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Tag: World Health Organization

Published on Leave a comment on Happy World Leprosy Day!

I'm not sure I'd put this in the same celebratory category as a new year's event (January 29 is Vietnamese new year and Chinese new year for 2025), but it is noteworthy. WHO publicizes this day, and it might surprise some in the US that we had 369 new US cases detected in 2023, including 4 children. Here's a global map:

Leprosy still is one of the most stigmatized diseases in the world, fed by rumor and superstition. WHO is a good source for factual information. Speaking of WHO ...

US Quits WHO - What Does This Mean?

Well, this executive order doesn't mean anything immediately, assuming the new administration doesn't somehow violate the agreement for giving a year's notice to WHO before leaving. The US is obligated to pay for 2025. I have no direct experience with WHO, but it is well-known to be a large bureaucracy with the usual ponderous systems that this brings. I did find some better information from one of the many information sources I read, this one written by epidemiologist Dr. Katelyn Jetelina. She previously worked at WHO in Geneva, and her January 23 post provides more insight into how the loss of US funding for WHO might impact world health. She documents many problems with the WHO, but also provides a stark look at what the loss of US funds could portend. The US is the largest donor to WHO.

I'm hoping cooler heads will prevail and this exit won't go through.

MMWR Disappears

I've been subscribing to CDC's Morbidity and Mortality Weekly Report for more than 40 years, way back to when the paper copy came to me in snail mail every week. The communications embargo for health information, detailed in a memo by the acting Secretary for HHS, put a hold until February 1 on federal agencies issuing any information that hasn't been reviewed by a presidential appointee. The memo does allow for exceptions that include critical information, again requiring some sort of political appointee approval.

The MMWR isn't particularly controversial in my mind. I read it every week, but I suspect most healthcare providers don't keep it on their nightstands, or whatever that equivalent is in today's digital world. As of now, the current issue is listed as January 16, with nothing about a January 23 edition. Presumably we will miss January 30 as well.

I'm not so worried about this now, I'm sure we'd hear if we need to take any urgent action with bird flu or other emergency, but I am concerned about whether political censorship will affect the credibility of this information in the long run. I can still remember the chaos early in 2020 and the insistence by some of the value of hydroxychloroquine, ivermectin, and even bleach as effective treatments.

And, speaking of avian flu ...

Avian Flu Update (without CDC)

The Infectious Diseases Society of America broadcast a bird flu webinar, usually done in conjunction with CDC, but this time CDC wasn't mentioned in the title and none of the speakers had CDC appointments. I was able to attend the session in its entirety, and the recording and slides are available to everyone. In spite of the official CDC absence, the speakers were bona fide experts, and I learned several things.

The molecular difference between highly pathogenic avian influenza and low (not lowly) pathogenic strains (slide 6):

Recent global spread of HPAI by wild birds (slide 11):

Spread to dairy cows facilitated by excellent replication in mammary glands and transmission among cows mainly via milking machines (slide 16):

Experience in California suggests that conjunctival swabs may have higher yield of H5N1 than nasopharyngeal swabs (slide 37):

Remember that conjunctivitis is common (80%) in current human cases of H5N1 but is not a prominent feature of seasonal influenza.

Sequencing of strains from human cases in California suggest that the human cases arose by independent cattle-to-human infection events (slide 40), explained by the red dots below appearing in separate phylogenetic trees:

Also some discussion ensued about various testing options. The short version is that none of the tests are approved for conjunctival specimens, and the sensitivity of various tests to identify influenza A H5 is uncertain. Also unknown is whether testing costs in commercial labs would be covered by various insurance plans.

The penultimate presentation was by Bethany Boggess Alcauter, PhD, from the National Center for Farmworker Health. She provided a unique perspective that enlightened me greatly. It starts with slide 72. It was very clear that farmworkers have difficult jobs with little labor protections (below is slides 75-78):

One can easily imagine how tough it is to monitor and manage infections in these workers who now have the added burden of being more targeted for deportation.

A final presentation by Dr. Richard Webby from St. Jude Children's Research Hospital summed up in slides 86 and 87 the current understanding of H5N1 evolution and how difficult it will be to predict the future:

Antibiotics Can't Beat Cold Steel for Appendicitis

Moving away from various pandemic and political concerns for a moment, a new randomized controlled trial suggests that medical therapy alone is inferior to appendectomy (aka appendicectomy in the article) for management of uncomplicated appendicitis in children 5-16 years of age. This was a multinational study at 11 sites (2 in the US) that enrolled a little over 900 children with suspected non-perforated appendicitis.

Prior studies have suggested antibiotic therapy alone is an acceptable management pathway, and I suspect we haven't heard the last on this issue. For now I'd go with surgical intervention as the better alternative.

WRIS

With the muzzle on federal authorities releasing new data, I was interested to see what my usual information sites had available to me this week to monitor winter respiratory viral infection activity. I'm happy to report that the CDC's Respiratory Illnesses Data Channel was updated on Friday as per usual.

The NREVSS Dashboard also was updated (the cutoff date is January 17, but this diagram has additional data compared to last week's report).

I'm not subscribing to any crystal ball methods for predicting how WRIS will progress; I've seen some intimations that covid will be mild this winter, but I worry that some folks are trying to fit covid into a seasonal virus pattern which so far we've learned is not true.

Any bets on whether we'll see MMWR this week?

Happy Year of the Snake! Sức khỏe dồi dào

https://chus.vn/year-of-the-snake/

Published on Leave a comment on The Year in Review

It's fashionable for this time of year to give some reflections on the events of the last 12 months; seemingly every pundit/publication does it in some form or another. I won't buck the trend. What follows is a bit of a "highlight reel," plus the 3 things I'm watching closely for next year.

The Unexplained Explained

Recently we all had the opportunity to watch as a mystery outbreak unfolded in the Democratic Republic of Congo. Was it a novel pathogen set to launch a new pandemic or simply a localized outbreak of a known pathogen, complicated by poor health resources delaying accurate diagnosis and treatment? It took a little longer than I predicted to unravel everything, but we now have an answer from WHO as of December 27. That's still pretty quick, the original alert from the Panzi health zone in the Kwango province was November 29. I'm reassured that our global public health system is working well for outbreak detection.

The case definition used for investigation was fairly broad: "any person living in the Panzi health zone from September 2024 to date, presenting with fever, cough, body weakness, runny nose, with or without one of the following symptoms and signs: chills, headache, difficulty breathing, malnutrition, body aches." Here's an excerpt from the report:

"As of 16 December, laboratory results from a total of 430 samples indicated positive results for malaria, common respiratory viruses (Influenza A (H1N1, pdm09), rhinoviruses, SARS-COV-2, Human coronaviruses, parainfluenza viruses, and Human Adenovirus). While further laboratory tests are ongoing, together these findings suggest that a combination of common and seasonal viral respiratory infections and falciparum malaria, compounded by acute malnutrition led to an increase in severe infections and deaths, disproportionally affecting children under five years of age."

In other words, it was a combination of known pathogens already present in the area, layered on a background of falciparum malaria and malnutrition: a perfect storm. Let's hope the added health resources will dampen the outbreak in this very rural, isolated region of the DRC. Nutritional support is particularly needed.

WHO 2024

The WHO published its look back at 2024, including "highlights, breakthroughs and challenges." Many countries achieved milestones in either elimination or significant decreases of a number of diseases, including human African trypanosomiasis, leprosy, lymphatic filariasis, trachoma, malaria, measles, and mother-to-child transmission of HIV, syphilis, and hepatitis B. Their Expanded Programme on Immunization celebrated its 50th anniversary this year, with an estimated 154 million deaths prevented, most of them infants.

WRIS

CDC took a bit of a holiday break this week, so the level of detail in reports is less. However, Winter Respiratory Infection Season is officially High nationally.

The big 3 (covid, influenza, and RSV) all are increasing at this point. I'm hoping they don't peak at the same time and cause big logjams in healthcare settings.

What I'm Watching For

Mpox

In spite of the few cases in North America, Asia, and Europe, mpox is still primarily an African problem. As we know, however, no communicable disease in one area is just a problem limited to that area - international spread is always a few contacts away. In that regard, I found a recent review/opinion article enlightening.

Of interest, smallpox (vaccinia virus) vaccine protects against mpox infection. Our success in eliminating smallpox and subsequent cessation of smallpox vaccination led to a new population susceptible to mpox infection. A major hurdle to control the outbreaks will be vaccinia virus vaccine testing and distribution to high risk populations.

Avian Influenza

The influenza A H5N1 viruses now circulating in birds (both domestic poultry and wild birds) and dairy cows is the most likely source of a new pandemic, but fortunately the risk is still very remote especially if the public health system can keep on top of tracking infections and characterizing variants.

In the past week we learned that feeding your cat raw pet food derived from poultry is not a good idea, it resulted in 1 cat death in Oregon. I think most of us could have predicted that. One thing for cat owners to keep in mind is that the current avian flu, while still causing some respiratory symptoms in felines, is noteworthy for neurologic symptoms.

Also this week we learned about the mutation found in the hemagluttinin gene segment in the Louisiana human patient with severe avian flu illness. This is the H1 part of the virus which is important for attachment to respiratory epithelial cells. Mutations in this area can increase the effectiveness of spread in humans. However, it is completely expected that a human infected with the virus and experiencing severe disease would develop these types of viral mutations. What would be more concerning is if an isolate from a bird or cow developed such mutations, because of the potential for wider spread.

The risk for widespread human A H5N1 infections is still extremely low. I'll be watching in 2025 for any evidence of human-to-human transmission as well as any significant changes in the virus circulating in the wild animal kingdom. Again, I'm reassured that surveillance is allowing for rapid sequencing of human isolates. I hope that resources continue to be available to track this virus in animal and human populations.

SARS-CoV-2

Covid remains a wild card. It has perhaps the highest mutation rate of any virus causing human disease, it has yet to develop a true seasonality like other coronaviruses making it difficult to plan vaccination recommendations, and infections are still relatively frequent plus underreported due to lack of resources for testing, public apathy, and misinformation/disinformation fueling political decision-making. In short, we're in big trouble if another new variant appears with significantly greater pathogenicity and infectivity.

WHO published another year in review on covid that included a big overview of what's happened since 2020. They do note that our tracking systems worldwide are diminished compared to earlier in the pandemic, so recent data are likely to be significant underestimates. In the post-pandemic phase, we all need to transition from the type of extensive pandemic case tracking into a more sustainable surveillance system similar to what we do for influenza.

I was surprised to see some areas blank for what's going on the US, perhaps due to delayed reporting, and I was also a bit overwhelmed trying to decide what graphs to display here; if you're interested I'd suggest perusing the document itself. First, I've copied a quick highlight summary:

  • While there are periodic waves of COVID-19 in some countries, SARS-CoV-2, the virus that causes COVID-19,
    largely circulates without clear seasonality and continues to infect, cause severe acute disease and post
    COVID-19 condition.
  • The impact of COVID-19 has varied by country depending on the circulating variants, national policies,
    capacities to respond and access to countermeasures.
  • WHO’s ability to monitor circulation, severity, virus evolution and impact is challenged by reduced
    surveillance, testing, sequencing, limited integration into longer term infectious disease prevention and
    control programs, and reporting, as Member States adapt from crisis management to longer term prevention
    and control of COVID-19.
  • Changes to COVID-19 surveillance over the past five years have been consistent and expected, adapting to
    the changing landscape of the pandemic. Many Member States are transitioning from comprehensive case
    reporting to integrating SARS-CoV-2 monitoring into existing respiratory disease and infectious diseases
    surveillance systems. This is an important step towards sustainable infectious disease surveillance,
    monitoring and risk assessment. At the present time, the integration of SARS-CoV-2 into existing influenza
    surveillance systems is variable across regionsranging from 41% in countries from the Western Pacific Region
    to 96% in countries in the European Region.

Here's a great overview of the past few years on a global level.

Even with more inaccuracies in tracking recently, it's nice to see how far we've come in lowering cases and deaths.

Here's a look at deaths by age group, but what isn't apparent in the graph is that mortality rates in infants are comparable to mortality in 20-45-year-olds. Another advertisement for vaccination of pregnant people, who themselves are in high risk group.

And here's the crazy lack of seasonality expressed as percentage of positive tests. I might be tempted to see a trend towards winter seasonality, but remember these data include the southern hemisphere and thus we should see a biphasic pattern if/when seasonality develops.

And lastly a look at how far our variants have drifted over time.

Auld Lang Syne

My apologies to Scotsman Robert Burns, but I must turn to Londoner (with Scottish heritage) Sir Rod Stewart for my favorite version of the song at Stirling Castle in Scotland, complete with bagpipes.

Wishing everyone a Safe and Happy New Year. See you next year.

Published on Leave a comment on Welcome to April

Maryland continues in its warming phase, I'm preparing to dust off the lawnmower and keep fingers crossed that it will start again this season. I'm also going to enjoy some family visiting later this week.

The COVID-19 national emergency declaration was already set to expire on May 11, but now the new Senate vote to end the declaration could accelerate the process. Regardless, expect a mess trying to clean up Medicaid eligibility and other insurance issues dealing with testing, treatment, and prevention.

In the meantime, keep an eye on India and variant XBB.1.16. Will this be our future in the US?

Covid Origins - Time to Inject Some Sanity

It is important to understand how SARS-CoV-2 originated, but unfortunately the discussion spilled over into a political issue. Recently the Department of Energy reversed itself, switching back from declaring that a laboratory leak was most likely to now stating an animal to human jump was the main suspect based on new analyses not yet peer-reviewed. While scientific debate is healthy, the political debate seems counterproductive to me.

With that in mind, a recent editorial in a somewhat obscure journal, The Lancet Microbe, helps place the issue in perspective. The unnamed authors stated, "With current genome editing technology it is easy to manipulate a virus in a laboratory, but it is much easier to manipulate public opinion with political language." They go on to make comparisons to the wild theories circulating in the early part of the HIV pandemic.

We may never know the true origins of this virus, it will likely depend on whether more data are stockpiled away in China that could be made public.

The PADO Priority List

Never heard of it? It is an acronym for the PAediatric Drug Optimization, a program from the World Health Organization which released the first priority list for antibiotic development in children. Simply put, it prioritizes global research gaps that need to be closed. You can download the document yourself, but the key points are important. Three antibiotics are already used in pediatrics, but optimal formulations do not exist: amoxicillin/clavulanate (I can't even estimate the number of occasions I've seen children develop GI complications from clavulanate overdose due to multiple confusing formulations), azithromycin, and nitrofurantoin. They also mention cefiderocol which is still undergoing research trials in children but could be useful for mult-drug resistant Gram negative infections.

I'm glad to learn that WHO has initiated this program and hope it helps progress for those 4 antibiotics. As you may know, the US has the Best Pharmaceuticals for Children Act in place to help complete clinical trials for drugs already FDA-approved but without pediatric labelling.

A Breakthrough Understanding in Severe Pediatric Hepatitis?

I didn't see much about this in the lay press, but 3 articles just published in Nature may be a real breakthrough in understanding the etiology of those clusters of severe acute hepatitis cases worldwide last year. Coinfection with adeno-associated virus type 2 (AAV2) seems to be the common link. I last mentioned this problem almost a year ago, on May 15, 2022. The articles are available only through subscription, but I'll summarize each.

One study looked at 16 cases in the US meeting CDC case definition criteria. The cases were from 6 different states, and researchers tested several sample types (blood, plasma, liver, NP swab, stool) from these cases and compared to samples (blood, serum, plasma) from 113 control with other diagnoses: acute hepatitis with another defined etiology, acute gastroenteritis, non-hepatic inflammatory conditions, and blood donors.

Above is a snapshot of just the hepatitis of defined etiology controls where you can see a striking association of AAV2 detection (pink) in the cases (Ca) on the far left. The authors also noted the cases they studied had a higher rate of adenovirus type 41 viremia (far right) than generally seen across the US and Europe. (Ad41 received a lot of attention early on as the primary etiology.) In addition to Ad41 these investigators also found EBV and HHV-6 more often in cases than in controls.

Next was a study of 32 affected children in Scotland, the first country to report the outbreak. Controls were healthy children and children with other human adenovirus-diagnosed illness but without hepatitis.

The figures and tables for this article are extensive and I had trouble choosing something not totally confusing to display. Above you will note that the acute fulminant hepatitis cases had strikingly high levels of AAV2 viral particles and AAV2-specific IgM antibody compared to various controls. The differences were less striking for presence of AAV2-specific IgG suggesting (as was already known) that prior AAV2 infection is not uncommon in the general population.

These researchers went a step further to look at host genetic susceptibility factors and found some association with HLA class II DRB1*04:01 allele.

The final article studied 38 children from the United Kingdom compared to 66 age-matched immunocompetent controls and 21 immunocompromised subjects. Again the data are extensive and complex, but suffice to say that this group also found high levels of AAV2 in samples from cases but not controls and also showed some evidence of human adenovirus and human herpesvirus type 6B as coinfecting agents perhaps triggering excessive AAV2 replication. These investigators also performed extensive immunologic studies that again showed some evidence of HLA association and a robust immune response in livers of case children, supporting a genetic/immunologic predisposition to AAV2 severe acute hepatitis.

This Wikipedia article isn't bad for a first introduction to AAV; they even have a sentence about the recent articles. AAV doesn't appear to produce any clinical disease by itself, but coinfection with herpesviruses and adenoviruses has been seen.

The fact that we have 3 separate labs with separate patient populations* all finding a link with AAV2, and 2 showing plausible genetic and immunologic explanations for pathogenesis, is strong evidence that AAV2 is the missing puzzle piece that points to a true clinical entity. We can expect future refinement of our understanding with important implications for therapeutic and preventive interventions.

*I did note some overlap of investigators/labs between the Scottish and UK reports but hope there wasn't overlap in the cases they reported.

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