In Episode 95 of the Infectious Disease Puscast, hosts Daniel Griffin and Sara Dong review literature from late November to early December 2025. The episode is heavy on viral updates, featuring positive data supporting single-dose HPV vaccination and a promising combination immunotherapy regimen for HIV, yielding sustained ART-free control in 7 out of 10 recipients. Critically, a controlled human infection model for the dengue prophylactic mosnodenvir showed efficacy but also rapid emergence of resistance. The hosts devote significant time to criticizing the ACIP's recent vote to end the universal Hepatitis B birth dose, calling it a predictable public health failure.
The review also highlights policy conflicts, specifically the IDSA’s refusal to endorse updated Community-Acquired Pneumonia guidelines due to concerns over non-evidence-based antibiotic use for viral infections. Fungal updates show that the established drug itraconazole remains non-inferior and safer than voriconazole for chronic pulmonary aspergillosis. Finally, a systematic review challenges the long-held dogma that benzimidazole derivatives are safe for treating Loiasis microfilaremia, linking them to delayed-onset encephalopathy.
Infectious Disease Literature Review (Nov/Dec 2025)
01:52 Chikungunya & Dexamethasone: A retrospective cohort study (BMC Infectious Diseases) suggests early, short, low-dose dexamethasone (4mg/day for 3 days) reduces the duration of acute fever (3 vs 5 days) and rheumatic symptoms (7 vs 10 days) without increased adverse events. As far as I can tell, this challenges the traditional supportive care approach and warrants proper randomized controlled trials.
03:32 HPV Vaccine Efficiency: A large NEJM trial confirms one dose of HPV vaccine (bivalent or nonavalent) is non-inferior to two doses over 5 years (>97% efficacy). This reinforces the WHO recommendation and supports moving toward a more efficient, single-dose global immunization strategy.
07:49 Dengue Prophylaxis (Mosnodenvir): A human challenge model (NEJM) demonstrated that a high dose of the oral antiviral mosnodenvir reduced DENV-3 infection in 60% of participants. However, resistance mutations (NS4B) were detected in all 14 treated participants who developed detectable viral RNA, making the long-term utility of this prophylactic questionable.
12:07 Hepatitis B Policy Failure: The ACIP voted to stop recommending the universal Hepatitis B birth dose for low-risk infants. This is strongly criticized; a JAMA viewpoint projected this change could increase perinatal HBV cases by 8% to 76% due to inevitable "leakage" in maternal screening/follow-up. This policy appears non-rational given the low cost and high protective value of the universal approach.
15:14 HIV Immunotherapy Success: A proof-of-concept study (Nature) using a combination immunotherapy (therapeutic vaccine, two bNAbs, TLR9 agonist) enabled 7 out of 10 participants to maintain viral control after stopping ART, demonstrating a path toward ART-free remission.
18:23 Rabies via Transplant: MMWR reported the 4th US case of transplant-transmitted rabies; a kidney recipient died 51 days post-transplant. The donor had been scratched by a skunk. Critically, three cornea recipients received prompt post-exposure prophylaxis (PEP) and survived, highlighting the importance of rapid intervention when donor risk is identified.
20:11 CMV CMI Testing: Two studies in CID (HCT and solid organ transplants) concluded that testing CMV-specific cell-mediated immunity (QuantiFERON-CMV) at the end of antiviral prophylaxis (e.g., letermovir) does not reliably predict who will develop subsequent CMV disease. I don't care about assays with low clinical utility.
28:55 CAP Guidelines Dispute (IDSA vs. ATS): IDSA refused to endorse the 2025 ATS CAP guidelines because they recommend empiric antibiotics for non-severe viral pneumonia patients (with positive viral assays). IDSA argues this promotes dangerous antibiotic overuse without evidence of benefit, preferring individualized decision-making to conserve antimicrobial effectiveness.
32:21 Lyme Incidence Artifact: An apparent decline in Lyme disease incidence in Massachusetts (JAMA Network Open) was found to be an artifact: it was driven by one major practice changing its policy to discourage treatment based solely on a screening ELISA result. Epidemiological data quality is susceptible to local administrative changes, which is unsurprising.
35:10 Chronic Aspergillosis Treatment: The VICTOR-CPA trial (Lancet ID) comparing Voriconazole to Itraconazole found Voriconazole was non-superior (69% vs 67% efficacy) but caused significantly more adverse events (55% vs 34%). Itraconazole remains the superior initial treatment option due to better tolerance.
37:27 Loiasis Safety Signal: A systematic review (Open Forum ID) identified six potential cases (including two fatalities) of encephalopathy following prolonged benzimidazole (e.g., albendazole) treatment for Loiasis. This challenges the long-standing "safety pearl" that these drugs are a safe alternative for reducing microfilarial loads prior to giving DEC.