Critical knowledge gaps regarding infection with Mycobacterium ulcerans, the cause of Buruli ulcer (BU), have impeded development of new therapeutic approaches and vaccines for prevention of this neglected tropical disease. Here, we review the current understanding of host-pathogen interactions and correlates of immune protection to explore the case for establishing a controlled human infection model of M. ulcerans infection. We also summarise the overarching safety considerations and present a rationale for selecting a suitable challenge strain.

In RNA-seq data processing, short reads are usually aligned from one species against its own genome sequence; however, in plant-pathogen interaction systems, reads from both host and pathogen samples are blended together. In contrast with single-genome analyses, both pathogen and host reference genomes are involved in the alignment process. In such circumstances, the order in which the alignment is carried out, whether the host or pathogen is aligned first, or if both genomes are aligned simultaneously, influences the read counts of certain genes. This is a problem, especially at advanced infection stages. It is crucial to have an appropriate strategy for aligning the reads to their respective genomes, yet the existing strategies of either sequential or parallel alignment become problematic when mapping mixed reads to their corresponding reference genomes. The challenge lies in the determination of which reads belong to which species, especially when homology exists between the host and pathogen genomes. This chapter proposes a combo-genome alignment strategy, which was compared with existing alignment scenarios. Simulation results demonstrated that the degree of discrepancy in the results is correlated with phylogenetic distance of the two species in the mixture which was attributable to the extent of homology between the two genomes involved. This correlation was also found in the analysis using two real RNA-seq datasets of Fusarium-challenged wheat plants. Comparisons of the three RNA-seq processing strategies on three simulation datasets and two real Fusarium-infected wheat datasets showed that an alignment to a combo-genome, consisting of both host and pathogen genomes, improves mapping quality as compared to sequential alignment procedures.

Human activity is changing global environments at an unprecedented rate, imposing new ecological and evolutionary ramifications on wildlife dynamics, including host-parasite interactions. Here we investigate how an emerging concern of modern human activity, pharmaceutical pollution, influences the spread of disease in a population, using the water flea Daphnia magna and the bacterial pathogen Pasteuria ramosa as a model system. We found that exposure to different concentrations of fluoxetine-a widely prescribed psychoactive drug and widespread contaminant of aquatic ecosystems-affected the severity of disease experienced by an individual in a non-monotonic manner. The direction and magnitude of any effect, however, varied with both the infection outcome measured and the genotype of the pathogen. By contrast, the characteristics of unexposed animals, and thus the growth and density of susceptible hosts, were robust to fluoxetine. Using our data to parameterize an epidemiological model, we show that fluoxetine is unlikely to lead to a net increase or decrease in the likelihood of an infectious disease outbreak, as measured by a pathogen\'s transmission rate or basic reproductive number. Instead, any given pathogen genotype may experience a twofold change in likely fitness, but often in opposing directions. Our study demonstrates that changes in pharmaceutical pollution give rise to complex genotype-by-environment interactions in its influence of disease dynamics, with repercussions on pathogen genetic diversity and evolution. This article is part of the theme issue \'Infectious disease ecology and evolution in a changing world\'.

Biological networks are characterized by diverse interactions and dynamics in time and space. Many regulatory modules operate in parallel and are interconnected with each other. Some pathways are functionally known and annotated accordingly, e.g., endocytosis, migration, or cytoskeletal rearrangement. However, many interactions are not so well characterized. For reconstructing the biological complexity in cellular networks, we combine here existing experimentally confirmed and analyzed interactions with a protein-interaction inference framework using as basis experimentally confirmed interactions from other organisms. Prediction scoring includes sequence similarity, evolutionary conservation of interactions, the coexistence of interactions in the same pathway, orthology as well as structure similarity to rank and compare inferred interactions. We exemplify our inference method by studying host-pathogen interactions during infection of Mus musculus (phagolysosomes in alveolar macrophages) with Aspergillus fumigatus (conidia, airborne, asexual spores). Three of nine predicted critical host-pathogen interactions could even be confirmed by direct experiments. Moreover, we suggest drugs that manipulate the host-pathogen interaction.

BACKGROUND: Pythium, soil-borne plant pathogens, are in the class Oomycetes. They are not true fungi, but are related to diatom and algae. There are two human pathogens including P. insidiosum and P. aphanidermatum. To date, only one case of pythiosis caused by P. aphanidermatum has been reported. We present herein the first case of P. aphanidermatum vascular pythiosis in Asia.
METHODS: A 47-year-old Thai woman, living in North Thailand, with ß thalassemia/hemoglobin E presented with acute recurrent arterial insufficiency of both legs. Emergent embolectomy with clot removal was performed. The pathology of the clot exhibited noncaseous granulomatous inflammation with many fungal hyphal elements. PCR identified P. aphanidermatum with 100% identity. Final diagnosis is vascular pythiosis. Unfortunately, the patient eventually expired after treatment with itraconazole, terbinafine, azithromycin, and doxycycline.
CONCLUSIONS: To date, only one case of pythiosis caused by P. aphanidermatum has been reported. We present herein the first case of P. aphanidermatum vascular pythiosis in Asia.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, causing respiratory syndrome and other manifestations. The clinical consequences of the SARS-CoV-2 infection are highly heterogeneous, ranging from asymptomatic and mild to severe and fatal conditions, with the highest mortality rate reached among elderly people. Such heterogeneity appears strongly influenced by the host immune response, which in turn is profoundly affected by aging. In fact, the occurrence of a low-grade inflammation and a decline in specific immune defense is generally reported in older people. Although the low ability of B cells to provide primary and secondary specific responses with a consequent increase in susceptibility to and severity of virus infections is generally described in elderly people, we would like to present here the particular case of a 100-year-old woman, who recovered well from COVID-19 and developed a long-term memory against SARS-CoV-2. Following the infection, the patient\'s blood was tested with both a classical ELISA and a specific Cell-ELISA addressed to measure the anti-spike S1 specific IgG released in plasma or produced in vitro by memory B cells, respectively. While showing negative on classical serological testing, the patient\'s blood was positive in Cell-ELISA up to 1 year after the infection. Our observation highlights a potential mechanism of B cell-dependent, long-term protection in response to SARS-CoV-2 infection, suggesting that in a case of successful aging, the absence of specific antibodies in serum does not necessarily mean the absence of immune memory.

The spread of the novel coronavirus 2019 (COVID-19) has caused a global pandemic. The disease has spread rapidly, and research shows that COVID-19 can induce long-lasting cardiac damage. COVID-19 can result in elevated cardiac biomarkers indicative of acute cardiac injury, and research utilizing echocardiography has shown that there is mechanical dysfunction in these patients as well, especially when observing the isovolumic, systolic, and diastolic portions of the cardiac cycle. The purpose of this study was to present two case studies on COVID-19 positive patients who had their cardiac mechanical function assessed every day during the acute period to show that cardiac function in these patients was altered, and the damage occurring can change from day-to-day. Participant 1 showed compromised cardiac function in the systolic time, diastolic time, isovolumic time, and the calculated heart performance index (HPI), and these impairments were sustained even 23 days post-symptom onset. Furthermore, Participant 1 showed prolonged systolic periods that lasted longer than the diastolic periods, indicative of elevated pulmonary artery pressure. Participant 2 showed decreases in systole and consequently, increases in HPI during the 3 days post-symptom onset, and these changes returned to normal after day 4. These results showed that daily observation of cardiac function can provide detailed information about the overall mechanism by which cardiac dysfunction is occurring and that COVID-19 can induce cardiac damage in unique patterns and thus can be studied on a case-by-case basis, day-to-day during infection. This could allow us to move toward more personalized cardiovascular medical treatment.

Age-associated inflammation and immune system dysfunction have been implicated as mechanisms that increase risk for adverse long-term procedural outcomes in older adults. The purpose of this study was to investigate relationships between baseline inflammatory and innate antiviral gene expression and outcomes after transcatheter aortic valve replacement (TAVR) in older adults with severe aortic stenosis.
We performed a retrospective case-control study comparing pre-procedural pro-inflammatory and Type 1 interferon (IFN) gene expression in 48 controls with favorable outcomes (alive 1 year after TAVR with improved quality of life [QoL]) versus 48 individuals with unfavorable outcomes (dead by 1 year or alive at 1 year but with reduced QoL). Gene expression was evaluated in whole blood via (1) pre-defined composite scores of 19 inflammation-associated genes and 34 Type I IFN response genes, and (2) pro-inflammatory and antiviral transcription factor activity inferred from promotor based bioinformatics analyses of genes showing > 25% difference in average expression levels across groups. All analyses were adjusted for age, gender, body mass index, diabetes, immunosuppression, cardiovascular disease (CVD), and frailty.
Relative to controls, those with unfavorable outcomes demonstrated higher expression of the pro-inflammatory gene composite prior to TAVR (p < 0.01) and bioinformatic indicators of elevated Nuclear Factor kB (p < 0.001) and Activator Protein 1 (p < 0.001) transcription factor activity, but no significant differences in Type I IFN-related gene expression.
These results demonstrate that a pro-inflammatory state prior to TAVR, independent of CVD severity and frailty status, is associated with worse long-term procedural outcomes.

A 77-year-old man with past medical history of granulomatosis with polyangiitis (GPA) on rituximab and prednisone, presented to the hospital with worsening cough and shortness of breath. He had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by nasal swab polymerase chain reaction (PCR) while asymptomatic, 6 weeks earlier. He started with cough and shortness of breath 2 weeks after his initial positive test. After developing symptoms, he tested negative twice by nasal swab PCR, but the PCR of his bronchioloalveolar lavage was positive for SARS-CoV-2. He did not develop antibodies against coronavirus. Prednisone 15 mg daily was continued, and he received remdesivir, and convalescent plasma with quick recovery. We reviewed the literature to search for similar cases. Our case suggests that SARS-CoV-2 infection in patients on rituximab may have an atypical presentation and the diagnosis may be delayed due to negative PCR testing in the nasal swab. Patients may benefit from treatment with convalescent plasma.

Pathogens are one of the main selective pressures that ancestral humans had to adapt to. Components of the immune response system have been preferential targets of natural selection in response to such pathogen-driven pressure. In turn, there is compelling evidence showing that positively selected immune gene variants conferring increased resistance to past or present infectious agents are today associated with increased risk for autoimmune or inflammatory disorders but decreased risk of cancer, the other side of the same coin. CD5 and CD6 are lymphocytic scavenger receptors at the interphase of the innate and adaptive immune responses since they are involved in both: (i) microbial-associated pattern recognition; and (ii) modulation of intracellular signals mediated by the clonotypic antigen-specific receptor present in T and B cells (TCR and BCR, respectively). Here, we review available information on CD5 and CD6 as targets of natural selection as well as on the role of CD5 and CD6 variation in autoimmunity and cancer.