Salmonella – Pediatric Infection Connection

Bye Bye Birdie?

Bud WiedermannJanuary 5, 2025January 5, 2025Leave a comment

Regular readers may recall my new infatuation with bird watching triggered by the gift of a video bird feeder from a daughter-in-law. In this era of avian influenza evolution, one might legitimately ask whether a septuagenarian should gown, glove, and mask when performing weekly seed replacement and monthly cleanings. The short answer is no; the birds at most bird feeders in the US are not displaying high rates of infection. I just won't be touching any dead fowl or starting a backyard chicken coop anytime soon.

Here's what I ran across this past week.

Managing the Febrile Infant

This is one of those conundrums that has plagued me since medical school in the late 1970s. It's not that we haven't made progress (GBS prophylaxis, for example), but we still lack reliable methods to distinguish which febrile newborns need empiric antibiotic therapy and which can be safely observed without antibiotics. The latest iteration in the discussion looked at prospectively-collected data from 2018-2023 on well-appearing febrile infants 8 - 60 days of age at a single center in Canada. The investigators were particularly interested in predictive data without using serum procalcitonin measurement. AAP Practice Guidelines recommend using PCT but also provide guidance for assessment if PCT measurements are not available in a timely manner.

From the sample of slightly less than 2000 infants the Canadian investigators developed a new decision rule, with some internal validation, to manage low-risk infants. The new rule maintained high sensitivity (and therefore high negative predictive value) while improving specificity from 51% to 84%, resulting in fewer infants receiving unnecessary therapy. The rule incorporated CRP, maximum temperature, and ANC. (IBI denotes Invasive Bacterial Infection.)

It's important to note, as the authors do, that this was a single center study. In general, it's wise to wait for validation from other sites (this was an urban tertiary care center) more similar to your own practice setting before implementing a new practice. Also, only 38 infants had IBI, not surprising since most fevers in infants are due to viral infections, but the low numbers of IBI cases might result in lower validity. This study, and any resultant guidelines, apply to a relatively healthy group; to qualify for the study, subjects had to be well-appearing, previously healthy infants of at least 37 weeks gestation. A number of standard exclusion criteria such as no prior antibiotics and no focal infections, underlying medical disorders, or other high risk factors for infection also were employed. This approach certainly could be an improvement to current guidelines, but 84% specificity is far from what I would want for ideal management of a frequent clinical problem.

Which IGRA Test is Better?

Testing for tuberculosis infection is at the top of diagnostic dilemmas that have plagued me for my entire career in medicine. Interferon gamma release assays are a big improvement over tuberculin skin testing primarily because they remove the error problems of application and interpretation of the skin test and are not affected by prior BCG vaccine administration. Aside from those circumstances, IGRAs have about the same sensitivity and specificity as skin testing.

A new study looked at discrepancies between the 2 main IGRA tests, Quantiferon and T-spot, in a multi-center US pediatric population. Subjects for this study were less than 15 years of age and had risk factors for TB infection, but were not thought to have active TB disease; in short, these were children being screened for latent tuberculosis infection. The rate of indeterminate test results was similar between the 2 tests, about 0.3%. However, the rate of positive tests was higher for Quantiferon than for T-spot.

Particularly interesting was that the reasons for the higher positivity of Quantiferon wasn't evident. It did not vary with the child's age (note too few positives in the children younger than 2 years of age to be confident of those results), whether the tests were borderline positive, i.e. close to the cutoff for positivity, or reason for performing the TB screening test.

This report doesn't tell us which test is better in this setting. We can't determine false positive or false negative rates from the data, a problem with every study of latent TB infection because the subjects would need to be followed for years without receiving preventive treatment, clearly unethical. We still have a lot to learn about TB.

Norovirus in the News

I've seen a lot lately, and not just the usual cruise ship headlines. Due to how norovirus outbreaks are reported, it's hard to know if what we are seeing now is something highly different from pre-pandemic years, but let me remind everyone that norovirus is a winter disease.

Also, remember that alcohol-based hand sanitizer won't work for norovirus; use real soap and water for an extended scrub. Norovirus vaccines of various types are under development, including a recently-launched phase 3 trial in adults in the UK.

Are My Red M&Ms on the Way Out?

I'm really not branching out from infectious diseases commentary and won't pretend to be an expert on cancer-causing chemicals, but we've all seen the concerns about red dye #3 in foods in recent news reports. Maybe this is a bow to the new political administration and possible public health leadership. Regardless, from afar I'm confused about why a compound that is associated with cancer in laboratory animals, and is essentially a food cosmetic is still on the market.

Believe it or not, there is a pediatric infection connection with red food colorings. I first heard about this 1965-66 pediatric Salmonella outbreak at the Massachusetts General Hospital from a pediatric resident present at the time who later became one of my mentors. Summarizing a lot of data and leaving out my mentor's colorful anecdotes which may be embellished, the source of the outbreak was a red dye used for measuring intestinal transit time - give the dye capsule and watch for red-colored stools. The key component was carmine, derived from a cochineal insect Dactylopius coccus that produces the red pigment carminic acid. These insects are found primarily in Mexico and Central America, and processing at the time was found to be ineffective at killing Salmonella.

The food industry seems dependent on food colorings, but I'd prefer less additives that serve only to colorize my food.

WRIS

Some of my CDC tracking sites are still a bit behind due to the holidays, but we are certainly in full-blown Winter Respiratory Virus Season. The Influenza-Like Illness map is leaning towards the red end of the visible light spectrum (note CDC seems to have moved blue outside of its normal position in the spectrum!).

The drivers are primarily influneza A and RSV. Covid is low but rising, and covid wastewater monitoring suggests we'll see a significant uptick in the coming weeks.

Avian Influenza

This is still a low probability for concern but should be closely watched. This past week saw a more complete report of the case of severe avian flu in a Canadian teenager that reminded me how poorly news reports and press releases characterize specific cases. I had initially thought, based on news reports, that the severe disease might be due to secondary bacterial complications, but in fact this was just bad, high viral load, avian influenza. We now know that the child was an obese (BMI was "greater than 35") 13-year-old-girl, previously healthy except for mild asthma, who required intubation and ventilation, then ultimately ECMO, for survival. She first became ill on November 2, was seen in an emergency department with conjunctivitis and fever on November 4 and sent home, then admitted in respiratory distress on November 7 and transferred to an intensive care unit on November 8. She had multiple complications including renal failure requiring hemodialysis. She was off all oxygen therapy by December 18.

One additional concern in the report was the presence of a mutation in the hemagglutinin gene that might facilitate better adaptation to the human respiratory tract, similar to the Louisiana adult with severe avian flu infection. We need to keep a close watch in general on avian flu mutations in wildlife but also in humans, particularly those who have severe disease with high viral loads that facilitate mutations that increase human adaptation. Still, there is no evidence of human-to-human transmission which is the most reassuring finding at present.

I've been trying to monitor how the federal government is prioritizing avian flu. Last summer the USDA introduced a program to compensate poultry farmers for monetary loss due to avian flu infecting their flocks, and a proposed update was announced recently. I know that researchers at CDC, NIH and elsewhere are working hard on variant assessments and development of stockpiles of effective vaccines and alternative antiviral agents.

Our 39th President

I'd be very remiss if I didn't stop to comment on President Carter's passing. He certainly had an up-and-down stint during his 1 term as president, but his subsequent work in public health was phenomenal. Take a moment to review the public health accomplishments via the Carter Center. I hope our current and future leaders will take a page from his playbook as we deal with upcoming public health challenges.

Guinea worm disease is a major impediment to a farmer's ability to work. Dressed in his farming clothes, Nuru Ziblim, a Guinea worm health volunteer in Ghana, educates children on how to use pipe filters when they go to the fields with their families. Pipe filters, individual filtration devices worn around the neck, work similarly to a straw, allowing people to filter their water to avoid contracting Guinea worm disease while away from home. In May 2010, with Carter Center support, Ghana reported its last case of Guinea worm disease and announced it had stopped disease transmission a year later.

Location: Ghana | Date: February 2008 | Photo: The Carter Center/L. Gubb

Beautiful Beetles

Bud WiedermannApril 21, 2024April 21, 2024Leave a comment

I finished a wonderful novel last week; among other things, it reminded me of the beauty, complexity, and destructive forces in nature, certainly applicable to infections, pathogens, and vectors of disease.

The past week saw more publications than I could cover in depth (or that readers could tolerate, probably), so I had to narrow things down even more than I usually do. If you're feeling particularly adventuresome, some of the topics I excluded pertain to a new phase I Chlamydia vaccine trial that could prove to be a breakthrough eventually, more advice on use of the new pentavalent meningococcal vaccine, an in vitro study suggesting nasal epithelial properties account for less severe covid disease in children, and a tularemia outbreak in Utah beavers. I also left out the growing Salmonella outbreak linked to organic basil, though I did alert one of my sons who often shops at a store featuring the tainted product. Here's what made the cut this week.

Respiratory Disease Transmission is Not Binary

Most things in biology and medicine aren't binary, even if we tend to reduce our thinking to that level to simplify things. For example, most lab tests aren't just positive or negative, even though they are reported that way. The cutoff between those two choices are made to maximize specificity and sensitivity of the tests, but they don't necessarily work for all circumstances.

The World Health Organization provided an important new proposal for changing our longstanding terminology for spread of respiratory infections as either droplet or aerosol (airborne). It's just not that simple, as SARS-CoV-2 painfully taught us. I found I couldn't improve on WHO's explanation of the complexity of pathogen transmission through the air, so here it is verbatim with some highlights in red that are mine:

The following descriptors and stages have been defined by this extensively discussed consultation
to characterize the transmission of pathogens through the air (under typical circumstances):

Individuals infected with a pathogen, during the infectious stage of the disease (the source), can generate particles containing the pathogen, along with water and respiratory secretions. Such particles are herein described as potentially ‘infectious particles’.
These potentially infectious particles are carried by expired airflow, exit the infectious person’s mouth/nose through breathing, talking, singing, spitting, coughing or sneezing and enter the surrounding air. From this point, these particles are known as ‘infectious respiratory particles’ or IRPs.
IRPs exist in a wide range of sizes (from sub-microns to millimetres in diameter). The emitted IRPs are exhaled as a puff cloud (travelling first independently from air currents and then dispersed and diluted further by background air movement in the room).
IRPs exist on a continuous spectrum of sizes, and no single cut off points should be applied to distinguish smaller from larger particles, this allows to move away from the dichotomy of previous terms known as ‘aerosols’ (generally smaller particles) and ‘droplets’ (generally larger particles).
Many environmental factors influence the way IRPs travel through air, such as ambient air temperature, velocity, humidity, sunlight (ultraviolet radiation), airflow distribution within a space, and many other factors, and whether they retain viability and infectivity upon reaching other individuals.

WHO still proposes a somewhat binary system of IRP spread, with "airborne transmission/inhalation" denoting pathogens which can spread at both short and longer distances, depending on various factors, versus "direct deposition," e.g. someone sneezes on you. It still may be confusing, but this is an important attempt to get past somewhat misleading advice such as a establishing a standard 6-foot distance between persons waiting in line.

Children and Adolescents Likely Still Benefit From Covid Vaccination

CDC has an update on covid vaccine effectiveness and durability, looking at the original monovalent vaccines over the time period from mid-December 2021 to late October 2023. Two doses of vaccine were 52% (95% CI 33%-66%) effective against hospitalization in the 5 - 18 year-old age group if vaccines were received no more than 4 months prior to hospitalization. From 4 to 12 months, protection against hospitalization waned significantly to 19% (95% CI 2%-32%). The report doesn't mention children less than 5 years of age, I suspect because vaccine authorization occurred later, numbers vaccinated are too small, and hospitalization was too uncommon to give reliable numbers.

Vaccine Adverse Events: New Numbers and a Terrific Interactive Web Site

The National Academies of Science, Engineering, and Medicine published new reports on adverse events from covid vaccines as well as an assessment of shoulder injuries from all vaccine administrations. The reports are excellent, but I fell in love with their web site. The NASEM group used levels of evidence to summarize current knowledge about various vaccine adverse events. The categories are evidence that a) establishes a causal relationship; b) favors acceptance of a causal relationship; c) inadequate to accept or reject a causal relationship; or d) favors rejection of a causal relationship. (Certainly this is far from a binary categorization!)

For covid vaccination they looked at six categories of adverse events: cardiac and vascular, female infertility, hearing conditions, immune-mediated events, neurologic events, and sudden deaths. The interactive web site allows you to pick and choose among various topics and subtopics and vaccines. Here's what the portion on myocarditis looks like:

Here's a look at acute biceps tendinopathy from vaccine administration in general:

You can also access the pdf version of the report (note it is a pre-publication proof, could contain some typos) to look at the summary and/or more details.

A Significant Change for Syphilis Screening From ACOG

I'm thrilled to see new recommendations for syphilis screening of pregnant people from the American College of Obstetricians and Gynecologists. I feel like my practice is a congenital syphilis quagmire right now. This updated recommendation gets away from the risk-based approach for screening which has always been a bit vague and clearly less useful with the resurgence of syphilis in the US. Now, every pregnant person should have syphilis testing 3 times: at the first prenatal visit, during the third trimester, and at birth. Previously a pregnant person with good prenatal care could escape with being screened only once early in pregnancy, a practice that would miss recent infection or infection acquired later in pregnancy. They also remind us that 40% of congenital syphilis occurs in infants whose mothers did not receive prenatal care; syphilis screening should be considered for pregnant people at every interaction with the healthcare system, such as emergency or urgent care visits.

Fake News From USDA?

Because of the avian flu concerns in the US, I've been trying for the first time to use alerts from the US Department of Agriculture on the status of avian influenza in wildlife and domesticated animals, including the recent importance of dairy animals. So far the alerts aren't telling me much, just clogging my in box with unhelpful information. So, I was a bit dismayed to see a recent NY Times article criticizing USDA transparency. Unfortunately the article requires a subscription, but it mentions an "obscure" USDA update (that I didn't receive) mentioning influenza A H5N1 further spreading among dairy cow herds and from there to poultry. More distressing to me is a claim in the Times article stating that asymptomatic infections have been discovered in a herd, but not yet reported by USDA; this is important since screening advice for dairy farmers currently is focused on symptoms in the cattle, with no screening of healthy-appearing cows. Perhaps USDA hasn't reported this asymptomatic infection possibility because it hasn't been verified, but one hopes they will be more transparent (and provide better updates) than they have so far. CDC learned a lot about public communication and transparency during the covid pandemic that should inform communications from USDA and other government agencies that we depend on.

Measles

Only 4 new cases reported in the last week, hoping we stay in this lull for a good while.

Elm Beetle Romance

That novel I finished recently was Daniel Mason's North Woods; it's had mixed reviews but I thoroughly enjoyed it. The author happens to be a psychiatrist, and this recent offering from him is an entertaining look at the happenings in a house in rural Massachusetts over several centuries. I had a great chuckle from a brief description of Dutch elm disease complete with a steamy sex scene involving elm bark beetles. Maybe I need to get out more.

Tag: Salmonella