Dengue, Malaria, HIV Cure, and Others — First Cold Snap of the Winter ID Link-o-Rama

Absolutely brutal temperatures arrived up here in Boston over the past week, just in time for the peak holiday season, and we’ve even had a dusting of snow. Here’s proof, in case you don’t believe me.

Of course, this isn’t stopping teenage boys from walking to high school in just shorts and sweatshirt hoodies, which is yet another reminder that this demographic is wired differently from the rest of the world. Can’t they feel the cold?

The other big news over here is the relaunching of NEJM Journal Watch to NEJM Clinician. You can read more about the changes in NEJM, and in the meantime I’ll continue as an Associate Editor and writing away ID-themed blog posts right here — just like this one. If you’ve subscribed (there’s an email sign-up box to the right), you’ll continue to get notifications via email whenever new stuff appears here.

And if you haven’t subscribed, what are you waiting for?

On to a grab bag of interesting ID Links:

1. An antiviral with activity against dengue virus makes an appearance. In a human challenge study conducted in healthy volunteers, the high dose of the experimental antiviral mosnodenvir lowered DENV-3 RNA load significantly more than placebo, with no reported adverse events. Given the complexity and challenges associated with dengue vaccination, an antiviral strategy would be very welcome.

2. Follow-up blood cultures after treatment of endocarditis are not useful in asymptomatic patients. In a study of 598 episodes of endocarditis, follow-up blood cultures drawn within 14 days after completing antimicrobial therapy detected only two recurrences (≈ 1.5 %) — and both patients had symptoms. Note that 10 other follow-up cultures were positive with a different bug, and work-up ruled out endocarditis. In other words, don’t do this unless clinically warranted.

3. An HIV cure after stem cell transplant — this time with a twist. A 60-year-old man treated for acute myeloid leukemia received an allogeneic stem-cell transplant from a donor heterozygous for CCR5 Δ32 (i.e., only one copy of the mutation), yet achieved sustained, ART-free remission of HIV‑1 for over 6 years. Extensive reservoir testing found no replication-competent virus in blood or intestinal tissues, and HIV-specific antibodies and T-cell responses waned, suggesting the virus may have been eradicated. This is Cure #10*, if you’re keeping score.

(*That last link is to Dr. Samuel Hume’s awesome Substack — he’s a medical resident in England and publishes medical breakthroughs each week! )

4. Online rogue pharmacies, most of them based outside the United States, continue to push ivermectin as a miracle cure.  Covid was just the beginning — now we’re deep into using this anti-parasitic agent for advanced cancer and serious neurologic conditions. From the treatment of choice for strongyloides to a leading role in health conspiracy theories and medical grift, ivermectin sure has had an unlikely path.

5. Remove IL-23 and IL-17 inhibitors from immunosuppressive therapies that require pre-treatment testing for latent tuberculosis. This welcome consensus statement reminds us that not all biologics* are created equal, and when it comes to TB reactivation risk, most are not in the same league as TNF-inhibitors. As a reminder, IL-23 and IL-17 inhibitors (there are lots of them!) are used mostly for treatment of psoriasis, various rheumatologic conditions, and inflammatory bowel disease.

(*What’s the precise definition of a “biologic” anyway?)

6. A single-dose four-drug regimen for malaria was as effective as standard of care. Yes, more good news on the malaria treatment front! The four drugs came in two combination products: sulfadoxine-pyrimethamine and artesunate-pyronaridine. Such an approach could greatly improve treatment adherence. This adds to the advance with ganaplacide (a new drug) plus lumefantrine, which I reported on in my annual ID gratitude post. Noting the relatively little attention these studies got in standard ID circles, I checked with my brilliant ID friend, colleague, and parasitology expert Dr. Christina Coyle: “Seems like a big deal! Am I wrong about this?” She confirmed — “Great breakthroughs!” Thanks, Christina.

7. Herpes zoster incidence increases shortly after the first vaccine dose of the vaccine. Data come from an analysis of two large Australian databases, showing an 11-fold increased risk of zoster in the first 3 weeks after the first dose. Most cases were mild, and this was not observed after the second dose; in fact, case incidence declined. Suspect this phenomenon is due to the immune activation triggered by this virus, which can be dramatic — and analogous to the rise in zoster incidence shortly after starting ART in people with HIV.

8. A study of inhaled clofazimine for treatment of pulmonary M. avium complex was halted due to futility. I’ve already branded this drug The Weirdest Antibiotic on the Planet, noting that when given as pills for this indication, “we really don’t know if it works.” It certainly didn’t work in this study, so these results burnish clofazimine’s infamous reputation only further.

9. A single dose of the HPV vaccine worked really well. In this large randomized trial of 20,330 girls aged 12–16, one dose of either a bivalent or nonavalent HPV vaccine was noninferior to two doses in preventing persistent infection with high-risk types HPV-16 or HPV-18 over 5 years. With vaccine effectiveness 97% in all study arms, this strategy could greatly expand utilization of this vaccine in developing countries, where most of the cervical cancer cases now occur.

10. A large series of PCR-confirmed cases of Oropouche virus disease gives a more balanced perspective on disease severity than previously studies. Describing nearly 500 PCR-confirmed Oropouche fever cases in Peru in the first 9 months of 2024, the study reports that patients presented with headache, fever, myalgia, and arthralgias; most cases were mild, but 2% required hospitalization. It’s a reminder that Oropouche virus disease remains a plausible cause of “dengue-like” febrile illness in travelers to Latin America.

11. MMWR reported a recent fatal rabies case in a patient who had received a transplanted kidney from a deceased donor with undiagnosed rabies. The donor apparently had experienced a “skunk scratch” and the virus was of a bat variant — hence bat to skunk to human transmission is suspected. No other cases from this donor have been reported, including three cornea recipients who underwent graft removal and received post-exposure prophylaxis. A reminder that though overwhelmingly safe and beneficial from the individual and societal perspective, organ donation will continue to have a low but non-zero risk of serious infection transmission.

12. The Advisory Committee on Immunization Practices (ACIP) voted 8–3 to rescind the universal recommendation that newborns receive a first hepatitis B shot at birth. They now advise that only babies whose mothers test positive (or whose maternal status is unknown) get the birth dose, with others left to “individual decision-making.” Since others in our field have extensively weighed in (mostly in protest), I’ll take this space to note that “horizontal” transmission of hepatitis B within households is far more likely with hepatitis B than with HIV and hepatitis C, and that many children diagnosed with hepatitis B historically acquired it from an unknown source. And agree with this headline describing the new ACIP meetings as “beset by incompetence, bias, and procedural chaos.” I like this aside by the author, Dorit Reiss, a law professor who focuses on vaccine policy:

Several observers of ACIP compared the meeting to a clown car, but my husband, Fred, reminded me that clowns are seasoned professionals who work very hard on their shows, and this meeting did not reflect such professionalism.

Oy, one fears for their next steps.

13. Intravenous iron use for treatment of iron deficiency anemia during acute infections was not associated with worse outcomes. A large retrospective cohort analysis of >85,000 adults hospitalized with acute bacterial infections and concurrent iron-deficiency anemia found that those receiving IV iron had significantly lower 14- and 90-day mortality, along with greater long-term hemoglobin gains, compared with matched controls not given IV iron. With the usual caveats about retrospective studies and the difficulty of controlling for baseline differences, and the limitations of conference abstracts, the data nonetheless challenge a long-held assumption (and a widely cited systemic review) suggesting that IV iron is harmful during active infections.

14. It’s not easy being the child of an aging parent with an ID problem. The link is to a story from my life. It includes some nifty drawings by my sister Anne. Hope you find it relatable!

Bundle up, Northeasterners!

(I think that’s a word.)