CEPI announces support for more Lassa fever, MERS vaccines

The Coalition for Epidemic Preparedness Innovations (CEPI) and Inovio Pharmaceuticals yesterday announced a partnership to support Inovio's development of candidate vaccines against Lassa fever and Middle East respiratory syndrome coronavirus (MERS-CoV).

The agreement to support the vaccines is the second made by CEPI, a coalition formed in 2017 to develop new vaccines against a list of high-priority diseases. In early March it announced a similar partnership with Themis Bioscience to further work on two other vaccines against Lassa fever and MERS-CoV.

According to the terms of the newly announced partnership, CEPI will fund up to $56 million over 5 years to help push Inovio's two vaccines—INO-4500 against Lassa and INO-4700 against MERS-CoV—through phase 2 trials. The two groups said their shared goal is for the two vaccines to be available as soon as possible for emergency use.

The agreement contains options to establish investigational stockpiles of both vaccines.

Richard Hatchett, MD, chief executive officer of CEPI, said in a statement that epidemics don't respect borders and can destroy lives and economies, requiring quick strategies to prepare for threats. "Partnering with Inovio is a considerable move forward for CEPI's vaccine portfolio and developing a global insurance policy against these diseases," he said.

CEPI is a collaboration between the governments of Norway, Germany, India, and Japan, plus the Bill & Melinda Gates Foundation, Wellcome Trust, and the World Economic Forum. The group launched in early 2017 with $460 million in funding and an initial focus on developing vaccines against MERS-CoV, Lassa, and Nipah virus.
Apr 11 CEPI press release
Mar 7 CIDRAP News scan "
CEPI's first partnership will pursue Lassa fever, MERS vaccines"


Coartem now recommended as safe treatment for malaria in pregnancy

A study today by researchers with the US Centers for Disease Control and Prevention (CDC) in Morbidity and Mortality Weekly Reports (MMWR) shows strong evidence of the safety and efficacy of using artemether-lumefantrine (AL, or Coartem) to treat malaria in the second and third trimesters of pregnancy.

Historically, treatment for malaria in pregnant women in the United States has been limited to mefloquine or quinine plus clindamycin, but as concern is growing over mefloquine resistance and the limited availability of quinine, officials are considering other treatment options.

The Food and Drug Administration approved the use of AL in 2009, but it did not approve it for pregnant women, because some animal research data showed poor pregnancy outcomes. But a comprehensive literature review of studies conducted in Asia and Africa (where AL is used in pregnancy) showed that use in pregnancy is efficacious at the doses currently recommended for non-pregnant women.

"On the basis of the strength and quality of this evidence, CDC recommends AL as an additional option for treatment of uncomplicated malaria in pregnant women in the United States during the second and third trimesters of pregnancy at the same doses recommended for nonpregnant women,” the authors said.

US women in their first trimesters should still be treated with either mefloquine or quinine plus clindamycin, the study authors said, but AL should be considered if neither are available.

According to the CDC, 1,700 cases of imported malaria are recorded in the United States each year. About 37% of these cases occur in women, including 5% to 6% who are pregnant at the time they are infected.
Apr 13 MMWR


Advanced insecticidal nets protect against malaria, study shows

Long-lasting insecticidal nets made with piperonyl butoxide (PBO) should be widely used to reduce malaria transmission, as they offer more protection than standard insecticide nets, according to a study published yesterday in The Lancet.

PBO nets and a long-lasting indoor residual spraying formulation of the insecticide pirimiphos-methyl are two newer interventions meant to disrupt malaria transmission and help fight growing insecticide resistance in mosquitoes. This was the first randomized, controlled trial (RCT) to assess the performance of PBO nets and pirimiphos-methyl spray against the standard pyrethroid insecticide nets. The study was conducted in Tanzania, in 10,560 households that included 15,469 children.

Researchers measured effectiveness by tracking malaria infections in children ages 6 months to 14 years, assessed by surveys at 4, 9, 16, and 21 months post-intervention. They found that malaria infection prevalence after 9 months was lower in the two groups that received PBO long-lasting insecticidal nets than in the two groups that received standard long-lasting insecticidal nets (29% versus 42%). The PBO long-lasting insecticidal net effect was sustained after 21 months: 45% versus 62%.

Indoor residual spraying also led to a lower incidence of malaria; in groups that received indoor residual spraying disease prevalence was 28%, compared with 44% in groups that did not.

"The RCT provides new evidence on the added value and risks of combining indoor residual spraying and long-lasting insecticidal nets, particularly PBO nets," the authors said. As a result of this study, the World Health Organization gave interim endorsement to combined pyrethroid-PBO nets in September 2017.

In an accompanying comment, Gerry F. Killeen, PhD, and Hilary Ranson, of the Liverpool School of Tropical Medicine wrote that the study "shows conclusively that insecticide resistance does undermine the effects of malaria vector control, and that tackling it with insecticides or insecticide combinations to which local vectors remain susceptible improves impact."

They added, "While these findings are welcome, it is disappointing that they have only been very cautiously adopted at [the] global policy level thus far."
Apr 11 Lancet
Apr 11 Lancet


Multiple 2017 norovirus outbreaks linked to dried seaweed in Japan

A dried, shredded seaweed product called nori caused 2,094 Japanese people to become sick with norovirus illness in 2017, according to a study yesterday in Emerging Infectious Diseases. The outbreaks demonstrate that dehydrated food is capable of spreading nororvirus, the authors wrote.

Seven norovirus outbreaks occurred in rural Japan in January and February of last year. In all outbreaks, officials detected norovirus GII.P17-GII.17 in stool specimens of patients. The outbreaks were tied to school lunches, prepared bento boxes, and business offices where food was served, including nori. Both rice and salads were topped with small amounts of nori.

"In these nori-related outbreaks, the traceback of implicated nori product revealed that the norovirus infectivity remained for >2 months at ambient temperature under dry conditions," the authors said. "However, the percentage of persons with gastrointestinal symptoms gradually decreased from the date of nori production, suggesting a decline in norovirus infectivity over time under dry conditions."
Apr 11 Emerg Infect Dis


Three countries report more H5N6 avian flu in wild birds

In avian flu outbreak developments over the past week, Denmark, Sweden, and Hong Kong reported new highly pathogenic H5N6 detections in wild birds, and Taiwan reported several more poultry outbreaks involving H5N2.

In Denmark, tests on 70 wild birds found dead since January have yielded positive results for 13, according to an Apr 10 government statement translated and posted by Avian Flu Diary (AFD), an infectious disease news blog. The birds that tested positive for the virus, which included one wild swan, were mainly from North Jutland and southwest Zealand regions.

A few days earlier, Sweden reported a new H5N6 detection in a white-tailed eagle found dead on Mar 16 near Blekinge County in the far south of the country, according to an Apr 6 report from the World Organization for Animal Health (OIE). The bird was tested at the National Veterinary Institute as part of routine surveillance.

And Hong Kong reported that H5N6 was detected in a crested myna found dead on Apr 4, the OIE said in an Apr 9 notification. The report said no poultry farms, wetlands, or nature reserves are located within 3 kilometers of where the bird was found and no spread of the virus has been identified.
Apr 10 AFD post
Apr 6 OIE report on
H5N6 in Sweden
Apr 9 OIE report on
H5N6 in Hong Kong

Meanwhile, Taiwan reported five more H5N2 outbreaks on poultry farms, with start dates ranging from Mar 26 to Apr 2. Meat ducks, meat geese, and layer hens were among the affected birds. Four outbreaks occurred in Yunlin County, while a fifth was detected in Pingtung County. In total, the virus killed 1,469 of 28,031 susceptible birds, and the survivors were culled to control the spread of the disease.
Apr 9 OIE report on H5N2 in Taiwan

Stewardship / Resistance Scan for Apr 12, 2018

News brief

Study finds overreporting of healthcare-associated C diff in urban hospital

A study yesterday in the American Journal of Infection Control has found that only 62% of reported cases of healthcare facility–onset Clostridium difficile (HO-CDI) at a New York hospital met clinical criteria.

In the study, investigators at New York-Presbyterian Weill Cornell Medical Center performed a retrospective chart review on 212 cases of HO-CDI reported by the hospital to the Centers for Disease Control and Prevention in 2015. The cases had been identified using the polymerase chain reaction (PCR) test for the C difficile toxin B gene on unformed stool specimens collected more than 3 days after admission. They categorized the cases into six clinical surveillance groups: community-acquired infection, recurrence/relapse, asymptomatic colonization, colonization with self-limited symptoms, possible HO-CDI, and probable HO-CDI.

The investigators found that, of the 212 cases, 51 (24%) met the clinical surveillance definition of probable HO-CDI, and 81 (38.2%) could be considered possible HO-CDI cases. Thirty-nine cases (18.4%) were classified as colonization with self-limiting symptoms, 31 cases (14.6%) were classified as community-acquired, four cases (1.9%) were considered asymptomatic colonization, and six cases (2.8%) were classified as recurrence/relapse. All but two of the patients were treated with antibiotics.

The authors of the study suggest that the misclassification of HO-CDI may in part result from the use of stool softeners and laxatives, which were given to 73 patients (34.3%) within 24 hours of testing. But they also cite the inability of widely used PCR testing to distinguish active CDI infection from symptomatic colonization with diarrhea due to other causes.

They conclude, "Ongoing review of reported HO-CDI cases is critical for guiding efforts to improve the diagnosis, treatment, and control of C difficile to ensure the reliability of HO-CDI surveillance as a meaningful quality metric."
Apr 11 Am J Infect Control abstract


Small Japanese study finds MCR-1 gene in men who traveled to Vietnam

A small study by Japanese researchers in the journal Infection and Drug Resistance illustrates the role that international travel could play in the spread of dangerous antibiotic resistance genes.

The researchers from Osaka University followed 19 Japanese men who made 34 trips to Vietnam between June 2015 and August 2016. Recent reports have indicated the presence of Escherichia coli harboring the mobile colistin resistance gene MCR-1 in food animals, farmers, and urban residents in Vietnam. Because of the concerns about widespread dissemination of MCR-1, the researchers wanted to investigate whether travelers could bring MCR-1–harboring E coli back to Japan after a short-term stay in the country.

Fecal specimens were collected from travelers before and after their trips to Vietnam and analyzed for bacterial identification, antibiotic susceptibility, and production of genetic resistance elements. Overall, 175 isolates of extended-spectrum beta-lactamase (ESBL)-producing E coli were identified; in 30 of 34 travel events, the travelers brought the ESBL-producing E coli back to Japan. This is noteworthy because the dissemination of ESBL-producing E coli is low in Japan. The ESBL-producing isolates exhibited 100% resistance to ampicillin and cefotaxime.

In addition, the researchers found that three of the travelers brought back ESBL-producing E coli that also harbored the MCR-1 gene. None of the men were treated with antibiotics, and MCR-1 was not detected in samples collected 3 weeks later.

"Our study supports the notion that even short-term travel can bring colistin-resistant strains back to the country of origin," senior author Yoshimasa Yamamoto, PhD, said in a university press release. "In a globalized community in which travel to developing countries is common, the spread of colistin-resistant bacteria is a significant concern to worldwide health. We need to ensure that proper surveillance and public hygiene measures are in place, so that we can minimize the dissemination of highly resistant strains to the greatest extent possible."
Mar 12 Infect Drug Resist study
Mar 30 Osaka University press release


New report lists drivers of irrational antibiotic use in Europe

The European nonprofit organization Health Action International has released a new report outlining the major drivers of irrational antibiotic use in Europe, along with potential remedies.

The report, written by researchers from Sweden's Karolinska Institutet, suggests that among the general public, the lack of knowledge and awareness about antibiotics and antibiotic resistance, access to antibiotics without a prescription, and leftover antibiotics from earlier prescriptions are the most significant drivers of inappropriate antibiotic use. For healthcare providers, they cite attitudes toward antibiotic use and resistance, lack of adequate education on antibiotic prescribing, pharmaceutical promotion, lack of rapid diagnostic tests, and patient pressure.

To counter irrational antibiotic use, the authors recommend more education for healthcare providers and the public, strategies to optimize antibiotic use (including infection prevention and control measures and take-back programs for unused antibiotics), stronger data on antibiotic use and resistance, tougher regulations on pharmaceutical promotion, and the development, implementation, and coordination of national action plans on antibiotic resistance. They also call for more support for research into new antibiotics and diagnostics.

Research by the European Surveillance of Antimicrobial Consumption Network has shown that large variations in antibiotic use exist across Europe, with higher use in southern Europe and lower use in northern Europe.
Apr 5 Health Action International report

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