Oropouche fever – Pediatric Infection Connection

Seeing You in September

Bud WiedermannSeptember 1, 2024September 2, 2024Leave a comment

This month always bring me back to The Happenings version of "See You in September;" I remember it fondly from my junior high school era. The Harvest Month often is a transition period from summer to fall/winter infections.

The Respiratory Infection Front

Right on schedule, the ACIP published its official flu vaccine recommendations. Nothing new in there, but it's a good one-stop shopping place for seasonal flu information. Things remain calm on the overall respiratory illness view, and covid may have reached its peak.

However, I'm still waiting for covid wastewater trends to start heading down in most areas of the country (same link as above). We may not be out of the woods yet.

Also note that the covid vaccine from Novavax was authorized by FDA this week. I'll be interested to see how effectiveness compares to that of the mRNA vaccines; Novavax targets a slightly earlier variant (JN.1) than the Pfizer and Moderna products which used KP.2. KP.2 is decreasing in prevalence in the US but still is more closely related to the current variants KP.3.1.1, KP.2.3, KP.3, and LB.1.

We have more longterm follow-up information about myocarditis and covid, looking at both vaccine- and natural infection-associated complications compared to other ("conventional") etiologies. It looked specifically at individuals 12-49 years of age hospitalized with myocarditis. Without going into great detail, it was clear that vaccine-associated complications were less common than with myocarditis associated with conventional or SARS-CoV-2 infection; however, confidence intervals were wide for several of the outcomes due to low numbers of events.

I was excited to see a new update from the HIVE (Household Influenza Vaccine Evaluation) program that has been monitoring households in Michigan since 2010 and was expanded to cover other respiratory infections in later years. The new update covers the years 2015-2022. (The watermark in the figures below signifies this is an accepted manuscript that hasn't yet appeared in the print journal.) Even though it's limited to southeast Michigan, it is valuable data because it is an ongoing active surveillance program in these volunteer households and gives us a glimpse of how the pandemic affected other virus epidemiology.

Far Away Challenges

Mpox continues to rage in the DRC and other areas of Africa, with exported cases appearing in far-flung countries. In addition to vaccine, these countries need better front line diagnostic tests. WHO has requested test manufacturers to apply for emergency approval.

On the polio front in Gaza, we've all heard the good news that there will be a pause in fighting to allow for vaccine administration, but it remains to be seen if this will really happen. Regardless, this will be an extremely difficult undertaking, targeting over 600,000 unprotected children in the region.

Bugs Transmitting Bugs

Healthcare providers and the general public are understandably reeling from all the information about various outbreaks of vector-borne infections. It's important to keep in mind 2 main points: 1) Nothing is happening this year that hasn't happened before in the US. This is the season for vector-borne viral infections. 2) Global warming has increased both the range of these vectors, introducing these infections to areas that haven't seen them in past years, and also increased the season length that these infections circulate. We could see increases in all these infections in coming years.

Here's a breakdown of some of the viruses being hyped in the news.

West Nile Virus

Approximately 70-80% of infections are asymptomatic. The most feared complication, neuroinvasive disease, occurs in <1% of all infections but has a 10% mortality and higher rates of permanent neurologic sequelae such as paralysis. So far in 2024, we have had 289 cases from 33 states in the US, with 195 being neuroinvasive (reflecting the fact that only the worst cases get tested for WNV, not any change in asymptomatic rates). Here are some maps for prior years in the US:

As of now, nothing out of the ordinary for West Nile disease in the US. But, it's pretty common if you recognize that we're only identifying maybe 1% of infections.

Dengue

Here the risk is very high in Puerto Rico, but otherwise mostly restricted to travelers from the current epidemic/endemic areas. Some border states, especially Florida, are more likely to see autochthonous (locally acquired) cases. The asymptomatic infection rate is about 75%; 5% of the symptomatic infections progress to severe dengue with capillary leak syndrome and/or hemorrhagic complications. IMPORTANT CLINICAL PEARL: severe dengue usually appears when things otherwise look good - start of afebrile phase after 2-7 days of the febrile phase. This is the time to be very vigilant if dengue is suspected. The slide below (#42 in the pdf) is taken from a wonderful IDSA/CDC Clinician Call webinar this past week, available at https://www.idsociety.org/globalassets/idsa/multimedia/clinician-call-slides--qa/8-28-2024-clinician-call.pdf and https://www.idsociety.org/multimedia/clinician-calls/cdcidsa-clinician-call-update-on-dengue--other-vector-borne-diseases/.

Here are some numbers from the main CDC website above.

For 2024, the only locally acquired cases in the US have been in Puerto Rico (2676 cases), US Virgin Islands (85), and Florida (21), though those numbers are certain to rise since the season isn't over and reporting in general is delayed. If you add in the travel-associated cases, we've seen a little over 4000 in the US.

Oropouche Virus

This is a relatively mild illness for the most part. The asymptomatic infection rate is around 40%, but 4% of those with symptoms will develop neuroinvasive disease. Now there is concern for vertical transmission in pregnant people, still not completely clear. Management guidelines for infants with possible intrauterine infection are updated and available.

Although I was aware of Oropouche virus previously, this is the first year I've ever heard of the term "sloth fever" which only applies if you acquire the infection in the jungle. This is a slide from that same IDSA/CDC webinar, slide 69 in the pdf.

Oropouche may be over with in South America now, and the main risk area remaining is Cuba. CDC reported 21 US cases in travelers returning from Cuba.

Eastern Equine Encephalitis

Saving the worst for last. It's very uncommon, but you definitely don't want EEE. The encephalitis picture occurs in <5% of those infected with EEE virus, but of those with encephalitis the mortality rate is 30%, and 50% of survivors have permanent sequelae.

We've had 4 cases in 2024 so far. Here's data from prior years:

This is a horrible disease. Certainly precautions such as mosquito spraying and personal protection from bites should be implemented in areas where the virus has been identified.

Earworms

Not wanting to end on a depressing note from the rare but severe EEE disease, I thought of earworms. I'm not referring to the real earworm infecting corn ears, nor RFK Jr.'s brain worm, but rather the more contemporary use of the term. Last week I went down the rabbit hole for the Maurice Williams song "Stay," and this entire past week I've been unable to get it out of my head. Maybe I'll replace it with "See You in September."

“There never was a good war or a bad peace.” 2

Bud WiedermannAugust 18, 2024August 18, 20242 Comments

This quote from a Benjamin Franklin letter written 241 years ago still rings true. It's not hard to list bad traits of war, but I find that sometimes we overlook war's contribution to infectious disease outbreaks. Now we're seeing yet another example of this that could expand if not controlled.

Last week revealed a bundle of things to mention, I've tried to trim the list as best I could.

Oropouche HAN

Now the CDC has jumped on the Oropouche virus bandwagon with a new alert via the Health Alert Network. Most useful to front line healthcare providers is an approach for when to consider Oropouche infection more likely:

Consider Oropouche virus infection in a patient who has been in an area with documented or suspected Oropouche virus circulation within 2 weeks of initial symptom onset (as patients may experience recurrent symptoms), and the following:
- Abrupt onset of reported fever, headache, and one or more of the following: myalgia, arthralgia, photophobia, retroorbital/eye pain, or signs and symptoms of neuroinvasive disease (e.g., stiff neck, altered mental status, seizures, limb weakness, or cerebrospinal fluid pleocytosis); AND
- No respiratory symptoms (e.g., cough, rhinorrhea, shortness of breath); AND
- Tested negative for other possible diseases, in particular dengue. If strong suspicion of Oropouche virus disease exists based on the patient’s clinical features and history of travel to an area with virus circulation, do not wait for negative testing for other infections before contacting your state, tribal, local, or territorial health department.

As I've said previously, it's a clinical syndrome similar to dengue or chikungunya; note the absence of prominent respiratory symptoms. Cuba and Brazil travel has been associated with imported Oropouche in other countries; the disease is also experiencing a rise in Colombia, Peru, and Bolivia.

Mpox

Similarly, we now have mpox reported from Sweden in a traveler returning from an area of Africa where clade I disease has been active. Details are scant, but it was certainly only a matter of time before this happened. Clade I seems to have a higher mortality rate than the more common clade II variant, but it's hard to get precise numbers, much less whether anything is different about the clade Ib variant now being seen. Transmission epidemiology seems to be slightly different than the clade II epidemic of a couple years ago which stemmed primarily from men who have sex with men. In this year's clade I iteration, infections also are being spread by heterosexual encounters, usually via sex workers, and also within households. Young children and pregnant women are at highest risk for complications including fatal outcomes. Like most sexually transmitted infections, public health measures are hindered by infected people not being willing to disclose their sexual contacts. In the Democratic Republic of Congo, the epicenter of the clade I outbreak, homosexuality is not officially illegal but societal norms in the DRC are not favorable to LGBT individuals.

Effective mpox vaccines exist for preventive measures, but a recent press release from the NIH had discouraging news about antiviral therapy. Tecovirimat, aka TPOXX, had been useful in clade II disease. Now, in a placebo-controlled randomized trial of almost 600 mpox-infected subjects in the DRC, tecovirimat outcomes for mortality and for time to improvement were the same as with placebo recipients. I'd like to see the actual study results, but I tend to trust NIH press releases more than most others. CDC has a nice update and map.

Parvovirus B19 Alert

Parvo B19 infection isn't a notifiable disease in the US, so if concern has arisen it usually means something dramatic is going on. This week CDC issued a HAN notice about this infection. The disease is well known to pediatric healthcare providers and to many parents as erythema infectiosum or fifth disease. It's a minor illness unless a pregnant person is infected, with subsequent risk of miscarriage or severe fetal anemia and non-immune hydrops fetalis. Individuals with chronic hemolytic conditions are at risk for aplastic crisis and severe anemia, and immunocompromised people have higher risk of complications. Read more if you need a refresher.

Is It Time for Universal Screening for Congenital CMV?

Last week's MMWR reported on the first 12 months' experience with Minnesota's universal newborn screening program for cCMV; it began in February 2023. 184 of 60,115 (0.31%) newborns screened on a dried blood spot had positive CMV results. Note that screening dried blood spots is less sensitive than other methods; 3 infants with cCMV with negative blood spot results and were picked up by other means. Buried in the report was the interesting finding that of 11 infants with permanent hearing loss, 4 passed their hearing screening test as newborns. Clearly we need more than universal hearing screening to identify at-risk infants. I look forward to further outcome data on Minnesota's program.

Dinner at the Sick Restaurant (apologies to Anne Tyler)

I like to think of myself as an adventuresome diner, but probably I would have drawn the line at these 2 delicacies I found at ProMED, the listserv I've used for decades.

Chicken liver sashimi is a new one on me, but now linked to an outbreak of campylobacteriosis in Japan. (You'll need Google translate for this one.) Perhaps slightly less disgusting is the idea of smoked non-eviscerated fish. Recent testing found a commercial product potentially contaminated with botulinum spores; thankfully no clinical cases have been reported. I've eaten sardines from a can. They also are non-eviscerated, but apparently the fish reported this week were capelin and exceeded the length allowable for packaging non-eviscerated fish. The product was produced and distributed by a company in Florida.

Covid

Meanwhile, let's not forget about our old friend. National wastewater levels are still up.

Levels might be tapering off in some parts of the country.

Meanwhile, clinical indicators suggest we're going to be seeing increasing cases the next few weeks at least. Here's an example with percent test positivity from the same link as above. It's a little higher than it was a year ago, though it's difficult to compare time periods since different factors now drive test-seeking behavior.

Meanwhile, if we can believe news reports (the FDA can't disclose approvals ahead of time), the new KP.2 variant-based mRNA covid vaccines should be available later this week. The Novavax vaccine presumably will be ready a little later. Timing for when to get the new vaccine should be based on individual considerations, including immunocompromised state, travel plans, and other factors. However, trying to predict the amount of covid activity over the coming months is only slightly better informed than a roll of the dice. Here's the current forecast from CDC.

Polio in Gaza

Not that it's unexpected, but a case of polio has been reported in a 10-month-old child in Gaza. This child would have been born just near the start of the new war and presumably was never immunized. Breakdowns in the health system as well as with clean water and sanitation are ideal for a reappearance of polio; it hasn't been seen in Gaza in 25 years. The UN has called for a "polio pause" to allow vaccine distribution. I try to avoid political statements in this blog, and I won't change that now, but I think my old friend Ben Franklin had it right about war.

Batesian Mimicry

To end on a lighter note, when I first saw this term I immediately thought of Norman Bates and "Psycho," perhaps Hitchcock's most famous movie. But no, it's not (spoiler alert) Norman mimicking his mother. This refers to Henry Lewis Bates' 1862 publication on butterflies in the Amazon. For an easier read, try this Wikipedia page. It explains my astonished update in last week's post that the mysterious black butterfly in our garden was in fact a dark variant of the easily recognized tiger swallowtail. Apparently it is an example of Batesian mimicry whereby a vulnerable butterfly species develops the ability to mimic a less desirable (to predators) butterfly. In this case, the tiger swallowtail mimics the unpalatable and toxic pipevine swallowtail. I mentioned last week that I had probably forgotten a lot about what I learned about butterflies in my childhood. I certainly don't remember anything about Batesian mimicry or dark tiger swallowtails. Needless to say, I've been down a rabbit hole all week about this. When I went back to my 3 texts on butterflies, all mentioned the black variant in the tiger swallowtail section but not in the sections on black-colored swallowtails where I was looking. As you can see below taken from "Mimicry and the Swallowtails," they are very different but in fact have subtle similarities that escaped me.

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.

Joys of Summer Bites

Bud WiedermannJuly 28, 2024July 28, 2024Leave a comment

The one or two regular readers of this blog know that I'm a favorite companion at outdoor summer activities, not because of my scintillating conversational repartee but rather due to my fabulous mosquto/gnat magnet properties. No one near me needs to worry about bug bites; all those bloodsuckers are feasting on me. One morning this week I gathered a couple dozen bites in a very short time and have been scratching ever since. I've been waiting for symptoms of West Nile virus infection, nothing so far. Meanwhile, another vector-borne disease may have worse consequences than previously known.

But first, ...

Covid Summer Surge

In spite of many breathless news reports, this is still nothing to get worked up about, other than for high-risk individuals to consider returning to masking in crowded indoor spaces and employing other mitigation strategies. Some of the lay reports seem to forget that wastewater levels are not the same as actual infections. Wastewater covid detections might be decreasing, especially in the West.

Percentage of emergency department visits due to Covid, one rough measure of clinical illness, is increasing though still at low levels.

Meanwhile, we have a little more clarity on one aspect of long covid. In one study, myalgic encephalitis/chronic fatigue syndrome in adults was no more common following covid than following an acute infection-like illness that was negative for covid. I've long been concerned that case definitions and studies haven't been focused on the heterogeneity of long covid. Fortunately, some studies are geared to looking at the ME/CFS cases separately from post-covid symptoms that might be related to end-organ damage persisting after severe pulmonary or other infection.

Avian Flu

Similarly, the highly pathogenic avian flu A H5N1 continues to crop up in dairy and poultry workers but doesn't seem to represent a broad risk to others, with no known human-to-human transmission. I neglected to mention last week some preliminary results from the seroprevalence study in Michigan dairy workers: none of 35 tested workers had antibody to the virus, suggesting that asymptomatic infections aren't common. However, we need a sample size larger than 35 to get a better handle on this.

Last week's MMWR contained a report supporting the impression that this particular avian flu strain in humans is a very mild disease.

Wash Your Parsley

Did you know that the FDA performs regular microbiologic surveillance sampling of foods? Last week they reported results from sampling of basil, parsley, and cilantro, 3 of my favorite herbs. Below are numbers for the prevalence of various pathogens in different herbs; 95% CI are in parentheses.

Herb	Cyclospora cayatenensis	Salmonella spp	Escherichia coli
Cilantro	9.2% (4.4-16.5)	2.8% (1.1-5.7)	0% (0-1.5)
Parsley	1.3% (0.5-2.6)	0.9 (0.4-1.8)	0.1% (0.4-1.8)
Basil	0% (0-2.6)	0.7 (0.1-2.7)	0.7% (0-1.4)

For comparison, grocery store Salmonella spp. contamination rates for chicken vary from about 8 to 24%, depending on the study.

Want Some Listeria With Your Liverwurst?

CDC has been investigating a Listeria outbreak linked to deli counter sliced foods, and now one brand of liverwurst tested positive for Listeria. It's possible that a single product could have contaminated slicing devices, causing Listeria to end up in other deli foods. I hope your favorite deli counter practices good cleansing practices for their slicing machines. If not, you might get a side of Listeria with other deli products too.

Ever Heard of Oropouche?

Probably not, unless you are an infectious disease nerd or familiar with the island of Trinidad or the Amazon basin. Oropouche virus (OROV) is still known by the old practice of using a geographic term to name it Now we have new attention focused on this virus, previously thought to cause a relatively harmless though uncomfortable febrile illness. It was first discovered on Trinidad in 1955, in a forest worker from Vega de Oropouche, Trinidad. OROV is endemic to the Amazon basin, and Brazil is seeing a big upsurge in Oropouche fever this year.

With that have come some troubling new reports. OROV is an arbovirus related to dengue, and it mostly causes an acute febrile illness with sometimes very painful myalgias, similar to dengue, zika, chikungunya, malaria, and similar infections. It is transmitted primarily by Culicoides paraensis, a biting midge, but also can be transmitted by other biting insects including Culex mosquitoes.

Last week the Brazilian health ministry confirmed 2 deaths from Oropouche fever, both in healthy young women. The clinical descriptions resemble dengue hemorrhagic fever. Also, the Pan American Health Organization is investigating possible vertical transmission of the virus from 2 infected mothers. One pregnancy resulted in miscarriage, the other with intrauterine fetal death. PAHO has issued guidelines for evaluating possible vertical transmission of OROV. These studies should help us understand if OROV is similar to Zika virus's ability to cause fetal malformations and other severe outcomes. [Note that you may need to activate Google Translate to read these links.]

Meanwhile, I haven't seen any C. paraensis around my house.even though they do range into the northern US, including Maryland. They are pretty tiny, can be less than a millimeter, so good chance I would miss them. I'm somewhat curious to know if I'm also a midge magnet, but really I'd rather not find out.

Tag: Oropouche fever