Ebola: Reports from the front lines

Dr. Noah Rosenberg “Ebola was never the only killer here, and our ability to appropriately diagnose and treat these patients is woefully limited.”

Alpert Medical School professors Michael Smit and Noah Rosenberg are in Sierra Leone and Liberia respectively, treating Ebola patients. There are some signs of a slowdown in the epidemic, but the doctors emphasize that the virus must be fought “until the last case.”

PROVIDENCE, R.I. [Brown University] — In a limited sense, two Brown University medical professors who have been fighting Ebola in West Africa this winter have good news to report. They have seen some signs of slowing disease transmission. But the broader reality of what Ebola has done in Sierra Leone and Liberia is grim, according to Drs. Michael Smit and Noah Rosenberg.

Ebola shouldn’t just be contained, they note: It must be treated until all cases are resolved.

Smit, assistant professor of pediatrics and a physician at Hasbro Children’s Hospital, arrived in Sierra Leone Dec. 3, 2014, and will remain there through Jan. 18. Rosenberg, clinical assistant professor of emergency medicine and a Lifespan doctor, arrived in Liberia in mid-December and will stay until Jan. 27. They answered questions for medical science writer David Orenstein about what they are doing and seeing, and what people back in the States need to know.

Please describe a typical day.

NR: I arrive at 7 a.m. and meet with the overnight doctor and nurses to discuss our patients. My team pulls on full personal protective equipment and enters the high-risk area. We examine each patient, inquire about their current symptoms, give routine supportive medications and IV fluids if needed. We take blood to test for Ebola. We remove our equipment while being intermittently sprayed with chlorine. Rounds repeat in the afternoon and we often make an additional trip for a new admission. In the evening we meet with the night team and then rest to return in the morning.

Dr. Michael Smit “The effect of the epidemic goes far beyond those infected with Ebola virus. ... The economic impact on the country is devastating.

MS: I am the medical team leader of one of four medical teams at the Mateneh Ebola Treatment Center (ETC). Our days differ depending on which shift we are working. When working the early shift, we eat breakfast around 7 a.m. and drive to the ETC. We change into our work uniforms of scrubs and rubber boots at the ETC. At 7:30 we receive signout on the patients from the overnight team. We then assign personnel to conduct the nursing rounds, physician rounds, admissions, and discharges. During the heat of the day, we try to limit time in the high-risk area in personal protective equipment (PPE) to one hour. We deliver meals, administer medications, place intravenous catheters, and draw blood for laboratory tests. We triage admissions as they come through the ambulance bay. We also process discharges. These include survivors discharged home and deaths transferred to the morgue. At the end of the shift, we sign out the patients to the oncoming team, change back into our civilian clothes, and go back to the compound to eat. The late and overnight shifts are the same as the early shift for the most part.

What do you observe and hear about the status of the epidemic where you are?

NR: The exponential growth of the epidemic is clearly over in Liberia, but sporadic outbreaks are likely to continue until every case has been eliminated from West Africa, which may take months. Most of our new admissions now test negative for Ebola; they frequently die nonetheless. This may seem counterintuitive, but Ebola was never the only killer here, and our ability to appropriately diagnose and treat these patients is woefully limited.

MS: It is difficult to assess the status of the epidemic from here. We have limited access to the Internet, so our updates of what is happening are intermittent. As for what we observe, after a slow start from our opening in mid-December, we saw a steady increase in cases in our district in Bombali. Over the last week, admissions have decreased. The reason for this is not clear. We hope that it reflects a reduction in transmission, but we cannot assume this given the complexities of case identification and transport here.

What do people in the United States most need to know, based on what you are experiencing?

NR: Before the epidemic Liberia suffered from a large disease burden and severely limited health care system. Decades of civil war, sparked by inequality and tension between descendants of indigenous West Africans and freed slaves, wrecked the infrastructure and economy. Not only was the U.S.A. responsible for the founding of Liberia, but many of the struggles here today have their origins in the slave trade. Ebola will soon fade from the news but the epidemic has only worsened an already grave condition. We have a special responsibility to Liberia and it deserves our sustained attention.

MS: People in the United States need to know that the epidemic here is far from over. Even in a situation with diminished transmission, the United States needs to send personnel and resources here to combat Ebola until the last case. The effect of the epidemic goes far beyond those infected with Ebola virus. The schools here in Sierra Leone have been closed for months. Teen pregnancy is increasing as a result. The economic impact on the country is devastating, with some estimates setting the economy back 10 years. Also, people in the United States need to know about the dedication and resilience of the local and international healthcare workers who are fighting the epidemic, often under challenging physical and emotional conditions.

Source: Brown University

Gut microbiota influences blood-brain barrier permeability

Uptake of the substance Raclopride in the brain of germ-free versus conventional mice.
Credit: Miklos Toth

A new study in mice, conducted by researchers at Sweden's Karolinska Institutet together with colleagues in Singapore and the United States, shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function.

The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes -- which therefore play an important role in the protection of the brain.

The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.

"We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus," says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. "In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma."

The team also showed that the increased 'leakiness' of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this 'leakiness' could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. 

The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.

According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.

"These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology," says Professor Sven Pettersson, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. "Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier."

Source: Karolinska Institutet

Doctor who survived Ebola received experimental drug treatment

On 28 September, 2014, a 38-year old doctor, who was in charge of an Ebola virus treatment unit in Lakka, Sierra Leone, developed a fever and diarrhea. He tested positive for the virus on the same day. He was placed on a ventilator and on kidney dialysis, and was given antibiotics together with a 3-day course of an experimental drug called FX06 -- a fibrin-derived peptide that has been shown to reduce vascular leakage and its complications in mice with Dengue hemorrhagic shock. Credit: © nito / Fotolia

On 28 September, 2014, the 38-year old doctor, who was in charge of an Ebola virus treatment unit in Lakka, Sierra Leone, developed a fever and diarrhea. He tested positive for the virus on the same day. The doctor was airlifted to Frankfurt University Hospital on the 5th day of his illness and admitted to a specialized isolation unit.

Within 72 hours of admission he developed signs of vascular leakage and severe multi-organ failure, including the lungs, kidneys, and gastrointestinal tract. He was placed on a ventilator and on kidney dialysis, and was given antibiotics together with a 3-day course of an experimental drug called FX06 -- a fibrin-derived peptide that has been shown to reduce vascular leakage and its complications in mice with Dengue hemorrhagic shock.

A marked improvement in vascular and respiratory function was seen under the combined measures of intensive care and drug treatment. After a 30-day observation period, no Ebola virus genetic material was detected in the patient's blood plasma. The patient was released from hospital and is now with his family.
"Even though the patient was critically ill, we were able to support him long enough for his body to start antibody production and for the virus to be cleared by his body's defenses," explains Dr Wolf.

"In terms of improving treatment for Ebola patients, we have shown how intensive care medicine can successfully be applied under strict isolation conditions," adds senior author Professor Zacharowski, head of the Department of Anaesthetics and Intensive Care Medicine at Frankfurt University Hospital."
The authors conclude by calling for FX06 to be evaluated in clinical trials.

Source: The Lancet

'Non-echolocating' fruit bats actually do echolocate, with wing clicks

In a discovery that overturns conventional wisdom about bats, researchers reporting in the Cell Press journal Current Biology on Dec. 4 have found that Old World fruit bats -- long classified as "non-echolocating" -- actually do use a rudimentary form of echolocation. Perhaps most surprisingly, the clicks they emit to produce the echoes that guide them through the darkness aren't vocalizations at all. They are instead produced by the bats' wings, although scientists don't yet know exactly how the bats do it.

In a discovery that overturns conventional wisdom about bats, researchers reporting in the Cell Press journal Current Biology on December 4 have found that Old World fruit bats--long classified as "non-echolocating"--actually do use a rudimentary form of echolocation. Perhaps most surprisingly, the clicks they emit to produce the echoes that guide them through the darkness aren't vocalizations at all. They are instead produced by the bats' wings, although scientists don't yet know exactly how the bats do it.

"I was surprised by the fact that all of the fruit bats we recorded clicked and by the fact that clicks are produced by the wings," says Yossi Yovel of Tel Aviv University in Israel. "Arjan and I still find that hard to believe."

Yovel and postdoctoral fellow Arjan Boonman got their first hint about the fruit bats from a friendly man on a bus in Indonesia who told them about a species of bat that clicked with its wings. As further confirmation, Boonman found a single old paper about a fruit bat with wings that clicked, but it wasn't clear whether those clicks were good for anything.

Rather than look for that one earlier-described species in particular, Yovel suggested something else: "Why not check other fruit bats?"

They selected a total of 19 wild individuals representing three species of fruit bat and different parts of the evolutionary family tree to find that all of them did produce audible clicks with their wings.

"We did all we could to prove it wrong, including sealing the bats' mouths and anesthetizing their tongues, but nothing stopped them from clicking, except for when we interfered with their wing flaps," Yovel says.

Further study showed that two of the three species increased their clicking rate by a factor of three to five or even more when placed in a dark tunnel, implying that the clicks are a natural behavior for the bats.

Tests of the animals' ability to find their way in the dark showed that the fruit bats do have echolocation abilities, although they are poorer than those of other echolocating species. The fruit bats constantly crashed into thick cables, but they could readily learn to discriminate between larger objects: an acoustically reflective black board versus a similar-looking sheet of cloth. Even with large objects, however, the fruit bats didn't exactly come in for a smooth landing, suggesting that their ability is rather rudimentary in comparison to that of bats that rely on clicks produced from their larynxes.

The findings are interesting in light of earlier suggestions that echolocation may have evolved initially for bats to identify and avoid crashing into large objects such as cave walls, Boonman and Yovel say. The new discovery in fruit bats offers insight into how this sophisticated ability in other bats may have evolved over time, although it is unlikely that the laryngeal clicks of those other bats evolved directly from fruit bats' wing clicks. In fact, Yovel says, it's possible that echolocation in bats has independently evolved many times.

"When we study extant species of echolocating bats, we see a developed sensory system that has been adapted and improved over millions of years of evolution," Yovel says. "The rudimentary echolocation of the fruit bat is one example of how the first types of echolocation may have evolved."

Source: Cell Press