Second India state reports suspected Nipah cases as outbreak source eyed

Authorities in a second Indian state are investigating two suspected Nipah virus infections, both of them in people who had traveled to Kerala state where they had contact with infected patients, Reuters reported today, citing a health official in Karnataka state.

The cases involve a 20-year-old woman and a 75-year-old man from the city of Mangalore. Both are receiving treatment, and their samples were sent for testing, with results expected by tomorrow, according to the report.

In another outbreak development, health officials in Kerala state said a bat-infested well in a house in Kozhikode district has been identified as the likely source of the Nipah virus outbreak, which has so far led to 10 deaths in two of the state's districts, Xinhua reported today. The well where the bats were found were in the home of the first patient who died in the outbreak. Some of the bats were caught and sent for lab testing, and the well has been sealed.

District health officials say 19 people are being treated, including two in critical condition, and 11 deaths have been reported, The Hindu, an English-language newspaper based in India, reported today.

Shri J.P. Nadda, India's health minister, said in a statement yesterday that two confirmed cases had a history of contact with the index case, and both patients were treated at Calicut Medical College Hospital, where they died from their infections. Seven patients are still hospitalized. Nadda urged the public not to believe rumors on social media and not to spread panic about the disease.

Nipah virus is primarily spread to humans from animals, with fruit bats as the natural hosts, but limited human-to-human transmission has been reported among family members and caregivers through contact with body fluids of infected patients, as occurred in past outbreaks in Bangladesh and India.

There are no treatments or vaccines targeted to Nipah virus, but it is a priority disease on the World Health Organization (WHO) research and development blueprint.
May 23 Reuters story
May 23 Xinhua story
May 23 Hindu story
May 22 Indian health minister statement
May 22 WHO Nipah virus fact sheet and R&D blueprint


CEPI, IAVI announce partnership to develop Lassa virus vaccine

In a move to speed the development of a vaccine against Lassa virus, the Coalition for Epidemic Preparedness Innovations (CEPI) and the International AIDS Vaccine Initiative (IAVI) on May 21 announced a partnership to develop a new vaccine candidate with the goal of creating a stockpile to help battle future outbreaks.

CEPI will provide $10.4 million to support the first phase of development of IAVI's replicating viral vector-based Lassa vaccine candidate. The agreement includes an option to invest up to a total of $54.9 million over 5 years, including the stockpile.

Earlier animal studies found that the vaccine induced strong immune responses and was highly efficacious. IAVI has signed up a global group of partners in the program, including the Viral Hemorrhagic Fever Consortium, a network of clinical research centers in Africa.

Richard Hatchett, MD, CEPI's chief executive officer, said in the statement, "Lassa fever presents an ongoing public health threat to many parts of West Africa and has demonstrated repeatedly that it can cause large epidemics. The IAVI vaccine has shown great promise in early studies and IAVI has devised an innovative and potentially transformative model for developing it."

The new agreement is the third that CEPI has signed since it launched in 2017. Founded to streamline and fund new vaccine candidates, the group is supported by the governments of Norway, Germany, India, and Japan; the Bill & Melinda Gates Foundation; Wellcome Trust; and the World Economic Forum.

Lassa fever is one of CEPI's list of three targets, which also includes Middle East respiratory syndrome coronavirus (MERS-CoV) and Nipah virus. On Apr 11 CEPI announced support for Lassa and MERS-CoV vaccines that are in development at Inovio Pharmaceuticals.
May 21 CEPI press release
Apr 12 CIDRAP News scan "CEPI announces support for more Lassa fever, MERS vaccines"


Updated estimate puts annual US flu price tag at $11.2 billion

A new estimate of flu's burden on the United States economy each year puts the cost at $11.2 billion, a research team from Australia and the United States reported yesterday in Vaccine.

The group's findings are the first update of flu burden numbers in about a decade and use sources that weren't available when the last assessment was made. They said the current assessment is needed to help policymakers evaluate flu prevention strategies.

To calculate the cost burden, the team looked at flu outcomes such as non-medically attended illnesses, clinic visits, emergency department visits, hospitalization, and deaths and applied them to the 2015 US population. They estimated both direct healthcare costs and indirect costs, such as absenteeism. They presented their results by five age-groups: children younger than 5, children 5 to 17, adults 18 to 49, adults 50 to 64, and seniors age 65 and older.

Of the $11.2 billion (range $6.3 to $25.3 billion) in economic burden, $3.2 billion was from direct medical costs and $8 billion was attributed to indirect costs such as lost productivity. "This updated estimate suggests that substantial costs from influenza remain despite the vaccination efforts in the U.S. setting," the authors wrote.

Seniors had the largest share of total direct costs, mainly reflecting hospitalizations. Most indirect costs were attributed to working-age adults, chiefly from productivity costs related to lost income due to flu-related deaths.

The new estimate is substantially lower than the estimate from a decade ago, which was $26.8 billion (range $12.8 to $53.2 billion) because of variation in estimates in the number of events related to flu, the unit costs of the events, and different study methods.

"The high cost of influenza illness suggests that further efforts are required to increase influenza vaccination uptake in the U.S. to help reduce this burden," the team said.
May 22 Vaccine abstract


FDA issues guidance on anthrax pre-exposure prophylaxis drugs

The US Food and Drug Administration (FDA) today issued final guidance for drug companies to use for developing pre-exposure prophylaxis for inhalational anthrax.

Though there are FDA-approved drugs for treating Bacillus anthracis infection and for postexposure prophylaxis, so far there is no way to protect people who may be exposed or may have inhaled the B anthracis spores and have not yet shown any symptoms. Examples include first responders who face an imminent exposure risk.

In a brief today, the FDA said its final guidance is the result of a multiyear effort to advance its policy for developing inhalational anthrax treatments. Since clinical trials in humans can't be conducted because naturally occurring anthrax is rare and clinical challenge would be unethical, the final guidance clarified that drugs developed for inhalational anthrax prophylaxis can use evidence from animal studies, known as the Animal Rule, to support approval.

FDA Commissioner Scott Gottlieb, MD, said in the statement, "Since the 2001 anthrax attacks, the U.S. government's efforts to protect the nation from bioterrorism threats have continued to evolve. We now know that a comprehensive preparedness plan for potential anthrax threats must account for both pre- and post-exposure scenarios." With that in mind, the FDA has taken steps to modernize its guidance on inhalational anthrax to advance the development of new drugs for prophylaxis, prior to exposure, he added.
May 23 FDA brief


Researchers use infrared technology to detect Zika virus in mosquitoes

The light-based method of analysis called near-infrared spectroscopy (NIRS) can detect Zika virus in mosquitoes more accurately, faster, and cheaper than traditional methods, a study today in Science Advances reports.

Researchers from Australia, Brazil, and the United States conducted the tests on Aedes aegypti mosquitoes, the main insect vector for transmitting Zika. They found that NIRS can detect the virus in the heads and thoraxes (midsections) of the mosquitoes with 94.2% to 99.2% accuracy.

The investigators say this technique is 18 times faster and 110 times cheaper than quantitative reverse transcription polymerase chain reaction (RT-qPCR), a technique commonly used to screen for pathogens in mosquitoes.

NIRS has previously been used on mosquitoes that transmit malaria in Africa to determine their age and species, the authors say, but this is the first time it has been tried for detecting viruses in mosquitoes. The authors say the next step is to test the technique in the field.
May 23 Sci Adv abstract

Stewardship / Resistance Scan for May 23, 2018

News brief

NDM, MCR-1 resistance genes found in same E coli isolates in China

Chinese scientists yesterday reported on the emergence of extensively drug-resistant (XDR) Escherichia coli carrying both New Delhi metallo-beta-lactamase (NDM) and MCR-1 genes in chickens at slaughter in China and detailed the features of two novel NDM-carrying plasmids.

In a letter in the Journal of Antimicrobial Chemotherapy, the investigators said they collected 50 fecal samples from chickens at a slaughterhouse in Qingdao, which sits on the Yellow Sea in eastern China. They recovered 33 E coli isolates from the samples.

Two of the strains showed resistance to imipenem and had an XDR pattern. Polymerase chain reaction and Sanger sequencing confirmed that the strains harbored both NDM and MCR-1. In one isolate the resistance genes were located on separate plasmids, while on the other the NDM gene was on a plasmid and the MRC-1 gene was on a chromosome. Plasmids are mobile pieces of DNA that can transfer to other bacteria of either the same or different species.

NDM-1 was first detected in 2008 and confers resistance to a broad range of beta-lactam antibiotics, including carbapenems. MCR-1 was first identified in China in 2015 and confers resistance to colistin, an antibiotic of last resort. So the detection of both of them in the same bacterium warrants increased concern over XDR pathogens that may be untreatable.

In addition, the scientists write, "To the best of our knowledge, this study identified for the first time the presence of blaNDM-1 gene in phage-like IncY plasmid, which has been associated with mcr-1 and blaVIM-1. Although phage-like plasmid is non-conjugative, it can be integrated into conjugative plasmids via recombination." They also note that one MCR-1 was found on an IncI2 plasmid that was almost 99% identical to a plasmid belonging to IncK2, which has been tied to the spread of MCR-1 in E coli in Europe.
May 22 J Antimicrob Chemother letter


Study find sharps containers pose no risk of C difficile infection

A microbiological investigation published yesterday in the American Journal of Infection Control has found the containers used to safely dispose of needles and other sharp medical instruments pose no risk of Clostridium difficile infection (CDI).

The investigation was following up on a 2015 study that found that a significantly lower rate of CDI in hospitals that used disposable sharps containers (DSCs) over those using reusable sharps containers (RSCs), but did not propose a scientific explanation for how the containers might spread CDI to patients. The hypothesis was that the statistical association found in the previous study was an artifact and that DSCs and RSCs may have a low spore burden but no fomite potential.

The study was conducted in three stages. In the first, 197 RSCs were swabbed for the presence of C difficile before processing. In the second stage, RSCs were challenged with high C difficile densities to evaluate the decontamination process. In the third stage, the investigators sampled 50 DSCs and 50 RSCs in CDI patients' rooms in seven hospitals to determine whether they differed in their carriage rate of C difficile spores. The investigators combined this evidence with epidemiologic studies, clinical requirements, and chain-of-infection principles.

The results showed that C difficile spores were found on 9 of 197 (4.6%) RSCs prior to processing, but that processing completely removed all spores. In CDI patient rooms, the C difficile carriage rate was 8% with RSCs and 16% with DSCs, but the investigators found an insufficient number of spores on either type of container to constitute an infective dose. In addition, because sharps containers are no-touch and healthcare workers must remove gloves after sharps disposal, a mode of transmission to the patient is impossible.

"In examining epidemiologic, microbiologic, chain-of-infection and test-of-evidence criteria, we could find no scientific evidence or mechanism whereby sharps containers could be implicated in CDI transmission," the authors write.
May 22 Am J Infect Control study

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