5 minute read

Ivan attended the annual global congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) held in Munich on 17-21 April. This was an enormous conference, which attracted about 18,000 participants from 100 countries this year. Indeed, lots of researchers, clinicians, as well as representatives of public bodies and biotech companies were moving between sessions and exhibitions non-stop throughout the days. There were 20 simultaneous sessions every day in numerous formats including keynote talks, educational sessions, clinic case reports, recent literature overviews, “meet-the-expert” symposia, industry exhibitions, innovation pitches, and poster sessions.

Ivan was particularly interested in hearing about relevant infectious diseases from the perspective of epidemiologists and clinicians, the state-of-the-art in diagnostic technologies, and use cases for molecular diagnostics. Here are some highlights he took home from the congress.

Epidemiologists’ thinking. An outbreak is detected by observing changes in the usual disease pattern: location, season, demography affected, incubation period, and so on. This is why continuous surveillance with all available means including event reports (especially on drops in school attendance and on food poisonings) and various molecular diagnostics at hospitals. When an outbreak is suspected, a team of investigators is set up, a case definition is created (who?, where?, when?, what?) with three levels of sensitivity (suspected, probable, confirmed). Then the cases are searched for, causes are hypothesized and the hypotheses are tested with statistics, sampling, and diagnostics. Additional investigations like pathogen typing are also carried out to establish clonal relations between isolates. Various typing methods are used (antigen tests, MLVA, RAPD, FTIR, MLST, WGS, and importantly, the highest resolution is not always a priority. For example, if a disease is rare, severe, or spreading very quickly, speed is prioritized. On the other hand, in slowly evolving pathogens with high prevalence and low diversity, reproducibility is prioritized. Control measures are taken at any stage of the investigation as soon as possible. Finally, findings and conclusions have to be communicated to colleagues, policy makers, and media.

Innovations in PCR. The U.S. company Watchmaker Genomics pitched the next generation of engineered nucleic acid polymerases with high thermostability, speed, and tolerance to inhibitors. Increased thermostability enables the use of higher temperatures, so secondary structures of DNA and RNA melt better, the enzyme itself doesn’t degrade mid-reaction, which enables amplification of longer regions. Inhibitor-tolerant polymerases enable PCR in crude lysates of difficult inhibitor-rich samples such as blood. This opens the door for faster lab protocols omitting the nucleic acid extraction step entirely.

The Chinese company Sansure presented point-of-care systems for fast qPCR (amplifiers and enzymes). Their fast polymerases paired with advanced thermal elements enable a 15-minute PCR. The amplifiers are portable, with specialized models having features like direct sample loading (for in situ PCR), high multiplexity (multiple fluorescence detecting channels), and independent reaction protocols for samples in different wells. These technologies push the conventional qPCR into the point-of-care domain, as it is no longer confined to centralized laboratories with bulky thermocyclers and hour-long workflows.

Adoption of new diagnostics is challenging. The importance of good tools for molecular diagnostics in infectious diseases, including point-of-care methods, was stressed countless times by speakers. However, while researchers and some innovators are very optimistic about some of the latest methods, national healthcare systems are generally reluctant to adopt them. A test can be perfectly sensitive and specific but never make it to the real application due to lack of insurance coverage, funding for equipment, and system-level support (quality control, infrastructure). In addition, clinicians may lack confidence in performing tests or interpreting results, while they are highly skilled in recognizing “textbook symptoms” after years of training and practice. Even if doctors do use new diagnostic tests, the results often do not taken into account. From the viewpoint of policymakers, new tests often do not have enough added value if patients eventually get diagnosed and treated in settings that already exist.

Hybrid parasite species. Some important pathogens are able to form interspecies hybrids, which have genetic material from both species. For example, trematodes Schistosoma haematobium (cause diseases in humans) hybridize with Schistosoma bovis (cause diseases in ruminants). The genetic and genomic side of the hybridization is currently studied, but it is already clear that diagnostics based on a single marker may fail, while surveillance and control of Schistosoma might get very complicated due to the need to differentiate between the closely related species and their hybrids, and take control measures in human and in livestock simultaneously. The hybridization might be extremely dangerous as the hybrids are capable of backcrossing, which enables introgression, that is, introduction of genes from one species into another. Schistosoma spp. can thus make an interesting use case of diagnostics based on unique species-specific genomic regions and genus-specific regions. Additional examples of interspecies hybridization can be found within the genera Leishmania (protozoans), Cryptococcus (fungi), and Candida (fungi).

Keynotes. Naturally, there were many distinguished speakers, so Ivan learned some new names.

Abdoulaye Djimde (Mali) gave a talk on malaria, its diagnostics, institutional efforts in surveillance, and progress toward its elimination in Africa. He also hosted a session on malaria, where speakers demonstrated how WGS and amplicon sequencing are currently used to surveil the causative agent, Plasmodium spp., both in centralized facilities and field container labs. At the session, Ivan was introduced to the concept of polyclonal infection, where an individual might get infected multiple times with different variants of the same species of a parasite, which complicates surveillance and diagnostics. In the light of this, P. falciparum and P. vivax could make an important use case for unique genomic region discovery.

Nicholas Day (Thailand) lectured on epidemiology of typhus, the history of its treatment and research in Asia, and diversity of Rickettsiaceae (causative agents), among which he mentioned Orientia Tsutsugamushi (scrub typhus). This species’ genome is extremely variable, highly reduced and unusually repetitive for a bacterium. O. Tsutsugamushi could make a curious extreme case to use and test tools for finding unique genomic regions.

Edward Holmes (Australia) gave an overview of RNA viruses’ evolution, host range flexibility (how viruses “jump” between host species), and how trading in wildlife had already caused the coronavirus pandemic and would cause the next one if left unregulated. He also spoke about application of AI in virology and promoted several papers submitted for review: “A genome-scale language model uncovers animal viruses with zoonotic potential” (Xu et al.), “ViralHunter: a dual-modal artificial intelligence network for predicting virus-host interactions” (Bai et al.), and one that could be of great interest for our group, “Alignment-free phylogenetic inference via hyperbolic protein language models” (Shan et al.).

Updated: