Research | Some flu viruses potentially more dangerous than others

Certain subtypes of avian influenza viruses have the potential to cause more severe disease in humans than other avian influenza subtypes and should be monitored carefully to prevent spread of disease, according to a study published this week in mBio®, the online open-access journal of the American Society for Microbiology.

The work, directed by researchers at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., found that flu viruses expressing the low pathogenicity avian H1, H6, H7, H10 or H15 hemagglutinins (genes that encode the major surface protein for the virus) led to fatal infections in mice and caused more cell damage in normal human lung cells grown in culture as compared to avian influenza viruses with other subtypes. The 1918 H1 subtype hemagglutinin has been already identified as a key virulence factor in the pandemic influenza virus of 1918. That virus, which caused the so-called “Spanish flu,” spread rapidly around the world, resulting in approximately 50 million deaths.

“Viruses with these avian hemagglutinins have some type of inherent virulence motif to them, in that they induce a marked inflammatory response in mammals including human cells in culture,” said senior study author Jeffery K. Taubenberger, MD, PhD, chief of the Viral Pathogenesis and Evolution Section of NIAID’s Laboratory of Infectious Diseases. In 2013-2014 there have been close to 400 cases of avian influenza H7N9 infections in people in China, many severe, along with small numbers of severe human infections with H10N8 and H6N1 subtypes. “From a public health and epidemiology standpoint, it’s useful to know that avian viruses of these subtypes (for example, H6, H7, or H10) might lead to more severe infections in humans and is something to look out for.”

In a specialized laboratory , Taubenberger and colleagues developed a series of viruses mimicking 13 subtypes of contemporary low pathogenicity avian influenza A viruses. Each avian influenza virus tested was genetically identical to each other except that they expressed different hemagglutinin subtypes. After growing the viruses in culture, the researchers inoculated them into mice and watched to see what would happen. This approach allowed a direct comparison of the role of different hemagglutinins in virulence.

The viruses expressing the H1, H6, H7, H10 and H15 subtypes all caused rapid weight loss and fatal pneumonia infections within a week. By contrast, the H2, H3, H5, H9, H11, H13, H14 and H16-expressing viruses caused only mild weight loss but no significant disease.

The research team performed a similar test using hemagglutinins from two 2013 H7N9 flu viruses from outbreaks in Anhui and Shanghai, China, with similar results in mice. They also took a subset of these viruses and put them in culture with normal human lung cells that line the airways. The cells had developed into a thick layer called an epithelium. The disease-causing viruses like H1 and H7 caused mature cells to rapidly die over a couple of days, leaving just a thin lining behind.

These results suggest that hemagglutinins may not require immune cells to trigger cell damage but instead may cause programmed cell death or other molecular processes that could ultimately lead to enhanced disease or fatalities, Taubenberger said. In the future it will be important to tease out the differences in the hemagglutinins’ structural features and investigate the molecular processes involved as the viruses infect mammalian cells, he said.

Meanwhile, until more is understood about how flu viruses cross from animals to humans and spread, more research is needed into producing a more broadly protective “universal” flu vaccine that may ultimately offer the best protection against future pandemics, he said.

The study was supported by the National Institute of Allergy and Infectious Diseases and the Defense Threat Reduction Agency.

Research | Police face higher risk of sudden cardiac death during stressful duties

Police officers in the United States face roughly 30 to 70 times higher risk of sudden cardiac death (SCD) when they’re involved in stressful situations–suspect restraints, altercations, or chases–than when they’re involved in routine or non-emergency activities, according to a new study from Harvard School of Public Health (HSPH) and Cambridge Health Alliance (CHA). It is the first study to provide data that demonstrates the impact of stressful duties on on-duty SCD.

The researchers also found that physical training activities–which police don’t consider to be particularly stressful–were associated with roughly 20- to 25-fold higher SCD risk than routine law enforcement work.

The study will appear online November 18, 2014 in BMJ (British Medical Journal).

“Although we suspected that strenuous police duties could trigger sudden cardiac deaths in vulnerable officers, we were struck by the magnitudes of the risks and their consistency across different statistical models,” said Stefanos Kales, associate professor in the Department of Environmental Health at HSPH, chief of occupational and environmental medicine at CHA, and senior author of the study.

Previous epidemiologic studies of firefighters by Kales and his colleagues have shown, like the current study, that SCD risk is elevated during stressful duties as compared with nonemergency duties. In addition, studies of the general population have found that strenuous activity such as vigorous exercise or snow shoveling–especially among those who are physically inactive–can precipitate heart attacks and sudden cardiac deaths.

Researchers examined 441 sudden cardiac deaths among police officers that occurred between 1984 and 2010, and they were able to identify the duty associated with death in 431 of the cases. Data came from the National Law Enforcement Officers Memorial Fund and the Officer Down Memorial Page. The researchers combined the information on sudden cardiac deaths among police with estimates of the proportion of time that police officers spend on various duties, based on surveys from front-line officers and police chiefs.

They found that police officers’ risk of sudden cardiac death was 34 to 69 times higher during restraints or altercations; 32 to 51 times higher during pursuits; 20 to 23 times higher during physical training; and 6 to 9 times higher during medical or rescue operations, as compared with routine or non-emergency activities. The researchers also found that SCD accounts for up to 10% of all U.S. on-duty police deaths.

The study’s findings suggest the need for cardiovascular disease prevention efforts among law enforcement officers. “Our findings have important public health implications for health promotion among law enforcement officers and call for the implementation of primary and secondary cardiovascular disease prevention efforts such as lifestyle and medical interventions to reduce officer’s risk of sudden cardiac death,” said Kales.

Other Harvard School of Public Health authors include first author Vasileia Varvarigou, visiting scientist in the Department of Environmental Health; Andrea Farioli, also a visiting scientist in the Department of Environmental Health; and Maria Korre, a doctoral candidate in occupational health.

Funding came from the Harvard-NIOSH Education and Research Center Grant No. 2 T42 OH008416-08 and the Monica Odening ’06 Internship & Research Fund in Mathematics (Hamilton College).

“Law enforcement duties and sudden cardiac death among police officers in United States: case distribution study,” Vasileia Varvarigou, Andrea Farioli, Maria Korre, Sho Sato, Issa J. Dahabreh, Stefanos N. Kales, BMJ, online Nov. 18, 2014, doi: 10.1136/bmj.g6534

Research | Digoxin associated with higher risk of death and hospitalization

Digoxin, a drug commonly used to treat heart conditions, was associated with a 71 percent higher risk of death and a 63 percent higher risk of hospitalization among adults with diagnosed atrial fibrillation and no evidence of heart failure, according to a Kaiser Permanente study that appears in the current online issue of Circulation: Arrhythmia and Electrophysiology.

Digoxin is a drug derived from digitalis, which has been used for more than a century for heart-rate control in patients with atrial fibrillation, and it remains commonly used for this purpose worldwide. Current clinical practice guidelines for the management of atrial fibrillation recommend the use of digoxin alone for resting heart-rate control in sedentary individuals.

“Our findings suggest that the use of digoxin should be re-evaluated for the treatment of atrial fibrillation in contemporary clinical practice,” said study co-author Anthony Steimle, MD, Chief of Cardiology at Kaiser Permanente Santa Clara Medical Center. “Given the other options available for heart-rate control, digoxin should be used with caution in the management of atrial fibrillation, especially in the absence of symptomatic systolic heart failure.”

The results of this study follow on the findings by many of the same investigators in a 2013 study that revealed digoxin was associated with a 72 percent higher rate of death among adults with newly diagnosed systolic heart failure.

The current study was conducted between Jan. 1, 2006 and June 30, 2009 among almost 15,000 adults within Kaiser Permanente’s Northern and Southern California regions who had recently diagnosed atrial fibrillation and no prior heart failure or digoxin use. Researchers examined the independent association between newly initiated digoxin use and the risks of death and hospitalization.

During the study period, 4,858 or 17.8 percent of the participants initiated digoxin use. There were 1,140 deaths among the study cohort, with a significantly higher rate of death in digoxin users compared with non-users (8.3 vs. 4.9 per 100 person years). At the same time, there were 8,456 hospitalizations for any cause, and the rate of hospitalization was higher for patients who received digoxin compared with those who did not (60.1 vs. 37.2 per 100 person years).

“Digoxin remains commonly used for rate control in atrial fibrillation, but very limited data exist to support this practice — mostly small, older clinical studies with very limited follow-up that did not assess the long-term effects of digoxin on mortality or hospitalization,” said Alan S. Go, MD, senior author of the study and research scientist at the Kaiser Permanente Division of Research in Oakland, California.

“In contrast, this study included the largest and most diverse sample of adults with incident atrial fibrillation not complicated by heart failure treated in clinical practice reported to date, with results that were consistent across age and gender,” said Dr. Go. “We believe these findings, which build on earlier work, have significant value in guiding clinical cardiology decision-making in regard to digoxin use in the modern era.”

Other authors on the study include James V. Freeman, MD, MPH of Yale University School of Medicine; Kristi Reynolds, PhD, and Teresa N. Harrison, SM, of the Department of Research and Evaluation, Kaiser Permanente Southern California; Margaret Fang, MD, MPH, of the University of California, San Francisco; Natalia Udaltsova, PhD, and Niela K. Pomernacki, BA, of the Division of Research, Kaiser Permanente Northern California; Leila H. Borowsky, MPH, of Massachusetts General Hospital; and Daniel E. Singer, MD, of Harvard Medical School.

The study was supported by the National Heart, Lung and Blood Institute and the National Institutes of Health [RC2 HL101589 and U19 HL91179], and the American Heart Association Pharmaceutical Roundtable-Spina Cardiovascular Outcomes Research Center program [0875162N].

Research | Eighty percent of kidney dialysis patients unprepared for natural disaster or emergency

Eighty percent of kidney dialysis patients surveyed were not adequately prepared in the event of an emergency or natural disaster that shut down their dialysis center.

But after receiving individualized education from a multidisciplinary team of doctors, nurses, dieticians and social workers, 78 percent of these patients had become adequately prepared, according to a Loyola University Medical Center study.

Anuradha Wadhwa, MD, and colleagues, reported findings during the ASN Kidney Week 2014 meeting.

Patients with kidney failure rely on dialysis treatments to survive. The treatments, typically three times a week for about four hours, remove wastes and extra fluids from the blood.

Researchers surveyed 124 patients at a Loyola outpatient dialysis center. During dialysis sessions, patients were asked whether they:

  • Believed they were prepared for an emergency.
  • Had an emergency plan they had discussed with a family member or dialysis unit.
  • Knew of a back-up dialysis facility.
  • Were familiar with an emergency diet that is key to survival in the event of a missed dialysis session. The diet includes limiting fluid intake and avoiding potassium-rich foods.

Patients who answered yes to all four questions were considered to be prepared. But while 60 percent of the patients thought they were prepared for an emergency, the survey found that only 20 percent were actually prepared. However, 95 percent of patients were interested in learning about preparedness.

Following this initial survey, a multidisciplinary team of doctors, nurses, dietitians and social workers discussed emergency preparedness while meeting individually with patients during dialysis sessions. Patients also were given educational materials and purple cards created by Kidney Community Emergency Response. The laminated, wallet-size cards contain emergency information, and are meant to be carried at all times.

The one-on-one education made a dramatic difference. A follow-up survey found that following the educational sessions, 78 percent of the patients were prepared for an emergency, and 99 percent said the emergency information they received was useful.

“This study highlights that a multidisciplinary approach in an outpatient dialysis unit setting is feasible and effective in educating patients about disaster preparedness,” Dr. Wadhwa said.

The study is titled “Disaster Preparedness in Dialysis Patients via Multidisciplinary Approach.” Dr. Wadhwa is an assistant professor in the Division of Nephrology of Loyola University Chicago Stritch School of Medicine. Co-authors of the study, all at Loyola, are Vinod K. Bansal, MD, FACP, FASN, a professor of Nephrology and medical director of Chronic Dialysis; Karen Griffin, MD, FACP, a professor of Nephrology; and Stephanie Pesenko, a graduate student.

Research | Creating trust in the time of Ebola

One of the key reasons the Ebola outbreak got out of control in West Africa in the early days of the crisis was a lack of trust among community members, frontline health workers and the broader health system, suggests new Johns Hopkins Bloomberg School of Public Health research.

Had the citizens and their health care community developed a trusting relationship prior to the outbreak, important messages about the disease and how to stop its spread would likely have gotten through to people much sooner and slowed the march of Ebola, says Timothy Roberton, MPH, MA, a DrPH candidate in the school’s Department of International Health.

Roberton visited Guinea in July, spending two weeks with the Guinea Red Cross as part of a study initiated and funded by the International Federation of Red Cross and Red Crescent Societies. He was based in Gueckedou, the town on the nation’s southern border with Sierra Leone where the current Ebola outbreak began last winter. In an effort to understand the drivers of the outbreak, Roberton and his colleagues interviewed 41 Red Cross staff and volunteers who had been mobilized to raise Ebola awareness and teach families how to protect themselves. By then, Ebola had already spread from Guinea into Sierra Leone and Liberia. Now a handful of cases have also been diagnosed in Europe and the United States.

In many villages, the messages about Ebola – how to identify its symptoms, to go to health facilities if symptoms appear, not to touch anyone who is sick, to isolate the sick, not to handle the bodies of the dead – got through and families adopted safe practices. But in some villages, he says, people refused to listen. They didn’t believe Ebola existed or thought it was scaremongering to secure humanitarian aid for their poor nation or a foreign plot to steal body parts. In those cases, the public health messages of the Red Cross volunteers were ignored.

Often, the Red Cross advice went against the way the Guineans had lived for generations. It is customary to clean the bodies of the dead, for example. But touching those who have died of Ebola promotes the spread of the disease. Villagers instead were being told not to touch the bodies or to place them into body bags before burial – concepts that were abhorrent to them and were often disregarded.

“This is a nation where many people are hesitant to seek health care at the best of times. Suddenly people are being told not to touch their sick children and to come to health facilities as soon as they have a fever,” Roberton says. “We assume as health professionals that everyone is just going to follow our advice, that we can fight these things with our intelligence and resources. But it’s not irrational that they chose to ignore the advice. Unless we appreciate how difficult it is for families to follow the guidance we give them, our Ebola control plans look wonderful on paper, but they’re going to fail.”

The importance of trust and strong relationships may seem obvious now, but it wasn’t well understood in the early days of the outbreak, Roberton says. While in Guinea, he learned of one village that had deaths from Ebola but essentially barricaded themselves in, refusing any help. It took a group of politicians and religious leaders to get together and drive to the village to meet with elders there in the hopes that the Red Cross could have the time and space to educate the village about the dangers.

The success of future public health campaigns in places like West Africa, Roberton says, requires stronger and more trusting relationships between health workers and community members, so families will believe and accept future campaigns’ important health messages.

“In order to control the current outbreak and prevent similar ones in the coming decades, health professionals in Guinea and other countries must take urgent steps to cultivate the confidence of community members in the health system and in emergency responders,” he says.

Research | Penn study shows bed bugs can transmit parasite that causes Chagas disease

The bed bug may be just as dangerous as its sinister cousin, the triatomine, or “kissing” bug. A new study from Penn Medicine researchers in the Center for Clinical Epidemiology and Biostatistics demonstrated that bed bugs, like the triatomines, can transmit Trypanosoma cruzi, the parasite that causes Chagas disease, one of the most prevalent and deadly diseases in the Americas.

The role of the bloodsucking triatomine bugs as vectors of Chagas disease–which affects 6 to 8 million worldwide, mostly in Latin America, and kills about 50,000 a year–has long been recognized. The insects infect people not through their bite but feces, which they deposit on their sleeping host, often around the face, after feeding. Bed bugs, on the other hand, are usually considered disease-free nuisances whose victims are left with only itchy welts from bites and sleepless nights.

In a study published online this week in the American Journal of Tropical Medicine and Hygiene, senior author Michael Z. Levy, PhD, assistant professor in the department of Biostatistics and Epidemiology at the University of Pennsylvania’s Perelman School of Medicine, and researchers at the Universidad Peruana Cayetano Heredia in Peru conducted a series of laboratory experiments that demonstrated bi-directional transmission of T. cruzi between mice and bed bugs.

In the first experiment run at the Zoonotic Disease Research Center in Arequipa, Peru, the researchers exposed 10 mice infected with the parasite to 20 uninfected bed bugs every three days for a month. Of about 2,000 bed bugs used in the experiment, the majority acquired T. cruzi after feeding on the mice. In a separate experiment to test transmission from bug to mouse, they found that 9 out of 12 (75 percent) uninfected mice acquired the parasite after each one lived for 30 days with 20 infected bed bugs.

In a third experiment, investigators succeeded in infecting mice by placing feces of infected bed bugs on the animal’s skin that had either been inflamed by bed bug bites, or scraped with a needle. Four out of 10 mice (40 percent) acquired the parasite by this manner; 1 out of 5 (20 percent) were infected when the skin was broken by the insect’s bites only. A final experiment performed at the Penn bed bug lab in Philadelphia demonstrated that bed bugs, like triatomines, defecate when they feed.

“We’ve shown that the bed bug can acquire and transmit the parasite. Our next step is to determine whether they are, or will become, an important player in the epidemiology of Chagas disease,” Levy said. “There are some reasons to worry–bed bugs have more frequent contact with people than kissing bugs, and there are more of them in infested houses, giving them ample opportunity to transmit the parasite. But perhaps there is something important we don’t yet understand about them that mitigates the threat.”

T. cruzi is also especially at home in the guts of bed bugs. “I’ve never seen so many parasites in an insect,” said Renzo Salazar, a biologist at the Universidad Peruana Cayetano Heredia and co-author on the study. “I expected a scenario with very low infection, but we found many parasites–they really replicate well in the gut of the bed bugs.”

Wicked Cousins

Bed bugs and kissing bugs are distant cousins but share many striking similarities. Both insects hide in household cracks and crevices waiting for nightfall and the opportunity to feed on sleeping hosts. They are from the same order of insects (Hemiptera) and both only feed on blood. (One main difference is their size: kissing bugs are five times as big as a bed bug). With so much in common, it seemed logical to the authors that the kissing bug’s most infamous trait, the transmission of T. cruzi, is also shared by the bed bug.

Other investigators have shared this suspicion. In 1912, just three years after Carlos Chagas described the transmission of the disease by kissing bugs, French parasitologist Émile Brumpt recounted that he had infected almost 100 bed bugs exposed to an infectious mouse, and then used them to infect two healthy mice. Decades later an Argentine group replicated his work. These experiments, largely ignored during the recent bed bug resurgence, missed one key point.

“Mice can hunt and eat bed bugs,” said Ricardo Castillo-Neyra, DVM, PhD, coauthor and postdoctoral fellow at the Universidad Peruana Cayetano Heredia and Penn. “The older studies were almost certainly only documenting oral transmission of the parasite. Our work shows for the first time that bed bugs can transmit the parasite when their feces are in contact with broken skin, the route by which humans are usually infected.”

Emerging Problem

More people in the U.S. are infected with T. cruzi now than ever before. The Centers for Disease Control and Prevention estimates that the number of Chagas disease cases in the U.S. today could be as high as 300,000.

“There have always been triatomine bugs and cases of Chagas disease in the U.S., but the kissing bugs we have here don’t come into homes frequently like the more dangerous species in South and Central America do,” Levy said. “I am much more concerned about the role of bed bugs. They are already here–in our homes, in our beds and in high numbers. What we found has thrown a wrench in the way I think about transmission, and where Chagas disease could emerge next.”

Equally worrying is the invasion of bed bugs into areas where Chagas disease is prevalent, especially in countries where traditional insect vectors of the parasite have been nearly eliminated, Levy said. In these areas, bed bugs will be repeatedly exposed to T. cruzi, and could re-spark transmission where it had been extinguished.

“Bed bugs are harder to kill than triatomines due to their resistance to common insecticides.” Levy said. “No one is prepared for large scale bed bug control. If the parasite starts to spread through bed bugs, decades of progress on Chagas disease control in the Americas could be erased, and we would have no means at our disposal to repeat what had been accomplished.”

Often referred to as a silent killer, Chagas disease is hard to diagnose in its early stages because the symptoms are mild or absent. The parasites are hidden mainly in the heart and digestive muscle and over time can cause cardiac disorders and sometimes digestive or neurological problems. In later years, the infection can lead to sudden death or heart failure caused by progressive destruction of the heart muscle. Although there are some drugs to treat Chagas disease, they become less effective the longer a person is infected.

The long asymptomatic period of Chagas disease complicates surveillance for new outbreaks of transmission. In Arequipa, Peru, thousands became infected with the parasite before a case appeared in the hospital. The same could happen in cities in the United States if the parasite were to emerge in the bed bug populations, the authors say.

“Carlos Chagas discovered T. cruzi in triatomine insects before he saw a single case of the disease,” Levy said. “We need to learn from his intuition–check the bugs for the parasite.”

Other co-authors of the study include Aaron W. Tustin, Katty Borrini-Mayorí and César Náquira.

Research | USF – Subtle shifts in the Earth could forecast earthquakes, tsunamis

Earthquakes and tsunamis can be giant disasters no one sees coming, but now an international team of scientists led by a University of South Florida professor have found that subtle shifts in the earth’s offshore plates can be a harbinger of the size of the disaster.

In a new paper published today in the Proceedings of the National Academies of Sciences, USF geologist Tim Dixon and the team report that a geological phenomenon called “slow slip events” identified just 15 years ago is a useful tool in identifying the precursors to major earthquakes and the resulting tsunamis. The scientists used high precision GPS to measure the slight shifts on a fault line in Costa Rica, and say better monitoring of these small events can lead to better understanding of maximum earthquake size and tsunami risk.

“Giant earthquakes and tsunamis in the last decade – Sumatra in 2004 and Japan in 2011 – are a reminder that our ability to forecast these destructive events is painfully weak,” Dixon said.

Dixon was involved in the development of high precision GPS for geophysical applications, and has been making GPS measurements in Costa Rica since 1988, in collaboration with scientists at Observatorio Vulcanológico y Sismológico de Costa Rica, the University of California-Santa Cruz, and Georgia Tech. The project is funded by the National Science Foundation.

Slow slip events have some similarities to earthquakes (caused by motion on faults) but release their energy slowly, over weeks or months, and cannot be felt or even recorded by conventional seismographs, Dixon said. Their discovery in 2001 by Canadian scientist Herb Dragert at the Pacific Geoscience Center had to await the development of high precision GPS, which is capable of measuring subtle movements of the Earth.

The scientists studied the Sept. 5, 2012 earthquake on the Costa Rica subduction plate boundary, as well as motions of the Earth in the previous decade. High precision GPS recorded numerous slow slip events in the decade leading up to the 2012 earthquake. The scientists made their measurements from a peninsula overlying the shallow portion of a megathrust fault in northwest Costa Rica.

The 7.6-magnitude quake was one of the strongest earthquakes ever to hit the Central American nation and unleased more than 1,600 aftershocks. Marino Protti, one of the authors of the paper and a resident of Costa Rica, has spent more than two decades warning local populations of the likelihood of a major earthquake in their area and recommending enhanced building codes.

A tsunami warning was issued after the quake, but only a small tsunami occurred. The group’s finding shed some light on why: slow slip events in the offshore region in the decade leading up to the earthquake may have released much of the stress and strain that would normally occur on the offshore fault.

While the group’s findings suggest that slow slip events have limited value in knowing exactly when an earthquake and tsunami will strike, they suggest that these events provide critical hazard assessment information by delineating rupture area and the magnitude and tsunami potential of future earthquakes.

The scientists recommend monitoring slow slip events in order to provide accurate forecasts of earthquake magnitude and tsunami potential.

The authors on the paper are Dixon; his former graduate student Yan Jiang, now at the Pacific Geoscience Centre in British Columba, Canada; USF Assistant Professor of Geosciences Rocco Malservisi; Robert McCaffrey of Portland State University; USF doctoral candidate Nicholas Voss; and Protti and Victor Gonzalez of the Observatorio Vulcanológico y Sismológico de Costa Rica, Universidad Nacional.

Mali | Six cases of Ebola with six deaths – Major contact tracing effort underway

This situation assessment was updated on 21 November to include new information received overnight, including improvements in contact tracing, the death of the sole surviving patient and more details about the last 3 cases in the transmission chain.

As of today (21 November), Mali has officially reported a cumulative total of 6 cases of Ebola virus disease, with 6 deaths. Of the 6 cases, 5 are laboratory confirmed and one remains probable as no samples were available for testing.

These numbers include the 2-year-old girl who initially imported the virus into Mali and died of the disease on 24 October.

Intensive tracing and monitoring of the child’s numerous contacts, including many who were monitored in hospital, failed to detect any additional cases. All 118 contacts, including family members, have now passed through the 21-day incubation period without developing symptoms.

The virus was almost certainly re-introduced into Mali by a 70-year-old Grand Imam from Guinea, who was admitted to Bamako’s Pasteur Clinic on 25 October and died on 27 October. He has been reclassified as a Guinea case, as he developed symptoms in that country. No samples were available for testing.

Pasteur Clinic: direct and indirect links

All 5 cases in this new outbreak are linked, 4 directly and 1 indirectly, to the patient in the Pasteur Clinic.

The first was a 25-year-old male nurse who worked at the clinic and was assigned to care for the Imam. He was hospitalized on 8 November. His case was laboratory-confirmed on 11 November and he died the same day.

The second case was confirmed in a doctor who worked at the clinic and treated the Imam. He developed symptoms on 5 November and was hospitalized on 8 November. Laboratory confirmation was received on 12 November. He died on 20 November.

The remaining 3 cases occurred in a family. The Imam visited this family when he arrived in Bamako on 25 October, prior to his admission at the Pasteur Clinic. The 51-year-old father subsequently visited the Imam at the clinic.

The father developed symptoms on 7 November and died on 10 November from an undiagnosed cause.

His 57-year-old wife developed symptoms on 29 October. She was admitted to another clinic on 11 November and then transferred to a hospital on 12 November. She died that same day.

The third case is the son. He visited yet another clinic on 5 November, was not admitted, and died at home on 14 November. Ebola infection was laboratory-confirmed in the wife and the son.

Stepped up contact tracing

A massive effort is currently under way to identify all potential chains of transmission, monitor contacts, and prevent the outbreak from growing larger. At present 327 contacts have been identified and 310 (95%) of these have been placed under daily surveillance.

This rigorous “detective” work shows that the deceased nurse from the Pasteur Clinic had the largest number of contacts, at 98, including 75 family members.

As the successful experiences in Senegal and Nigeria show, aggressive contact tracing, which seeks to find and break every chain of transmission immediately after an imported case, can hold the number of additional cases to very small numbers and support a rapid end to the outbreak.

The Ministry of Health, with assistance from the WHO country office, has augmented the number of staff engaged in contact tracing by drawing on polio surveillance teams and using local medical students with training in epidemiology.

In addition, WHO has deployed 10 epidemiologists through its Global Outbreak Alert and Response Network, or GOARN.

The country is also ramping up its capacity to perform exit screening at the Bamako airport.

Guinea: Many mourners attended the funeral

The Imam was buried in his native village of Kourémalé, Guinea, on 28 October. That event has now been investigated. Thousands of mourners may have attended the funeral. Some of them touched the body as part of the traditional funeral ceremony. About 300 contacts are being traced.

Experts in Mali and at WHO agree that Mali will remain at risk of further imported cases as long as transmission across the border is ongoing.

Madagascar | Plague outbreak – 119 cases including 40 deaths

On 4 November 2014, WHO was notified by the Ministry of Health of Madagascar of an outbreak of plague. The first case, a male from Soamahatamana village in the district of Tsiroanomandidy, was identified on 31 August. The patient died on 3 September.

As of 16 November, a total of 119 cases of plague have been confirmed, including 40 deaths. Only 2% of reported cases are of the pneumonic form.

Cases have been reported in 16 districts of seven regions. Antananarivo, the capital and largest city in Madagascar, has also been affected with 2 recorded cases of plague, including 1 death. There is now a risk of a rapid spread of the disease due to the city’s high population density and the weakness of the healthcare system. The situation is further complicated by the high level of resistance to deltamethrin (an insecticide used to control fleas) that has been observed in the country.

Public health response

The national task force has been activated to manage the outbreak. With support from partners – including WHO, the Pasteur Institute of Madagascar, the “Commune urbaine d’Antananarivo” and the Red Cross – the government of Madagascar has put in place effective strategies to control the outbreak. Thanks to financial assistance from the African Development Bank, a 200,000 US dollars response project has been developed. WHO is providing technical expertise and human resources support. Measures for the control and prevention of plague are being thoroughly implemented in the affected districts. Personal protective equipment, insecticides, spray materials and antibiotics have been made available in those areas.


Plague is a bacterial disease caused by Yersinia pestis, which primarily affects wild rodents. It is spread from one rodent to another by fleas. Humans bitten by an infected flea usually develop a bubonic form of plague, which produces the characteristic plague bubo (a swelling of the lymph node). If the bacteria reach the lungs, the patient develops pneumonia (pneumonic plague), which is then transmissible from person to person through infected droplets spread by coughing. If diagnosed early, bubonic plague can be successfully treated with antibiotics. Pneumonic plague, on the other hand, is one of the most deadly infectious diseases; patients can die 24 hours after infection. The mortality rate depends on how soon treatment is started, but is always very high.

WHO recommendations

WHO does not recommend any travel or trade restriction based on the current information available. In urban areas, such as Antananarivo, the surveillance of epidemic risk indicators is highly recommended for the implementation of preventive vector control activities.

Saudi Arabia | Five additional cases of MERS including two deaths

Between 12 and 16 October 2014, the National IHR Focal Point for the Kingdom of Saudi Arabia (KSA) notified WHO of 5 additional cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 2 deaths.

Details of the cases are as follows:

1. A 42-year-old female nurse, non-national, from Taif city who developed symptoms on 13 October. She was admitted to a hospital on 14 October. The patient was exposed to a laboratory-confirmed case of MERS-CoV. She has comorbidities but no history of contact with camels or raw camel products consumption. Also, she has no history of travel in the 14 days prior to the onset of symptoms. Currently, the patient is in stable condition and under isolation.

2. A 60-year-old male from Taif city who developed symptoms on 14 October. On the same day, he was admitted to a hospital. The patient had comorbidities. On 8 October, he received dialysis in the same room used to dialyze a laboratory-confirmed MERS-CoV. He had no history of contact with camels or raw camel products consumption. He also had no history of travel in the 14 days prior to the onset of symptoms. The patient passed away on 15 October.

3. An 82-year-old male from Hawtah Bani Tamim city who developed symptoms on 3 October. On 5 October, he visited a hospital in Alkharj city, where he stayed for 6 days. Then, he drove to Riyadh, where he was admitted to a hospital on 11 October 2014. The patient has comorbidities. He has had no contact with animals but resides in an area with heavy presence of camel farms. In addition, the patient has a history of raw camel milk consumption in the 14 days prior the onset of symptoms. He has no history of travel in the 14 days prior to the onset of symptoms. Currently, the patient is in stable condition.

4. A 44-year-old male from Riyadh city who developed symptoms on 7 October. He was admitted to a hospital in Riyadh on 11 October 2014. The patient has comorbidities. He has frequent contact with animals but he has no history of contact with camels or consumption of raw camel products in the 14 days prior to the onset of symptoms. The patient travelled to Dammam city in the 14 days that preceded the onset of symptoms. Currently, he is admitted to the ICU.

5. A 70-year-old male from Al Huwaya town who developed symptoms on 8 October. He was admitted to a hospital in Taif city on 10 October. The patient had comorbidities. The patient had contact with animals but he had no history of contact with camels or consumption of raw camel products in the 14 days prior to the onset of symptoms. Also, he had no history of travel in the 14 days prior to the onset of symptoms. The patient was in critical conditions and admitted to the Intensive Care Unit (ICU) but passed away on 28 October.

Contact tracing of household contacts and healthcare contacts is ongoing for these cases.

The aforementioned 5 cases, including 2 deaths, had already been accounted for in the previous MERS-CoV DON (7 November). Therefore, the total numbers of cases and deaths remain unchanged. Globally, WHO has been notified of 909 laboratory-confirmed cases of infection with MERS-CoV, including at least 331 related deaths.

WHO advice

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for acute respiratory infections and to carefully review any unusual patterns.

Infection prevention and control measures are critical to prevent the possible spread of MERS-CoV in health care facilities. It is not always possible to identify patients with MERS-CoV early because like other respiratory infections, the early symptoms of MERS-CoV are non-specific. Therefore, health-care workers should always apply standard precautions consistently with all patients, regardless of their diagnosis. Droplet precautions should be added to the standard precautions when providing care to patients with symptoms of acute respiratory infection; contact precautions and eye protection should be added when caring for probable or confirmed cases of MERS-CoV infection; airborne precautions should be applied when performing aerosol generating procedures.

Until more is understood about MERS-CoV, people with diabetes, renal failure, chronic lung disease, and immunocompromised persons are considered to be at high risk of severe disease from MERS‐CoV infection. Therefore, these people should avoid close contact with animals, particularly camels, when visiting farms, markets, or barn areas where the virus is known to be potentially circulating. General hygiene measures, such as regular hand washing before and after touching animals and avoiding contact with sick animals, should be adhered to.

Food hygiene practices should be observed. People should avoid drinking raw camel milk or camel urine, or eating meat that has not been properly cooked.

WHO does not advise special screening at points of entry with regard to this event nor does it currently recommend the application of any travel or trade restrictions.

Be well. Practice big medicine.