Wednesday, March 29, 2017

Sickle cell cluster in India

Sickle cell disease is mainly diagnosed in those with African ancestry, from Malaria infested areas (we didn't see many cases in the highlands of Zimbabwe, for example, but we did diagnose cases in the kids of Miners, who came from Mozmbique etc).

Once in awhile, in the US, you might pick up a case in "white" people, especially from Mediterranean areas (although Thalessemia is much more common).

The reason is that both these disease give some protection from Malaria

But AlJ reports that some of the indigenous tribes of India also have a high rate of the disease

In India, the disease was first detected in 1952 among indigenous tribes in the Nilgiri Hills of south India. That same year, some migrant labourers working in the tea gardens of Assam state were also diagnosed with the hereditary disease. Of Chhattisgarh's 7.5 million strong indigenous tribal population, at least 20 percent, particularly among the Gond tribe, are affected by sickle cell disease, according to Dr Patra.

Friday, March 17, 2017

Opiod epidemic: is it from doctors giving pain pills?

CDC report. of a survey

A total of 1,294,247 patients met the inclusion criteria, including 33,548 (2.6%) who continued opioid therapy for ≥1 year. Patients who continued opioid therapy for ≥1 year were more likely to be older, female, have a pain diagnosis before opioid initiation, initiated on higher doses of opioids, and publically or self-insured, compared with patients who discontinued opioid use in <365 days 
so the numbers are high: But the percentage is actually quite low.

and they don't include the question WHY the medicines were used:

. Third, information on pain intensity or duration were not available, and the etiology of pain, which might influence the duration of opioid use, was not considered in the analysis. 

and after a long analysis they note the elephant in the room:

Finally, prescriptions that were either paid for out-of-pocket or obtained illicitly were not included in the analysis. 

a lot of "prescription drug abuse" is from stealing medicine, or buying it on the street, but never mind.

momjones article here 

Conventional wisdom holds that overprescribing is fueling the epidemic: Someone injures himself, is prescribed painkillers, and quietly develops an addiction. But that's not the whole story: According to federal data, most people start out by taking the painkillers of a friend or family member. The best predictor of prescription opioid abuse is a history of other drug abuse, according to a recent study in Addictive Behaviors. Experimentation typically starts during adolescence or young adulthood.
and only a small percentage get them from doctors (36%). One wonders if a lot get them from "pill doctors" who give out thousands of them for any reason, but again that is not the question.

more data here.

92 percent of people do not abuse drugs of any sort.

and one wonders about the definition of "misuse". Probably they mean not prescribed by a doctor for that episode:

Among people aged 12 or older in 2015 who misused prescription pain relievers in the past year, the most commonly reported reason for their last misuse of a pain reliever was to relieve physical pain (62.6 percent), which is the reason pain relievers are prescribed (Table B.11). Even if the reason for misuse was to relieve physical pain, use without a prescription of one's own or use at a higher dosage or more often than prescribed still constituted misuse.

ditto for other drugs: it might not be "abuses" but "self medication".

As for the hype that the drug companies pushed narcotics for pain: Why, yes.

Most of the "assisted suicides" by Dr Kavorkian were in patients with uncontrolled pain. Hospice doca and those in pain clinics started using narcotics in contolled amounts because they had fewer side effects than other medicines. (NSAID mainly, which cause GI bleeds, heart and kidney problems).

If you get rid of the pain, most people can simply be withdrawn from their narcotics slowly. Some like the mild buzz from them and continue, so that is abuse. And others aren't in pain but steal/borrow or take them to get high.

The 1960's idea of getting high (along with normalizing marijuana to get high) is the precursor for the idea that if you feel unhappy that drugs will make you happy.

This is a social problem, and the cure is religion.

But that is another story for another time.

Yellow fever vaccine (why a few cases of vaccine failed)

WHO reports almost a thousand cases of the yellow fever, and 30 million given the vaccine to stop the epidemic
in Angola

Mass vaccination is the key focus of the response strategy to control the yellow fever outbreak and prevent international spread. As of today, Angola has vaccinated 13 million people, representing 52% of its population against yellow fever, covering 51 municipalities of 11 provinces.
Commendable progress has been made in tackling this outbreak. However, the next rainy season expected for September usually leads to an increase in the number of mosquitoes that could result in new cases
there was a race to get enough vaccine: A lot of countries sent their supplies to these countries and drug companies worked furiously to make enough doses to stop the epidemic,.. and right now there are no new cases reported in that area of Africa.

But a few cases were found in those who reported getting the vaccine.

CDC analysis of a small group of those diagnosed with yellow fever here.

Among 2,907 suspected cases of yellow fever, 459 (16%) patients had documentation of receipt of yellow fever vaccine. 
this is good news: It means most people who got it didn't get the vaccine
 376 (82%) (of the 459) also had documented RT-PCR results, but only 51 (14%) had positive RT-PCR test results
This means most of those who got the disease after the shot did not get any immune response from the vaccine, and that is why they got sick.
This happens with any vaccine: ten to 20 percent of people have sluggish immune systems, often due to chronic disease and/or malnutrition.

but what about those 51 who got the vaccine, got an immune response to it, but got sick anyway?

Among the 51 patients who received positive RT-PCR test results, symptom onset occurred after vaccination in 32 (63%).

Among the remaining 19, five were excluded because they had not been vaccinated, eight because their symptoms preceded vaccination, and six because they had no documented vaccination date.

so maybe they didn't get the vaccine after all, or were already sick with the disease when they got the shot.
Among the 32 patients who received positive RT-PCR test results after vaccination, 24 (75%) were male, the mean age was 20 years (standard deviation = 12 years), and 13 (41%) died.
this is the usual death rate.

why young males? Maybe because they were more likely to be exposed to mosquitos?

Eighteen (56%) received positive test results for yellow fever viral RNA after postvaccination day 13, and 11 (34%) received positive test results during days 0–13; the sample collection date was missing for three patients. Symptom onset occurred during postvaccination days 0–10 in 17 (53%) patients, and after day 10 in 15 (47%). Distribution of vaccination dates was uniform, implying no clustering by date. Information about location of vaccination was not available to assess clustering by place.

so most of those who got yellow fever after the vaccine were already infected, or got infected shortly after the shot.

In some cases, there was no immune response

In a few, there was an immune response but they got the disease anyway.

what they are worried about is the 32 they sifted out that could have "caught" yellow fever from the vaccine, or if they already had it.

DNA testing will show if it is a wild sttrain (i.e. from local epidemic) or if the vaccine virus mutated into full strength. But this has not been done yet and will probably be in a report in the near futuer.

Live weakened viruses are used for some diseases, and they sometimes mutate back. This is a major problem with Polio, where a half dozen cases of people (usually in contact with a kid who got the oral vaccine) would catch the stronger polio the old fashioned way (via the usual finger/feces/water route).

not in this paper: there is a lot of HIV and other infections that cause a weakened immune system in that area of Africa.

also not in the paper: If some of the cases were given smaller than usual dosages (something done if there were shortages). 

People with HIV are encoraged to get the inactivated vaccines, but cautioned about the live vaccines for this reason.

HIV interferes with some types of immune response , but malnutrition and chronic disease also interfere with the immune response.

but not everyone who gets sick develops the entire syndrome, so actual cases might be higher. From the WHO:

Once contracted, the yellow fever virus incubates in the body for 3 to 6 days. Many people do not experience symptoms, but when these do occur, the most common are fever, muscle pain with prominent backache, headache, loss of appetite, and nausea or vomiting. In most cases, symptoms disappear after 3 to 4 days.A small percentage of patients, however, enter a second, more toxic phase within 24 hours of recovering from initial symptoms. High fever returns and several body systems are affected, usually the liver and the kidneys. In this phase people are likely to develop jaundice (yellowing of the skin and eyes, hence the name ‘yellow fever’), dark urine and abdominal pain with vomiting. Bleeding can occur from the mouth, nose, eyes or stomach. Half of the patients who enter the toxic phase die within 7 - 10 days.

Thursday, March 9, 2017

Yellow fever update

I have posted about the outbreaks of yellow fever over the past few months (In Angola, which spread to the Congo and even a few cases to China, and a different outbreak in rural Brazil)

but now the UKMail says the Brazilian cases are spreading.

more here at CBSNews

According to the Pan American Health Organization, health officials have confirmed 371 yellow fever cases, including 241 deaths. Hundreds more cases are being investigated. This high number of cases is out of proportion to the number reported in a typical year, Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID) and colleague Catharine Paules, M.D., explain in a letter published this week in the New England Journal of Medicine.

 Since the areas in Brazil currently affected by the outbreak are close to major urban centers, including Rio de Janeiro and Sao Paolo where millions of people live, infectious disease experts are concerned that the virus could spread into city populations there for the first time in decades. Yellow fever is spread from one person to the next by Aedes aegypti mosquitoes — the same species that transmits Zika virus.

the problem: These moquitoes are in the USA: the Yellow Fever epidemic of the 1790's killed 20 thousand people in Philadelphia. 

and the world supply of vaccine was pretty well used up in the Angola epidemic...

the problem: The incubation period is 3-6 days and there is no "prodromal" time with low grade sypmtoms. When you get it, you get very sick quickly, and are infectious for a few days (spread via mosquitoes).

so if you have the virus, and you are traveling, you could indeed fly all  over the globe before you knew you were sick.

Travelers need to be told to go to the ER if they get sick, during the week after they arrive, and tell the docs where you had been. They will isolate you from mosquitoes so it won't spread to anyone.

If the mosquitoes are under control (or if it is wintertime) the chances are it won't spread. And if mosquito control is being done, it shouldn't spread. China's cases did not cause en epidemic due to this.

Thursday, March 2, 2017

Sickle cell disease: latest news of a possible cure?

BBC news reports that a Paris teenager with Sickle cell disease, treated by genetic manipulation (using a virus) seems to be okay and well two years later.

Is this a possible cure?

Healthy red blood cells are round, but the genetic defect makes them sickle shaped,
Photo credit: SPL.
Medscape article here:

Hydroxyurea, which stimulates fetal hemoglobin production, is the only disease-modifying therapy for SCD; allogeneic hematopoietic stem cell transplant is curative. Fewer than 18% of people with severe SCD find transplant matches. For them, autologous transplant with a corrected beta globin gene — gene therapy — is a tantalizing chance at a possibly one-time treatment. 

 Jean-Antoine Ribeil, MD, PhD, from the Reference Centre for Sickle Cell Disease, Necker Children's Hospital, Paris, France, and colleagues introduced a lentiviral vector bearing an antisickling variant of HbA into a boy when he was 13 years old. The patient "had complete clinical remission with correction of hemolysis and biologic hallmarks of the disease," they write.

in plain English, when the body is stressed, the red blood cells change shape to a "C"... these cells then can't get through the small tiny blood vessels. Then the low oxygen in the areas where they clog up circulation gets lower in oxygen, causing more and more cells to change shape and block circulation.

Hydroyurea cuts down this as does aggressive treatment of infections (antibiotics) and stopping dehydration when sick.

Several cures have been proposed: Bone marrow transplants of the stem cells that make blood would work, but it has a lot of risks/side effects, and you need a good donor match.

This treatmen uses a virus to snip in a new piece of DNA to fix the problem.

Gizmodo has a ong article here about possible treatments.

Sickle cell disease affects about 100,000 people in the US, most of whom are black. It is an inherited genetic disease caused by a mutation of a single letter in a person’s genetic code.
This single-letter mutation makes it a promising candidate for cutting edge technologies, like the gene-editing technique CRISPR-Cas9, and other gene therapies. Recently, a rush of new research has sought to address it. Two other gene therapy studies for sickle cell are underway in the US —one at UCLA and another at Cincinnati Children’s Hospital. Yet another is about to start in a collaboration between Harvard and Boston Children’s Hospital. Last fall, researchers all demonstrated the ability to correct the mutation in human cells using CRISPR, though that strategy will yet have to surpass significant scientific and political hurdles before reaching clinical trials.
In the new study, researchers took bone marrow stem cells from the boy and fed them corrected versions of a gene that codes for beta-globin, a protein that helps produce normal hemoglobin. The hope was that those altered stem cells would interfere with the boy’s faulty proteins and allow his red blood cells to function normally. They continued the transfusions until the transplanted cells began to produce normal-shaped hemoglobin. In the following months, the numbers of those cells continued to increase until in December 2016, they accounted for more than half the red blood cells in his body. In other words, so far so good.

HPV and colon cancer

NYTimes: There is an increase in colon cancer in the young.

Obesity and sedentary lifestyles are also associated with colorectal cancer, as are heavy alcohol use and chronic conditions like inflammatory bowel disease and Type 2 diabetes, all of which are on the rise. But experts are not entirely convinced these are the only reasons colorectal cancer is increasing among young people. While rates of cancers tied to human papillomavirus, or HPV, have been rising in recent years, that virus causes mainly cancers of the cervix, anus or the back of the throat, and only a small number of cases of rectal cancer.

there are three types of colon cancer: anal cancer, which is known to be partly caused by HPV, Rectal cancer, which clinically has become a lot rarer since I started in medical school, and colon cancer, which seems to be about the same.

I've never seen an Anal cancer, which is associated with HPV. However, we did have a family cluster of genetic colon cancer in ourObjibwe patients. However, colon cancer is more common in Black Americans (and west Africans, but interestingly enough not in the South or East Africans, who eat a high fiber diet, hence the push for fiber).

We used to be urged to do rectal exams to find rectal cancer back in the 1960's, but you know, I hadn't seen any cases in the last ten years I worked. For some reason (diet?) most of the cases went upstream, and so routine sigmoidoscopies stopped being urged and routine colonoscopies, which were harder to do and mainly done by experts, took their place.

Instapundit wonder if anal sex is part of the reason. and lots of comments there.

So what does the NYT say?

t found that in adults ages 20 to 39, colon cancer rates have increased by 1 percent to 2.4 percent a year since the mid-1980s, while rates declined over all among those 55 and older. Rates among adults 40 to 54 increased by 0.5 percent to 1.3 percent a year since the mid-1990s.
Rectal cancer incidence rates among adults in their 20s increased even more sharply, rising by 3.2 percent a year from 1974 to 2013. And while rectal cancer rates have declined over all among people 55 and older since 1974, rates in people 50 to 54 increased between 1989-90 and 2012-13. 
 By 2012-13, nearly 30 percent of all rectal cancers were being diagnosed in people under age 55, compared with 15 percent of all rectal cancers being found in this age group in 1989-90, the study reported.

epidemiology suggests diet is a large part of the problem link 

the NYT and studies above are only doing 30 year comparisons. I date back 45 years which is why my comments are slightly different, and of course most of my work was with poor whites/Hispanics in rural area or with AmerIndians, so genetically different and different diets.

But the rate hasthis cancer has changed in the last century:

Before the 1900s, colorectal cancer was relatively uncommon in the U.S., but its incidence rose dramatically over the last century in parallel with economic development. Worldwide, the majority of colorectal cancers continue to occur in industrialized countries, although incidence rates are rapidly rising in less-developed nations as they increasingly adopt features of a Western lifestyle. Migration studies also demonstrate a higher lifetime incidence of colorectal cancer among immigrants to high-incidence, industrialized countries compared to residents remaining in their native, low-incidence countries. Taken together, these data highlight the importance of environmental influences on colorectal carcinogenesis. 

one of the interesting findings mentioned in the article is that Aspirin and NSAID use is associated with a lower rate of colon cancer. LINK2

I am not sure wat to make of the NYT article about young cancers, i.e. under age 50. HPV? Diet? Chemicals in the environment?

There actually has been a decrease in eating fat in the US population, as evidenced by the lowering of heart attack/ASCVD. So is it the type of fat?

Complicated problem.