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

WHO contemplates reforms after admitting missteps on Ebola

World Health Organization (WHO) Director-General Margaret Chan addresses the media during a special meeting on Ebola in Geneva on Jan. 25, 2015. Photo by Pierre Albouy/REUTERS.

In a special session on Sunday, the World Health Organization debated how to reform itself after acknowledging the organization had botched its response to the 2014 Ebola emergency. 

“The Ebola outbreak revealed some inadequacies and shortcomings in this organization’s administrative, managerial, and technical infrastructures,” WHO Director-General Margaret Chan said. At its headquarters in Geneva, Chan presented a series of proposals aimed at ending the current outbreak, as well as reinforcing preparedness globally and guaranteeing the WHO’s ability to address future large-scale outbreaks. 

She stressed the need to streamline recruitment for emergencies, as the current process is “too slow” and emphasized the need for a “one WHO” approach that employs universal operating procedures and tools for responding to emergencies. According to Chan, the current rules for reporting outbreaks – International Health Regulations (IHR) – created to prevent national health emergencies from becoming global crises, are too thin. But the largest lesson she and others at WHO learned during the outbreak fight was that well-trained, and appropriately paid health care workers, are essential to stemming the spread of disease. 

To date there have been more than 21,000 Ebola cases and over 8,400 deaths. “The volatile microbial world will always deliver surprises, Chan said. “Never again should the world be caught by surprise, unprepared.”

Source: WHO

Multiple allergic reactions traced to single protein

This is a mast cell. Credit: Priyanka Pundir/University of Alberta

Johns Hopkins and University of Alberta researchers have identified a single protein as the root of painful and dangerous allergic reactions to a range of medications and other substances. If a new drug can be found that targets the problematic protein, they say, it could help smooth treatment for patients with conditions ranging from prostate cancer to diabetes to HIV. Their results appear in the journal Nature on Dec. 17.

Previous studies traced reactions such as pain, itching and rashes at the injection sites of many drugs to part of the immune system known as mast cells. When specialized receptors on the outside of mast cells detect warning signals known as antibodies, they spring into action, releasing histamine and other substances that spark inflammation and draw other immune cells into the area. Those antibodies are produced by other immune cells in response to bacteria, viruses or other perceived threats. However, "although many of these injection site reactions look like an allergic response, the strange thing about them is that no antibodies are produced," says Xinzhong Dong, Ph.D., an associate professor of neuroscience in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine.

To zero in on the cause of the reactions, Benjamin McNeil, Ph.D., a postdoctoral fellow in Dong's laboratory, first set out to find which mast cell receptor -- or receptors -- responded to the drugs in mice. Previous studies had identified a human receptor likely to be at fault in the allergic reactions; McNeil found a receptor in mice that, like the human receptor, is found only in mast cells. He then tested that receptor by putting it into lab-grown cells and found that they did react to medications that provoke mast cell response. He found similar results for the human receptor that previous studies had indicated was a likely culprit.

"It's fortunate that all of the drugs turn out to trigger a single receptor -- it makes that receptor an attractive drug target," McNeil says.

To find out whether eliminating the receptor really would eliminate the allergic reactions, the research team also disabled the gene for the suspect receptor in mice. These "knockout" mice did not have any of the drug allergy symptoms that their genetically normal counterparts displayed.

The researchers are now working to find compounds that could safely block the culprit receptor in humans, known as MRGPRX2. Such a drug would not prevent true allergic reactions, which produce antibodies, but only the pseudoallergic reactions triggered by MRGPRX2. Still, it could improve the lives of many patients, says McNeil, by lessening the drug side effects they currently endure. Medications that trigger MRGPRX2 include cancer drugs cetrorelix, leuprolide and octreotide; HIV drug sermorelin; fluoroquinolone antibiotics; and neuromuscular blocking drugs used to paralyze muscles during surgeries.

Dong's research group is also looking into the possibility that MRGPRX2 could be behind immune conditions such as rosacea and psoriasis that don't stem from medication use.

Source: Johns Hopkins Medicine

Researchers ferret out a flu clue

Professor Michael Jennings, Deputy Director of the Institute for Glycomics. Credit: Image courtesy of Griffith University

Research that provides a new understanding as to why ferrets are similar to humans is set to have major implications for the development of novel drugs and treatment strategies.

Published in the journal Nature Communications, the research is a collaboration between Professor Michael Jennings and other researchers from the Institute for Glycomics, Griffith University and collaborators at the University of Queensland and the University of Adelaide.

The team has shown for the first time that ferrets share a mutation that was previously thought to be unique to humans, among the mammals. This helps to explain why the molecular characteristics of ferrets so uniquely mimic human susceptibility, severity and transmission of influenza A virus strains.

Professor Michael Jennings, Deputy Director of the Institute for Glycomics, says these findings open up a completely novel approach to tackling human diseases from influenza through to cancer.

"For over 80 years we've known that ferrets are uniquely susceptible to human influenza A virus, but the precise reason was unknown," Professor Jennings said.

"We have shown that ferrets have a mutation in a gene required to make a crucial sugar called sialic acid. Most animals can make two types of sialic acid. Ferrets, like humans can make only one. Different flu strains have preferences for the type of sialic acid they bind to cause infection. Because ferrets can only make the human form of this sugar, they are naturally "humanized" for the receptors recognised by human strains of the flu virus."

Source: Griffith University

Drugs in the environment affect plant growth

Lettuce plants (stock image). The potential for some chemicals to influence plants is becoming increasingly relevant, particularly as waste management systems are unable to remove many compounds from our sewage. Drugs for human use make their way into soil through a number of routes, including the use of sewage sludge as fertilizer and waste water for irrigation.
Credit: © riderfoot / Fotolia

By assessing the impacts of a range of non-steroidal anti-inflammatory drugs, the research has shown that the growth of edible crops can be affected by these chemicals -- even at the very low concentrations found in the environment.

Published in the Journal of Ecotoxicology and Environmental Safety, the research focused its analysis on lettuce and radish plants and tested the effects of several commonly prescribed drugs, including diclofenac and ibuprofen. These drugs are among the most common and widely used group of pharmaceuticals, with more than 30 million prescribed across the world every day.

The potential for these chemicals to influence plants is becoming increasingly relevant, particularly as waste management systems are unable to remove many compounds from our sewage. Drugs for human use make their way into soil through a number of routes, including the use of sewage sludge as fertilizer and waste water for irrigation.

This study looked for a number of changes in edible plants, assessing factors such as water content, root and shoot length, overall size and how effectively the plants photosynthesised.

Each drug was shown to affect the plants in very specific ways, with marked differences between drugs that are closely related. For example, drugs from the fenamic acid class affected the growth of radish roots, whilst ibuprofen had a significant influence on the early root development of lettuce plants.

Dr Clare Redshaw, one of the scientists leading the project at the Medical School's European Centre for Environment & Human Health, said: "The huge amounts of pharmaceuticals we use ultimately end up in the environment, yet we know very little about their effects on flora and fauna. As populations age and generic medicines become readily available, pharmaceutical use will rise dramatically and it's essential we take steps towards limiting environmental contamination. We haven't considered the impact on human health in this study, but we need to improve our understanding quickly so that appropriate testing and controls can be put in place."

There have been growing concerns about the presence of pharmaceuticals in the environment, particularly as evidence emerges of the effects they can have on the development of animals and antibiotic resistance in bacteria. Yet their ability to affect plant growth is poorly understood.

This study marks an important step in an emerging research field attempting to assess how very low concentrations of drugs can affect the growth of crucial crop plants. It specifically considered the non-steroidal anti-inflammatory drugs tolfenamic acid, meclofenamic acid, mefenamic acid, diclofenac, naproxen and ibuprofen.

Source: University of Exeter