This Week in Infectious Disease — Jun 6, 2026

Welcome to This Week in Infectious Disease. This week we're covering 10 notable papers spanning the global fight against antimicrobial resistance, new insights into host immunology and viral reservoirs, and key updates in prevention and therapeutics. We'll also note two important dispatches from the field on drug-resistant malaria and the Sudan Virus. Let's dive in.

We begin with antimicrobial resistance, a theme that dominated the literature this week with papers on surveillance, drug development strategy, and a potential new antibiotic. A sobering report in *Emerging Infectious Diseases* highlights the dire state of global surveillance for ceftriaxone-resistant *Neisseria gonorrhoeae* [9]. The authors note that the efficacy of ceftriaxone is increasingly threatened by strains with the mosaic penA 60.001 allele, first seen in 2015 and now found globally. A systematic literature search found that nearly half of all documented isolates were detected after 2022 in England and Australia, countries with robust surveillance systems. Epidemiologic data frequently linked these infections back to the Asia-Pacific region. The clinical implication is that the true prevalence of ceftriaxone resistance is likely severely underreported, and clinicians should maintain a high index of suspicion for treatment failure, particularly in patients with relevant travel history. This problem of resistance outpacing our response is exactly what a framework proposed in *The Lancet Infectious Diseases* aims to prevent for tuberculosis [10]. The authors argue that the rapid emergence of resistance to new drugs like bedaquiline threatens the long-term viability of all-oral regimens for multidrug-resistant TB. They propose a roadmap for integrating the development of drug susceptibility testing concurrently with new drug development. This involves structured partnerships between drug developers, diagnostic manufacturers, and regulators to ensure resistance detection keeps pace with novel drug introductions, thereby safeguarding these precious new treatments. While surveillance and strategy are critical, we also need new agents. A paper in *Nature* offers a hopeful example, describing a new antibiotic called manikomycin [4]. Researchers isolated this cyclic depsipeptide from *Streptomyces rimosus*—the same bacterium that gave us oxytetracycline. By using improved fractionation to find minor products, they discovered a compound that kills multidrug-resistant Enterobacteriaceae. Structural and biochemical analyses revealed a unique mode of action: manikomycin binds to the E-site of the large ribosomal subunit, a previously underexploited target, and hinders the translocation step of protein synthesis. This work demonstrates that even well-studied natural sources may still hold novel chemical scaffolds for antibiotic development.

Shifting from the microbe to the host, two papers explore how the immune system interacts with pathogens and how we can manipulate it for therapeutic benefit. A fascinating study in *Science Translational Medicine* challenges a core concept of HIV pathogenesis, revealing a previously overlooked component of the viral reservoir [8]. Researchers found that HIV-1 infection can directly convert CD4-positive T cells into CD8-positive T cells. Mechanistically, the viral protein R, or Vpr, drives this change by upregulating TGF-beta 1. These converted CD8 T cells, which are functionally HLA class II-restricted, were found in people living with HIV but not in healthy controls. Critically, these cells were shown to harbor transcriptionally active viral RNA or intact proviral DNA, even in patients on suppressive antiretroviral therapy. This discovery broadens our understanding of the latent reservoir's heterogeneity and has major implications for future cure strategies. In a different context, a proof-of-concept study in *The New England Journal of Medicine* demonstrates a powerful way to manipulate the immune system for transplantation [5]. The report details the first two patients in a clinical trial who underwent kidney transplantation after being desensitized with CAR T-cell therapy. These candidates were highly sensitized, with anti-HLA antibody levels that made finding a match nearly impossible. By using a dual-targeted therapy against both CD19 on B-cells and BCMA on plasma cells, the researchers were able to eliminate the sources of these antibodies, paving the way for successful transplantation. This represents a potential breakthrough for patients previously considered untransplantable due to high sensitization.

Finally, we turn to prevention, with a look at global public health, molecular risk stratification, and a key negative clinical trial. First, a major economic evaluation in *The Lancet* commemorates the 50th anniversary of the Expanded Programme on Immunization, or EPI [1]. The numbers are staggering. From 1974 to 2024, the program cost an estimated 937 billion dollars globally. However, it generated over 15 trillion dollars in economic benefits just from averted productivity losses due to mortality. This represents an aggregate benefit-cost ratio of 16 to 1. The program was found to be cost-saving in all 194 WHO member states, with measles vaccination providing the highest return on investment. From the population level down to the individual, a study in *Cell* used machine learning to identify a 14-protein plasma signature that can predict lung cancer risk more than five years before diagnosis [2]. This signature was elevated in smokers and individuals exposed to particulate matter. Importantly, when applied to data from the CANTOS trial, the signature helped identify individuals who seemed to benefit more from anti-IL-1-beta therapy. This suggests such a biomarker could make targeted cancer prevention strategies more feasible by lowering the number needed to treat. But not all preventive strategies in high-risk patients are successful. The TRACK randomized trial, published in *JAMA*, provides a crucial negative result [3]. Investigators studied whether low-dose rivaroxaban, at 2.5 mg twice daily, could reduce cardiovascular events in patients with advanced chronic kidney disease. The trial, which included over 1400 patients, was stopped early for lack of efficacy. Over a median follow-up of 1.7 years, there was no difference in the primary composite outcome of cardiovascular death, MI, stroke, or peripheral artery events between the rivaroxaban and placebo groups. Furthermore, rivaroxaban was associated with a significantly higher rate of major bleeding, which occurred in 8.8% of patients on the drug versus 6.0% on placebo. The clinical message is clear: in this high-risk population, low-dose rivaroxaban offers no cardiovascular benefit and causes significant harm. Also of note this week are two important reports in *The New England Journal of Medicine* on the ongoing challenges of treating artemisinin-resistant severe malaria in Uganda [6] and a recent outbreak of Sudan Virus Disease, also in Uganda [7], reminding us of the constant need for vigilance and field-level response to emerging threats.

If you only have time for one paper this week, make it the TRACK trial in *JAMA* [3]. It provides a definitive answer to a common clinical question, showing that low-dose rivaroxaban should not be used for cardiovascular prevention in patients with advanced chronic kidney disease due to a lack of efficacy and increased bleeding risk.

Here are the key takeaways from this week in Infectious Disease. First, for patients with advanced CKD, do not use low-dose rivaroxaban for cardiovascular prevention; it increases bleeding without reducing ischemic events [3]. Second, be aware that ceftriaxone-resistant gonorrhea is likely far more common than surveillance data suggests, especially in patients with travel history to the Asia-Pacific region. Maintain a low threshold for test-of-cure [9]. Third, a new finding in HIV pathogenesis reveals that CD8-positive T cells can be part of the latent viral reservoir after converting from CD4-positive cells. This complicates our understanding of latency and will be critical for future cure research [8]. And finally, on a global scale, the 50-year WHO Expanded Programme on Immunization has been a phenomenal economic success with a 16-fold return on investment, providing powerful data to advocate for vaccine funding [1].

That's your roundup for This Week in Infectious Disease. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.