News Scan for Nov 30, 2017

News brief

Gene study tracks insecticide resistance across Africa

In the largest-ever genetic study of mosquitoes, researchers tracked the movement of insecticide resistance between different African regions and identified several rapidly evolving resistance genes that could be used to develop new tools for tracking resistance, monitoring insecticide use, and developing new control methods. The team from the Wellcome Trust Sanger Institute reporting its findings yesterday in Nature.

The investigators collected Anopheles gambiae mosquitoes, a species that transmits malaria, from 15 locations across eight African countries and sequenced the DNA of 765 of the insects. Their analysis found extreme genetic diversity, much higher than the team expected, compared with most other animal species, a factor that enables rapid evolution.

Sequencing also revealed rapid evolution of several genes that had previously been linked to insecticide resistance. The variants were emerging independently in different parts of Africa and were also being spread across different African regions during mosquito migration.

Martin Donnelly, PhD, study author who is with the Liverpool School of Tropical Medicine, said in a Sanger Institute press release, "Our study highlights the severe challenges facing public efforts to control mosquitoes and to manage and limit insecticide resistance."
Nov 29 Nature abstract
Nov 29 Sanger Institute press release

In other malaria developments, a collection of seven review articles published in PLoS Medicine today spells out a new research agenda for eliminating and eradicating malaria. The reports are from the Malaria Eradication Scientific Alliance, which began discussing the agenda, conducting six panels and including input from 180 experts.

The efforts are a follow-up of a collection of nine reports published in 2011 that identified knowledge gaps about the disease and key strategies and tools to control it.

The latest collection covers basic science; combination interventions and modeling; diagnostics, drugs, and vector control; insecticide and drug resistance; reservoir characterization and transmission measurement; and health systems and policy research.

Regina Rabinovich, MD, from the Harvard T.H. Chan School of Public Health, who led the group, said the papers provide a framework for research funders, the World Health Organization, and individual countries.
Nov 30 PLoS Medicine report
Nov 30 PLoS press release

Analysis of university mumps outbreak shows no asymptomatic cases

A mumps outbreak earlier this year at the University of Washington in Seattle involved no asymptomatic students who shed the virus, a study today in Morbidity and Mortality Weekly Report (MMWR) concludes.

The first case was reported to public health officials on Feb 8, and by Jul 19, 42 cases were reported—16 of them confirmed. Of the 42 cases, 32 (63%) involved university fraternity or sorority members. All patients had received two or more doses of measles, mumps, and rubella (MMR) vaccine, according to current recommendations.

In response to the outbreak, local public health officials provided supplemental MMR doses to 235 members of eight fraternity or sorority houses reported the most cases. Researchers swabbed the inside cheek of 160 of these students, and all swabs came back negative for mumps virus.

The authors concluded, "Mumps outbreaks have increased in recent years in the United States; from 2015 through 2016, the proportion of outbreak-related cases increased from 63% to 78%. Further evaluations to better understand the prevalence of mumps virus shedding among vaccinated populations are needed to guide outbreak surveillance and control."
Dec 1 MMWR report

Gavi to introduce typhoid vaccines into developing nations

Gavi, the Vaccine Alliance, has allocated $85 million for introducing typhoid conjugate vaccines into low-income nations, where millions of children are at risk for the disease, the organization announced today in a news release.

A new typhoid conjugate vaccine manufactured by Bharat Biotech International Ltd and first licensed in India in 2013 is currently under review for pre-qualification by the World Health Organization. Vaccines from five additional manufacturers are also under development and expected to be available from 2018 to 2022, the release says. Gavi expects the first countries to apply in 2018 and vaccine rollout to happen in 2019.

"Typhoid fever imposes a dramatic burden on children in the poorest nations affecting countries, communities and families," said Ngozi Okonjo-Iweala, MD, Gavi board chair. "This vaccine will be a lifesaver for millions of children, especially those living without access to clean water or sanitation."

"This vaccine is safe, effective and can provide lasting protection,” said Seth Berkley, MD, Gavi CEO. "The growing spread of drug resistant strains of typhoid is a major threat, not just to individuals but also to our efforts to control the disease, and requires us to prioritise prevention strategies. Strong coverage through routine immunisation together with efforts to improve access to clean water and hygiene will play a key role in dramatically reducing the disease."
Nov 30 Gavi news release

Flu Scan for Nov 30, 2017

News brief

Experts say production challenges show need for better flu vaccines

Recent reports of mutations introduced by egg-based flu vaccine production arriving on the heels of a tough flu season in Australia raise worries about a similarly difficult season ahead for the United States, experts said in a New England Journal of Medicine commentary yesterday.

Authors from the National Institute of Allergy and Infectious Diseases (NIAID) and the World Health Organization (WHO) collaborating center in Australia wrote that Australia had a record number of lab-confirmed flu infections, mostly from the H3N2 strain, with higher-than-average hospitalizations and deaths. An early estimate of vaccine effectiveness against H3N2 was only 10%. For comparison, the vaccine's effectiveness against H3N2 in the last Northern Hemisphere flu season was 34%.

The implications of Australia's season for the Northern Hemisphere's flu season aren't clear, but health officials are worried, because the vaccine composition is the same as for the Southern Hemisphere. "As we prepare for a potentially severe influenza season, we must consider whether our current vaccines can be improved and whether longer-term, transformative vaccine approaches are needed to minimize influenza-related morbidity and mortality," they said.

In their commentary, the group said problems underscore a need for research into better manufacturing systems, antigens, and platforms. The main goal, though, is to someday develop a universal flu vaccine that would eliminate the need for yearly immunization for seasonal flu while protecting against new subtypes, including pandemic strains.

Despite the current vaccine's limitations, people should still get their annual flu shots, they wrote, especially since they can reduce the risk of severe illness and death.
Nov 29 N Engl J Med commentary
Nov 29 NIAID press release

Altering vaccine virus mutation might boost FluMist protection

Researchers at Johns Hopkins Bloomberg School of Public Health recently identified a genetic mutation in the FluMist inhaled flu vaccine that might be used to restore the effectiveness of the vaccine. The team reported its findings in the most recent edition of Vaccine.

After scientists identified a drop in protection against the 2009 H1N1 strain in the United States, federal vaccine advisors recommended that it not be used for the previous and current flu seasons, a dramatic turnaround after the group's 2014 preferential recommendation for healthy kids ages 2 to 8.

The company that makes FluMist, MedImmune, has been working to identify reasons for the gap in protection and has said it could be linked to reduced fitness of the H1N1 vaccine component.

In the new study, the researchers identified a previously overlooked mutation in the gene encoding the M2 viral protein that reduces virus production, which they found in two of the vaccine strains. When they reversed the mutation in one of the viruses, replication became more active in lab-cultured human nasal cells, triggering more robust production of immune proteins. The activity boost also ramped up production of the immune protein interferon lambda, also suggesting an increased immune response.

The team said that in principle, the mutation site—and maybe others on the vaccine virus—could be used as "dimmer switches" to adjust the vaccines strength up or down, striking a balance between robust immune response without causing illness.

Andrew Pekosz, PhD, professor in Bloomberg's department of molecular microbiology and immunology, said in a press release from the school that the next step is to make a panel of live attenuated influenza vaccine viruses with different mutations to see if researchers can increase replication rates to protect children and other age-groups better in the past few years.
Dec 4 Vaccine abstract
Nov 28 Johns Hopkins press release