Chagas disease reactivation in a heart transplant patient infected by domestic Trypanosoma cruzi discrete typing unit I (TcIDOM)

Background Trypanosoma cruzi, causative agent of Chagas disease, displays high intraspecific genetic diversity: six genetic lineages or discrete typing units (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a particular distribution pattern across the Americas, and is loosely associated with different transmission cycles and hosts. Several DTUs are known to circulate in Central America. It has been previously suggested that TcI infection is benign and does not lead to chronic chagasic cardiomyopathy (CCC). Findings In this study, we genotyped T. cruzi parasites circulating in the blood and from explanted cardiac tissue of an El Salvadorian patient who developed reactivation Chagas disease while on immunosuppressive medications after undergoing heart transplant in the U.S. as treatment for end-stage CCC. Parasite typing was performed through molecular methods (restriction fragment length polymorphism of polymerase reaction chain amplified products, microsatellite typing, maxicircle sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as lineage-specific serology. We show that the parasites infecting the patient belong to the TcI DTU exclusively. Our data indicate that the parasites isolated from the patient belong to a genotype frequently associated with human infection throughout the Americas (TcI DOM ). Conclusions Our results constitute compelling evidence in support of TcI DTU’s ability to cause end-stage CCC and help dispel any residual bias that infection with this lineage is benign, pointing to the need for increased surveillance for dissemination of this genotype in endemic regions, the USA and globally

TOI-431/HIP 26013: a super-Earth and a sub-Neptune transiting a bright, early K dwarf, with a third RV planet

Stars and planetary system

TOI-431/HIP 26013: A super-Earth and a sub-Neptune transiting a bright, early K dwarf, with a third RV planet

We present the bright (Vmag = 9.12), multiplanet system TOI-431, characterized with photometry and radial velocities (RVs). We estimate the stellar rotation period to be 30.5 ± 0.7 d using archival photometry and RVs. Transiting Exoplanet Survey Satellite (TESS) objects of Interest (TOI)-431 b is a super-Earth with a period of 0.49 d, a radius of 1.28 ± 0.04 R, a mass of 3.07 ± 0.35 M, and a density of 8.0 ± 1.0 g cm-3; TOI-431 d is a sub-Neptune with a period of 12.46 d, a radius of 3.29 ± 0.09 R, a mass of 9.90+1.53-1.49 M, and a density of 1.36 ± 0.25 g cm-3. We find a third planet, TOI-431 c, in the High Accuracy Radial velocity Planet Searcher RV data, but it is not seen to transit in the TESS light curves. It has an Msin i of 2.83+0.41-0.34 M, and a period of 4.85 d. TOI-431 d likely has an extended atmosphere and is one of the most well-suited TESS discoveries for atmospheric characterization, while the super-Earth TOI-431 b may be a stripped core. These planets straddle the radius gap, presenting an interesting case-study for atmospheric evolution, and TOI-431 b is a prime TESS discovery for the study of rocky planet phase curves

Identification of metabolically quiescent Leishmania mexicana parasites in peripheral and cured dermal granulomas using stable isotope tracing imaging mass spectrometry

Leishmania are sandfly-transmitted protists that induce granulomatous lesions in their mammalian host. Although infected host cells in these tissues can exist in different activation states, the extent to which intracellular parasites stages also exist in different growth or physiological states remains poorly defined. Here, we have mapped the spatial distribution of metabolically quiescent and active subpopulations of Leishmania mexicana in dermal granulomas in susceptible BALB/c mice, using in vivo heavy water labeling and ultra high-resolution imaging mass spectrometry. Quantitation of the rate of turnover of parasite and host-specific lipids at high spatial resolution, suggested that the granuloma core comprised mixed populations of metabolically active and quiescent parasites. Unexpectedly, a significant population of metabolically quiescent parasites was also identified in the surrounding collagen-rich, dermal mesothelium. Mesothelium-like tissues harboring quiescent parasites progressively replaced macrophage-rich granuloma tissues following treatment with the first-line drug, miltefosine. In contrast to the granulomatous tissue, neither the mesothelium nor newly deposited tissue sequestered miltefosine. These studies suggest that the presence of quiescent parasites in acute granulomatous tissues, together with the lack of miltefosine accumulation in cured lesion tissue, may contribute to drug failure and nonsterile cure. IMPORTANCE Many microbial pathogens switch between different growth and physiological states in vivo in order to adapt to local nutrient levels and host microbicidal responses. Heterogeneity in microbial growth and metabolism may also contribute to nongenetic mechanisms of drug resistance and drug failure. In this study, we have developed a new approach for measuring spatial heterogeneity in microbial metabolism in vivo using a combination of heavy water (2H2O) labeling and imaging mass spectrometry. Using this approach, we show that lesions contain a patchwork of metabolically distinct parasite populations, while the underlying dermal tissues contain a large population of metabolically quiescent parasites. Quiescent parasites also dominate drug-depleted tissues in healed animals, providing an explanation for failure of some first line drugs to completely eradicate parasites. This approach is broadly applicable to study the metabolic and growth dynamics in other host-pathogen interactions

The return of the spin period in DW Cnc and evidence of new high state outbursts

DW Cnc is an intermediate polar which has previously been observed in both high and low states. Observations of the high state of DW Cnc have previously revealed a spin period at ∼38.6 min, however, observations from the 2018 to 2019 low state showed no evidence of the spin period. We present results from our analysis of 12 s cadence photometric data collected by Next Generation Transit Survey of DW Cnc during the high state which began in 2019. Following the previously reported suppression of the spin period signal, we identify the return of this signal during the high state, consistent with previous observations of it. We identify this as the restarting of accretion during the high state. We further identified three short outbursts lasting ∼1 d in DW Cnc with a mean recurrence time of ∼60 d and an amplitude of ∼1 mag. These are the first outbursts identified in DW Cnc since 2008. Due to the short nature of these events, we identify them not as a result of accretion instabilities but instead either from instabilities originating from the interaction of the magnetorotational instability in the accretion disc and the magnetic field generated by the white dwarf or the result of magnetic gating