H5N1

Saudi Arabia: Critical care response to a hospital outbreak of MERS

Via Annals of Intensive Care: The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study. This is the first report of its kind I can recall. Excerpt:

Background 

Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). To learn from our experience, we described the critical care response to the outbreak. 

Methods 

This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted.  

Results 

Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). 

In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. 

Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians.  

Conclusions 

Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.

MMWR: Characteristics of children aged <18 years with Zika virus disease acquired postnatally

Via MMWR, an early release report: Characteristics of Children Aged <18 Years with Zika Virus Disease Acquired Postnatally — U.S. States, January 2015–July 2016. Excerpt from the discussion section:

This series of 158 children with postnatally acquired Zika virus disease corroborates previously published reports suggesting that the clinical course of Zika virus disease is typically mild in children, as it is in adults. In this case series, only two children were hospitalized, and no deaths occurred. Serious complications of Zika virus disease, such as Guillain-Barré syndrome, were not reported for any children in this analysis. 

However, health care providers should be aware of potential serious consequences of Zika virus disease, including neurologic manifestations, and should notify state health departments of all Zika virus disease cases.  

Severe disease following Zika virus infection in children has rarely been reported. Two deaths possibly associated with postnatally acquired Zika virus disease have been reported among children, including a Brazilian girl aged 16 years with possible hemorrhage and a Colombian girl aged 15 years with sickle cell disease who developed severe acute respiratory distress syndrome, hemothorax, and splenic sequestration. 

Guillain-Barré syndrome and meningoencephalitis also have been reported rarely among children during the recent outbreak in Brazil.** No deaths or neurologic complications following Zika virus infection in children were reported after outbreaks in Yap State, Micronesia, or French Polynesia. Further evaluation is needed to determine the incidence of severe disease manifestations, risk factors for more severe illness, and long-term outcomes of postnatally acquired Zika virus infection in children.  

Almost half of the pediatric patients with Zika virus disease in this series were aged 15–17 years, with a slight female preponderance. The relatively higher proportion of cases in females and older children might be related to health care–seeking or testing bias (e.g., girls who are or might become pregnant might be more likely to seek care or to be tested) or older children being more likely to travel and thus to be exposed to Zika virus. In addition, clinicians might be less likely to suspect Zika virus infection in younger children, because the signs and symptoms (rash and fever) are nonspecific and similar to those associated with other childhood rash illnesses (e.g., roseola or scarlet fever) or drug reactions.

Hong Kong: HKU breakthrough in fight against bird flu

When University of Hong Kong experts say something looks good, I believe them. Via The Standard, a March 17 report: HKU breakthrough in fight against bird flu.

University of Hong Kong scientists hope an experimental drug used for acute respiratory distress syndrome could better treat the dreaded bird flu H5N1 virus. 

The School of Public Health first discovered that H5N1 causes severe pneumonia by impairing proteins called sodium and chloride transporter molecules in the lungs that help draw fluid out of the organs. 

With the discovery of the mechanism of infection, the scientists have begun laboratory testing an experimental treatment for H5N1 using mesenchymal stromal cells. 

The bone marrow-derived stromal cells are already undergoing clinical trials for sepsis and acute respiratory distress syndrome in the United States. 

But no one has tested whether the same cells also could be effective against viral respiratory infections such as flu. 

The treatment strategy could also be used against other bird flu viruses, H7N9 and H9N2, as well as MERS and SARS coronaviruses, said the lead researcher, the school's assistant professor Michael Chan Chi-wai. 

Using laboratory mice, the 14-member team found that H5N1 infection impaired fluid clearance in the lungs' alveoli tiny sacs that allow oxygen and carbon dioxide to move between the lungs and bloodstream more than did seasonal virus. 

The infected cells release "soluble factors" that impair the alveolar sodium and chloride transporters, the team said. 

"Mesenchymal stromal cells prevented or reduced this effect in vitro and in vivo in H5N1-infected mice. These cells provide a potentially effective treatment for acute lung injury in severe influenza," the report concluded. 

Chan said: "We showed that when mice are infected with H5N1, it will inhibit the proteins and the mice developed edemas, lung infection and died. If we treat mice with mesenchymal stromal cells so that activity of sodium and chloride transporter proteins return back to normal, it resolved the edemas."

The study was published in PNAS, but I don't think it's online yet. If you know where the link is, please let me know and I'll update this post.

Saudi Arabia: Management and long-term survival of severe MERS cases

Thanks to Greg Folkers for sending the link to this report in Respiratory Care via PubMed.gov: Acute Management and Long-Term Survival Among Subjects With Severe Middle East Respiratory Syndrome Coronavirus Pneumonia and ARDS. The abstract and then a comment:

BACKGROUND: Data on the management, clinical course, and outcome of critical patients with Middle East respiratory syndrome coronavirus are scarce. We report here our experience and long-term outcome of such patients. 

METHODS: Subjects intubated for management of ARDS from Middle East respiratory syndrome coronavirus pneumonia and ARDS during the April-May 2014 outbreak were included. Their characteristics, ICU course, management, and outcome were evaluated. 

RESULTS: Fourteen subjects, including 3 health-care workers, met study criteria. Besides 2 health-care workers, all subjects had comorbidities. Predominant symptoms were fever, cough, and dyspnea. The worst median PaO2 /FIO2 ratio of 118 post-intubation was seen on the third day, and median APACHE II score was 27. All subjects received lung-protective ventilation and 1 mg/kg/d methylprednisolone infusion for ARDS. Eleven subjects received ribavirin and peginterferon α-2a. 

Subjects had a critical ICU course and required neuromuscular blockade (n = 11; 79%), required rescue therapy for respiratory failure (n = 8; 57%), developed shock (n = 10; 71%), and required renal replacement therapy (n = 8; 57%). Declining C-reactive protein levels correlated with clinical improvement despite continued positive real-time polymerase chain reaction results. Nine subjects died in ICU. Five subjects, including 3 health-care workers, were discharged from hospital and were alive after 1 y. 

CONCLUSIONS: Middle East respiratory syndrome coronavirus pneumonia with ARDS has high mortality in subjects with comorbidities. The mainstay of treatment is meticulous ARDS management. Those who survived the acute infection and its complications remained well after 1 y in our study. The role of ribavirin and interferon warrants urgent further evaluation.

Just five survivors out of 14 cases sounds alarming, and the treatments required indicate that a critical MERS patient really is desperately ill. This is one of the few Saudi-authored MERS reports I've seen in the last three years, and I hope we see many more.

Does MERS pose a serious threat to China?

Via the Council on Foreign Relations' Asia Unbound blog, a post by Yanzhong Huang: Does MERS Pose a Serious Threat to China? Click through for many links. Excerpt:

Last Friday, China confirmed its first case of Middle East Respiratory Syndrome (MERS) in Guangdong province. The now-confirmed South Korean MERS patient, who ignored travel warnings and lied about his conditions when flying to China, had been in close contact with seventy-seven people in the province. As of June 1, sixty-four have been quarantined while the thirteen others remain to be found. 

The relatively recent memory of China’s SARS outbreak in addition to the similarities between the diseases has magnified concerns that a similar outbreak could occur with MERS. Also originated in Guangdong, the SARS virus triggered one of the most serious social political crises in China. 

Like SARS, MERS is caused by a coronavirus (MERS‐CoV) that makes a species jump from animals to humans. Many people with MERS can develop severe complications such as pneumonia. There is currently also no vaccine or drug that works against MERS. Like SARS, a majority of the severe MERS cases are treated with the help of ventilators. 

But MERS patients generally develop severe acute respiratory illness faster than those with SARS. In critically ill MERS patients, the median time from onset to death is twelve days, compared to twenty-one days for SARS patients. The case fatality rate of MERS is about 40 percent, much higher than H1N1 and SARS. In view of the lethality of the virus, the local hospital that received the first MERS patient purposefully drew mostly from among unmarried medical workers for assignment to the team that would treat potential MERS patients. 

But what is the likelihood of the virus evolving into a major outbreak in China? Answer: not very high. First, 90 percent of the MERS cases are concentrated in the Middle East, notably Saudi Arabia. There are indeed cases reported in Europe, Africa, North America, and Asia, but—with Korea an exception—these cases are sporadic and without sustained community transmission. 

Second, compared to many infectious diseases, MERS has only limited human to human transmission. The virus is not airborne. Many infections are hospital acquired or caused by unprotected close contact with sick family members. On average, one MERS case will lead to 0.6 to 0.7 secondary cases, which makes the virus transmission rate much lower than SARS (on average two to five secondary cases per patient) or Ebola (on average one to two secondary cases per patient). 

Also, unlike what was found in the SARS outbreak, true MERS “super-spreaders” (i.e., a person who infects a significantly greater number of other people than the average stricken patient) so far have not been identified. The limited transmission of the virus might explain why none of the sixty-four quarantined people who had close contact with the original Korean patient in Guangdong has shown any abnormality. 

Third, China has developed a relatively robust surveillance and response capacity to deal with infectious diseases like MERS. Over the past decade, China has increased its spending on public health and completed a four-level disease prevention and control framework starting from the county level up to the national level. Its Internet-based disease reporting system enables hospitals to directly report suspected disease cases to the China Center for Disease Control (CDC). 

Since 2012, China has reportedly developed an emergency response plan for diseases like MERS and trained its medical staff in how they should handle suspected or probable MERS cases. Indeed, right after the South Korean Ministry of Health alerted China to the situation, it took only four hours for local health authorities to locate and isolate the first MERS case.

ARDS in a Spanish Ebola patient

Thanks to Greg Folkers for sending the link to this report in The Lancet Respiratory Medicine: Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. The patient was Teresa Romero, whose case was first mentioned here last October. The summary:

Background 

In the current epidemic of Ebola virus disease, health-care workers have been transferred to Europe and the USA for optimised supportive care and experimental treatments. We describe the clinical course of the first case of Ebola virus disease contracted outside of Africa, in Madrid, Spain. 

Methods 

Herein we report clinical, laboratory, and virological findings of the treatment of a female nurse assistant aged 44 years who was infected with Ebola virus around Sept 25–26, 2014, while caring for a Spanish missionary with confirmed Ebola virus disease who had been medically evacuated from Sierra Leone to La Paz-Carlos III University Hospital, Madrid. We also describe the use of experimental treatments for Ebola virus disease in this patient. 

Findings 

The patient was symptomatic for 1 week before first hospital admission on Oct 6, 2014. We used supportive treatment with intravenous fluids, broad-spectrum antibiotics, and experimental treatments with convalescent plasma from two survivors of Ebola virus disease and high-dose favipiravir. On day 10 of illness, she had acute respiratory distress syndrome, possibly caused by transfusion-related acute lung injury, which was managed without mechanical ventilation. Discharge was delayed because of the detection of viral RNA in several bodily fluids despite clearance of viraemia. The patient was discharged on day 34 of illness. At the time of discharge, the patient had possible subacute post-viral thyroiditis. None of the people who had contact with the patient before and after admission became infected with Ebola virus. 

Interpretation 

This report emphasises the uncertainties about the efficacy of experimental treatments for Ebola virus disease. Clinicians should be aware of the possibility of transfusion-related acute lung injury when using convalescent plasma for the treatment of Ebola virus disease.

China: Clinical study of hemorrhagic fever with renal syndrome

Thanks to China Medical News for tweeting the link to this PLOS ONE report: Clinical Study of Critical Patients with Hemorrhagic Fever with Renal Syndrome Complicated by Acute Respiratory Distress Syndrome. The disease is caused by hantaviruses. The abstract:

Objectives 

The aim of this study was to investigate the clinical characteristics and outcomes of critical patients with hemorrhagic fever with renal syndrome (HFRS) complicated by acute respiratory distress syndrome (ARDS). 

Materials and Methods 

To observe the demographic, epidemiological and clinical characteristics, and to explore the predictive effects for prognosis in laboratory findings, we conducted a detailed retrospective analysis of clinical records for critical patients with HFRS complicated by ARDS, treated at the center for infectious diseases, Tangdu Hospital, between January 2008 and December 2012. 

Results 

A total of 48 critical patients with laboratory confirmed HFRS accompanied by ARDS were enrolled in the study, including 27 survivors and 21 non-survivors, with a fatality rate of 43.75%. 

Thirty-one individuals (64.6%) contracted HFRS between the months of September and December. The non-survivors tended to have lower incidence of overlapping phase (P = 0.025). There were no obvious differences in the needs for mechanical ventilation (MV) and renal replacement therapy (RRT), except for the need for vasoactive drugs between the survivors and non-survivors (P = 0.001). 

The non-survivors were found to have higher frequencies of encephalopathy, refractory shock and multiple organ dysfunction syndrome (MODS), lower incidences of acute renal failure (ARF) and secondary hypertension (P<0.05). The non-survivors tended to have lower levels of serum creatinine (Scr) (P<0.001) and fibrinogen (Fib) (P = 0.003), higher incidences of prolonged prothrombin time (PT) (P = 0.006) and activated partial thromboplastin time (APTT) (P = 0.020) and higher levels of aspartate aminotransferase (AST) (P = 0.015), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P<0.05). 

Conclusion 

The high mortality rate of critical patients with HFRS complicated by ARDS emphasizes the importance of clinicians’ alertness and timely initiation of systemic supportive therapy.