Possible Ebola treatment ZMapp receives FDA fast-track status
Mapp Biopharmaceuticals announced yesterday that its experimental Ebola treatment ZMapp received fast-track status to gain US Food and Drug Administration (FDA) approval.
The San Diego, Calif.–based company has been administering ZMapp in West African clinical trials, though with Liberia reporting no new Ebola cases since July and case incidence declining in Sierra Leone and Guinea, ZMapp's effectiveness has been difficult to test.
The FDA grants fast-track status to pharmaceuticals that potentially address unmet needs and treat serious conditions. The new status may allow Mapp Biopharmaceuticals and its commercial division, LeafBio, Inc., to more quickly file a Biologics License Application for marketing ZMapp in the United States.
ZMapp was administered to the first two American Ebola patients, who survived. The drug is made with three lab-engineered monoclonal antibodies designed to attack Ebola surface proteins. Antibodies are grown in tobacco plants by Kentucky BioProcessing.
Currently, no drug has been approved to treat Ebola, which since last year has caused 28,220 cases and 11,291 deaths, primarily in West Africa.
Sep 17 MAPP Biopharmaceuticals press release
Addition of inactivated polio vaccine enhances immunogenicity
A study of poliovirus immunization among newborns found that use of inactivated poliovirus vaccine (IPV) increased seroconversion rates when added to a trivalent or multi-dose bivalent oral poliovirus vaccine schedule, according to findings yesterday in The Lancet.
The open-label, randomized controlled trial followed 782 newborns at four hospitals in India. Research was funded by the World Health Organization (WHO), which began recommending an immunization schedule comprising three or four doses of bivalent type 1 and type 3 oral poliovirus vaccine (bOPV) and one dose of inactivated poliovirus vaccine (IPV) in January 2014.
Healthy newborns were assigned to one of five immunization groups: group 1 (163 babies receiving trivalent OPV), group 2 (153 babies receiving trivalent OPV and IPV), group 3 (155 babies receiving bOPV), group 4 (156 babies receiving bOPV and IPV), and group 5 (155 babies receiving bOPV and two doses of IPV).
OPV was administered at birth, 6 weeks, and 14 weeks; IPV was given intramuscularly at 14 weeks. Seroconversion against poliovirus was measured at 18 weeks.
The immunologic response to IPV was greater than expected for poliovirus type 1 and type 3 and as expected for poliovirus type 2. The combination of trivalent OPV and IPV was significantly superior to the use of trivalent OPV alone (P < 0.0008), with 98% of newborns in the IPV group converting against type 1, 100% against type 2, and 99.3% against type 3.
The combination of bOPV and IPV was superior to the use of bOPV alone (P = 0.0153), with 99.4% of newborns in the IPV group seroconverting against type 1, 68.6% against type 2, and 99.4% against type 3.
The findings suggest that the newly recommended vaccination schedule and the addition of IPV to the regiment greatly improves immunogenicity of the poliovirus vaccine, especially against poliovirus type 3, the authors conclude.
Sep 17 Lancet study
Another biolab breach noted as Pentagon says probe over
As part of its ongoing investigation into Pentagon labs, USA Today reported yesterday that a senior Army lab researcher in Utah in 2007 tossed out a test tube containing live anthrax spores and sent the tested batch to other labs. A separate story noted that the Army has completed its probe into biosecurity lapses without releasing details.
The 2007 incident involved a principal investigator (PI) at a Dugway Proving Ground facility that has been at the center of a probe into the shipping of live Bacillus anthracis, which causes anthrax, around the country and to at least nine other nations, as well as other safety and security breaches.
Twelve pages of redacted documents released to USA Today by the Department of Health and Human Services' Office of Inspector General account the incident. The PI was using chlorine dioxide to inactivate B anthracis—which was deemed a scientifically acceptable method at the time—even though Dugway didn't have a standard operating procedure for using the chemical.
The researcher found that a colony of the bacteria grew in a cell culture in one test tube, indicating that the chlorine dioxide kill step did not work. Instead of investigating further, the PI simply threw the test tube with the live culture away and shipped the remaining samples in the batch.
"The PI's notes do not explain why the viable colony grew, whether the inactivation procedure was performed properly, or why the remaining tubes were not retested for viability," one of the documents notes.
Sep 17 USA Today story on testing misstep
Meanwhile, the emergency probe into biosecurity breaches at Department of Defense (DoD) labs is now completed, though the shuttering of nine high-security Army labs will remain for now, USA Today reported in a separate story yesterday.
"Once the review results are compiled, the US Army will develop a plan to address any deficiencies," Lt. Col. Jesse Stalder, an Army spokesman, said in a statement. "This process will take some time and, once complete, more information will be made available."
In addition to B anthracis, samples of Yersinia pestis, which causes plague, and encephalitis viruses might also have been improperly shipped from DoD labs.
Sep 17 USA Today story on completion of probe
Spanish study finds no genetic risk for severe pH1N1 disease
A study of severe and mild 2009 H1N1 (pH1N1) found no significant host genetic factors that might cause or aggravate severe disease, according to findings published yesterday in PLoS One.
In an effort to determine why pH1N1 caused severe disease in people without prior risk factors, researchers analyzed 547,296 genome-wide single nucleotide polymorphisms (SNPs) from a sample of 49 people with severe pH1N1 disease, 107 mild cases, and 549 members of the general population.
Samples from case-patients with severe pH1N1 infections in 2009 and 2010 were obtained from three hospitals in Spain, samples from patients with mild disease came from the Spanish Influenza Case-Control Study, and the general population SNPs were retrieved from the nation's CeGen-PRB2-ISCIII genotyping database.
Researchers found no significant genetic factor that could explain why pH1N1 affected some people more severely than others. The one SNP that tested above significance level encodes an enzyme that, in rats, regulates neural development and has no connection to immunologic or inflammatory activity. Identification of the SNP as significant was assumed to be a false-positive.
Limitations of the study include its low sample size and its applicability only to a population of primarily European ancestry, the researchers said.
Sep 17 PLoS One study
Danish study finds human MRSA risk related to livestock proximity
A Danish study found that human infections with methicillin-resistant Staphylococcus aureus (MRSA) have been increasing steadily in the country and are associated with exposure to livestock and contact with livestock workers, according to a study yesterday in Eurosurveillance.
Livestock, particularly swine, are a reservoir for the recently derived MRSA CC398-IIa, which is responsible for 40% of new MRSA cases in Denmark, the Netherlands, and Germany. The first MRSA CC398-IIa infection in Denmark was reported in 2004.
Researchers from Denmark's Statens Serum Institut analyzed MRSA isolates collected from 1999 to 2011 by the national MRSA registry and repository; the registry has been mandatory since 2007.
Of 7,429 MRSA samples identified in the registry, 416 were MRSA CC398-IIa. More than half of MRSA CC398-IIa isolates (237, or 57%) were multidrug resistant. After asymptomatic carriers were excluded, 148 samples came from people with infections, 51 of whom had no exposure to livestock.
Incidence of MRSA CC398-IIa infections rose steadily in Denmark from 2004 to 2011, showing a linear annual increase of 66% (incidence rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5 to 1.9; P < 0.00001).
Infected people who were not exposed to livestock tended to live within 5 kilometers of livestock workers. The risk of MRSA CC398-IIa infections among people not exposed to livestock was significantly higher in the 25 Danish municipalities where exposed patients lived compared with the rest of Denmark (IRR, 2.5; 95% CI, 1.1 to 5.7; P = 0.041).
Researchers said that, given the recent increase of MRSA CC398-IIa infections in Denmark, spillover from livestock to the community via livestock workers is likely occurring and highlights the need to closely monitor infection rates, especially in municipalities at greater risk.
Sep 17 Eurosurveillance study