Using viruses to kill Tuberculosis bacteria

This article was first published in Research Matters. Read the article, as it appeared on researchmatters.in, here.

Viruses are infamous for the infectious diseases they cause in different organisms — the year 2020 has proved it for us to see. But, a virus that causes an infection in one organism could be harmless in another. The Nipah virus, for example, is harmless in bats but causes a deadly disease in humans. Likewise, there are a group of viruses called bacteriophages that infect and kill bacteria but are harmless in humans. Within this group of viruses are myriad individuals, each one specific to certain bacteria.

In a recent study, researchers from the Indian Institute of Science (IISc), Bengaluru, have found that a cocktail of bacteriophages could kill Mycobacterium tuberculosis – the bacteria that causes Tuberculosis (TB), and its cousin Mycobacterium smegmatis­. The study was led by Rachit Agarwal, Assistant Professor at the Centre for BioSystems Science and Engineering, IISc, and the findings were published in the journal Frontiers in Microbiology.

Tuberculosis (TB) is one of the top 10 causes of death worldwide. It affected 10 million people and killed 1.4 million of them last year. India has the highest burden of TB worldwide, with nearly 4.5 lakh deathsreported in 2018. When M. tuberculosis infects a person, their immune system launches an attack against it. A group of immune cells, called macrophages, engulf the bacteria to form a packet inside the cell containing the bacteria with a slightly acidic environment. Typically, this packet would fuse with another component inside the cell, called the lysosome, which would make the environment more acidic and thereby kill the bacteria.

However, M. tuberculosis and its relatives have a smart way of escaping this process. They not only block this process of creating a more acidic environment, but they also thrive in an acidic environment and in low-oxygen conditions where other cells would die! They switch to a state in which they do not multiply fast, but grow slowly, residing inside these acidic compartments made by the body’s immune system.

Doctors treat tuberculosis with a combination of drugs that includes antibiotics. Over the years, the indiscriminate use of antibiotics has led the bacteria to develop resistance to these drugs, resulting in antibiotic-resistant tuberculosis infection. India also has the highest burden of such infections.

“The main motivation behind our study was the fact that antibiotic-resistance has been on the rise and is predicted to be a major global health crisis soon,” says Yeswanth C Kalapala, the lead author of the study.

In recent years, researchers have explored the use of bacteriophages against tuberculosis bacteria to curb their growth and kill them. The current study is no different. The researchers have studied how bacteriophages work against Mycobacterium in various disease-mimicking environments.

“We found that these bacteriophages were effective against Mycobacterium in various disease-mimicking conditions like acidic environment, low oxygen concentration and nutrient starvation,” says Rachit.

The researchers first studied the effect of single bacteriophage on the growth of Mycobacterium and later used a mixture of them — five different bacteriophages against M. smegmatis, and three against M. tuberculosis — in their lab.

“The bacteria develop some tolerance against individual phages over time, but a cocktail of phages inhibit the growth of the bacteria for a longer time and delay the development of tolerance to phages,” explains Pallavi R Sharma, one of the authors of the study.

The researchers found that the cocktail was effective in acidic environments, low-oxygen and low-nutrition conditions — all of which are present in cells infected with tuberculosis. It was also working against slow-growing bacteria. They then used the cocktail in combination with rifampicin, an antibiotic conventionally used to treat TB, on lab-grown bacteria. They found that the combination had a synergistic effect in reducing the growth when compared to the using either one separately.

As TB cases caused by antibiotic-resistant bacteria are on the rise, the authors also looked into the effect of the phage cocktail on an antibiotic-resistant strain of M. smegmatisM. smegmatis generally do not cause a disease, but behave similar to other Mycobacteria. This allows researchers to use this bacteria in laboratory conditions where safety requirements are lesser than those for the use of M. tuberculosis, while giving them an idea of how M. tuberculosis might behave in similar conditions. Besides, M. smegmatis reproduce faster than M. tuberculosis. So, the authors used the antibiotic resistant M. smegmatis as a model to study how other antibiotic resistant Mycobacteria react to phage cocktails.

“We found that the five-phage cocktail was effective in infecting and killing antibiotic-resistant M. smegmatis. We also saw that the phage cocktail complemented rifampicin and eliminated the bacteria that were resistant to it,” says Yeswanth.

Following these interesting observations, the researchers are planning to study the effect of these phage cocktails on Mycobacterium tuberculosis growing inside human cells cultured in the lab and animal models like mice.

“We wish to see how this therapy can be used in animals and later translated to humans to treat TB, particularly in the case of drug-resistant TB,” signs off Rachit.

COVID-19: A day in the life of a healthcare worker

India has seen a steady increase in the number of reported COVID-19 cases in the last two months. While the country languishes under the weight of the pandemic, our healthcare workers are giving their all to the fight against the pandemic. Here is a story of a healthcare worker who treats COVID patients.

4.30 AM.

The alarm rings.

It’s time to wake up, do the domestic chores, get ready, and report to work.

“God, I hope I don’t get exposed [to the virus] today,” she thinks to herself as she gets ready to go to the frontline – to the war, as some would call it. The war that is fought using medical science, complemented with compassion, care, and love.

Susan Thomas is a staff nurse working in the Intensive Care Unit (ICU) designated for COVID-19 patients in a private hospital in Bengaluru. Before the pandemic, her duty used to last 8 hours a day, six days a week. But things have been different since the end of March. She has been working for about 12-14 hours a day, five days a week.

On a typical day at work, Susan goes into the COVID ICU after she has put on the personal protective equipment (PPE). There, her predecessor updates her about the status of the patients and hands them over to her care.

“It’s a lot of pressure and it’s physically exhausting,” Susan says. “It’s more than just taking care of patients. There is also the paperwork that must be done. All this extra work takes up a lot of time, but we have to do it for the good of everyone. There is very little time to have food or even to take a break in between.”

She has to protect herself while treating the patient. Even the smallest mistake or negligence can get her infected. It’s quite an ordeal. The PPE makes the routine work also difficult. “I am soaked in sweat for the most part of the day. And things get worse when I have my periods,” Susan says. While on duty, she hums a tune or sings a chorus to keep herself calm and make the patient also feel better.

After the long day at work, all she just wants to do is to get home, take a shower and hit the bed with the hope that her patients get better. Although she tries not to think about her patients when she is going to sleep, it seems impossible sometimes. I tell myself, “Hey, stop thinking about your patient now!”

The ordeal of being in treating patients during a pandemic is not only physically exhausting but is also mentally taxing. Susan combats this challenge by making the best of the days when she is not working. She cooks, listens to music, prays, and catches up on the lost sleep, getting herself ready for another week of fighting the pandemic.

Christian Medical College: Ida Scudder’s legacy to the Vellore community

Dr Ida Sophia Scudder – the founder of Christian Medical College (CMC), Vellore – breathed her last sixty years ago on this day. But her life and legacy continue to inspire hundreds of thousands across the world. An American by origin, Dr Ida spent her lifetime uplifting the community in Vellore through her medical practice. Her work is never more relevant than now when we are facing a pandemic. In this article, I have attempted to highlight some of the contributions of Dr Ida Scudder,  and others, which continue through CMC, Vellore. 

It would be hard to believe that the town which once greeted medical officers, who tried to vaccinate people to contain the plague, with sticks and stones would later be the first in the country to be polio-free. The person whose life and legacy was mainly influential in bringing this change was a woman physician by name, Ida S. Scudder. Dr Ida Scudder and the professionals at the medical college she founded – Christian Medical College (CMC) – transformed the community in Vellore to what it is today.

CMC, Vellore, is renowned globally for its many achievements in the field of medicine. One of the major contributions of the medical college, through which the legacy of Aunt Ida continues, is its community service. From Dr Ida Scudder’s efforts in containing the plague outbreaks to Dr Paul W Brand’s accomplishments in rehabilitating lepers and Dr T Jacob John’s leadership in eradicating polio and containing HIV/AIDS, CMC’s services to public health have not only impacted Vellore and India but has also influenced the world.

It all began one night at Tindivanam, Tamil Nadu, when 20-year-old Ida Scudder encountered a life-changing incident. Three men – a Brahmin, an upper-caste Hindu, and a Muslim – approached Ida seeking help for their wives who were in labour. Ida explained that she had no medical training, but her father who was a missionary doctor could help them. But none of them would agree. In Ida’s words, the Brahmin drew himself up and said, “Your father come into my caste home and take care of my wife! She had better die than have anything like that happen.” The Muslim also responded with similar words saying, “She had better die than have a man come into the house.” Ida could not sleep that night. She wrote about this incident later, “Within the very touch of my hand were three young girls dying because there was no woman to help them.” She spent the night in anguish, torn between a great life in America and the need to serve the people in India. Ida had come to Tindivanam only to take her ailing mother back to the USA. Until that night, she wanted to enter Wellesley College and “continue in the happy free life of a young woman in America.”

The next day, Ida sent a servant to check what had happened to the three women only to hear that all of them had died the previous night. She shut herself in the room. After much thought and prayer, Ida told her parents that she wanted to go home and study medicine to come back and help such women in India.

In 1895, Ida entered the Women’s Medical College of Philadelphia. It was a time when women were not welcome as qualified surgeons and doctors. Three years later, when Cornell opened its doors for the first time for women students of medicine, Ida transferred there for better opportunities. As Mary Pauline Jeffrey writes in her biographical account of Ida Scudder, some students at Cornell often “did things to make women feel that they were foreign bodies.” Nobody would have imagined then that about 50 years later, Ida would be admitting male students to the Women’s Medical College she founded at Vellore!

On January 1, 1900, Dr Ida Scudder landed in India. She started running a clinic in a 12*8 feet room at her house. Meanwhile, she worked toward realizing the hospital for which she had received a donation of $10,000 while in the USA. In 1902, the 40-bedded Mary Taber Schell Memorial Hospital opened. Her vision was that women should have equal access to quality healthcare as men, regardless of their religious or socio-economic status. In 1909, Dr Ida established a school of nursing and in 1918 she established a medical college for women. The medical college was called Missionary Medical College for Women. In 1945, it was renamed as Christian Medical College and in 1947 CMC opened its doors to male students.

The tiny clinic and the hospital thus grew to be the medical college that would have many firsts to its credit. Dr Ida was deeply connected with the community she lived in – a legacy that the medical college would become renowned for. This was never more relevant to us than now. In 1903, when the plague hit Vellore, as many as 17 people were dying every day. In 1904, the total number of cases in India had reached 1,100,000 before preventive measures showed any sign of success. At that time, along with the municipal commissioner, Dr Ida “sallied forth to grapple with the deadly epidemic. Into the homes of the community in Vellore these two went, enforcing sanitary measures and administering prophylactic inoculations.”

Half a century from then, Dr Paul Brand carried that torch making another mark in the community in Vellore. Realizing his life’s calling at CMC, Dr Paul established the New Life Center at Vellore to rehabilitate lepers and dispel the stigma that prevailed even among medical professionals. Dr Paul also performed the world’s first reconstructive surgery on leprosy patients at CMC, Vellore.

Paul Brand
From Left to Right: Drs Brand, Scudder, Balfour, Chandy. Picture Source: http://www.cmch-vellore.edu

A couple of decades later, Vellore became the first town to eradicate polio. An alumnus of CMC, Dr T. Jacob John led the initiative of making Vellore polio-free and later headed the national efforts in eradicating polio. In his own words in conversation with the journal Current Science, “Globally, Vellore was the centre conducting such basic and problem-solving research on polio from the mid-1960s.” Dr Jacob John headed the virology services at CMC from 1967-1995. During this time, he also played a key role in India’s efforts to contain HIV/AIDS.

Dr Ida Scudder’s legacy continues through the work of CMC. The medical college has produced some of the best doctors, surgeons and scientists in the country, who have been recognized for their work.  Of special note in the context of public health, epidemiology and community medicine are experts like Dr Gagandeep Kang, Dr T. Jacob John, Dr Jayaprakash Muliyil and others.

At this time, when the country is faced with an epidemic, Dr Ida Scudder’s legacy serves as a reminder of what empathy, compassion and boldness can help one achieve. It is her legacy that we need now – of providing quality and compassionate healthcare for all sections of society.

Sources:

*All the quotations with no explicit mention of the source are from the book: Ida S. Scudder of Vellore (2014). By Mary Pauline Jefferey.

https://www.vellorecmc.org/who-we-are/history/

https://friendsofvellore.org/about/history-of-cmc/

https://www.theguardian.com/news/2003/aug/27/guardianobituaries.health

https://leprosyhistory.org/database/person31

https://www.currentscience.ac.in/Volumes/114/03/0436.pdf

 

Bengaluru based start-up designs an anti-touch band

Grasp bionics, a Bengaluru-based start-up has devised an anti-touch band. The band stops people from accidentally touching the face.

As of today, there are 37916 active cases of COVID-19 in India and the epidemic has claimed 1886 lives. The increase in the number of cases led the government to declare a nationwide lockdown, which has now been extended for the third time. While these restrictions are in place, scientists and innovators are striving hard to fight the epidemic. With no vaccine or drug currently available, one can only take precautionary measures like physical distancing, restricted movement, hand hygiene and wearing masks.

A study shows that, on average, we touch our face about 23 times in an hour. And we know that a person can get infected with the virus if one touches the face after touching an infected surface. So, as we come out of this lockdown, touching the face can now be riskier than ever.

group photo-01
Team Grasp Bionics. L to R: Nilesh Walke, Vinay V, Arvind Sahu, Varsha, Abhijith R

Grasp Bionics, a Bengaluru based start-up, has devised an interesting solution to this problem. “We observed that however cautious we are, we tend to touch our nose and mouth. When it is intentional, we may do it after washing our hands. But most of the time it is accidental.” Vinay V, Co-founder & Director of Grasp Bionics, said. “We thought that a solution for this could be of huge benefit during the removal of lockdown. That is how we came up with this anti-touch band.”

The band restricts the movement about the elbow thereby the touch on the face. It is made of cloth and costs about 100 rupees apiece. The team is working with local tailors for mass production as it could also be a source of income for the tailors who may not have regular work during the lockdown and phased relaxation.

“We plan to make the band available for purchase in general stores & medical stores,” Vinay said. The team is looking for distributors, who can make their product available to the customers. They are also working on making the design open-source so that people can make DIY anti-touch bands.

Grasp Bionics is a MedTech company that builds bionic devices like prosthetic arms. Their flagship product PURAK is a wearable prosthetic limb that provides better control and sense for those who have lost their arms. The team was a winner of Elevate 2019, a program organized by Department of IT & BT, Government of Karnataka, to identify and fund 100 start-ups with innovative ideas.

Here is a video of how the band works. Place your order for the band here.

Staying home and staying productive

Staying productive while staying home has been a great challenge for me. Perhaps you can relate to this. In my opinion, productivity need not be measured directly in terms of the work we put into our jobs or degree curriculum. It could be anything that helps us realize our purpose and fulfil it – something that helps us develop our existing skills or build a new one, something that helps us become better human beings.

Stay productive
Staying productive. Picture Courtesy: viralsolutions.net

As we step into the last week of the national lockdown, I thought it might be useful to discuss some measures that I am trying to take help me be more productive. Since I was struggling with this myself, I looked up places to find help – spoke to a couple of friends, thought about it myself and read up. Here are some practical tips that I found and am trying to follow.

Know what you want to do

To do list
To-do lists are handy in accomplishing tasks

Like Benjamin Franklin said, “If you fail to plan, you are planning to fail.” I understood that planning my quarantine days is crucial for my productivity. I also realized that it is important to break this down to smaller tasks. To-do lists come in handy to accomplish small tasks. I have noticed that I have gotten more work done when I have listed down the things I should be doing. But it is one thing to make a to-do list and another thing to fill pages. I have noticed that it is important to have realistic, daily to-do lists. Over-ambitious to-do lists have made some of my days more unproductive than those without a to-do list at all.

Set up a workspace

Workspace
Set up a workspace

The other day I saw a meme about waking up just minutes before a zoom call. I could totally relate to it. But then I realized that it might just make my day worse. Since a couple of days now, I have tried and worked around a make-shift workspace for me. That helps me get a little serious about the things that I do, at least when I am around there.

Rethink the smartphone

smartphone
Rethink the smartphone

This is where the struggle is real for me. I am so hooked to my phone that I find myself helplessly landing in social media every few minutes or hours – WhatsApp, Facebook, Twitter, YouTube.

As I was pondering over this, I was reminded of Randy Pausch’s advice on Time Management in The Last Lecture. He said, “Time must be explicitly managed, like money. You can always change your plan, but only if you have one. Ask yourself: Are you spending your time on the right things? Develop a good filing system. Rethink the telephone. Delegate. Take time out. Time is all you have. And you may find one day that you have less than you think.” One part of this advice that has always stood out for me, yet been the most difficult to work upon, is “rethink the telephone.” Perhaps in today’s world, it would be more appropriate to say “rethink the smartphone.”

I have now started listening to songs and podcasts as playback while I work on other things. That doesn’t mean that I don’t watch movies, shows or videos. I often find myself starting with an educational video and ending up in a standup special just minutes from when I started. But I am trying to balance the two, which has been a struggle.

One thing at a time

multitasking-dont-do-it
Multi-tasking doesn’t work for me. Picture Courtesy: upsidelearning.com

I find it difficult to understand people embracing multitasking. It’s not that I haven’t tried it, but every time I  tried I either made a mess of the situation or did a half-hearted job in all the tasks. This is one reason I came to terms with the fact – multitasking is not for me. I now try to prioritize things and do one thing at a time.

Into the lockdown

FB_IMG_15871970482436805
Me during Quarantine. Picture Source: 9GAG (Facebook)

I remember the first day of this year – a year of new beginnings. I was starting as a graduate student, anxious but excited.

Days rolled on. I was attending lectures, learning from labmates and exploring the campus when news about a viral outbreak in a neighbouring country was doing the rounds. It was one province in China thousands of miles away. “That shouldn’t affect me,” I thought – but boy was I wrong!

Japan, South Korea, Iran, Italy – new COVID-19 cases emerged from more countries at an alarming rate. The epidemic was taking the shape of a pandemic. India had limited local transmission then, was a comforting thought.

Things came to a halt when I received an e-mail that directed us to evacuate the hostel in two days. The institute would be shut for two weeks. After cribbing about the overreactive measure, I came to terms with the fact that I had to pack my bags and leave.

The first week was quite productive. I kept myself busy spreading awareness about COVID-19, writing articles and blog posts. Midway through the second week, the energy dwindled.

Staying indoors was never a problem for me. I remember the time when I was at home applying for jobs after my master’s – I stayed home for 20 days straight. So when the nationwide lockdown was announced, it didn’t seem like a big deal.

With the lockdown extended, it is clear that we are in this for the long haul, but staying productive has been the greatest challenge for me. Some days are better than the rest, thanks to my advisor and labmates. The virtual lab meetings and skill development sessions are real refreshers – it’s always great to learn new things. I also have my courses online, which keep me busy for a few hours in the week. At other times, I am writing something (like this blog post), surfing the internet, reading, chatting, or binging on Netflix.

TB talk: an interview on World Tuberculosis Day

On World Tuberculosis Day (March 24, 2020), I interviewed Priyadharshini M V, project assistant in Mycobacterium Diseases in Animal Network (MyDAN) lab at Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Chennai. She holds an M.Tech in Biotechnology and worked as a medical geneticist in Centre for Medical Genetics, Chennai, prior to her work at TANUVAS. In this interview, she elaborates on TB, the challenges and mitigation strategies in India, and how the general public can contribute to the fight to eradicate TB. 

New Doc 2020-03-25 13.18.53 (1)   h5FQsSizWwiUWBXMmhYkD8-320-80

Left: Priyadharshini M V. Right: A depiction of Mycobacterium tuberculosis in a patient’s lung. Picture retrieved from livescience.com

Could you please tell a little bit about TB and how badly India is affected by TB?

TB is an airborne disease caused by the bacterium Mycobacterium tuberculosis (Mtb). It is the leading cause of death from an infectious disease worldwide and claims about 3 lives every minute. TB is curable and preventable. The bacteria usually attack the lungs (pulmonary TB) but can also attack other parts of the body like the kidney, spine, and brain.

Not everyone infected with TB bacteria becomes sick. So, there are two TB-related conditions: latent TB infection (LTBI) and TB disease (active TB). Many people who have latent TB infection never develop TB disease, but there are a few exceptions. If it is not treated properly, TB can be fatal. There are also the multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of TB that occur, but they are still rare.

India accounts for about a quarter of the global TB burden. Worldwide, India is the country with the highest burden of TB – both TB and MDR TB. There are an estimated 79,000 multi-drug resistant TB patients among the notified cases of pulmonary TB each year. India is also the country with the second-highest number (after South Africa) of estimated HIV associated TB cases.

How does a person get infected with TB? What are the symptoms of the disease?

The TB bacteria are introduced into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings. People nearby may breathe in these bacteria and become infected.

TB disease in the lungs may cause symptoms like a bad cough that lasts 3 weeks or longer, pain in the chest, coughing up blood or sputum (phlegm from deep inside the lungs). There are also other symptoms like weakness or fatigue, weight loss, loss of appetite, chills, fever, sweating at night.

Could you describe some measures taken by the government to curb this disease?

The Government of India aims to eliminate TB by 2025. This was announced by Shri J P Nadda, Union Minister of Health and Family Welfare, in March 2017. For this, a lot of things set out in the National Strategic Plan 2017 – 2025 needs to be done.

According to the World Health Organisation (WHO), the elimination of TB means that there should be less than one case of TB for a population of one million people. TB treatment and care in India is provided in the public sector by the government’s Revised National TB Control Programme (RNTCP), which is responsible for implementing the government’s five-year plans to combat TB. India’s remarkable achievements in TB control in the last ten years include testing more than 80 million people, detecting and treating 15 million TB patients, and saving millions of lives as a result of the efforts of the RNTCP.

What are some of the plans in this new strategy of the government?

The financial resources for TB control for 2017-2025 are doubled, the diagnostic tool CB-NAAT is to be rolled out across the country, and the two drugs Bedaquiline and Delamanid are also scheduled for a broader rollout. First and second-line drug susceptibility testing is in use or at least on the agenda. Also, patients with TB are tested for HIV and patients with HIV are tested for TB. Drug treatment is moving from intermittent therapy to daily fixed-dose combinations.

 

Why, in your opinion, has the battle against TB in India been difficult?

India’s progress against the disease has not been consistent. As per WHO reports, it has been a persisting problem in developed countries. People infected with HIV are 19 times more likely to develop active TB. The risk of active TB is also greater in people suffering from conditions that impair their immune system. Malnourished or undernourished people are 3 times more likely to contract TB when compared to the others. So, it’s pretty obvious that India, being a third world country with two-third of its population in poverty and having the third-largest population suffering from AIDS, has been struggling to combat and eradicate TB. Shortage of resources and research is another big limitation.

How can the general public contribute to the fight against TB?

There are two important things one can do to contribute to the fight against TB: One is to create awareness about the disease and the other is to get the people who fall in the high-risk group to test for TB. People with HIV infection, people who were infected with TB bacteria in the last 2 years, babies, young children, people who inject illegal drugs, people who are sick with other diseases that weaken the immune system, people who were not treated correctly for TB in the past, and the elderly are at high risk of developing TB disease.

People who anticipate repeated or prolonged exposure or an extended stay over a period of the year may undergo annual testing. Additional preventive measures could include using personal respiratory protective devices. Tuberculosis germs don’t thrive on surfaces. You can’t get the disease from shaking hands with someone who has it or by sharing their food or drink.

If one has latent TB, he/she must take all of his/her medication, so he/she doesn’t develop active TB, which is contagious. People with active TB must limit their contact with other people at work, school, or home. They must cover their mouth when they laugh, sneeze, or cough and wear a surgical mask when they’re around other people during the first weeks of treatment.

People travelling to a place where TB is common must avoid getting close to or spending a lot of time in crowded places with people who have TB. Children in countries where TB is common should get the BCG vaccine.

Be empathetic: A message on World Down Syndrome Day

March 21, 2020: On World Down Syndrome Day, I interviewed Suruthi Abirami, a genetic counsellor, about her personal experience in helping people who are fighting this disorder. Suruthi Abirami currently works as a genetic counsellor and geneticist at Anderson Diagnostics and Labs, Chennai. She completed her postgraduate diploma in medical and genetic counselling from Kamineni Hospitals Pvt. Ltd. and her M.Tech in Genetic Engineering from SRM Institute of Science & Technology. She is a Level 1 Genetic Counsellor certified by the Board of Genetic Counselling, India.

Suruthi

Suruthi Abirami at Kamineni Hospitals Pvt. Ltd., Hyderabad

Could you please briefly share your journey as a genetic counsellor so far?

My journey of helping families with genetic disorders make informed decisions has been incredible. In a country like India, the challenging part for me is to consider the psycho-social and religious aspects of the families while making decisions. I counsel roughly about 20 patients in a week. I also provide scientific support for clinicians around the country. I help them understand the situation and offer the best genetic testing for the patient.

How has your experience with Down syndrome patients been?

With many new technologies that are available these days, most of the pregnant women around the country are offered prenatal screening for Down Syndrome and other genetic conditions. That means pregnant women are screened to see if the baby they are expecting has a risk of having Down syndrome. If the screening shows a high risk, a confirmatory test is done, and the couple is counselled to make informed decisions. So, most of my counselling in case of Down syndrome is for couples with a high risk of having a child with Down syndrome. I mostly counsel them before the child is born. When the confirmatory test is positive, I counsel them about the condition, prognosis and management.

From your experience, how prevalent is this rare disease in India?

Down syndrome is no longer a rare disease in India. India lacks statistical data, but I think about 1 in 750 to 1000 births in India may have Down syndrome. By educating the public about the prenatal screening for Down syndrome, the situation can be improved.

What kind of problems do these Down syndrome patients deal with?

The main problem is social stigma and acceptance. The average life expectancy of individuals with Down syndrome is 60 years. But they need constant medical care because they suffer from different levels of intellectual disability, cardiac issues, thyroid dysfunction, poor muscle tone and low immune system.

What message would you like to share with the community on World Down Syndrome Day?

As we celebrate people with Down Syndrome today, I urge everyone to be empathetic. Show love and acceptance for people with Down syndrome and other genetic disorders. They deserve a life just like all of us and recognizing them as one among us means a lot to this community. At the end of the day, that is what every single person in this world with a rare disease or genetic disorder wants.

COVID-19: key terms you should know

2019 nCOV cryoEM structure

Side and top views of the structure of a protein – S protein – of 2019-nCoV.          Retrieved from the paper by Wrapp and others published in the journal Science.

With new COVID-19 cases being reported in India, there has been a deluge of information – news stories, articles and awareness campaigns – around it. Containment, social distancing, transmission, flattening the curve, epidemic, and pandemic are some terms that you will now find in most articles. In this short post, I try to explain some of these terms.

COVID-19, SARS-CoV-2, 2019-nCOV: COVID-19 (Coronavirus Disease) is an infectious disease caused by the most recently discovered coronavirus. Coronaviruses are a family of viruses that have RNA as their genetic material. Other viruses of this family include MERS (Middle East Respiratory Syndrome coronavirus), SARS (Severe Acute Respiratory Syndrome coronavirus) and viruses that cause common cold (E.g. Rhinoviruses). The new coronavirus was initially called 2019-nCOV (2019 novel coronavirus) when it was first identified in China. The virus is now named SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2). WHO announced the name of the new coronavirus disease as COVID-19 on February 11, 2020.

Endemic: A disease, or an infectious agent that causes it, is called an endemic when it is usually present in or is restricted to a community in a certain geographical area. For example, Kyasanur Forest Disease (KFD), commonly known as monkey fever is a viral disease endemic to South India. This is a disease seen in specific areas in South India. KFD is an endemic prevalent in Shimoga district of Karnataka.

Epidemic: When the number of disease cases is in excess than the normally expected numbers, then the disease is called an epidemic. The numbers of normally expected cases are defined specifically for each case. When the number or density of susceptible cases exceed a threshold (called an epidemic threshold), the event is defined as an epidemic.

Outbreak: When the disease cases that occur are more than what is normally expected, it is called an outbreak. For example, there were two outbreaks of Nipah in Kerala (2018 and 2019). Although epidemic and outbreak have overlapping definitions, an outbreak can be seen as the process of occurrence of an epidemic.

Pandemic: When a disease epidemic spreads across a continent or worldwide, it is called a pandemic. WHO characterized COVID-19 as a pandemic on March 11, 2020.

Infected person: A person who has the infectious agent, which causes the disease, in his body.

Incubation period: This is the time in which the infectious agent (say, a virus) is present in the host (an infected person), but the person has no symptoms. The incubation period for COVID-19 is 14 days or less. According to a study, the average incubation time for COVID-19 is 5.5 days. Less than 2.5% of the cases develop symptoms in 2.2 days and 97.5% of the cases develop symptoms in 11.5 days. Only 1 in 10,000 cases developed symptoms after 14 days.

Convalescent period: This is the time when an infected person recovers from the illness.

Transmission: The way in which a disease spreads from one person to another is called transmission. If the disease is transmitted from an infected person to a healthy person, it is called contact transmission. Contact transmission can be direct – when there is physical contact between the infected person and the healthy person, or indirect – where the infectious agent spreads by indirect means without direct physical contact. Indirect transmission can include droplet transmission or transmission by fomites.

Droplet Transmission: When an infectious agent (say, a virus) is transmitted through respiratory droplets that are propelled into the air by sneezing or coughing, it is called droplet transmission. When an infected person coughs or sneezes, droplets of moisture of different sizes contaminated with infectious agents are propelled out in the air. When these droplets contact the eyes, nose or mouth of a healthy person, he/she can get infected. Droplets are usually heavier and settle down to the ground quickly because of gravity. These droplets can be propelled to about 1 metre depending on the size of the particle and the force with which it is expelled.

Aerosol Transmission: When an infectious agent (say, a virus) is transmitted through aerosols (suspension of fine particles in the air) propelled into the air by sneezing or coughing, it is called aerosol transmission. When an infected person coughs or sneezes, aerosols of moisture of different sizes contaminated with infectious agents are propelled out in the air. Aerosols are lighter and can remain in the air for sometime before it falls. They can be propelled up to 3 metres depending on the size of the particle and the force with which it is expelled. SARS-CoV-2 is reported to be stable in aerosols for 3 hours.

Transmission by Fomites: Fomites are non-living objects that can be contaminated with infectious agents and can transmit the disease. These include water, plastics, metals – doorknobs, keyboards, phones, handrails etc. If an infected person sneezes or coughs and the droplets fall on fomites, the infectious agents can remain active on fomites for hours or days. When a healthy person touches an infected surface and then touches his/her nose, eyes or mouth, the infectious agent can get inside the body. A recent study has shown that SARS-CoV-2 can be viable for 3 hours in aerosols, and up to 3 days on stainless steel, copper and cardboard surfaces.

Local Transmission: When the source of infection is present with a locality, there is local transmission of the disease. That means if a person in Bangalore gets infected by someone who is in Bangalore, then there is a local transmission. This is referred to as stage II of the epidemic.

Community Transmission: When one cannot relate confirmed cases by chains of transmission (i.e., when one cannot trace the source of infection of all the different people in the chain) for a large number of cases, then it is called community transmission. In other words, if a person who has not come in contact with anyone known to be infected and has not travelled to any country when the virus is spreading tests positive, then there is community transmission. This is referred to as stage III of the epidemic.

Social distancing: It is the practice of maintaining more than the usual physical distance from other people. The purpose is to stop or slow down the spread of a disease that can be transmitted by physical contact, droplets, or fomites. The more distance you maintain from people, the lesser the risk of getting the disease.  

Flattening the curve:  This is a term used to indicate preventing a sharp peak of infections. During an epidemic, the disease spreads quickly as infected people come in contact with healthy people, who in turn come in contact with more people. Let us say there is one infected person (the person may or may not have developed symptoms). He/She hangs out with 3-4 friends. There is a possibility that these 3-4 people are now infected. These people now meet with more people, who in turn meet other people. Suddenly there is a sharp increase in the number of cases when all of these people develop symptoms within a few days. This overwhelms the healthcare system. If people practise social distancing, the chances of infection are lesser and, therefore, the sharp peak can be flattened as lesser cases are present in a given time. This can reduce the burden on the healthcare system.

Quarantine: The process of isolating people who have been exposed to an infection that can spread. The aim of quarantining is to contain – prevent the further spread of – the disease. Quarantine for 14 days is recommended for suspected COVID-19 cases.

Herd immunity: This is indirect protection for susceptible people in a community. In an outbreak, if a large proportion has become immune to the infection, they indirectly protect people who are not immune to the infection by disrupting the spread. Consider the situation with COVID-19. Let us say healthy people get infected. They become sick, isolate themselves (especially from people who are at higher risk of death by infection because of other health conditions) and eventually recover. When the number of recovered people increases in a population, they indirectly protect those who have not been infected as the chain can now be broken quickly.

Covidiot (informal use): This term is used to refer to a person who ignores the warnings regarding public health or safety and hoards goods denying them from their neighbours during the COVID-19 pandemic.

Sources:

https://www.cdc.gov/csels/dsepd/ss1978/glossary.html

https://www.who.int/emergencies/diseases/novel-coronavirus-2019

 

Scientists discover that structures inside mitochondria reshape continuously in living cells

Scientists from Heinrich Heine University Düsseldorf and University of California Los Angeles recently discovered that cristae – structures formed by the inner covering of mitochondria – keep remodelling continuously. The team led by Prof. Andreas S. Reichert made this discovery by seeing live cells using a high-end technique in microscopy. This technique, called stimulated emission depletion (STED) super-resolution nanoscopy, enables one to see details of an organelle in the cell – of the size of 50 nm (about 1000 times smaller than a speck of dust). The study was published in the journal EMBO Reports.     

CJ dyna,ics

STED nanoscopy images showing cristae remodelling 

Mitochondria are organelles in the cell popularly known as the powerhouse of the cell. They form a dynamic network, change their shape, fuse or split. As for their structure, mitochondria have two membranes covering them – the outer membrane and the inner membrane. The inner membrane folds inward to form structures called cristae (sing. crista), on which many important proteins reside. These proteins include ATP synthase – the machine that makes ATP, the energy currency of the cell. Curved, circular or pore-like structures called crista junctions separate the cristae and the rest of the inner membrane.

Other scientists have shown that abnormal or altered cristae in diseases like cancer, diabetes and neurodegeneration. In normal conditions, however, cristae are thought to be static. Scientists from Heinrich Heine University Düsseldorf and University of California Los Angeles led by Prof. Reichert have now found that the cristae membrane and crista junctions reshape continuously. They also found that a protein complex called the mitochondrial contact site and cristae organizing system (MICOS) orchestrate these remodelling events.

 “Prof. Reichert’s lab has been working on the mechanisms of cristae remodelling. We were working on the function of MICOS complex located at the crista junctions,” Dr Arun Kumar Kondadi, one of the first authors of the paper, said. But one could never investigate if the cristae were dynamic or not as there was no technique that enabled researchers to see the details inside an organelle. “For more than half a century, it was rather assumed that cristae are static,” Dr Kondadi said. “Super-resolution microscopy techniques paved us the way to discover something really fascinating.”

In this study, using STED super-resolution nanoscopy, researchers have shown that adjacent crista junctions come together and separate from each other reversibly in human cells. For this, the researchers stained cristae membranes using dyes (or marked proteins present on the inner membrane of mitochondria) and observed how the cristae remodel using STED super-resolution nanoscopy. These experiments showed that cristae undergo membrane remodelling continuously.

According to Prof. Reichert, as quoted in the Press Release from Heinrich Heine University, the observations of this study lead us to a new model – Cristae Fission–Fusion (CriFF) model – that cristae can stay as isolated vesicles within mitochondria and then re-fuse with the inner membrane after fission. The study shows that this fusion is carried out by the MICOS complex. MIC60 – one of the proteins of the complex – initiates the process and marks the crista junction. It then recruits other proteins of the MICOS complex (MIC10, MIC13, MIC19, MIC25, MIC26 and MIC27) and completes the assembly. These crista junctions now become the sites from where cristae form. These junctions keep merging and splitting. The cristae could, therefore, pinch off from these junctions and come back to the same junction or another.

This study has opened a new field in research where one could investigate how a mitochondrion ensures quality control within itself. For all we know now, remodelling and reshaping of mitochondria in a cell can control the fate of the cell. This study has gone one step ahead to show how structures within the mitochondrial remodel continuously. How these events inside mitochondria can affect the mitochondria, and how this impact on mitochondria can influence the cell will be interesting to study.

Read the full paper here

Image Courtesy & Article Source: EMBO Reports