in a place like New Kru Town is a different story. Everything here is shared: mattresses, toilets, food, the burden of caring for the ill. Pomney, 43, was from a slum himself, and he knew the odds he would face as he kept watch over the two little girls.

Or at least, on that Monday morning, he thought he did.

Into the slums

New Kru Town is a maze of sheet-metal shanties built on a small peninsula, about a mile long and a half-mile wide, that juts into the Atlantic. Depending on whom you ask, the population is 20,000 or 50,000. It's a place with open sewers and swarms of mosquitoes that seems as if it was constructed to facilitate the spread of disease. It is an overwhelmingly difficult place to do contact tracing.

"I know this is my job," Pomney would later say. "But I don't think it works here."

The day after Mary Nyanford's body was carried away, Pomney returned with a clipboard and rain boots. He started writing down the names of people who had had physical contact with her while she was sick.

First came her daughters, Princess and Georgina. Their father, a security guard, had been sent to an Ebola treatment centre weeks earlier, and the girls were left to take care of their mother when she became ill and refused to go to a hospital.

No names

Within an hour, Pomney had written the names of eight people.

"But there are really around 30," he said, "or maybe more."

Some people he visited wouldn't give their names. Others denied that they had been around Nyanford, apparently to avoid being ordered into the 21-day quarantine, even though it wasn't enforced.

"You all want to quarantine us, but how we going to eat? How we going to pee?" Cleo Tobar asked.

Perhaps there was reason, though, to be hopeful about the two girls. The disease had been raging across Liberia for seven months. The girls had heard what it could do to a person's body. They had listened to warnings on the radio. They had seen billboards that pronounced, "Ebola is real."

A pair of gloves

In her sixth-grade class, Princess had been taught by her teacher, Mr Ballah, that "you can't touch each other anymore." A community health worker distributed latex gloves in the area. When her mother got sick, Princess slipped on a pair.

"It was to be safe," she explained later.

But the gloves eventually became dirty. And when her mother got really sick, Princess forgot about them.

The day after their mother died, the girls' eyes were glassy. Pomney couldn't tell if it was from crying or something else. He looked at the girls. He wondered if the symptoms were starting to show.

"You got a fever?" he asked.

Both girls offered a muffled no. But Pomney didn't have a thermometer. No one did in New Kru Town. If the girls were infected, they would probably become contagious long before they were sent to a hospital. It made the quarantine critical.

A checklist for survival

Pomney rattled through a list of what the girls had to do.

"You guys need to stay here. You can't play or run around for 21 days," he said. "My aim is to get you early treatment if you're sick."

The girls looked at the ground and nodded.

Pomney thought he had covered everything. He never thought to ask them where they had stayed the previous night.

In a health professional's world, this is quarantine: No socialising with other people. No sharing food. No sharing a bathroom. Ebola is spread through the bodily fluids of highly infected people, and their vomit, urine and mucus can accumulate in bathrooms.

The reality on the ground

This is the world of Princess and Georgina: They share an outdoor toilet, without running water, with 25 other people. In their slum, 15 members of an extended family often sleep in one home. As for their shack, it had been locked by the body-collection team after their mother's body was removed, a precaution to keep people away from infected items. The team had also burned the family's mattress.

So the girls had spent the previous night with their grandmother, who lives across the unpaved alleyway. She, too, had Ebola.

Pomney didn't know this until someone pointed to the shanty and said, "They got a sick person in there."

Pomney looked at her through the doorway. The girls' grandmother, Miriam Nyanford, had covered her naked body with a bedsheet and was breathing heavily. On the wall someone had scrawled, "The Blood of Jesus Must Prevail."

"You all didn't call an ambulance?" he asked members of the family who had gathered in front of the house.

We called, but no ambulance came

"We called one but it never came," a man said.

Pomney called an ambulance from his cellphone. He turned to the girls, who were sitting in chairs outside their home and using sticks to draw in the dirt.

"That's indirect contact," he said, exasperated. "You can't be staying with her."

"Where else they going to sleep?" a neighbour asked.

Real time disaster

Scientists use formulas to map Ebola's transmission vectors and its exponential infection rate. But New Kru Town is a place where you can watch the virus's web grow outward in real time.

Every day that Pomney returned, he was approached by someone reporting a new case: a corpse that had been left on a mattress for three days until it started to decay, the body of an 11-month-old boy, a young man with a high fever who sat zombielike in front of his house.

"This whole area is infected," he said.

Pomney was left with hardly any contacts to trace, except for the two little girls whom everyone watched, waiting for symptoms to emerge.

On the third day of their quarantine, the girls played hopscotch with friends on a patch of sand between homes. They played checkers until Georgina got bored. They played with a little dog. They spoke about their mother.

"My mom bought me whatever I wanted. She bought me clothes," said Princess, who wore a pink sundress.

"She bought me food," Georgina said, "any kind of food I liked."

The evil ghost

They had heard about Ebola on the radio and in school, but it remained a mysterious, alien force. The men in moon suits aren't health-care workers, they're ghosts, Princess said. Ebola isn't just a virus, it's an evil spirit that takes over your body. To the girls, quarantine wasn't a public health precaution, it was something that might leave you alone and hungry.

And being alone was a terrifying new possibility. Since her mother died, Princess had had the same dream: She's washing her feet in front of the family's house when her mother suddenly appears. Her mom starts running, and Princess chases her through the sandy streets of New Kru Town. When Princess wakes up, itss the middle of the night and she's lying on the floor.

Princess and Georgina continued to sleep in the same rooms as their friends and relatives, and sat in large groups, sharing oranges and cookies.

"These girls are supposed to be in quarantine, but they're running around with other children," Pomney screamed when he arrived to check on them one morning.

"Everyone here is going to get infected," he said.

Then, almost on cue, someone came up to him.

"Bobby, we got a sick person over here," the man said.

Yellow fever

Pomney sighed and walked to the home pointed out by the man. Another member of the contact tracing team, John Shagbeh, joined him. When they got to the house, a few yards from where Mary Nyanford had died, a man in his early 20s was sitting with a hoodie covering his head, staring blankly.

"This guy needs to go to the hospital," Shagbeh said.

"We went to the doctor. He said it's yellow fever," the man's mother said.

The contact tracers didn't believe her. Many people in New Kru Town are desperate to avoid Ebola treatment centres, which they see as dangerous.

"If you don't go to the hospital, we will call the police on you," Shagbeh shouted. "You need to accept that this man is infected."

A crowd had gathered. Shagbeh and the sick man's mother continued shouting at each other while the man with either yellow fever or Ebola sat in his sweatshirt in the 100-degree heat.

Then a man from the local Unicef team, Chris Dassen, arrived. "These people need pampering, not hardness," he said to Shagbeh. "We don't need the police."

Shagbeh walked away.

"There's nothing the government of Liberia can do to enforce this quarantine," he said.

An overwhelmed system

In Nigeria, where there were 20 confirmed or probable cases of Ebola in July, tracers created a list of 894 contacts of the patients, and isolated and monitored them. Health workers conducted 18,500 face-to-face visits. Last week, the country was declared Ebola-free.

Now, in New York, officials are scouring the city to find anyone who might have had contact with Craig Spencer, a doctor, since he came down with the disease.

"The way to stop Ebola in its tracks is contact tracing," Tom Frieden, the head of the Centers for Disease Control and Prevention, said this month.

In the United States, four people have fallen ill with Ebola.

But in Liberia, where more than 4,600 people have been diagnosed with the disease since March, improvised contact tracing teams were formed only after Ebola had spread widely. There could be tens of thousands of contacts scattered across slums like New Kru Town.

Students, shopkeepers and stationery sellers

The country's public health system was almost nonexistent even before Ebola. In the United States, many contact tracers have advanced degrees in public health. In Liberia, they are former students or shopkeepers or security guards. Until June, Pomney sold stationery.

Liberia's contact tracers are supposed to make daily checks on victims' friends, relatives and neighbours, beginning as soon as the cases are identified. But in New Kru Town, the tracers said, it typically takes about 10 days before the process even begins. By that time, more people have typically developed symptoms.

Some days, no one came to check on Princess and Georgina. The girls walked around the area freely. They played with a headless Barbie doll in front of their home, where a flier on the wall advertised a lottery.

"Your American dream starts here," it said. "Win and live in the USA."

Five days into their quarantine, the girls' father suddenly returned. He was skinny and weak, wearing tattered clothes. He struggled to speak above a gravelly whisper.

He held a piece of paper bearing the letterhead of Doctors Without Borders, a nonprofit group treating Ebola victims.

"Nyanford Christopher has recovered from the Ebola Virus and is no longer infectious," it said.

No celebration

But there was no celebration. Nyanford learned that his wife had died. He learned that his mother was now in the hospital and his daughters had nowhere to sleep. He sat on the stoop of his home and hung his head.

Then he looked at Princess and Georgina, sitting next to him.

"I cannot conclude if they are OK or not," he said.

Nyanford forced open the door of his home that the body-collection team had locked. He saw the burned mattress.

"How I am supposed to take care of my family now?" he asked.

In the shack next door, the body of his sister, Alice Jallah, had been lying in a room for two days. The ambulance still hadn't come. The family had locked the room but left the radio on inside, with the corpse.

Wash your hands

That morning, through the thin metal walls, a public-service announcement blared into the ravaged neighbourhood.

"Wash your hands with chlorine and report all cases," the man's voice said. "If we do these things we can prevent ourselves from getting Ebola."

"How are you coming on?" Pomney asked the girls, six days after their mother died.

Each morning when he showed up in New Kru Town, he expected that it would be the day they started showing symptoms. But again, the girls said they were doing fine. There were no clear signs that they had contracted the disease.

It was Sunday, and the voices of church choirs rose above New Kru Town. The sermons were all about the spread of Ebola. Some pastors blamed the government for responding so slowly. Others blamed the people for refusing to take sick relatives to the hospital.

"You can't quarantine people here. We're all intertwined," said Aloysius Nimely, the pastor of Garden Street Temple Bible Wheel Church.

Three new bodies

As families attended church services, Pomney was running between houses. In three hours, he had heard about three new bodies. His job is not to remove the dead, but he was the only representative of the Liberian government in the slum, and he decided he had to do something.

He called the body-collection team. He waited with the families. He took out his clipboard and tried to diagram the web of physical contacts orbiting the deceased. Each time, he got a few names, and then he gave up. The circles were too wide. There were too many people who didn't want to give their names or didn't want to admit that they had had contact with the dead.

Exactly one week after Mary Nyanford's body was driven away, Pomney walked by Princess and Georgina, who were sitting in a circle with relatives.

"It's only a matter of time," he said. "One day, they're going to get it."

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