Saturday, March 26, 2016

Substandard medicines for TB

China is taking over the US pharmacology industry, so gets a bad reputation.

But the problem in quality control isn't limited to China:

The Manila Bulletin reports a medicine used for TB has been recalled by the FDA:



The FDA warned “that a specific batch of Rifampicin + Isoniazid + Pyrazinamide + Ethambutol HCl 150 mg/ 75 mg/ 400 mg/ 275 mg Film-Coated Tablet (Onecure) is being recalled due to the non-conformance to the specifications of assay and dissolution of the Rifampicin component as reported by the FDA Common Services Laboratory (CSL)-Alabang Testing & Quality Assurance Laboratory.” 
 Onecure is manufactured by Novartis (Bangladesh) Ltd. in Tongi, Bangladesh, imported in the Philippines by Sandoz Philippines Corporation and distributed by The Generics Pharmacy Inc.

so even though it has the name of big drug companies on the lable, the drug is substandard.

of course, they were caught.

How many "generics" or counterfeit medicines (i.e. manufactured to look like they were made by "big pharm" but are shoddy imitations) are around?

Small pox

Small pox is a live vaccine, meaning it will die if not stored correctly.

So how did they keep vaccines "viable" in the days before refrigeration?

Preventig smallpox by variolation (giving people a small dose of smallpox from a known case) goes back to antiquity, and was practiced in China and in Africa and some Muslim lands in the Middle East, but was introduced into England from the Ottoman empire partly thanks to Lady Montague (and into America by preacher Cotton Mather).

 Dr. Emmanuel Timoni of Constantinople promoted the practice that variolation began its spread through Western Europe. After coming across the practice in Constantinople, Timoni wrote a letter describing the method in detail which was later published in thePhilosophical Transactions in early 1714.[5]:77 His account would become the first medical account of variolation to appear in Europe. Although the article did not gain widespread notoriety, it caught the attention of two important figures in the variolation movement, Bostonian preacher Cotton Mather and wife of the British Ambassador to theOttoman EmpireLady Mary Wortley Montagu.

there were various regimens on how to do this: A chapter in the book The Hemmings Family describes the regimen and how Jefferson paid to have his slaves in Paris get variolated.

There were many smaller epidemics in the Americas,  but a lot of rural people were vulnerable, and this included those joining armies during the revolutionary war.

For example, black slaves who joined the British loyalists on the promise of freedom had a terribly high mortality rate when they got accidentally exposed.

In contrast, Washington, who had almost died of small pox as a youth and knew about variolation, recognized the threat and tried to protect his solders, first by quarantine and then by imposing variolation to any recruit who never had the disease (i.e. most of the recruits).

More HERE.

Weighing the risks, on February 5th of 1777, Washington finally committed to the unpopular policy of mass inoculation by writing to inform Congress of his plan. Throughout February, Washington, with no precedent for the operation he was about to undertake, covertly communicated to his commanding officers orders to oversee mass inoculations of their troops in the model of Morristown and Philadelphia (Dr. Shippen's Hospital). At least eleven hospitals had been constructed by the year's end.
Variola raged throughout the war, devastating the Native American population and slaves who had chosen to fight for the British in exchange for freedom. Yet the isolated infections that sprung up among Continental regulars during the southern campaign failed to incapacitate a single regiment. With few surgeons, fewer medical supplies, and no experience, Washington conducted the first mass inoculation of an army at the height of a war that immeasurably transformed the international system. Defeating the British was impressive, but simultaneously taking on Variola was a risky stroke of genius.
So Washington's controversial decision was one reason why the USA became an independent state: But ironically smallpox is also one reason why Canada never became part of this independent nation: The rebel forces sent to conquer Canada were essentially wiped out by smallpox.

in the days when small pox was rampant, finding a case to use for variolation was not a problem, especially since the dried sores from recovering cases could still spread the disease.

Enter Jenner, whose observation that dairy maids had beautiful complexions, and linked that observation to the fact they often contracted cowpox from milking, began the modern era of vaccines. Cowpox (which eventually evolved into the vaccinia virus) was essentially an "attenuated" vaccine, where giving a mild case of the disease gave you immunity, albeit sometimes only temporary immunity. Measles vaccine is another version of the attenuated virus being used.

Since the virus is live, it has to be kept in a controlled environment (i.e. refrigeration or freezing).

So how did they do that in the good old days before refrigeration? Vaccination would give you a small pustule for a short time only: In the days when it took weeks to travel across oceans or between cities, it would not persist long enough in a person to use by the time you arrived.

Key word: A person.

From Listverse:

(via a headsup from Presurfer)

Francisco Balmis’s Smallpox Mission.
Photo credit: Ecelan


The solution involved passing it arm to arm between orphans. Twenty-two orphan boys between eight and 10 were brought along and given the vaccine successively.
It reached Colombia, Ecuador, Peru, Venezuela, Cuba, and Mexico. Based on its success, Charles IV ordered the campaign to continue in the Philippines

this article includes a section on the Spanish and later the American attempts to vaccinate people in the Philippines. One major problem was that often the vaccination was not "successful": either the vaccine was of poor quality (i.e. not enough live virus, often from poor storage) or the vaccination was not done properly and no infection resulted.

another problem was that people didn't cooperate and get the vaccine, resulting in essentially the militarization or big brother government enforcing it on the unwilling.

Immunization produces "herd immunity", so that epidemics don't spread: Lower the herd immunity, and the unvaccinated are at risk. (the vulnerable include those who refused the vaccine by choice or where the vaccine didn't work: i.e. bad vaccine, or sometimes health problems so your body didn't produce antibodies).

One result was a lot of small pox cases continued so a lot of anti vaccine folk back then insisted the vaccine was evil: like today, the anti vaccine crowd was lead by celebrities, e.g. George Bernard Shaw.

the problem was complicated because now the disease was reported in government statistics, whereas in past days often cases died without being reported or were misdiagnosed: e.g. cases of chickenpox, impetigo. Also, mild cases of small pox where the vaccination was out of date  or "didn't take", but the person naively didn't get a booster vaccination, are reported.

Typical screed about manipulation by public health authorities such as this one ignores the simple fact: We don't see small pox nowadays, so if the vaccine programs didn't work, where are the cases now?

We had the small pox "headsup" after 9-11, where worries about bioterrorism included an attack with smallpox.

The problem was that if we saw a case, there were only two physicians in our small town who might recognize it. No, I was not one of them: even though I had worked in rural Africa, the disease had been eliminated from our area. But my husband saw it in Sulu (Philippines) in the early 1950's (the Moros didn't like vaccination) and one elderly psychiatrist saw it in the 1940's....the last US outbreak was in the late 1940's. Like other outbreaks, that last one was stopped by giving everyone in the area vaccinations (50 thousand people).

That is why a real problem is quality control. (again I refer to the Chinese story of a previous post of not storing vaccines correctly: The authorities know from experience that giving bad vaccines is worse than no vaccines: this could allow epidemics to arise while lowering the public trust that vaccines work, leading to fewer getting the vaccines, which could result in a death spiral to huge epidemics.)

Finally: The elimination of smallpox from the modern world is one of the unsung successes of the United Nations.

but even before the disease was eliminated, they stopped giving it to people in the USA because the "side effect profile" was high.

link2

The traditional vaccination had problems: Including spreading the pustule into open scratches in kids with ecsema, and in people with weak immune systems actually giving them a severe infection that could kill you. This includes spreading to caretakers with cancers, on chemo, or who had HIV: not just those who were vaccinated, but sometimes in those who accidentally touched the lesion.

The military however still gets the vaccine. That is because there is a worry about biowarfare by nut cases who might steal the few remaining small pox viruses from storage and release it.

So there is now a new vaccine used whose advantage is that it doesn't replicate in the body. PDF...

In other words, it doesn't give you a mini disease to make antibodies: It just gives you the virus that sits there and the body will make antibodies.

cross posted from my main blog.

Wednesday, March 23, 2016

Yellow fever outbreak

There is an outbreak of Yellow fever in Angola.

Vaccines will probably cut the spread.

from outbreak news:
they are planning to give the yellow fever vaccine to everyone in the capital (7 million plus people). And the article mentions the logistical problems.

UhOH:

A local who flew back to China after being there is being treated in a Shanghai hospital.

I guess we'll have to go back to the old days, when you carried a yellow booklet proving you had received yellow fever, small pox and cholera vaccines before they let you into some countries.

Vaccine conspiracies: Bahh. yet

I have worked in poor areas of the USA and overseas, and I tear my hair out when I see upper middle class celbrities etc. decry vaccines and have their stuff picked up by conspiracy sites, by "major" newspapers who report the controvery, and then by ignorant Mullahs (or sometimes bishops) who persuade people to avoid vaccines.

Attention: Measles kills. Whooping cough Kills. Polio cripples. Tetanus kills.

I've seen these things, and not just in the USA.

A lot of this is people needing a scapegoat for their child's autism etc. I always wonder how there are huge outcries against vaccines when much of the "epidemic" seems to be a change in the diagnostic criteria (and also that kids who 40 years ago would have been labled "retarded" and put into institutions, and parents went on to have more kids, and were assured the child was better off with "experts".

But now they are left at home for their parents to try to cope... in a society where extended families are non existant and where financially both parents are forced to work to keep in a middle class lifestyle...bearing the high cost of medical care, the loss of money from a job, and the inability to care for the other kids in the family...often parents divorce since often the stress of the child means that parents fight, blame each other subconsciously, and divorce).

So modern"bioethicists" insist it is better for the parents and the family just to kill the kids to avoid these terrible problems.

Ah, but another way to cope is to blame someone else.

I just read The Litigators, (audiobook link here) about a class action lawsuit and the legal shennaingans around it. It was probably fake (some problems but not the death pill claimed by the lawyers)...

but a subplot was about a child left brain damaged from lead in a toy. A toy manufactured in China. A toy subcontracted by an ethical firm that didn't know some corrupt manufacterer in China was cutting cost by using lead paint on a toy. In the book, the toy manufacter took responsibility and gave a huge settlement without fighting.

So was this based on reality?

2011 article in the NYDN:

Toxic lead replaced by even more toxic cadmium in children's toys, trinkets

Now that lead has been banned from children’s products, some Chinese manufacturers have been substituting the even more dangerous heavy metal cadmium, especially in costume jewelry, an Associated Press investigation reveals.
Cadmium is a known carcinogen that, like lead, can delay brain development in young children, leading to learning disabilities. Research also shows that long-term exposure can cause cancer and kidney problems.
but there were no cadmium standards in 2011 so Walmart pled they followed the letter of the law in selling such things.

In a written statement, Wal-Mart insists that it makes safety a priority. "We consistently seek to sell only those products that meet safety and regulatory standards," Wal-Mart states. "Currently there is no required cadmium standard for children's jewelry."
so is this still true in 2016?

This 2015 article from the Environmental working group webpage  notes the law hasn't been updated since 1976, and has denied consumer petitions to update standards in testing cadmium in toys and children's jewelry.

The dirty little secret is that it is not only big business avoiding regulations, but that much of the US manufacturing is now done overseas, where there is less oversite, and in places like China (and to a lesser extent India) where you can get away with it if you bribe the right people or if the regulator is a family member.

NaturalNews article 2013 about "organic food" from China...even if the farmers follow the law ..that irrigates using contaminated water.

we grow organic brown rice.

The bad news: brown rice concentrates some heavy metals. NYT article here.

most are small and not dangerous. Polished rice is healthier this way but has lost it's fiber and B vitamins.

Arsenic can come from ground water (especially deep wells: The use of clean deep well water in Bengladesh has cut deaths from dystentary but now they have an epidmic of arsenic).

But we are probably safe from pollution, being upstream from Manila...but what about all those newfangled mercury containing light bulbs thrown out carelessly here? or other toxins from the city dump upstream from our farm?


(note: Here we pretty well went broke following the law because we competed with rice growers who did use chemicals and pesticides when the regulator wasn't around.).

so anyway: Lack of environmental regulations not only hurt people but hurt those who try to follow the rules (how many US factories went under competing with substandard manufactured stuff from China? )

ah, but getting back to vaccine conspiracies:

Guess what: There is a major vaccine problem in China.

Via Weibo (the Chinese equivalent to twitter/facebook).

The Shandong State Food and Drug Administration is investigating the illegal distribution of vaccines, including those for hepatitis B and rabies, by nine different pharmaceutical companies. As authorities are checking where the vaccines have been sold, media are reporting they have been sold in a total of 24 different places, including municipalities and provinces all over China such as Beijing, Sichuan, Shandong, Shanxi, Hunan, Xinjiang etc.
This is original, researched content by What's on Weibo. You are free to link to this article. Please identify this website or author when you base content on this source or quote from it. Do not reproduce our content without permission – you can contact us at info@whatsonweibo.com, we’re happy to hear from you. Copyright (C) http://www.whatsonweibo.com. Read more at: http://www.whatsonweibo.com/vaccine-scandal-illegal/
a longer article on ChinaDaily:

A mother and daughter from Shandong province have allegedly sold vaccines worth 570 million yuan ($88 million) illegally since 2010 in China, posing severe health risks to users, police said on Friday.
It is believed to be the largest case of its kind in China in terms of the amount of money involved, according to media reports.
The police in Jinan, the provincial capital, confirmed an earlier report by the Paper, a Chinese news organization based in Shanghai, that the two suspects allegedly sold vaccines that were not properly refrigerated, as required by national standards, in 18 provinces and regions across the country.
and here is the kicker:

The fact that they are suspected of doing it for so long exposes flaws in the supervision system of the country’s vaccine industry, he said.
ya think?

ah, but the WHO lauds the entrance of China in to the world vaccine marketplace  (2014)at the same time that "counterfeit" and substandard drugs (mainly from China and India) are killing millions.

the article notes that it is not just manufacturing that has to be careful: You also have to store and ship the vaccines so they don't get hot and lose their ability to work.

and for those following the paper trail of donations to the CLinton foundation being used to get influence with the US Gov't, this is nor comforting:

The Clinton Health Access Initiative (CHAI) has been working with Chinese suppliers to support their applications for WHO prequalification for several vaccine candidates for the last two years, says Joshua Chu, CHAI’s Director, Vaccines Markets.The initiative also works with donors and other agencies to implement innovative market-based mechanisms, such as long-term volume guarantees, to make donor funds go further when purchasing vaccines. So far it has established volume guarantees with vaccine manufacturers in India and with other developing countries for other health products.
then there is this "Whoops":CZ magazine article that mentions the heptatis vaccine deaths.

and laments the meme: But they will be cheap! We Need Cheap!

So the conspiracy vaccine conspiracies will notice:

not just the mullahs or bishops but those in the USA:

this vaccine scandal was carelessness in storing and shipping.

But what about carelessness in manufacturing?

Or outright fraud, as in the heparin or melamine baby milk scandals, where regulation was in place and being done correctly, but the manufacturer figured out a cheaper way to make the stuff that woudn't be detected by ordinary regulatory testing.

Sigh.
-------------

Shanghai daily reports: China is going to fix the loopholes that let these ladies in business.

Lots of other suspects involved.





Sunday, February 21, 2016

Hansen's disease in ShagriLa

AlJazeerah has a nice article about Nepal's busy Leprosy hospital.

Despite the very low risk of infection, the stigma surrounding the disease can be extreme in Nepal. Patients are often isolated and abandoned by their families and communities in a country where the law prohibits infected people from working or marrying. In some rural areas, the disease is considered a curse from God as a punishment for sins committed in a former life.
a similar stigma is found in India, and was present in Europe and in the Bible.

Why? It is not very infectious, but it spreads quickly to children by skin to skin contact, and it leads to deformities that are ugly.

the clinic was founded by a British nurse, but the head doctor now is a local whose parents had the disease and he was raised in a lepersarium.

the disease is easily treated as an outpatient in places like Africa, where the stigma is less, but there is a need for inpatient treatment due to comorbidity (secondary infections of their wounds of example) and need to insure folks take their medicine (similar reason for TB hospitals). They also need specialized rehab work for their injuries and medical problems.

I say only one (mild) case in Zimbabwe, where outpatient treatment wiped it out, but there were still imported cases from Mozambique.

But there might be another reason for isolation.
Sister Humberta, one of our older nurses, had worked in one sanitarium. Once, when I had a patient with ulcers etc. and I asked her opinion if it was Hansen's disease, and she said no: It didn't stink like Leprosy. (it turned out to be ulcerated Kaposi's sarcoma, probably from HIV, which back then was not yet known about).

And in Liberia, I knew the doctor who ran the Hanson disease outreach. She had gone into easier work after the stress of working as a surgeon through the Nigerian civil war, and gotten her PhD in public health. Her job was to go to villages and find cases and put them on treatment, and then check them every three months or so that they were taking the medicines etc.

The outreach was funded by the Knights of Malta, a group beloved by conspiracy theorists.

The truth is more mundane: They are an "independent country" (which is now a mansion in Rome) and they issue their own passports.  UKIndependent article about that group.

. The 118,500 members, employees and volunteers are now in the charity business, working or supporting aid projects in some 120 countries on an annual operating budget of more than £150million.
Haiti, the Democratic Republic of the Congo, and most recently the Philippines, have all been recipients of its emergency relief. Most recently, it even started projects in Turkey, many of which support Syrian refugees, meaning that the eight-pointed Maltese Cross has returned to the modern incarnation of its old enemy.

y es, but conspiracy theories are more fun!

Friday, February 19, 2016

for later reading (blame colombus?)

an article on syphillis.

I'm too fuzzy minded to read it now, but the historical tracing of the epidemic from Columbus' sailors to Italy to the soldiers of Charles via the lovely Napolian ladies is pretty clear.

True, there may have been isolated cases before then, but given the promiscuity of the medieval days one does wonder why no one noticed it.

On the other hand, syphillis is related to yaws, which used to be common in Africa and spread by ordinanry skin contact. No, I've never seen a case. But early syphillis was a lot more virulent in the first hundred or so years it was in Europe, and could be spread by fairly innocuous ways like kissing (not deep kissing, but the cheek to cheek contact common those days when one greeted another, presumably via saliva containing germs and open skin...a few cases of HIV have been spread this way).

So is it new or old or just mutated?

More recently, Zuckerman was also part of a team that published a 2011 paper in the Yearbook of Physical Anthropology reviewing 54 different reports of treponemal disease in pre-Columbian Europe. None of the cases, they argued, presented evidence strong enough—either in the dating of the bodies or the signs of syphilis they displayed— to validate the pre-Columbian hypothesis.



and remember: They have found female DNA in a few people in Norway.

And of course, the cod fishermen would fish off the coast of Canada, so presumably could have visited the lovely ladies there.

Or did the Mali navy who got blown off course to Brazil catch it and bring it to Africa, or maybe they took yaws to Brazil? Remember, the "pristine rain forest" of the Amazon was very populated in those days with millions of farmers.

finally, even a rare case in China or Japan might have managed to get there via polynesians or just sailors who got blown off course.

The presence of African sweet potatoes in Polynesia sugggests that there were some contacts.


Saturday, February 13, 2016

Neanderthal DNA linked disease?

I only have a link to a summary, but this article claims that Neanderthal DNA is associated with a lot of diseases.

NASHVILLE, TENNESSEE—Researchers from Vanderbilt University used a database of 28,000 anonymous individuals, whose DNA samples were linked to their electronic health records, to look for Neanderthal DNA variants and see if they could be connected to modern health problems. “Our main finding is that Neanderthal DNA does influence clinical traits in modern humans: We discovered associations between Neanderthal DNA and a wide range of traits, including immunological, dermatological, neurological, psychiatric, and reproductive diseases,” evolutionary geneticist John Capra said in a press release

Problem number one:

Association does not mean causation.
It could be coincidence. And unless one proves the Neanderthal DNA was in the part of the genome that was associated with the disease, the question of coincidence is likely.
one example can be found in the newspaper article stating that Neanderthals were redheads, so that would explain why some Europeans had red hair. A closer examination showed that the genes were different.

Problem two: Neanderthal DNA varies by race.

it is higher in East Asians than Europeans, but is almost non existent in Africans

didn't Vanderbilt have DNA from African Americans?
Depression and addiction and autoimmune disease are present in African Americans too.

But then I see: "Actinic keratoses" (pre skin cancer lesions). Uh, this merely means someone is pale and goes out in the sun a lot. Again a racial trait due to melatonin (and yes, African albinos get skin cancer too). So do neanderthal genes increase the risk, or is it higher in whites, and white Europeans have more Neanderthal genes? (skin color seems to be paler in northern climates, e.g. Korea...think VitaminD deficiency and ricketts..the exception is those who eat fatty fish like salmon...e.g. Eskimos...think cod liver oil).

The immune problem seems to be identified with the location of the gene in other studies, but the rest of these sound like junk science.

UKMail article. suggests the "interbreeding" stuff might be more complicated than earlier articles suggest.

but what is not clear when they say "x percent" of humans have neanderthal genes, if they mean X percent of the population, or if 100 percent of folks have x percent of the Neanderthal dna.

from Natgeo

Everyone living outside of Africa today has a small amount of Neanderthal in them, carried as a living relic of these ancient encounters. A team of scientists comparing the full genomes of the two species concluded that most Europeans and Asians have between 1 to 4 percent Neanderthal DNA. Indigenous sub-Saharan Africans have no Neanderthal DNA because their ancestors did not migrate through Eurasia.

so back to the original article: Did they actually check out the gene or not?

 For example, a Neanderthal variant that increases blood coagulation may have sealed wounds more quickly and prevented infections. 
John Hawks article on DNA in populations.
Wonder what the percentages would show for Mongolians/Koreans/Native Americans, who were from Siberia, not Han Chinese.

guess I'll have to do a bit more study into this area, because right now I'm confused at what is being claimed.