The best of 2019 – an A–Z of infectious diseases research

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Acute flaccid myelitis

Acute flaccid myelitis (AFM) was first reported in 2012 and since then there have been over 500 cases reported; however, defining the cause has been a challenge. In January, a non-polio enterovirus – EV-D68 – was identified as the potential cause of an outbreak in Arizona. In addition, in October, researchers used a version of VirScan to search for enterovirus in the spinal fluid of AFM patients, discovering antibodies against enterovirus in almost 70% of AFM patients and strengthening the evidence. Going forwards, the National Institute of Allergy and Infectious Diseases (MD, USA) have called for a concerted research effort to develop non-polio enterovirus diagnostics, drug therapies, animal models and epidemiological studies in order to understand AFM better.

Blood–brain barrier

Research this year has shed new light on the role of the blood–brain barrier. First, the cytokine interferon gamma was identified as a major contributor of blood–brain barrier breakdown in central nervous system infections. Second, it was discovered Candida albicans can cross the blood–brain barrier, triggering an immune response resulting in the formation of granuloma-type structures and memory impairments.

Cannabidiol

Developing new drugs to combat growing resistance in bacteria is a big issue, and the year saw an in vitro study identify cannabidiol as possessing potent antibiotic properties. Cannabidiol was found to be active against Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pneumoniae, moreover, the potency of cannabidiol did not diminish with prolonged exposure to the bacteria.

DRC outbreak

The outbreak of Ebola in the Democratic Republic of Congo (DRC) has seen over 3100 cases and 2100 mortalities since it was first announced by the WHO on 1 August 2018. There have been many challenges in the first year of the outbreak, including instability, violence and mistrust, however, there have also been positive breakthroughs; a trial assessing four Ebola treatments has highlighted two drugs, REGN-EB3 and mAb114, that significantly improved survival rates, moreover, the vaccine rVSV-ZEBOV has been prequalified by the WHO. A second vaccine is now being introduced for testing in the DRC – although not without controversy – and with cases decreasing the trend is encouraging, but vigilance is key.

Environmental change

Climate change has been at the forefront politically this year but it has also had impacts in the field of infectious diseases. Research has suggested that climate change could have contributed to the emergence of Candida auris, could impact the distribution and capacity of vector-borne diseases and also could be linked to antimicrobial resistance – both contributing to the prediction of resistance but also potentially to increasing the transmission of resistance.

Fecal microbial transplant

Fecal microbial transplant is currently used to treat C. difficile under investigational new drug regulations in patients who have been unresponsive to standard therapies. However, in June the US FDA issued a warning over the risk of serious infections caused by multidrug-resistant organisms in investigational fecal microbial transplant after two immunocompromised adults developed invasive infections. The FDA has now determined that certain donor screening and stool testing protections are necessary for this procedure.

Gaming

Gaming might not be something typically associated with the field of infectious disease, however, over the past year several board games have been presented at conferences, aiming to be an educational tool to help raise awareness around some of the major challenges in infectious diseases. On a more abstract note, game theory, along with machine learning, has been used to develop a method for identifying antibiotic resistance genes, potentially presenting a more accurate tool.

HIV

The big news in HIV this year was that the second-ever individual achieved sustained remission from HIV-1 after ceasing antiretroviral treatment. Termed the ‘London patient’, the individual had been diagnosed with Hodgkin’s lymphoma, leading to chemotherapy and a hematopoietic stem cell transplant from a donor with two CCR5 Δ32 alleles. Although this was a groundbreaking event, it is not applicable to many cases, thus research on developing long-acting formulations for HIV continues, with several options coming through the pipeline.

Immunotherapy

CAR-T cells have been an exciting new prospect for cancer, however, a new study demonstrated that a cell-based therapy, termed convertibleCAR® could be useful for HIV. The therapy appeared to reduce the latent HIV reservoir in in vitro blood cultures from individuals on antiretroviral therapy, potentially propelling progress towards a HIV cure now that advances are being made in creating universal donor cells.

Jumping hosts

This year saw new information on how Plasmodium falciparum jumped hosts from gorillas to humans approximately 50,000 years ago. The research sequenced all Laverania species, identifying the gene rh5. Ancestral sequence reconstruction of rh5 proteins demonstrated that it could once bind both human and gorilla red blood cells, providing a molecular explanation for how the parasite evolved to infect humans.

Keeping consistent

The rates of sexually transmitted infections have been an increasing concern over the past few years. A study published in June noted that the global prevalence of four curable sexually transmitted infections – chlamydia, gonorrhea, trichomoniasis and syphilis – remains high, with over 1 million new cases every day.

Lost elimination status

Measles cases continued to grow in 2019; approximately 90,000 cases were reported in the European Region in the first 6 months, exceeding the number of cases recorded for the entirety of 2018, which numbered 84,462. In August the annual assessment from the European Regional Verification Commission concluded that the number of countries having achieved or sustained elimination of the disease has declined. Specifically, for the first time since verification began in 2012 four countries – the UK, Czech Republic, Albania and Greece – lost their elimination status.

Microbiome

The microbiome continues to be a big area of research; this year it was suggested that factors such as ocean swimming and common drugs could alter its make-up. In addition, researchers compiled the most comprehensive collection of human intestinal bacteria to-date, isolating over 100 new bacterial species from healthy individuals. However, the field still faces challenges, such as quality control, understanding complex communities and establishing causal relationships, raising the question, is the microbiome a great hope, or overhyped?

New strains and species

2019 saw the identification of several new strains and species – a new non-Leishmania parasite was identified in Brazil, a novel strain of toxin-producing Strep A was identified in the UK, six antibiotic-resistant strains of the probiotic bacteria Bacillus were discovered and the Bombali virus, a recently discovered species of the ebolavirus, was identified in bats in Kenya. In addition, the largest ever genomic study of C. difficile presented evidence that human lifestyles could be driving this bacteria to form new species.

Organotypic models

The advent of organotypic, three-dimensional models has allowed an increased understanding of many pathogens – including human papillomaviruses, which have previously proved a challenge due to their complex lifecycle. In May, Harvard’s Wyss Institute (MA, USA) developed an anaerobic organ-on-a-chip model of the microbiome, allowing a stable complex human microbiome to become established in direct contact with a vascularized human intestinal epithelium.

Phages

Phage therapy has remained an area of interest this year; in January the first US clinical trial for intravenous phage therapy gained FDA approval, only to then be cancelled after the funding company, AmpliPhi Biosciences Corporation (VI, USA), merged with C3J Therapeutics (CA, USA). However, there was more positive news in May, as it was reported that a cocktail of engineered phages was used to successfully treat a case of drug-resistant Mycobacterium abscessus. Other research has seen phages isolated from kitchen sponges, tap into quorum-sensing and trigger antiviral responses, allowing bacteria to evade the immune system.

Quick diagnosis

This year saw the development of a new rapid test for the earlier diagnosis of sepsis – something that is critically needed. The microelectrode device analyses a patient’s blood, with results being generated in under 3 minutes. The team hope that the low-cost test could become routine within the next 3–5 years.

Rising resistance

2019 saw the Centers for Disease Control and Prevention (GA, USA) update its report on ‘Antibiotic resistance threats in the United States’, which was previously published in 2013. The report contains new CDC data that demonstrate that, while the burden of antimicrobial-resistant threats is high at 2.8 million cases and over 35,000 deaths, mortality has decreased from the 2013 report, suggesting infection prevention and antimicrobial stewardship efforts have had an impact. In addition, the WHO released a new Technical Note to aid countries globally in improving their antimicrobial resistance surveillance.

Siderophores

The US FDA has approved the first siderophore antibiotic, cefiderocol (Fetroja), for complicated urinary tract infections. Cefiderocol inhibits bacterial cell wall synthesis by binding penicillin binding protein 3 and uses the siderophore to bind free iron and gain additional cell entry.

Tuberculosis

This year has seen the US FDA approve Pretomanid tablets in combination with bedaquiline and linezolid for the treatment of specific types of drug-resistant pulmonary tuberculosis. Additionally, new research has produced a novel blood test for tuberculosis that could also identify high risk of infection, identified a ‘suicide’ toxin–antitoxin system that could be a drug target and elucidated the role of antacid in tuberculosis pathogenesis, helping the bacteria to persist in macrophages.

UK tick-borne disease

Tick-borne disease has been a topic of interest in the UK this year; in July, a study suggested that in the UK new cases of tick-borne Lyme disease could be three-times higher than previous estimates, possibly exceeding 8000 cases in 2019. Furthermore, in October Public Health England confirmed the presence of tick-borne encephalitis virus in the UK for the first time, although it stated risk to the general public is still “very low”.

Vaccination and social media

With a rise in ‘fake news’ and misinformation owed to the advent of social media platforms, the rise of anti-vaccine sentiment via these channels has been a growing concern. In April we discussed vaccine confidence in a ‘post-truth’ world with a panel of experts including topics such as media balance, data transparency, compulsory vaccination and the role of social media. Later in the year some social media platforms did declare action, with Pinterest announcing it will ensure that searches for terms such as ‘measles’ and ‘vaccine safety’ will only bring up results from public health organizations – a step in the right direction.

Walls

Research this year has confirmed that bacteria can tolerate antibiotics by hiding their cell wall, known as ‘L-form switching’. L-forms of Escherichia coli, Enterococcus, Enterobacter and Staphylococcus were identified, allowing the bacteria to persist in elderly patients during antibiotic treatment before re-forming the cell wall and potentially causing further infection.

Xenleta

Nabriva Therapeutics (Dublin, Ireland) announced in August that the US FDA had approved their new drug applications for the oral and intravenous formulations of Xenleta™ (lefamulin) to treat adult patients with community-acquired bacterial pneumonia. This represented the first new antibiotic with a novel mechanism of action approved by the FDA in nearly two decades.

Yeasts

With rising resistance to antifungals, there is a need for new approaches and new drugs to treat fungal infections. At ASM Microbe (20–24 June 2019, CA, USA) this year some novel research was presented identifying novel antifungal proteins produced by Saccharomyces cerevisiae yeasts, assessing the impact of these proteins against fungal pathogen Candida glabrata, and pondering the potential these could hold in clinic.  

Zero WPV3 cases

On World Polio Day this year an independent commission of experts announced that wild type poliovirus type 3 (WPV3) had been eradicated worldwide, meaning that there have been zero WPV3 cases over the past 3 years (with good surveillance). This marks the second of three strains of poliovirus to be eradicated and represents a historic achievement.

2019 has seen a multitude of new discoveries, and although there is no telling what the next year might hold, we at Infectious Diseases Hub hope to keep covering the research highlights that 2020 brings us!

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