[HN Gopher] The Long Road to End Tuberculosis
       ___________________________________________________________________
        
       The Long Road to End Tuberculosis
        
       Author : tintinnabula
       Score  : 85 points
       Date   : 2024-11-04 21:38 UTC (7 days ago)
        
 (HTM) web link (www.asimov.press)
 (TXT) w3m dump (www.asimov.press)
        
       | sampo wrote:
       | > TB remains the deadliest infectious disease on Earth, killing
       | about 1.2 million people every year.
       | 
       | I would guess, in 2024 Covid killed more than 1.2 million people.
       | I guess many people are assuming that Covid was a temporary
       | disturbance, and will attenuate in the coming years. But what if
       | it doesn't but will keep at about the current levels from year to
       | year for a long time.
        
         | mauricioc wrote:
         | The WHO [0] reports 60 thousand Covid deaths this year so far,
         | and around 250 thousand deaths in 2023.
         | 
         | [0] https://data.who.int/dashboards/covid19/deaths
        
           | sampo wrote:
           | US CDC has about 40k deaths for 2024 so far [1] for United
           | States, and 76k for the year 2023 [2]. Maybe the WHO
           | dashboard is left unmaintained, or maybe many countries have
           | stopped reporting Covid deaths to WHO.
           | 
           | [1] https://covid.cdc.gov/covid-data-
           | tracker/#trends_totaldeaths...
           | 
           | [2] https://jamanetwork.com/journals/jama/article-
           | abstract/28235...
        
             | dgfitz wrote:
             | Or it's accurate.
        
               | tightbookkeeper wrote:
               | How is the _cause_ of death determined for 250k people?
               | 
               | EDIT: I got curious and looked up the CDC guidelines
               | https://www.cdc.gov/nchs/data/nvss/vsrg/vsrg03-508.pdf
               | 
               | > based on sound medical judgment drawn from clinical
               | training and experience, as well as knowledge of current
               | disease states and local trends
               | 
               | > the disease or injury which initiated the train of
               | morbid events leading directly to death
               | 
               | It goes on to suggest that if Covid was present they
               | strongly recommend including it. And even if you did not
               | diagnose Covid it can be a good assumption to make.
        
               | robertlagrant wrote:
               | There were upper and lower bound stats that accounted for
               | many discrepancies. The high numbers were "death with
               | covid", which means the covid might not've done it, and
               | the low numbers were "death by covid" where we were
               | (fairly) sure Covid did it due to lack of other factors,
               | but missed things where Covid tipped someone over the
               | edge.
        
               | tightbookkeeper wrote:
               | That sounds right. Based on my reading the CDC numbers
               | are basically death with Covid test or symptoms, with the
               | exception of an obvious distinct cause.
               | 
               | Which honestly I can't think of a better way for mass
               | data collection.
        
         | thenerdhead wrote:
         | This isn't even considering the latest being found about Covid
         | either for long term illness/disability, virus on tumors making
         | certain cancers grow faster, and sudden stroke/cardiac events.
         | 
         | We are heavily undercounting until we can definitively link it.
         | That requires families to consent to an autopsy and for
         | biomarkers to be finalized and used to confirm.
         | 
         | Researchers are pretty close to that nowadays though with micro
         | clots, viral rna persistence assays, and even pathology studies
         | which are all showing results this year and will be for years
         | to come.
        
         | Yeul wrote:
         | The difference is that TB kills young people. Old people have
         | to die from something it's irrelevant what eventually knocks
         | them out.
         | 
         | But with TB it was laying waste to people who were supposed to
         | be in their prime. That's why it was so insidious.
        
           | giraffe_lady wrote:
           | Covid turns young people into disabled people. Then we can
           | say "well they had preexisting conditions, it's irrelevant
           | what eventually knocks them out."
        
             | tightbookkeeper wrote:
             | Based on the percentage of young people who got Covid (very
             | high) and were disabled (very few), this doesn't seem
             | significant.
        
               | aredox wrote:
               | The difference with TB being that COVID infects 95% of
               | the population several times per year, turning those low
               | relative rates into higher and higher absolute numbers...
               | 
               | "Death by a thousand cuts"
        
               | tightbookkeeper wrote:
               | Can you estimate those absolute numbers for us?
        
               | giraffe_lady wrote:
               | Can you? You were the first to bring in a concrete claim
               | about them, that they are "very small."
        
               | tightbookkeeper wrote:
               | I'm not the one claiming Covid is as impactful or
               | dangerous as TB, a very unusual claim. Please make your
               | case.
        
               | aredox wrote:
               | Me neither, despite your flagrant attempt at putting a
               | strawman.
               | 
               | Maybe, you know, there is a middle ground between "as
               | impactful or dangerous as TB" and "negligible"?
               | Especially when so much is unknown about the SARS-CoV-2,
               | a virus that infects the whole body (not just the lungs)?
               | 
               | For reference, almost all the victims of SARS-CoV-1 are
               | still suffering from complications almost two decades
               | later, between permanent fatigue, pulmonary damage,
               | osteoporosis and bone necrosis, immune system
               | deregulation, cognition impairment... Which is, you know,
               | less worse than death and therefore TB, but still
        
               | Krssst wrote:
               | The CDC has measurements: https://data.cdc.gov/NCHS/Post-
               | COVID-Conditions/gsea-w83j/da...
               | 
               | Answer is a bit more of 1% young adults have significant
               | limitations caused by long COVID if I read it well. 2024
               | data.
        
               | Krssst wrote:
               | For reference, recent figures seem to be around 5% of
               | younger adults currently experiencing long COVID:
               | https://data.cdc.gov/NCHS/Post-COVID-
               | Conditions/gsea-w83j/da... (need to filter on the columns
               | quite a bit to reach the figures : "currently
               | experiencing long COVID, all adults" + "time period end
               | date" set to the latest)
               | 
               | But this figure also includes cases without significant
               | activity limitation. Significant activity limitations
               | from long COVID across all adults for younger adults is
               | slightly above 1%. Which is not negligible I think.
        
               | stevenAthompson wrote:
               | We know that infection with COVID causes permanent
               | changes to the body, and that those changes are damaging
               | to health. There have been studies that indicate this
               | damage might be cumulative.
               | 
               | We do not yet know what the long term impacts of
               | acquiring COVID repeatedly will be, but we're going to
               | find out.
               | 
               | It's my suspicion that those healthy young people will
               | have lungs like chain smokers, higher rates of certain
               | cancers, and a much higher propensity for certain
               | cardiovascular ailments in a few decades.
        
           | bryanrasmussen wrote:
           | young people have to die from something also, even if it's
           | just getting old. So it's irrelevant what eventually knocks
           | them out as well I guess.
        
             | alexey-salmin wrote:
             | Years of life lost from mortality (YLL) is a concrete and
             | reasonable metric, not just some hand-waiving about
             | everyone dying anyway.
        
         | ywvcbk wrote:
         | > I would guess, in 2024 Covid killed more than 1.2 million
         | people
         | 
         | Why? Seems extremely speculative.
        
         | tzs wrote:
         | COVID-19 appears to act similarly to the other coronaviruses
         | that are endemic in humans. There are two key properties.
         | 
         | 1. You don't develop an immunity to infection by them, but you
         | do become less likely to be made severely ill from subsequent
         | infections.
         | 
         | 2. The severity of illness from the first infection is
         | generally less if you are very young.
         | 
         | With the others it is thought that they probably did cause
         | deadly pandemics when they first crossed over to humans, but
         | did not cause much harm to babies or very young children, and
         | so by the next generation they were no longer a big deal.
         | 
         | Nowadays we don't even bother to have a name for infection by
         | them. We just lump them in with around 200 other viruses and
         | call what happens when we get sickened by any of them a "common
         | cold".
         | 
         | Pretty much everybody alive now was exposed to those viruses as
         | a baby, got mildly ill and got that first infection out of the
         | way, and then it is just a routine common cold to them when
         | they get older.
         | 
         | I don't think it is yet known if COVID-19 will fully follow
         | that path of those others. It still does cause severe illness
         | far more often than the common cold viruses even in people who
         | have been infected multiple times.
         | 
         | We probably won't know for sure until we see what happens over
         | several years with people who were very young during the
         | pandemic or were born after it.
         | 
         | For people older than that is is probably going to be something
         | that is more like a severe flu, where we'll have a vaccine each
         | year for the strains expected to be most common that year, and
         | while the vaccine won't stop you from getting sick it will
         | greatly increase you chances of not getting severely sick.
         | 
         | We are already seeing that. COVID-19 fell from the 4th highest
         | cause of death in the US in 2022 to the 10th highest in 2023,
         | with 76000 deaths. Compare to 246000 deaths in 2022 and 462000
         | in 2021.
        
       | sharpshadow wrote:
       | It's relieving that at least other branches of vaccine
       | development are not under the information regime as with COVID.
       | 
       | "However, environmental bacteria complicate the picture. If
       | present before vaccination, memory immune cells primed to destroy
       | the environmental relatives might cross-react with and neutralize
       | the BCG strain before it has a chance to set up an immune
       | response against itself and M. tuberculosis."
       | 
       | Nobody cared if one already had covid before administering the
       | vaccine and since the vaccine came late many have had a previous
       | infection already. The new mRNA vaccine utilities the body to
       | produce the actual pathogen and with already existing immunity
       | from a previous infection one's immune system starts to attack
       | the mRNA modified cells and pathogen product.
        
         | thenerdhead wrote:
         | Previous COVID infection enhances immunity, creating what we
         | call hybrid immunity. This happens because current vaccines
         | mainly target the spike protein, while natural infection
         | exposes the immune system to other parts of the virus.
         | 
         | New vaccines in development aim to include multiple proteins
         | and improved delivery methods, which could lead to longer-
         | lasting immunity. For now, hybrid immunity (infection plus
         | vaccination) offers broader protection, while vaccines safely
         | boost antibody levels without the risks of infection.
        
           | sharpshadow wrote:
           | An infection exposes the immune system to the whole virus
           | while the mRNA vaccine triggers the synthesis of the viral
           | spike protein which would be a specific part of the virus. It
           | can be called hybrid since it is a combination of a original
           | and novel technique but the underlying immune system still
           | deals with the invaders the same way and creates immunity
           | against them. Naturally an infection would be temporary but
           | with the mRNA technique it's a constant stream of spikes
           | which the immune system attacks to the source. One of the
           | issues here are the byproducts from the immune activity,
           | especially dangerous if the mRNA dosen't stay around the
           | injection area. Hybrid immunity without looking at the cons
           | is not the full picture and seeing some counterpoints about
           | vaccines was refreshing.
        
             | stevenAthompson wrote:
             | I would really love to see your peer reviewed study! Where
             | was it published?
        
       | amluto wrote:
       | A mystery not mentioned in the article: why is TB so unusual in
       | places like the US? The US does almost nothing to control TB. We
       | don't vaccinate. We don't routinely test (except in special
       | cases, but those cover very little of the population). We don't
       | treat latent cases unless they somehow get noticed. And yet the
       | incidence of symptomatic TB is low, and there's no sign of TB
       | developing resistance to whatever the US is accidentally doing
       | right.
        
         | alexey-salmin wrote:
         | Less public transport perhaps? I remember studies showing
         | strong correlation even though causation can be questionable
         | (less protected member of society in the first place). And
         | anecdotally the only person I know with TB never had known
         | cases neither at home nor at work, which basically leaves the
         | public transportation (which he was using 2-4 times a day at
         | the time) as the most likely source.
         | 
         | Another idea could be "better climate" but it's not obvious
         | when I look on the world map of TB incidence.
        
         | noodlesUK wrote:
         | TB is almost the archetypal disease of poverty.
         | 
         | Living on top of each other, especially in childhood &
         | adolescence, combined with other environmental and health
         | factors explains almost all of it. If you're malnourished and
         | your immune system is in bad shape, you're at risk. If you have
         | HIV, you're at risk and so on.
        
           | dyauspitr wrote:
           | That's still not an explanation. Kids in the US spend a lot
           | of time with other kids at daycare and school. It's a
           | transmittable bacterial disease. Why aren't people in the US
           | getting it more? Are you saying you have to be
           | mal/undernourished to get it?
        
             | noodlesUK wrote:
             | Malnourishment is a big part according to the WHO [1]
             | 
             | I'm no expert but I also suspect access to medical care is
             | also a big part, as typically only active cases spread the
             | disease. If you are symptomatic and get some antibiotics,
             | you might not spread it to very many people. If you're
             | symptomatic and go without treatment for ages, then you
             | might spread it to loads of other people.
             | 
             | As we learned during covid, small differences in R value
             | massively change the prevalence over time.
        
             | dghlsakjg wrote:
             | https://bmcpublichealth.biomedcentral.com/articles/10.1186/
             | s...
             | 
             | Unhealthy people are more vulnerable to TB, absolutely.
             | Infections in general are more prevalent in people who are
             | underfed, or living in bad conditions. Other risk factors
             | are exactly what you would expect: smoking, drinking, bad
             | fitness level, and being young or old.
             | 
             | TB rates are basically a function of 1. how immune
             | compromised your population is, and 2. How much access to
             | healthcare there is in the country (poverty, basically).
        
             | valarauko wrote:
             | The majority of healthy people develop a latent infection,
             | and won't manifest symptoms in their lifetimes. The
             | bacteria are encapsulated into nodules by the immune
             | system, which weaken if the immune system weakens. The
             | bacteria escape and active symptomatic infection occurs.
        
               | dyauspitr wrote:
               | Yeah but the US has very low levels of latent TB in the
               | population at only 4%. Compared that to places like
               | Brazil where 40% of the population has latent TB. It's
               | not the climate because in Russia 80% of the population
               | has latent TB.
        
               | valarauko wrote:
               | Yes, and it's a self-perpetuating cycle. If so few people
               | have latent TB, fewer people develop active TB that will
               | go on to infect others. As other comments have mentioned,
               | poverty and its resultant poor health is the biggest
               | correlation for developing active TB. I wonder if most of
               | the Russian latent infections happened during the
               | Soviet/Post Soviet collapse era, with newer latent
               | infections falling off as quality of life improved over
               | time?
        
               | skirge wrote:
               | quality of life improving in Russia is a very risky
               | statement. Soviets manipulated statistics and so does
               | current Russian government.
        
               | toast0 wrote:
               | In order to get latent TB, you need exposure to someone
               | with active TB. If someone with active TB meets the
               | healthcare system, you get a rapid response from health
               | departments. In May 2024, the Long Beach, CA declared a
               | public health emergency [1] based on a cluster of 14
               | cases. This kind of reaction is typical and makes it
               | difficult to spread to others, and keeps the levels of
               | latent TB low.
               | 
               | [1] https://www.longbeach.gov/press-releases/official-
               | city-of-lo...
        
               | fuoqi wrote:
               | 80% sounds like a BS number. It's cited on Wikipedia, but
               | references are either "opinions" or do not contain such
               | information at all.
               | 
               | A proper study [1] shows mean infection rate of ~20% in
               | the worst regions (Far East and North) with the highest
               | rate up to 47%. The situation should be better in the
               | western regions. For comparison, in the US studies show
               | ~4% infection rate [2], so situation in Russia is
               | relatively bad, but improves steadily since 90s and it's
               | far from being catastrophic as the 80% number paints it.
               | 
               | [1]: https://www.tibl-journal.com/jour/article/view/1706
               | 
               | [2]: https://www.cdc.gov/tb/hcp/clinical-overview/latent-
               | tubercul...
        
         | toast0 wrote:
         | My understanding is that TB doesn't spread while latent, it
         | needs to develop into active TB to spread.
         | 
         | The US healthcare system is tuned into TB cases and will alert
         | local health officials to do contact tracing, outreach, and
         | follow up with confirmed cases when they pop up.
         | 
         | Healthcare and childcare workers are routinely tested for TB in
         | areas with recent spread.
         | 
         | Doing screening on the general population doesn't seem
         | necessary, given the low estimated % of people with latent
         | infections and the low estimated % of latent infections that
         | will develop into active infections. It may make sense to
         | screen more people that have a higher risk if they develop
         | active TB or are at a higher risk of exposure.
         | 
         | Certainly, increased screening or vaccination would result in
         | improved outcomes for people whose TB infection was averted.
         | But those have to be weighed against the negative outcomes from
         | side effects of screening/treatment and vaccination.
        
         | classichasclass wrote:
         | While I can't deny the argument that US national anti-TB
         | efforts have become fragmented, possibly as a result of lower
         | incidence, BCG isn't an especially protective vaccine against
         | pulmonary disease and can interfere with TB skin testing, which
         | even in this age of generally available blood QuantiFERON
         | testing is still not uncommon. BCG does have greater value in
         | high-risk countries, and it may be most useful for kids in
         | those regions where TB meningitis is a bigger threat. It
         | doesn't make a lot of sense in a low-burden country, but
         | perhaps one day we'll have a better one.
         | 
         | - working in TB control since 2006
        
         | dghlsakjg wrote:
         | Overlay TB with poverty (or more accurately, per capita GDP) on
         | the map.
         | 
         | There are number of correlations with unhealthy activities like
         | smoking, drinking, fitness, etc... but the best indicator is if
         | you live in poverty, and/or if you're country is poor. Poor
         | areas of rich countries have higher TB, and poor countries in
         | general have higher incidences of poverty. Basically, less
         | access to healthcare and bad living conditions.
         | 
         | This is a good study here that explain the individual risk
         | factors, but the available maps also show a pretty clear
         | pattern:
         | https://bmcpublichealth.biomedcentral.com/articles/10.1186/s...
        
         | John23832 wrote:
         | Spitting has become socially unacceptable in the US. This is
         | due to large scale "anti-spitting" campaigns in the early 1900.
         | 
         | In the 19th century when spittoons were a thing in the US, TB
         | ran rampant.
         | 
         | There's also the widespread antibiotic use. The widespread
         | prescription of Doxycycline for everything inadvertently does a
         | lot.
        
         | susiecambria wrote:
         | I was exposed to TB at Children's Hospital in Washington DC and
         | it was only because I was seeking a part-time job at another
         | hospital while in grad school that I became aware. Got the
         | bubble at the public health department and by the time I drove
         | 40 minutes home, I was clearly positive, so off to Children's I
         | went to have the test read. Because I was a volunteer, I was
         | able to be xrayed immediately and prescribed drugs to take for
         | 9 months. And then, of course, the hospital came after me for
         | the cost of the xray, arguing that I could have been exposed
         | shopping at Talbot's.
         | 
         | I was not surprised to have been exposed. I volunteered a lot
         | of hours in the Children's ED so I had much greater exposure
         | than other people my age who were doing whatever you do when
         | you're 30. I think the doctors and nurses were surprised that I
         | did not freak out and docs to this day are a little surprised I
         | didn't. It was inactive and I was diligent taking the meds.
         | 
         | All this said, the point is that more needs to be done in the
         | US, particularly when we know where the greatest exposure
         | happens.
        
       | senadir wrote:
       | This lecture from John Green is a great full summary on the
       | history of TB https://www.youtube.com/watch?v=7D-gxaie6UI
       | 
       | He's also publishing a book about it
       | https://www.penguinrandomhouse.com/books/312472/everything-i...
       | 
       | Recently, John Green lobbied to get certain pharma companies to
       | lower the price of tests and vaccines
       | 
       | https://www.scientificamerican.com/article/how-advocates-pus...
       | 
       | Tuberculosis is not a medical problem, it's an inequality and
       | access problem. Tuberculosis is fully solved in advanced
       | countries yet less developed countries still suffer from it.
       | Pakistan has 260 death per 100k capita, the US has 2.6. The
       | highest 5 countries have at least 600 per 100k capita.
        
       | BWStearns wrote:
       | Oh hey, I had TB. It sucked. I had to be proper quarantined for 3
       | months, felt like shit for a whole year and a half, and nearly
       | died because I didn't realize I had any symptoms. I thought I was
       | just tired and depressed all the time because I hated my job, and
       | then one day I collapsed from what I thought was a heart attack.
       | 
       | I was/am otherwise healthy and must have just drawn the short
       | straw (or it was a very long dwelling infection from a trip
       | abroad years earlier). I really wish we vaccinated for it like
       | Europe. I'd have taken the little scar on my arm for reducing the
       | already small chance of dealing with that shit.
        
         | kylehotchkiss wrote:
         | BCG doesn't really do much beyond childhood, and even then,
         | just reduces the impact of the disease if you do get it.
        
       | kylehotchkiss wrote:
       | I almost lost a former partner to this disease. Totally changed
       | my life.
       | 
       | One of my first projects at my development consulting job was a
       | site build for an org working on vaccine candidates, which a
       | decade later, unfortunately haven't crossed the finish line.
       | 
       | So with a fairly personal connection with the disease, and the
       | nonzero chance I could one day develop it myself, I have a
       | personal interest in seeing progress in the space.
       | 
       | I saw an IAVI update the other day stating TB research is
       | currently only funded to the tune of 1 billion a year when they
       | need 6. 10.5 million infections a year reported. Remember the
       | countries where the disease have the biggest impact have limited
       | diagnostic abilities outside of cities and politically, these
       | countries are very quick to pretend the problem is solved when
       | the reality is that TB started speeding up again in the covid
       | days because the care programs for patients then was put on
       | pause.
       | 
       | If you wanna change the world and aren't just out for VC cash, go
       | design a mobile X-Ray unit to take into villages, work on an AI
       | model to diagnose from imagery, and work on figuring out how to
       | speed up the testing because a MGIT machine needing power 24/7 is
       | not the type of equipment you can always get in the places the
       | disease impacts.
       | 
       | Figure out how to get those little mycobacteria suckers to divide
       | quicker in agar (my limited biology education tells me mess up
       | the mycoic acid synthesis without killing it?) and then get
       | people a positive result in 3 days instead of 3 weeks. Remember:
       | the very good blood test (quantiferon gold) is banned in the
       | largest country in the world because it comes back positive for
       | the 1/3 of the population latently infected.
        
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       (page generated 2024-11-11 23:00 UTC)