wastewater – Pediatric Infection Connection

Summer Sleuthing 2

Bud WiedermannAugust 11, 2024August 11, 20242 Comments

Last week I mentioned I'd make a poor politician or salesman. I didn't mention other professions, but I wonder if I might have been a successful detective. I had a consult last week that took all of my sleuthing skills, a newborn exposed to maternal syphilis that required me to track down mother's history dating back to 2017 as well as a sibling who turned out to have been a patient of mine a few years ago - not the type of continuity of care I'm looking for. This newborn, like the sibling, will need IV penicillin treatment but most likely will be fine in the long run. The entire consult took me about 2 hours compared to my usual 1 hour. That's why pediatric ID docs are at the bottom end of physician reimbursement but also why I love the profession.

I've been involved in some other detective work recently, but first a review of what's bubbling up as summer is winding down.

More Oropouche Concerns

This is a stark example of today's world - no matter where an infectious disease outbreak occurs, it can affect all of us. The European Centre for Disease Prevention and Control has issued a travel alert for countries in Central and South America experiencing epidemic Oropouche virus disease. The EUCPC found 19 cases of Oropouche disease in European Union residents this year, all linked to travel to Cuba or Brazil. No such alert has been issued by the US CDC, but US citizens should take note.

Summer travel planning should include assessment of disease and other safety risks in foreign countries.

Mpox Redux

I had hoped mpox had settled into a mostly endemic situation in the US, which is in itself a defeat of sorts, but new concerns have arisen from the outbreak in the Democratic Republic of the Congo that could extend to the US. The CDC's Health Alert Network has issued a new alert as cases spill over from the DRC to neighboring Burundi, Rwanda, and Uganda. The clade involved, clade I, is more transmissible and perhaps has a higher mortality than the more common clade II. Risk of exportation to the US is still considered low due to infrequency of commercial air flights from these countries. The alert contains details for case management. Remember, at risk individuals (see below) should receive 2 doses of mpox vaccine.

Persons at risk:

Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who in the past 6 months have had one of the following:
- A new diagnosis of ≥1 sexually transmitted disease
- More than one sex partner
- Sex at a commercial sex venue
- Sex in association with a large public event in a geographic area where mpox transmission is occurring
Sexual partners of persons with the risks described in above
Persons who anticipate experiencing any of the above

Benefits of Vaccination

Speaking of vaccinations and CDC, the latest MMWR included an article estimating benefits, both economic and clinical, of childhood vaccinations over the period 1994-2023. One always needs to be wary of this type of modeling which by its very nature requires analysis of large administrative databases that can have some errors. However, the study authors were very careful and listed 4 study limitations.

First, the analysis didn't include influenza, covid, or RSV vaccination; we can all agree that would result in an underestimation of benefits. They also felt that the recorded immunization rates could be an underestimate, which in turn would underestimate costs of the programs. Similarly, the cost estimates didn't include federal, state, or local program management costs or excise taxes. Their fourth limitation point was that they were unable to consider contributions of other factors like hygiene or social distancing which could have lowered disease rates independently of vaccines. So, of the 4 limitations, 3 could result in overstatement of vaccine benefit. With those caveats, here are their numbers:

That's over a million deaths prevented and over 2 trillion dollars in societal savings.

Sniffles Status

We're still talking covid here, with flu and RSV almost nonexistent. Here's the latest ED visit numbers from CDC.

I was hoping covid wastewater would start to level off, but it is rising in all parts of the US (same link as above).

So, expect more covid in the coming weeks. For now, it seems we are stuck with both summer/early fall and winter covid surges.

Hieronymus Bosch

Not the painter but rather the seriously flawed detective character created by Michael Connelly. Probably the same fondness I have for the detective-like nature of pediatric infectious diseases practice also draws me to (mostly) noir detective literature. This summer I decided to look into somewhat more recent (compared to 1920s-1950s) detective series. Colin Dexter's first book in the Inspector Morse series, Last Bus to Woodstock (1975) was enjoyable, and I'll probably continue to the next installment. Now I've started the first book in the Harry Bosch series, Black Echo (1992). Both books are littered with beautiful writing, such as this musing by Bosch: "The sky was the color of bleached jeans and the air was invisible and clean and smelled like fresh green peppers."

I thought about that line as I was outside in the garden trying to figure out what species of butterfly was sampling the Joe-Pye-weed. I have a love of butterflies dating back to my childhood in south Texas, though I've forgotten almost everything I've learned from that time. We don't have nearly as many butterfly species in Maryland as in my home town, but it's still fun to watch and study them. This one black butterfly has been hanging around for several days; in fact, it's right outside my window now. Unfortunately I can't decide if it is the somewhat more common black swallowtail (Papilio polyxenes) or the rarer spicebush swallowtail (Papilio troilus). Real butterflies often don't look exactly like their pictures in reference materials. After several days and about 15 photos of different aspects of the wings and thorax, I decided to surrender and ask BAMONA (Butterflies and Moths of North America). I've submitted photos, dates, locations, and behavior details and now waiting on a reply from an expert. I'll let you know if they reply.

STOP THE PRESSES: BAMONA just sent me a reply, moments after my initial posting. It is a "dark-form female P. glaucus." For the uninitiated, this is the tiger swallowtail, but the picture below looks nothing like the typical tiger swallowtail. Also amazing, my iPhone identified the photo as P. glaucus, which I laughed as being another failure of artificial intelligence. You can bet I'll be reading more about this dark form butterfly.

Synbiotics? 4

Bud WiedermannDecember 17, 2023December 17, 20234 Comments

I'm only mildly ashamed to admit that when I saw a recent publication of a randomized controlled trial of symbiotic therapy for post-acute COVID-19 syndrome (PACS), I had no idea what the term meant. Now I know more, and the study brings up some intriguing thoughts but no direct answers.

First, let's talk about a couple other issues.

Winter Respiratory Illness Season

I'm inventing a new acronym, WRIS, just because I can. CDC went so far as to issue a Health Alert Network posting reminding all of us about the low vaccination rates for covid, influenza, and RSV as well as the availability of treatments for the first 2 infections. So far, flu vaccine coverage in the pediatric age range (6 months to 17 years) is about 36%, pretty poor. The post has a lot of good information throughout, but if you're pressed for time please at least take a look at Table 2 with its links for suggestions for discussions with the unimmunized.

Looking at CDC's weekly viral report page, respiratory illnesses continue to increase. Nationally, emergency department visits for WRIS continue to rise, driven largely by influenza. RSV may be past its peak.

RSV hospitalizations might be coming down, though the data are preliminary:

Influenza-like illness remains high in many states in the South:

Lastly, covid is till out there with high levels in wastewater suggesting we'll see a bigger bump in illness soon.

Although I've presented the national picture, be aware that many of these sites have the ability to display findings by state and other jurisdictions, so you can see what's going on in your area.

Is Pediatric Omicron Infection More Contagious Than We Thought?

That's certainly the implication of a recent study looking at duration of viral shedding in infected children over a 90-day period in early 2022. It's important to note that the study looked only at duration of positivity of PCR at high levels thought to link to infectivity, and also at rapid antigen test (RAT) positivity over time. So, it wasn't a direct measure of whether these children actually transmitted infection at home or in school. With this caveat in mind, they found that 25% of children still had presumed infectious viral loads by day 7 of illness, a bit longer than guidelines recommend for isolation. RAT positivity was a mixed bag as usual (the watermark in the graph just denotes "accepted manuscript" as this paper was published for early online access).

This article shouldn't change practice per se. Looking back at publications of covid spread from children, the results are highly variable with some studies suggesting children have little role in spread. With this much variation in study results, likely the issue is multifactorial, making it difficult to come to any broad generalizations that apply across ages, settings, and time.

Meningococcal B Vaccine and Shared Clinical Decision Making

A few weeks ago I mentioned that healthcare providers don't have enough information at their fingertips to allow parents and patients to truly participate in decisions about vaccination. A new publication about meningococcal serogroup B disease rates helps inform the discussion for meningococcal B vaccine. As you may recall, the ACIP and AAP recently updated meningococcal B vaccination information with the approval of a new pentavalent vaccine. Meningococcal B disease in the US is relatively rare, making risks pretty low overall regardless of vaccination status.

The authors looked at rates of meningococcal disease in persons 18-24 years of age in the years 2014-2017, so not altered by any pandemic considerations. They found 229 confirmed or probable meningococcal disease reports, for an overall rate of 0.18 per 100,000 person years. 120 of the 226 cases for which they had college status were undergraduates, the group at highest risk of meningococcal B infection in the US and the main target for any vaccine intervention. Of those 120 students, 89 had infection with serogroup B.

Students attending 2-year colleges did not have an increased risk of infection compared to non-college students. Only 4-year college attendees had increased risk, and the risk was higher among first-year students and among "Greek life" participants, probably because those groups have a bit more crowding and sharing of beverages, etc.

The authors had some excellent advice in their discussion:

"These findings might be useful for patients, parents, and clinicians when discussing whether to vaccinate adolescents against serogroup B before they go to college. Adolescents planning to live on campus at a 4-year college, particularly ones planning to engage in Greek life or attend schools known for their social life, may benefit more from vaccination. Immunity from MenB vaccines is known to wane quickly, but concentration of risk among first year college students means there is an opportunity to prevent relatively more disease by vaccinating students shortly before they go to college so that the timing of maximum protection overlaps with the highest period of risk."

"Requiring or recommending vaccination against serogroup B disease might not be a tenable policy decision for all colleges, but our findings suggest that 4-year colleges with large numbers of students participating in Greek life or with a high party school ranking might be most likely to benefit from such policies, as these schools were significantly more likely to experience serogroup B cases or outbreaks."

Did you catch that party school mention? Another aid for parents referenced in the study was a ranking of party schools. Those with high rankings presumably represent higher risk for meningococcal B disease. No surprise to me, my undergraduate school didn't make the list.

What I really wanted to know was the Number Needed to Vaccinate (NNV), i.e. how many students would need to be vaccinated to prevent 1 additional case of meningococcal B disease. I knew it would be high because this is such a rare event. It took a little work because I needed a denominator - I knew the number of cases, but I didn't know how many were in the risk group. I had to go to a supplementary table in the article, then look at web links to try to choose a reasonable denominator. I settled on the number of full-time students in undergraduate schools in 2017; it included both 2-year and 4-year colleges. That number, from the National Center for Education Statistics, was 12,085,000. Let's assume the MenB vaccines are 100% effective (they are not, but all are pretty close and I got tired of calculations) and that none of those 89 students in the study were vaccinated (the authors couldn't determine precisely the vaccination rates in their study). NNV is the reciprocal of the absolute risk reduction, which is the rate of infection in the control group (89/12,085,000) minus the rate in the experimental (vaccine) group, which we are assuming to be zero. Crunching those numbers gives us an NNV of 135,786. That is to say, we would need to vaccinate that number of students entering full-time college with a meningococcal B vaccine to prevent 1 additional infection. That NNV number is astronomical and orders of magnitude above NNV for other recommended vaccines. If we were doing a cost-benefit analysis of meningococcal B vaccine, it wouldn't jive at all, but what isn't taken into account is the panic that develops when a case of meningococcal disease occurs on a college campus. Also, I made a lot of assumptions in coming to that number, so it's really just a very rough ballpark. Any decision would need to balance vaccine risks (virtually zero; anaphylaxis from vaccination found 33 cases in 25,173,965 vaccination events in one study, a similar ballpark to the rate of meningococcal B disease above.) This all goes to show that using absolute risk reduction can be more informative than looking at relative risks, which are ratios. For example, in the meningococcal B rates study, participation in Greek life carried a 9.8-fold increase in infection risk compared to other students - a high number that doesn't convey the extremely low infection rates. News stories invariably talk about relative risks rather than absolute risks - bigger numbers sell more papers/advertisements.

So, you can see why those quoted discussion points from the authors are so important. If a parent/potential college student asked me about meningococcal B vaccine, I'd start with saying meningococcal disease is very rare but also very dangerous, with a high fatality rate if one is infected. The risk of getting the infection is very low, about equal to risk of having a life-threatening allergic reaction to any vaccine, both being very rare. [The provider could insert in here if they've ever seen in case of anaphylaxis with a vaccine.] If the plan is to attend a 4-year college, live in a dormitory or fraternity/sorority, and have an active "party" life, the risks for infection are higher though still rare. Some people might value having some more piece of mind and choose to receive vaccination; others may not. Regardless, if at school one hears that you have been exposed to someone with meningococcal infection, you need to follow specific guidance from the local health department or student health team without delay - antibiotic and/or vaccination might be life-saving.

What I Learned About Synbiotics

I'm exhausted after too much number crunching, let's look at a new study that certainly is food (pun intended) for thought. A few definitions first:

Prebiotic - a nondigestible food ingredient that promotes the growth of beneficial microorganisms in the gut

Probiotic - live microorganisms ingested to improve the gut microbiome

Synbiotic - a combination of prebiotic and probiotic substances

The randomized, double-blind, placebo-controlled study looked at 463 adult patients in Hong Kong who were previously diagnosed with covid and fulfilled a standard definition of PACS. The experimental group received twice daily oral doses ("sachets") consisting of 3 probiotic bacteria and 3 prebiotic compounds; the control group received vitamin C with inert additives such that the packets of oral doses were identical in appearance, smell, and weight. The choice of synbiotic elements was based specifically on prior Hong Kong microbiome studies that suggested beneficial elements. The main outcome of interest was change in PACS symptoms at 6 months.

Although there was no difference in quality of life or physical activity between the 2 groups, the treatment did seem to have a beneficial effect on several symptoms and was correlated with favorable microbiome changes.

Maybe some progress, we'll need to see more studies on synbiotic therapy for long covid, hopefully expanded to many different populations. I think I'll go get some yogurt for lunch.

Bug Art 2

Bud WiedermannNovember 26, 2023November 26, 20232 Comments

I hope everyone had a wonderful Thanksgiving holiday, I know I did. With 4 physicians and 2 other medical professionals at the the table this year, our family went through the usual dressing/stuffing discussions with risk of undercooking the stuffing resulting in higher salmonellosis risk. We remain asymptomatic.

Recently I watched a 3-part PBS series about the artist Frido Kahlo. It also featured her sometimes-husband, Diego Rivera, prominently; he was a better known artist than Kahlo for much of the 20th century. Little did I know, until a hot-off-the-presses review article, that he had a bit of microbiologic art featured in some of his works.

First, let's look at what's been going on, besides Thanksgiving, this past week.

Strep Throat Should Be Simple

Every now and then I go on a rant about strep throat. Of course sore throat is very common, and it sounds like a simple problem, but in fact it is one of the most poorly understood maladies I deal with. The combination of a common clinical problem with a pathophysiologic basis full of lacunae has resulted in generally poor management, most conspicuously in antibiotic overuse. The biggest problem is trying to determine someone who tests positive for GAS is just a streptococcal carrier who really has viral pharyngitis from someone with true streptococcal pharyngitis who would benefit from antibiotic treatment. With rare exceptions, identifying a streptococcal carrier is of no clinical utility and only serves to increase unnecessary antibiotic use. We badly need better diagnostic tools (both clinical and laboratory) as well as a better understanding of drivers of serious sequelae such as invasive disease and post-streptococcal arthritis, rheumatic fever, and glomerulonephritis.

Now we have a very intriguing study of essentially healthy children presenting with sore throat and then followed as a prospective cohort for 2 years, looking specifically at antigen testing, throat culture, streptococcal antibody levels, and outcomes. It was mainly designed to provide a framework with which to test upcoming vaccines for group A streptococcus - if you don't have accurate inclusion criteria and outcomes, it's pretty tough to measure vaccine effectiveness. I want to also mention here that of the 8 authors, only 1 was an actual clinician; the rest were all employees of a pharmaceutical company that develops vaccines. Normally that degree of for-profit pharma involvement in a trial would raise concern for implicitly biased interpretations of the results, but in this case we don't have a vaccine product involved in the study so perhaps less for me to fret about.

Children could be enrolled if they were from 3 to 12 years of age and did not have circumstances that could alter conclusions, including no documented group A streptococcal infections in the 6 months preceding study entry. Here's the protocol at study entry at the time of presentation with sore throat (RADT denotes a rapid antigen test for GAS):

Study subjects then had healthy visits at 3-month intervals for the remainder of the 2 years, as long as it was at least 6 weeks following sick visits. At the healthy visits they had throat culture for GAS, but not RADT, obtained. Serology for the sick visits included blood for antistreptolysin O, anti-DNase B, and antistreptococcal C5a peptidase antibodies. If GAS pharyngitis was diagnosed at sick visit 1, the children were treated as per standard by their clinician.

Definitions are important here. A GAS carrier was defined as a positive healthy visit GAS culture plus a positive RADT or culture at sick visit 1 that remained positive at sick visit 2 which occurred 7-10 days after completion of antibiotic therapy for the sore throat event. The researchers evaluated several definitions for GAS pharyngitis which I copy here:

I provide a lot of background for the study methods because they seem very well considered to me, plus I think it is helpful for clinicians to consider all of these possible case definitions when evaluating children with pharyngitis.

Now for the results. First, streptococcal antibody measurement is mostly useless to distinguish true infection from carrier state. That could have been predicted from multiple prior studies but is particularly important in monitoring antibody response in vaccine trials.

Don't look to this study to change your clinical practice if you already follow guidelines for management of GAS pharyngitis. What it does show is how difficult it will be to design trials for future GAS vaccine effectiveness. In the 1960s, a GAS vaccine likely caused an increase of acute rheumatic fever-like illness in vaccine recipients, and GAS vaccine development has been appropriately cautious since that time. GAS vaccine safety issues have been reviewed recently.

Also be aware that I had a few questions about the study that weren't addressed in the publication or the accompanying online supplemental information. I've emailed the first author, the one clinician in the study, and if I hear back I'll provide updates.

It's Beginning to Look a Lot Like ...

.... winter respiratory virus season. RSV, influenza (sorry, at the time I'm writing this we have no new FLUVIEW updates since the week ending November 11), and to a lesser extent wastewater covid all are on the upswing,

It doesn't qualify as a tripledemic yet, but stay tuned.

The Verdict on Last Season's Flu Vaccine

The 2022-23 influenza season was a bad one for pediatric hospitalizations, but we now have some final data on how well the influenza vaccine prevented such episodes.

The vaccine effectiveness is pretty good, in line with other seasons for the most part. The low vaccination rates are another key takeaway; I wish this would improve, but I'm not optimistic given the current upswing in vaccine hesitancy.

Holiday Season Puzzler

Here's a glimpse of Figure 2 from the Rivera review article. As you emerge from what I hope was a wonderful Thanksgiving holiday, see if you can identify the types of organisms that are depicted.

Tag: wastewater