Indian Express
January 29, 2021
January 28, 2021
More vaccines than takers
Exporting limited quantities of Covishield is wise as India is unlikely to meet its vaccination
target by July.
Ten days after the massive COVID-19 vaccination drive began in India to immunise 300
million high-risk individuals first, only over 1.95 million people were vaccinated as of January
25. It is true that while the U.S. took 10 days to breach the one-million mark and the U.K. took
18, India took only six days. The number of people vaccinated each day has been slowly but
steadily increasing since day one — from over 1.91 lakh on January 16 to about 3.35 lakh on
January 25.
Yet, seen in the larger context, the number of individuals vaccinated so far pales in comparison
to the number of children vaccinated each year under the universal immunisation programme.
About 25 million children are born each year in India. Millions of children are immunised
against 10 vaccine-preventable diseases within the first year of life across the country.
By end-December 2020, Serum Institute of India (SII) had already manufactured about 50
million doses of Covishield. Adar Poonawalla, Chief Executive Officer of SII, had told NDTV
that the company manufactures 2.4 million doses each day. On January 11, SII signed an
agreement with the Indian government to supply 11 million doses for local use.
A long way to go
At the current rate of 2 lakh jabs per day, it would take about eight years to immunise the target
population of 300 million people with two doses of the vaccine. This is provided that COVID-
19 vaccination is carried out on all seven days of the week. However, as the Health Ministry
has recommended that COVID-19 vaccination should not affect routine immunisation and
other health services, most States have been vaccinating only on four days a week. The most
populous State, Uttar Pradesh, vaccinates only twice a week.
A single session can vaccinate only 100 people. Until January 25, 35,785 sessions had been
held altogether, with the maximum number of sessions held on a given day touching 6,230 on
January 21. India plans to vaccinate the target 300 million people by July, which would mean
600 million doses to be administered within the next six months. That would require 33,333
sessions to be held on all seven days to vaccinate 100 people per session to complete the
vaccination target by July.
Faster vaccination
Ramping up the vaccination process can be achieved either by increasing the number of
vaccination sites or the number of sessions in a site or both. Since each session should have
five dedicated people, only large hospitals have increased the number of sessions held per day.
The government has permitted vaccine sites to hold only up to seven sessions per day.
Similarly, increasing the number of sites per day too would mean finding additional manpower
and other resources for each site.
However, increasing the number of sites and/or sessions per day alone will not serve the
purpose unless the site selection and number of sessions per site is based on a mapping of
people in a given area who are eligible for vaccination. Since one of the priority groups
included is people younger than 50 years with co-morbidities, only a bottom-up approach to
first identify eligible young people with co-morbidities can help in deciding the number of sites
and sessions needed in an area to cover the eligible population.
Editorial | Injecting confidence: On India’s COVID-19 vaccination drive
Given these complexities, India is unlikely to ramp up the number of people vaccinated per
day before the target date of July, and hence very unlikely to utilise all the 50 million doses
manufactured by SII by end-December before the vaccines reach the expiry date.
Covishield has a shelf life of six months from the date of production. The decision by the
government to allow the company to supply limited quantities of vaccines to other countries
before they reach the expiry date therefore makes eminent sense. Also, India stands to earn the
goodwill of many countries by allowing the export of Covishield, much like in the case of
hydroxychloroquine drug export.
https://www.thehindu.com/opinion/op-ed/more-vaccines-than-takers/article33678182.ece
January 25, 2021
Recovered patients less prone to reinfection, Covid variant: Study
https://epaper.hindustantimes.com/Home/ArticleView
January 22, 2021
Pfizer vaccine appears effective against coronavirus variant found in Britain: Study
Vials with a sticker reading, "COVID-19 / Coronavirus vaccine / Injection only" and a medical
syringe are seen in front of a displayed Pfizer logo in this illustration taken on October 31,
2020. Reuters file photo
The COVID-19 vaccine developed by Pfizer and BioNTech is likely to protect against a more
infectious variant of the virus discovered in Britain which has spread around the world,
according to results of further lab tests released on Wednesday.
The encouraging results from an analysis of blood of participants in trials are based on more
extensive analysis than those released by the U.S. drugmaker last week.
Last week, Pfizer said a similar laboratory study showed the vaccine was effective against one
key mutation, called N501Y, found in two highly transmissible new variants spreading in
Britain and South Africa.
The latest study, posted on bioRxiv.org but not yet peer-reviewed, was conducted on a synthetic
virus with 10mutations that are characteristic of the variant known as B117 identified in Britain
Among the 11 authors of the study are Ugur Sahin and Oezlem Tuereci, co-founders of
BioNTech. Sahin is chief executive and his wife Tuereci is chief medical officer.
It provides further hope as record numbers of daily deaths from COVID-19 are reported in
Britain, which is believed to be driven by the more transmissible variant. It also means vaccine
development would for now not have to start all over again.
But the virus needs to be continuously monitored to check that changes maintain protection by
vaccines, the study said.
For the test, blood samples drawn from 16 vaccinated participants in prior clinical trials were
exposed to a synthetic virus called pseudovirus which was engineered to have the same surface
proteins as B117, as characterised by 10 hallmark mutations.
The antibodies in the blood of the volunteers given the vaccine, known as Comirnaty, or
BNT162b2, neutralised the pseudovirus as effectively as the older coronavirus version that the
product was initially designed for.
Experts said the findings were reassuring and not surprising and results from similar studies on
the South African variant would be keenly watched.
"This makes it very unlikely that the UK variant will escape from the protection provided by
the vaccine," said Jonathan Stoye, a specialist in virus science at Britain's Francis Crick
Institute. "It will be interesting to carry out the same experiments with the South African
variant." BioNTech has said it plans to publish a more detailed analysis of the likely effect of
its vaccine on the South African variant within a few days.
The world is pinning its hopes on vaccines to rein in the coronavirus, first detected in the central
Chinese city of Wuhan at the end of 2019, as many countries impose tighter and longer
lockdowns to try to bring the pandemic under control.
Variants and vaccines
The variants are said by scientists to be more transmissible than previously dominant ones, but
they are not thought to cause more serious illness.
"The South African strain has been detected in the UK - albeit currently in small numbers - but
does seem to be increasing in recent weeks," said Paul Hunter, a professor in medicine at
Britain's University of East Anglia.
"Variants with this mutation could reduce vaccine efficacy, though most likely all current
vaccines would still be highly effective."
Experts have called for continued testing to establish whether vaccines will protect people as
the virus mutates.
COVID-19 has killed more than 2 million people worldwide.
Preparation for potential COVID-19 vaccine strain changes would be "prudent", the study said
on Wednesday.
The Pfizer/BioNTech COVID-19 vaccine and the one from Moderna Inc, which both use
synthetic messenger RNA technology, or mRNA, can be quickly adapted to address new
mutations in the coronavirus if necessary. Scientists have suggested the changes could be made
in as little as six weeks.
AstraZeneca, Moderna and CureVac are also testing whether their respective shots will protect
against the fast-spreading variants. They have not released the results of those tests.
https://www.tribuneindia.com/news/health/pfizer-vaccine-appears-effective-againstcoronavirus-
variant-found-in-britain-study-201182
Antidepressants ineffectual for back pain and osteoarthritis
Most clinical practice guidelines recommend antidepressants for long term (chronic) back pain
and hip and knee osteoarthritis
Antidepressants ineffectual for back pain and osteoarthritis
Most clinical practice guidelines recommend antidepressants for long term (chronic) back pain
and hip and knee osteoarthritis
A study published by the British Medical Journal (BMJ) provides evidence that stimulant
medications are generally inadequate for back and osteoarthritis pain, despite being broadly
utilized for these conditions.
The findings, based on moderate certainty evidence, show that for people with back pain the
effects were too small to be worthwhile, but for osteoarthritis, a small beneficial effect cannot
be ruled out.
Most clinical practice guidelines recommend antidepressants for long term (chronic) back pain
and hip and knee osteoarthritis, yet evidence supporting their use is uncertain.
To address this knowledge gap, researchers led by Giovanni Ferreira at the University of
Sydney set out to investigate the effectiveness and safety of antidepressants for back and
osteoarthritis pain compared with placebo.
Their findings are based on analysis of published data from 33 randomised controlled trials
involving more than 5,000 adults with low back or neck pain, sciatica, or hip or knee
osteoarthritis.
The trials were designed differently and were of varying quality, but the researchers were able
to allow for this in their analysis. Most of the data came from industry-sponsored trials.
The researchers set a difference of 10 points on a 0 to 100 point scale for pain or disability as
the smallest worthwhile difference between groups - a threshold commonly used in other
studies of chronic pain.
https://www.tribuneindia.com/news/health/antidepressants-ineffectual-for-back-pain-andosteoarthritis-
201648
South African coronavirus variant may escape antibodies, cause reinfection, say scientists
Scientists believe the findings underscore the prospect of reinfection with such distinct variants
of the virus carrying these mutations, and ‘may foreshadow reduced efficacy of current spikebased
vaccines’
South African coronavirus variant may escape antibodies, cause reinfection, say scientists
A lineage of the novel coronavirus, first reported to have emerged in South Africa, escapes
neutralisation by antibodies from recovered COVID-19 patients, says a new study which raises
questions on the possibility of reinfection by this strain.
According to the yet-to-be peer reviewed study, published in the preprint platform bioRxiv, the
novel lineage of the coronavirus—501Y.V2—has mutations in nine parts of its spike protein,
which enables it to infect human cells.
In the research, the scientists, including those from the University of the Witwatersrand in
South Africa, tested the neutralisation activity of plasma from patients who recovered from
prior infection with other strains of the coronavirus against the 501Y.V2 variant.
They found that nearly half—21 of 44—of the samples had no detectable neutralising activity
against this variant.
According to the scientists, 501Y.V2 shows “substantial or complete escape from neutralising
antibodies in COVID-19 convalescent plasma”.
“Here we show that the 501Y.V2 lineage, that contains nine spike mutations, and rapidly
emerged in South Africa during the second half of 2020, is largely resistant to neutralising
antibodies elicited by infection with previously circulating lineages,” the researchers wrote in
the study.
They believe the findings underscore the prospect of reinfection with such distinct variants of
the virus carrying these mutations, and “may foreshadow reduced efficacy of current spikebased
vaccines”.
Commenting on the study, clinical virologist Julian Tang from the University of Leicester in
the UK, said this variant could escape neutralising antibody responses largely due to the
presence of two mutations in the spike (S) region — one in the 484th amino acid position and
the other in the 417th molecule of the protein.
“This may reduce some efficacy from S-protein-based vaccine-induced antibodies in some
people,” Tang said.
However, he added that the study also noted considerable binding to the 501Y.V2 virus by
other non-neutralising antibodies, which the virologist believes could still offer some
significant protection against this variant.
“The study also acknowledges that it could not assess the impact of this virus variant on T-cell
responses so some additional defence will arise from this, as well as other naturally existing
innate components of the immune system in those infected in addition to any residual vaccine
protection,” Tang said.
“Further real life studies will be needed to assess the true impact of this South African 501Y.V2
variant on the vaccinated South African population outside of a laboratory context and in the
presence of other natural human immune responses,” he added.
Calling the findings “potentially concerning”, Liam Smeeth, Professor of Clinical
Epidemiology at the London School of Hygiene and Tropical Medicine, however, said these
were laboratory findings, adding that “it would be unwise to extrapolate to clinical effects in
humans at this stage”.
Smeeth said the study did, however, raise the possibility that immunity gained from past
COVID-19 infection may be lower for re-infection with the South African variant.
Lawrence Young, virologist and professor of molecular oncology, Warwick Medical School,
concurred.
https://www.tribuneindia.com/news/health/south-african-coronavirus-variant-may-escapeantibodies-
cause-reinfection-say-scientists-201675
January 21, 2021
Don’t doubt Indian vaccines
Covaxin vaccine being administrated at Rajiv Gandhi Govt. General Hospital on Sunday.
Vaccination is important to prevent a second wave
Several people have questioned the emergency approval given to the indigenously developed COVID-19 vaccine. They have demanded efficacy data and cast aspersions on the regulatory machinery. Such views will only increase vaccine hesitancy.
It is not the case that the vaccine developed indigenously is being pushed by vested interests, while the international vaccines are great. Questions have been raised about the Moderna and Pfizer vaccines too, which have reported more than 90% efficacy. As Peter Doshi wrote in The BMJ, questions have been raised about the exclusion of individuals from the efficacy analysis for ‘important protocol deviations’; the higher rate of medication in the vaccine arm to prevent side-effects due to reactogenicity; the processes of the primary event adjudication committees, comprising the companies’ own employees; vaccine efficacy in those who already had COVID-19; the non-availability of raw trial data; and so on.
Efficacy assessment
Efficacy would actually mean testing, say, 10,000 individuals who have been given the vaccine versus an equivalent number not given the vaccine in terms of the number who get the infection. Can these vaccines prevent transmission? We may have to wait at least six months to get meaningful results. Efficacy would reflect in the rate of hospitalisation, ICU cases and deaths. With a declining level of infection, perhaps the virus is weakening in India on its own, as is the case with most pathogens. This makes efficacy assessment of a vaccine very difficult.
The question of antibody-dependent enhancement, a phenomenon in which virus-specific antibodies enhance the severity of the virus, and in some cases the replication of the virus, has been put on the back burner with experts suggesting it may not be a major issue. It depends on vaccine design and it is not known whether all the candidate vaccines have been tested for this phenomenon.
In the case of the rabies vaccine, efficacy assessment is based on the virus neutralisation capacity of the serum from the vaccinated individual, assessed in terms of international units. It is a surrogate marker for efficacy, since the candidate vaccine cannot be tested in an experimental population that is administered the virus or bitten by rabid dogs, for validation. At this stage, no one can predict whether the COVID-19 vaccine candidates can protect against the circulating mutants. The SARS-CoV-2 virus is both intellectually and medically challenging. But there has been no prevention strategy in history other than vaccination to save lives. Therefore, vaccination of the population is very important for protection against fresh infections and a second wave, although the duration of protection is not known for any vaccine candidate. It is well known that some people take the flu vaccine every year.
The SARS-CoV-2 pandemic has been extraordinary, both in terms of positive and negative developments. The cooperation among the scientific community, industry and regulatory agencies has been truly remarkable in making vaccine development and deployment possible in less than two years, a process that would otherwise take 10-15 years. The future timelines for research and development, product development and expectations will be very different. On the negative side, we have tall claims by political leaders in the West on vaccines, major scientific journals coming under pressure to publish data with poor peer review, vaccine nationalism, etc.
Moving ahead
Given the context of the pandemic, it would be prudent for India to go by safety studies (Phase I and II) and assessment of virus neutralisation assays with the serum. It is also not appropriate to doubt the integrity of the expert committee advising the Drugs Controller General of India (DCGI). The DCGI is not just an individual to be pressured; it follows due process for making an informed decision regarding emergency use, or, as is called in India, approval for restricted use.
It is understandable that limited approval has been given in clinical trial mode, where individuals vaccinated will be monitored regularly. Though no particular vaccine candidate should be favoured, candidates with proven safety studies and efficacy, as assessed based on the virus neutralisation potency of the sera, should be allowed to go ahead. One or two more months into the trial could have given partial data to satisfy interim efficacy assessment, but we will get real data on efficacy only after vaccinating the masses. Eventually, affordability could become an issue. Selective criticism of indigenous efforts will only jeopardise such efforts. India has a huge population to be vaccinated and we need to move ahead.
https://www.thehindu.com/opinion/op-ed/dont-doubt-indian-vaccines/article33603184.ece
India's vaccine diplomacy
https://epaper.tribuneindia.com/2966411/The-Tribune/TT-21-January-2021#clip/57877840/660aff52-6927-446a-901b-62ae77e5c6a9/1030:1166.255548947306
January 19, 2021
January 14, 2021
All set for vaccine rollout amid probing questions
https://epaper.tribuneindia.com/2958886/The-Tribune/TT-14-January-2021#clip/57723003/760a68f7-c7c7-441d-8700-74abe0b28bb5/1594:824.0000000000001
January 12, 2021
January 07, 2021
Air pollution raises risk of pregnancy loss in India, south Asia: Lancet study
An estimated 349,681 pregnancy losses per year in south Asia were associated with exposure
to PM2.5 concentrations, accounting for 7% of annual pregnancy loss in the region from
2000-2016
Poor air quality is associated with a considerable proportion of pregnancy loss in India,
Pakistan, and Bangladesh, according to a modelling study published in The Lancet Planetary
Health journal, which says such losses are more common in north India and Pakistan.
An estimated 349,681 pregnancy losses per year in south Asia were associated with exposure
to PM2.5 concentrations that exceeded India’s air quality standard (more than 40 μg/m³),
accounting for 7% of annual pregnancy loss in the region from 2000-2016, the study says.
For air pollution above WHO air quality guideline, exposure may have contributed to 29% of
pregnancy losses. Although WHO’s guidelines aim for a safer level of air pollution, the
authors note that India’s standard is a more realistic target level, given the high average levels
of air pollution in the region and the need to balance practical governance and public health.
Considered the first such study to estimate the effect of air pollution on pregnancy loss across
the region, it says limitations in the survey data mean that it was unable to distinguish
between natural pregnancy loss and abortions, which may have led to an underestimation of
the effect of air pollution on natural pregnancy loss.
The researchers included 34,197 women who had lost a pregnancy, including 27,480
miscarriages and 6,717 stillbirths, which were compared to live birth controls. Of the
pregnancy loss cases, 77% were from India, 12% from Pakistan, and 11% from Bangladesh.
The authors combined data from household surveys on health from 1998-2016 (from women
who reported at least one pregnancy loss and one or more live births) and estimated exposure
to PM2.5 during pregnancy through combining satellite with atmospheric modelling outputs.
They created a model to examine how exposure to PM2.5 increased women’s risk of
pregnancy loss, calculating risk for each 10 μg/m³ increased in PM2.5 after adjusting for
maternal age, temperature and humidity, seasonal variation, and long-term trends in
pregnancy loss.
Using this association, they calculated the number of pregnancy losses that may have been
caused by PM2.5 in the whole region for the period 2000–16 and looked at how many
pregnancy losses might have been prevented under India’s and WHO’s air quality standard
(40 μg/m³ and 10 μg/m³, respectively).
Gestational exposure to PM2.5 was associated with an increased likelihood of pregnancy
loss, and this remained significant after adjusting for other factors. Each increase in 10 μg/m³
was estimated to increase a mother’s risk of pregnancy loss by 3%, the study says.
Lead study author Tao Xue of Peking University says: “South Asia has the highest burden of
pregnancy loss globally and is one of the most PM2.5 polluted regions in the world. Our
findings suggest that poor air quality could be responsible for a considerable burden of
pregnancy loss in the region, providing further justification for urgent action to tackle
dangerous levels of pollution.”
https://www.hindustantimes.com/india-news/air-pollution-raises-risk-of-pregnancy-loss-inindia-
south-asia-lancet-study/story-Gfnrtiq4OnCDrtX52bSeEL.html
NFHS data shows several maternal and child health interventions have led to improved outcomes
Though overall trends do suggest an improvement in population control, use of modern
contraception, reproductive and child health, immunisation and social determinants of health,
a complete overhaul is needed to identify and address the multidimensional aspects of child
malnutrition.
While states have shown an increase in exclusive breastfeeding and adequacy of diets, about
half of them have shown an increase in rates of malnutrition, wasting and underweight
children.
Population-based surveys form the bedrock of the country’s health information systems. Use
of accurate and nationally representative data can be instrumental in policy planning,
programme design, health system monitoring and management of financial and human
resources. Hence, the release of the National Family Health Survey-round 5 (NFHS-5), which
covers about 6.1 lakh sample households to provide estimates for 707 districts, serves as a
litmus test to evaluate India’s prospects for achieving improved health and well-being for its
population. In the first phase, data from 22 states and UTs has been released from the latest
survey conducted in 2019-2020.
The biggest highlight comes from the data on Total Fertility Rate (TFR), which has come
down to 2.1 or below (replacement level) in all states and UTs, except Bihar (3), Meghalaya
(2.9) and Manipur (2.2). This finding is substantial given India’s longstanding investment in
population control, which has also been instrumental in our poverty alleviation efforts. This
correlates with the data on the overall use of modern methods of contraception, which has
increased in 20 out of 22 states, though female sterilisation continues to be the most dominant
method. Since universal uptake of contraception in developing countries may take more time,
other socio-demographic variables like age at marriage play an equally important role in
reducing fertility rates. The data show that the number of women marrying before the legal
age has fallen in 17 out of 22 states and UTs, with Nagaland, Maharashtra, Jammu &
Kashmir and Sikkim as the top performers. Also, indicators on teenage marriage and
childbearing have improved in 17 states/UTs.
In terms of antenatal care, 17 of 22 states/UTs saw an increase in ANC visits during the first
trimester with Nagaland, Bihar and West Bengal demonstrating the highest increase. But
when we look at the data on interventions for anaemia reduction in mothers, consumption of
IFA tablets by pregnant women for 180 days or more has increased in almost all states/UTs
(except Karnataka), though this has not resulted in a parallel reduction in anaemia levels
among pregnant women. These findings do reflect the need to consider complementing IFA
tablets with the provision of more natural sources of iron, folic acid and other micronutrients
in the diet.
A case where maternal and child health interventions have translated into improved health
outcomes is the uptake of institutional deliveries. According to the WHO, nearly 3/4th of the
neonatal deaths are attributable to preterm births, intrapartum complications and sepsis —
most of which can be addressed through appropriate medical care at the time of delivery. In
this regard, there has been a consistent increase in institutional delivery, with 14 out of 22
states and UTs having more than 90 per cent of newborns being delivered in institutional
facilities. Similarly, 14 out of 22 states/UTs have seen a decline in neonatal mortality.
While women’s empowerment is a wide construct, indicators like household decision
making, control over personal hygiene choices and assets like bank accounts and mobile
phones are good proxies for evaluation. As per the NFHS-5 data, majority of women (80 per
cent) participated in at least three household decisions. More than 64 per cent of younger
women in each of the 22 states/UTs, except Bihar at 59 per cent, are now using hygienic
methods of protection during menstruation. More women now own a personal mobile phone
and the percentage of women with bank accounts has jumped to over 70 per cent across each
of the 22 states/UTs of India (except Nagaland) in 2019-2020.
It is heartening to see almost all states and UTs report a drastic increase in the number of
households with a constructed toilet, improved drinking water as well as clean cooking fuel.
All three indicators are critical in improving public health in India, especially for women.
While indoor air pollution has been linked with major respiratory disorders with women
being disproportionately affected, population-level coverage of sanitation facilities has been
associated with a reduction of infectious disease like diarrhoea, which can take a substantial
toll on child mortality. Additionally, women are spending more time in school with the
percentage of women who completed at least 10 years of schooling jumping by at least 6 per
cent points in the past five years across states and UTs, except Daman & Diu and Tripura.
While states have shown an increase in exclusive breastfeeding and adequacy of diets, about
half of them have shown an increase in rates of malnutrition, wasting and underweight
children. To act upon the underlying determinants, we have to understand that indicators like
stunting, for example, can be multifactorial. Stunting can be affected by variables like
indicators of the mother a child is born to, economic situation of the household, adequacy of
diets, water and sanitation facilities, as well as interventions for nutrition promotion and
health. An encouraging example is from Bihar, which has shown a decline of stunting rates
by about 5.4 per cent points over the past five years.
At the same time, NFHS-5 data also show an increase in the rates of obesity in children and
risk factors for chronic diseases in adults like hypertension and blood glucose, which
represent the flip slide of the malnutrition problem.
In conclusion, we should fall short of generalising these results for the country both because
data from phase 2 is yet to come and summary figures may overlook how contextual health
and nutritional outcomes of the population can be. Though overall trends do suggest an
improvement in population control, use of modern contraception, reproductive and child
health, immunisation and social determinants of health, a complete overhaul is needed to
identify and address the multidimensional aspects of child malnutrition.
https://indianexpress.com/article/opinion/columns/early-nfhs-5-data-indicates-severalmaternal-
and-child-health-interventions-have-led-to-improved-outcomes-7135833/
Study suggests gut microbe may promote breast cancers
A microbe found in the colon and commonly associated with the development of colitis and
colon cancer also may play a role in the development of some breast cancers, according to
new research.
The research was led by investigators with the Johns Hopkins Kimmel Cancer Center and its
Bloomberg~Kimmel Institute for Cancer Immunotherapy. Breast tissue cells exposed to this
toxin retain a long-term memory, increasing the risk for disease.
In a series of laboratory experiments, researchers discovered that when enterotoxigenic
Bacteroides fragilis (ETBF) was introduced to the guts or breast ducts of mice, it always
induced growth and metastatic progression of tumour cells. A description of the work is
published in the January 6 issue of the journal Cancer Discovery.
While microbes are known to be present in body sites such as the gastrointestinal tract, nasal
passages and skin, breast tissue was considered sterile until recently, says senior study author
Dipali Sharma, Ph.D., a professor of oncology at Johns Hopkins Medicine.
The study is a first step to show the involvement of ETBF in breast cancer development,
Sharma says. Additional studies are needed to clarify how ETBF moves throughout the body,
whether ETBF can be a sole driver to directly trigger the transformation of breast cells in
humans, and/or if other microbiota also have cancer-causing activity for breast tissue.
“Despite multiple established risk factors for breast cancer, such as age, genetic changes,
radiation therapy and family history, a large number of breast cancers arise in women
harbouring none of these, indicating the need to look beyond,” Sharma says.
“Our study suggests another risk factor, which is the microbiome. If your microbiome is
perturbed, or if you harbour toxigenic microbes with oncogenic function, that could be
considered an additional risk factor for breast cancer.”
Sharma and colleagues performed several experiments to study the role of ETBF. First, they
performed a meta-analysis of clinical data looking at published studies comparing microbial
composition among benign and malignant breast tumours and nipple aspirate fluids of breast
cancer survivors and healthy volunteers. B. fragilis was consistently detected in all breast
tissue samples as well as the nipple fluids of cancer survivors.
In the lab, the team gave the ETBF bacteria by mouth to a group of mice. First, it colonized
the gut. Then, within three weeks, the mouse mammary tissue had observable changes
usually present in ductal hyperplasia, a precancerous condition.
In additional tests, investigators found that hyperplasia-like symptoms also appeared within
two to three weeks of injecting ETBF bacteria directly to the teats of mice and that cells
exposed to the toxin always exhibited more rapid tumour progression and developed more
aggressive tumours than cells not exposed to the toxin.
Breast cells exposed to the toxin for 72 hours retained a memory of the toxin and were able to
start cancer development and form metastatic lesions in different mouse models. Investigators
also found the Notch1 and beta-catenin cell signalling pathways to be involved in promoting
EBFT’s role in breast tissue.
In clinical studies, the investigators have started looking for microbiome changes among
breast cancer patients to see how this impacts tumour progression and response to therapy.
Meanwhile, Sharma says, “we definitely should try to maintain a healthy microbiome,
including eating a healthy diet and exercising, and maintaining the correct body mass index.”
Down the road, screening for microbiome changes could be as simple as stool sample tests,
said lead author Sheetal Parida, a postdoctoral fellow at Johns Hopkins Medicine. “This is
just one indicator, and we think there will be multiple,” she said.
“If we find additional bacteria responsible for cancer development, we can easily look at the
stool and check for those. Women at high risk of developing breast cancer might have a high
population of some of these.”
https://www.hindustantimes.com/lifestyle/study-suggests-gut-microbe-may-promote-breastcancers/
story-AS2Tws5fWsxj8m7bcALfoJ.html
January 06, 2021
Govt should next focus on well-being of the child from womb to first five years
India continues to be successful in preventing child deaths, but the health and nutrition of the
surviving, living child has deteriorated, somewhat worryingly.
The NFHS has 42 indicators related to child’s health and nutrition (there is one indicator on
school enrolment which falls outside the scope of this analysis).
The recently released fifth round of the National Family Health Survey (NFHS-5) provides
new and reliable evidence to assess some dimensions of micro-development performance
before COVID struck. The survey covers health, nutrition (of mother and child) and the overall
quality of lives.
In a recent piece on these pages (‘New welfarism of India’s Right’, IE, December 22) we had
argued that the data illustrated significant gains achieved by the government in respect to its
distinctive approach to redistribution and inclusion that we called New Welfarism. This
involved the subsidised public provision of essential goods and services, normally provided by
the private sector. Access to banks accounts (especially for women), clean fuel for cooking,
toilets and power had increased and at a significantly faster pace since 2015 than before.
Here, we provide preliminary evidence on the health and nutrition of the child in India. Since
the latest round only has data for 17 states and five Union territories, our findings cover only
54 per cent of India’s population. Madhya Pradesh, Uttar Pradesh, Punjab, Rajasthan and Tamil
Nadu are notable exclusions. Another point to emphasise is this: The New Welfarism was
consciously driven by the Centre and it could, therefore, reasonably claim credit for its success.
In contrast, many of the child-related outcomes are also determined by state-level
implementation, therefore neither success nor failure can be attributed to one source. With
those caveats, we explain the data and then present our results.
The NFHS has 42 indicators related to child’s health and nutrition (there is one indicator on
school enrolment which falls outside the scope of this analysis). Indicators fall into nine
categories and each of these can be divided into outcomes and inputs as the table shows. For
example, neonatal, infant and under-5 mortality rates can be thought of as outcomes. Similarly,
all the nutrition indicators —stunting, wastage, excess wastage, underweight and overweight
—as well as the prevalence of diarrhoea, acute respiratory illness (ARI) and anaemia can also
be classified as outcomes. In contrast, the post-natal care indicators relating to visits made by
health workers, the provision of vaccinations and Vitamin A, and the extent and nature of
feeding for the child can be classified as inputs (details of the NFHS questions are available
online).
The input indicators are not easy to aggregate in easy or obvious ways, so we leave that as
material for future research. Instead, we present some findings on the 11 child outcomes below.
First, though, some nuances. We score wasting (weight for height of children) as an
improvement because even though the gains were marginal, they reversed a negative trend
between 2005 and 2015. However, the wasting outcome must be treated with caution because
trends on wasting move contrary to those of “severe wasting” even from 2005. There is also
one indicator we have ignored, since it is difficult to classify: Underweight, where there were
marginal gains, but a slowdown relative to the past.
Now, for the results, which can be summarised as: India continues to be successful in
preventing child deaths, but the health and nutrition of the surviving, living child has
deteriorated, somewhat worryingly.
Of the 10 outcomes, there have been improvements in four (Figure 1). It is readily apparent
that India continued to make progress in preventing child-related deaths (neonatal, infants and
under-5). That said, the pace of improvement in child mortality slowed down relative to the
previous 10 years. For example, between 2005 and 2015, the infant mortality rate came down
by nearly 2 percentage points per year while between 2015 and 2019 that pace halved to 1
percentage point per year (post-2015, the mortality lines are flatter than before in Figure 1).
Whether some slowing should be expected because India is now close enough to the desirable
benchmark is an open question.
Figure 2 shows the six indicators where outcomes have deteriorated. These all relate to what
happens after survival: The health (anaemia, diarrhoea, and acute respiratory illness (ARI)) and
nutrition (stunting, and overweight) of the child deteriorated between 2015 and 2019. In none
of these cases is the aggregate deterioration driven by outliers, that is, by one or two states.
Moreover, the absolute deterioration in health and nutrition indicators must be seen against the
fact that they reversed the historic trends of steady improvements. That is particularly true of
the prevalence of diarrhoea and anaemia and to a lesser extent of stunting and acute respiratory
illness (post-2015, the lines slope downwards whereas they sloped upwards from 2005-2015).
Several factors probably play a role in explaining these outcomes. As already noted,
implementation capacity of individual states probably played an important role. Sector-specific
factors such as changing diets are also implicated. But the fact of a broader deterioration in
outcomes hints at the likelihood of a common factor, namely the macro-economic growth
environment, which determines employment, incomes and opportunities. At the least, it is safe
to conjecture that some of these outcomes are inconsistent with the narrative of a rapidly
growing economy.
We mentioned earlier that the NFHS provides data on child-related inputs. These need to be
examined too. Suppose it turns out that the Centre and the states have done a good job in
improving the quality and quantity of inputs that go into the child, then there would be a real
puzzle: Why do outcomes and inputs diverge? Indeed, as we showed in our earlier piece, the
government has made great strides in providing a number of basic needs to households such as
toilets, clean cooking fuel, power and bank accounts. Those developments would also serve to
aggravate the puzzle of why the health and nutrition of the child in India has deteriorated.
As discussed in Chapter 5 of the Economic Survey of 2015-16, perhaps the next big welfare
initiative of the government, building on the considerable success of its NewWelfarism, should
be a mission-mode focus on the well-being of the early child (and of course the mother), from
the womb to the first five years, which research shows is critical for realising its long run
potential as an individual.
https://indianexpress.com/article/opinion/columns/national-family-health-survey-childnutrition-
development-services-malnutrition-mortality-rate-7134409/
Brain cancer linked to tissue healing
Researchers have found that the healing process that follows a brain injury -- from trauma to
infection and stroke -- could spur tumour growth.
"Our data suggest that the right mutational change in particular cells in the brain could be
modified by injury to give rise to a tumour," said Peter Dirks, Professor at the University of
Toronto.
The finding, published in the journal Nature Cancer, could lead to a new therapy for
glioblastoma patients who currently have limited treatment options with an average lifespan of
15 months after diagnosis, the researchers said.
"Glioblastoma can be thought of as a wound that never stops healing," Dirks said.
"We're excited about what this tells us about how cancer originates and grows, and it opens up
entirely new ideas about treatment by focusing on the injury and inflammation response," he
added.
The researchers applied the latest single-cell RNA sequencing and Machine Learning (ML)
technologies to map the molecular make-up of the glioblastoma stem cells (GSCs), which
Dirks' team previously showed are responsible for tumour initiation and recurrence after
treatment.
They found new sub-populations of GSCs that bear the molecular hallmarks of inflammation
and which are commingled with other cancer stem cells inside patients' tumours.
It suggests that some glioblastomas start to form when the normal tissue healing process, which
generates new cells to replace those lost to injury, gets derailed by mutations -- possibly many
years before patients become symptomatic, Dirks said.
Once a mutant cell becomes engaged in wound healing, it cannot stop multiplying because the
normal controls are broken and this spurs tumour growth, according to the study.
The team collected GSCs from 26 patients' tumours and expanded them in the lab to obtain
sufficient numbers of the rare cells for analysis. Almost 70,000 cells were analyzed by singlecell
RNA sequencing, which detects what genes are switched on in individual cells -- an effort
led by Laura Richards, a graduate student in Pugh's lab.
The data confirmed extensive disease heterogeneity, meaning that each tumour contains
multiple sub-populations of molecularly distinct cancer stem cells, making recurrence likely as
existing therapy is unable to wipe out all the different sub-clones.
A closer look revealed that each tumour has either of the two distinct molecular states - termed
"Developmental" and "Injury Response" - or a gradient between the two.
According to the researchers, the developmental state is a hallmark of the glioblastoma stem
cells and resembles that of the rapidly dividing stem cells in the brain before birth.
But the second state came as a surprise. The researchers termed it "Injury Response" because
it showed an upregulation of immune pathways and inflammation markers such as interferon
and TNFalpha, which are indicative of wound healing processes.
https://www.tribuneindia.com/news/health/brain-cancer-linked-to-tissue-healing-194122
Brown fat may protect against cardiac, metabolic conditions
Brown fat may protect against cardiac, metabolic conditions
People with detectable brown fat are less likely to suffer cardiac and metabolic conditions
ranging from Type-2 diabetes to coronary artery disease, a new study suggests.
Brown fat, also called brown adipose tissue, helps maintain your body temperature when you
get too cold. Unlike white fat, which stores calories, brown fat burns energy and scientists hope
it may hold the key to new obesity treatments.
"For the first time, it reveals a link to lower risk of certain conditions. These findings make us
more confident about the potential of targeting brown fat for therapeutic benefit," said Paul
Cohen, Assistant Professor at The Rockefeller University Hospital in the US.
The study, published in the journal Nature Medicine, confirms and expands the health benefits
of brown fat suggested by previous studies.
For the study, the researchers reviewed 130,000 PET scans from more than 52,000 patients and
found the presence of brown fat in nearly 10 per cent of individuals.
Several common and chronic diseases were less prevalent among people with detectable brown
fat. For example, only 4.6 per cent had Type-2 diabetes, compared with 9.5 per cent of people
who did not have detectable brown fat. Similarly, 18.9 per cent had abnormal cholesterol,
compared to 22.2 per cent in those without brown fat.
Moreover, the study revealed three more conditions for which people with brown fat have
lower risk: hypertension, congestive heart failure, and coronary artery disease -- links that had
not been observed in previous studies.
Another surprising finding was that brown fat may mitigate the negative health effects of
obesity. In general, obese people have increased risk of heart and metabolic conditions; but the
researchers found that among obese people who have brown fat, the prevalence of these
conditions was similar to that of non-obese people.
"It almost seems like they are protected from the harmful effects of white fat," said Cohen.
The role of brown fat is more mysterious in other conditions like hypertension, which is tightly
connected to the hormonal system.
"We are considering the possibility that brown fat tissue does more than consume glucose and
burn calories, and perhaps actually participates in hormonal signalling to other organs," the
researcher said.
The team plans to further study the biology of brown fat, including by looking for genetic
variants that may explain why some people have more of it than others -- potential first steps
toward developing pharmacological ways to stimulate brown fat activity to treat obesity and
related conditions..
https://www.tribuneindia.com/news/health/brown-fat-may-protect-against-cardiac-metabolicconditions-
194121
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