At a time when much of the world seems unpredictable and a bit scary, it's nice to focus on family and friends for a respite. I'm enjoying Father's Day, but as usual I went off on a tangent. I guess I had never noticed that the official designation is a singular possessive, the same for Mother's Day. Why aren't we recognizing all fathers and mothers on these days? I think I found the answer, but first let's see what's going on in the pediatric infectious diseases world.
Big Changes at ACIP
The big news this week is the shakeup in the Advisory Committee on Immunization Practices as the HHS Secretary removed all current members and so far has replaced 8 who appear to have mostly different expertises from the traditional makeup of the panel. The move was met with virtually unanimous condemnation from US medical societies. These events have strengthened my resolve to avoid political discussions in these posts; I am not an expert in political science or journalism. Instead, I'll cling even more tightly to skills I've worked hard to refine: analyzing and translating medical science into guidance for clinical pediatric practice. Therefore, I'll focus on what was imbedded in the HHS Secretary's opinion published in the Wall Street Journal (link not provided due to subscription requirement) as well as in a general press release. Only the WSJ article provided some rationale for the move, and I'll address those sources.
First was a link to a December 2009 report from the Office of the Inspector General with the objective "[t]o determine the extent to which the Centers for Disease Control and Prevention (CDC) and its special Government employees (SGE) on Federal advisory committees (committees) complied with ethics requirements." It did not mention anything specific about ACIP members, but they would have been included in the SGE category for the CDC. The OIG report had 4 findings:
- For almost all special Government employees, CDC did not ensure that financial disclosure forms were complete in 2007.
- CDC did not identify or resolve potential conflicts of interest for 64 percent of special Government employees in 2007.
- CDC did not ensure that 41 percent of special Government employees received required ethics training in 2007.
- Fifteen percent of special Government employees did not comply with ethics requirements during committee meetings in 2007.
The document was very thorough but didn't go into more detail about specifics, so hard to know if these discrepancies were substantive enough to impact the SGEs' duties. Also, you'll note it deals with the status in 2007, and the report itself mentions that CDC had already begun to correct the deficiencies at the time of publication.
I've served as an SGE in previous years, though only for the NIH and FDA and never having anything to do with vaccines. I had to look back at my cv to get particulars. In 2004, 2005, 2008, and 2009 I was involved with the Expert Advisory Panel for the Best Pharmaceuticals for Children Act of the National Institute of Child Health and Human Development. This is a group that tried to prioritize drugs that had been poorly studied in children; usually they had already been approved for adult use and it was unlikely that pharmaceutical companies would want to fund clinical trials in children, so this was a mechanism to provide funding for such trials. From 2006-2008 I was a member of the Anti-Infective Drugs Advisory Committee for the FDA. Then from 2009-2016 I was an SGE for FDA and was occasionally called to join specific committee discussions for the Center for Drug Evaluation and Research and the Center for Device and Radiologic Health of the FDA. Then in 2023 I was asked to fill out forms to be available as an SGE for the FDA's Pediatric Advisory Committee, but I haven't been called to serve.
I only mention all this to indicate that I know all about these forms. I counted at least a dozen that I completed for the 2023 application; it included, for example, declaring any foreign activities to include emoluments, the Foreign Gifts and Declaration Act, and a prohibition from being a foreign agent or lobbyist. I had to complete online trainings, including ethics training. The forms are very convoluted and tedious to complete, and this comes from someone who basically had no conflicts to declare. It's very easy to miss putting a date at the top of a page or making some other minor technical error with the forms.
My conclusion from the 2009 OIG report is that there appeared to have been numerous discrepancies in documenting clearance for CDC SGEs, but it isn't possible to determine whether this had any impact on deliberations. Also, it involves a situation from 18 years ago.
The second link from the WSJ article goes to a 2003 United Press International article expressing concern about conflicts of interest regarding a rotavirus vaccine that was eventually pulled from the market due to cases of intussusception (found in post-marketing studies). It's impossible for me to interpret the UPI article which seemed to focus more on quotes from anti-vaccination lawyers and activists.
In short, my opinion is that the evidence cited in the WSJ article as the rationale for firing all ACIP members had little relevance to, and didn't support, the current action.
Of note, FDA just extended approval of the Moderna RSV vaccine, which had been approved for adults 60 years of age and older and uses the mRNA platform, for individuals 18-59 years with at least one underlying health problem. I'm waiting for that June 25-27 ACIP meeting to see how any of this may, or may not, impact the vaccine recommendation process for this vaccine and many others that are planned for discussion.
Should All Infants With Suspected Febrile UTI Have Viral Respiratory Swabs?
Urinary tract infection in infants is relatively common, so one might expect that management strategies are well-established. Unfortunately, similar to another common outpatient infection, group A streptococcal pharyngitis, the studies are all over the place with much confusion existing for decades. The reason for this is the common denominator for UTI and GAS pharyngitis: we don't have a great gold standard for presence of infection. For UTI, no combination of urine culture colony count, urinalysis features, inflammatory markers, or clinical features can distinguish true infection from simply asymptomatic bacteriuria or contaminated culture. Remember, the urethra is not a normally sterile site - bacteria are always present. For GAS pharyngitis, the same is true for laboratory and clinical features, confounded by the relatively high prevalence of GAS carriage in the pharynx, around 15% in children.
Researchers in the Pediatric Emergency Care Applied Research Network (PECARN) looked retrospectively at their database to evaluate the role of respiratory viral testing in febrile infants 61-90 days of age with suspected UTI. The PECARN database has been going for a long time and is well respected, but it also is saddled with some of the problems tied to any administrative database in that it collects and stores clinical data without a specific protocol for studies to be performed; e.g. not all the children in this UTI study had the same set of lab tests of interest (urine, blood culture, respiratory virus testing, etc.) obtained.
The study covered the time period from 1/1/12 to 4/30/24 and included children 61-90 days of age with documented temperature of at least 38 C either at home or at one of the participating 17 emergency departments around the country where they sought care. Using their inclusion and exclusion criteria, they started out with 18,291 eligible infants. Excluding infants who had missing UA, blood culture, and respiratory testing, 3678 or about 20% of the originally eligible infants formed the main focus of the analysis.
The results showed that UTI and bacteremia were less common in infants with positive respiratory virus testing.
Note, however, that the respiratory viral testing could be any form of testing, such as a single test for SARS-CoV-2 all the way to a multiplex respiratory panel that, by the way, includes bacteria as well as viruses. Also, the investigators lumped positive rhinovirus/enterovirus tests into a single rhinovirus label, an important point for me. I'm wondering if they did that because of the common misconception that enteroviruses, because of the name, don't cause respiratory illness. Enteroviruses are in fact a very common cause of mild upper respiratory infection.
Here's the breakdown by respiratory virus type from both a figure in the main article and a table in the supplemental data.
The investigators concluded that, along with the usual deference to the need to further study, "[c]linicians can obtain fewer diagnostic tests for IBI evaluation in these febrile infants who test positive for respiratory viruses, or may engage caregivers in shared decision-making about urine and blood testing." Shared clinical decision-making is a tough order in any practice setting; how feasible is that in a busy emergency department where most testing is ordered all at once?
But here's a big concern I have with the study that I did not see addressed in the discussion or the accompanying editorial. Behavior of various microbes included in respiratory pathogen panels can be very different. In particular, some pathogens such as enteroviruses, adenoviruses, and Mycoplasma pneumoniae normally persist in the body for weeks to months following initial infection. Using a very sensitive test like PCR that can detect nucleic acid remnants of infection extends the period of positivity. So, a positive test for any of those agents at 61 days of age could reflect an infection that happened at 2 weeks of age. Enterovirus infection is very common, especially in late summer, and usually is asymptomatic even in the first weeks of life. Designating all positive rhinovirus/enterovirus tests as rhinovirus is a bit misleading, since most of them are enteroviruses. I wish the authors had broken down their data based on year (pandemic versus pre- or post) and time of year.
This study does add a lot to our understanding of these challenging medical scenarios but does not, in my opinion, reach the level of changing practice to increase the use of respiratory testing in this age group. We need prospective studies that are very difficult (and expensive) to carry out on a large scale.
Know Your Arboviruses
The most recent MMWR had an interesting update on West Nile virus and other arboviruses reported in 2023. Here's the map for neuroinvasive WNV showing the highest activity in the middle part of the US.
The other pesky arboviruses were much less common but should be kept in mind.
These viruses have overlapping clinical signs and symptoms, most overlap to the extent that it's not possible to distinguish one from the other clinically. All can cause nonspecific febrile illnesses, but it's only the more severe cases that end up being tested and diagnosed.
Looking at long-term data, Powassan virus likes to hang around in 2 geographic areas:
..... as does Jamestown Canyon virus.
In spite of the name, La Crosse virus infection is not at all restricted to Wisconsin.
I'm torturing you with these maps in the hopes they can serve as a memory trigger if you happen to encounter children with unexplained fevers, especially with possible neurologic symptoms, and remember to ask about summer travel history.
Father's Day
I'm enjoying a leisurely Father's Day, looking forward to seeing my three sons* soon.
The explanation for the apostrophe placement wasn't that satisfying to me. Apparently Anna Jarvis, the creator of Mother's Day, codified the singular possessive form to indicate that each family should celebrate their own mother, not all the mothers in the world. The spelling carried over to dads as well. I was unable to verify this explanation from original source documents.
*Not a reference to one of my favorite TV shows from the early 1960s. I recall identifying with the youngest son Chip.
