27 July 2020 | Vol.3 |#30

NEWS BULLETIN A WEEKLY PUBLICATION FROM NIRT LIBRARY

PM to launch COVID-19 testing facilities in Kolkata, Noida and Mumbai Monday COVID-19 affects HIV Jul 26, 2020 and tuberculosis care

These labs will also reduce turnaround time and exposure of lab Quarraisha Abdool Karim et.al. personnel to infectious clinical materials. Science 24 Jul 2020: Vol. 369, Issue 6502, pp. 366-368 DOI: 10.1126/science.abd1072

New Delhi, Prime Minister Narendra Modi will launch on Monday "high throughput" COVID-19 testing facilities in Noida, Mumbai, and Kolkata, which will ramp up testing capacity and help strengthen early detection and treatment in the country, the Prime Minister's Office said.

The virtual launch event will be attended by Union Health Minister Harsh Vardhan and the chief ministers of Maharashtra, The GeneXpert cartridge-based platform is used West Bengal and Uttar Pradesh -- Uddhav Thackeray, Mamata routinely at the CAPRISA clinic in Durban, South Banerjee, and Yogi Adityanath respectively. Africa, to rapidly test for tuberculosis and HIV viral load, but it is now also being used to test for COVID-19. The three high throughput testing facilities have been set up strategically at ICMR institutions -- National Institute of Cancer Continued in page no.19 evention and Research in Noida, National Institute In a social media live event organised by the for Research in Reproductive Health in Mumbai World Health Organisation from Geneva on Friday, and National Institute of Cholera and Enteric the scientist said that more waves of the infection Diseases in Kolkata. These will be able to test over would be required to get to a stage of natural 10,000 samples in a day, a statement from the immunity. Therefore, she warned, that at least for Prime Minister's Office said. the next year or so, the world needs to be geared up to do everything possible to keep the novel These labs will also reduce turnaround time and coronavirus at bay while scientists work on exposure of lab personnel to infectious clinical vaccines. Meanwhile, therapeutics will help keep materials. The labs are enabled to test diseases death rates low and allow people to get on with other than COVID-19 as well, and post the their lives. pandemic, will be able to test for Hepatitis B and C, HIV, Mycobacterium tuberculosis, For this concept of herd immunity, you need 50 to cytomegalovirus, chlamydia, Neisseria and 60 per cent of the population to have this dengue, the statement said immunity to be actually able to break those chains of transmission, explained Swaminathan. That's much easier to do with a vaccine; we can achieve it faster and without people getting sick

and dying. So, it is much better to do it that way, No COVID-19 herd immunity yet, will to achieve herd immunity through natural infection. We would have several waves [of take time - WHO Chief Scientist infection] and unfortunately also the mortality that Most people who recover from COVID-19 develop we see, she said. neutralising antibodies, which means a vaccine has a good chance of offering protective immunity, she She added: Over a period of time, people will start said. developing natural immunity. We know now from Jul 25, 2020 the studies that have been done in many of the affected countries that usually between 5 to 10 per cent of the population has developed antibodies. In some places it's been higher than

that, up to 20 per cent.

As there are waves of this infection going through

countries, people are going to develop antibodies and those people will be hopefully immune for some time and so they will also act as

barriers and brakes to the spread of this infection, Swaminathan, a paediatrician from India and a globally recognised researcher on tuberculosis

and HIV, said. London, Jul 24 (PTI) The chief scientist of the WHO, Dr Soumya Swaminathan, on Friday warned that The scientist, who was addressing a range of the concept of herd immunity, or a large section questions on coronavirus vaccines and of the population developing antibodies against therapeutics, said that for the foreseeable future it COVID-19, is still a long way off and can be sped is important to be focussed on doing the "right up by a vaccine. thing" such as public health measures that are known to work while the world waits for a vaccine. Even if the clinical trials are successful and we The medical assistance is under the aegis of an have a couple of vaccines by the end of this year, ongoing WHO anti-tuberculosis programme in DPRK, we still need the hundreds of billions of doses, it said. which will take time, she said. Jul 25, 2020 Elaborating on vaccine development, the chief New Delhi: India has extended medical assistance scientist said there are over 200 candidates in worth about USD 1 million to North Korea in some stage of development as she highlighted response to a request received from the World the extraordinary speed at which the science has Health Organisation (WHO), the Ministry of External been moving around the understanding of the Affairs said on Friday. novel coronavirus.

India is sensitive to the shortage of medical supply Vaccine development is normally quite a lengthy situation in the Democratic People's Republic of and laborious process the more candidates we Korea (DPRK) and decided to grant humanitarian have, the more opportunities we have for success, assistance of USD 1 million in the form of anti- she said. tuberculosis medicines, the MEA said.

Most people who recover from COVID-19 develop The medical assistance is under the aegis of an neutralising antibodies, which means a vaccine ongoing WHO anti-tuberculosis programme in has a good chance of offering protective DPRK, it said. immunity, she said. The consignment of medicines was handed over

to DPRK authorities by Indian Ambassador to DPRK Asked about the fearful prospect of never getting Atul Malhari Gotsurve in the presence of a WHO a vaccine for COVID-19, Dr Swaminathan representative. admitted that we have to entertain the possibility that we may have to learn to live with this virus .

Right now it seems frightening; what will we do if we don't have a vaccine? But it is a possibility, there is no 100 per cent guarantee that we will have one. Let's hope we do. But we know, now, Mumbai: BMC to set up dedicated RT- what are the measures that we can take to PCR labs to enhance COVID-19 minimise the spread of this infection, such as testing capacity by 1200 a day maintaining distance, hand washing, respiratory The RT-PCR labs will be set up at BMC run Sion, hygiene and wearing of masks, she said. Cooper and Nair hospitals. The officials have said The coronavirus has so far claimed over 6.3 lakh they have submitted work orders for new machines. lives with more than 15.5 million confirmed cases Jul 22, 2020 across the world, according to Johns Hopkins Mumbai: The Brihanmumbai Municipal University COVID-19 tracker. Corporation (BMC) has started work on setting up

dedicated Reverse Transcription Polymerase

Chain Reaction (RT-PCR) testing labs in the city to increase COVID-19 testing capacity by 1200 a day. India extends medical assistance worth about USD 1 million to North These RT-PCR labs will be set up at BMC run Sion, Cooper and Nair hospitals. Korea: MEA

NIRT Library News Bulletin 3 According to a report in Mumbai Mirror, officials Dr Gilbert is one of the leading vaccinologists in the said they have submitted work orders for new world. She is professor of vaccinology at Oxford machines. University’s Jenner Institute and one of the two founders of its spin-out company, Vaccitech. Six RT-PCR labs are already functioning at the Written by Dipanita Nath , Edited by Explained Desk government-run KEM and Kasturba, JJ Hospital, July 26, 2020 Haffkine Institute and National Institute for Research in Reproductive Health and National Institue for Virology in Mumbai.

The need for more testing came after the Indian Council of Medical Research (ICMR) and Union health ministry demanded to enhance testing capabilities in view of the 'evolving scenario'. "The work on setting up RT-PCR labs has already started. Currently, we are using a cartridge-based nucleic acid amplification test (CBNAAT) to check for COVID-19. CBNAAT is basically used for Professor Sarah Gilbert, who is leading development of a coronavirus vaccine at Oxford University, in Oxford, April 24, 2020. diagnosing drug-resistant tuberculosis," the report (Mary Turner/The New York Times) quoted Dr Sujata Bavje, head of microbiology department at Sion Hospital. Earlier this week, there was positive news on the "With the help of new RT-PCR machines, we would Oxford vaccine candidate, one of a clutch of be able to conduct at least 400 tests a day. frontrunner candidates to protect the world from Cooper Hospital was also setting up a similar the SARS-CoV-2 virus that had, until Friday (July 24) facility," Dr Bavje added. morning, infected nearly 15.5 million people and killed over 630,000 worldwide. Dean of Nair Hospital said his team is already running RT-PCR labs at Kasturba Hospital. Leading its development is a British scientist who "The union health ministry and Indian Council of plays the oboe, cycles to work, and is the mother Medical Research (ICMR) have asked state of triplets. Dr Sarah Gilbert was famous in the governments to enhance COVID-19 testing scientific community as a brilliant vaccinologist; facilities by adding RT-PCR labs," said Dr Mohan with the success in early trials, she — and Joshi, Dean of Nair Hospital. ChAdOx1 nCoV-19, the vaccine candidate her team is working on — has been spotlighted as Meanwhile, the Medical Council of India (MCI) never before. has made it compulsory for all medical colleges in the country to set up RT-PCR labs. Gilbert and co-authors published the results of the early trials in the medical journal, The Lancet, on

July 20, titled “Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial”. They wrote: Meet Dr Sarah Gilbert, one of the “ChAdOx1 nCoV-19 showed an acceptable scientists leading the race to find a safety profile, and homologous boosting coronavirus vaccine increased antibody responses.” Which means that the vaccine candidate had induced an immune

NIRT Library News Bulletin 4 response (which is what vaccines are supposed to Kettering High School for Girls, she was quiet, do), and was safe for people. polite, and studious, getting a lot of ‘A’s in studies. Gilbert belongs to a family of musicians, and her mother, Hazel, was part of the town’s operatic What is Dr Gilbert’s work in the field of vaccine society. By the age of 17, however, Gilbert was development? sure that she wanted to be a medical researcher.

After obtaining a degree in biology at the Dr Gilbert is one of the leading vaccinologists in University of East Anglia and a PhD in biochemistry the world. She is professor of vaccinology at from the University of Hull, Dr Gilbert worked at a Oxford University’s Jenner Institute, a prestigious number of biotechnology companies, among vaccine research centre, and one of the two them Delta, where she learnt about making founders of its spin-out company, Vaccitech, medicines. which develops immunotherapy products to treat and prevent infectious disease and cancer. Profiles on Prof Gilbert have noted that she

became a vaccine specialist rather by accident. For more than 15 years, Dr Gilbert has been In 1994, when she entered Oxford University to join making and testing vaccines that trigger T cells — Professor Adrian Hill’s lab in a senior postdoc a type of white blood cells — to respond to position, it was to work on human genetics. “That antigens from malaria, influenza, and tuberculosis, highlighted the role of a particular type of immune among others. response in protection against malaria, and so the

Her work also includes developing vaccines for next thing to move on to was to make a vaccine influenza and emerging diseases such as Lassa, that would work through that type of immune Nipah, CCHF, and Middle East Respiratory response — and that’s how I got into vaccines,” Syndrome (MERS). MERS, which appeared in 2014, she told UK’s The Telegraph newspaper in an too, is caused by a coronavirus. “A vaccine interview. against MERS has been tested in clinical trials in the UK, and is now in trials in Saudi Arabia, where By 2007, Dr Gilbert, who had become a reader at the virus is endemic,” says Gilbert’s page on the Oxford University three years previously, had won Jenner Institute website. a project grant from the Wellcome Trust, and had begun work on an influenza vaccine. She has The vaccine for MERS involved using the developed two vaccines for the disease so far, adenovirus (which causes common colds) from a and has said that her ultimate aim is to be able to chimpanzee embedded with the genetic develop her team of scientists to be the leaders in material of the MERS virus. For the Covid- vaccine research in the world. 19 vaccine, the Oxford scientists used the adenovirus of a chimpanzee embedded with the genetic material from the spike protein, which the coronavirus uses to pierce the cell. In tests till now, bodies of participants have responded as if they were infected with the coronavirus.

What is known about the acclaimed scientist’s life away from her work? Dr Gilbert has not given many interviews since the publication of the results of the early phase trials. A doctor takes blood samples for use in a coronavirus vaccine trial Earlier profiles of the scientist in the UK media have in Oxford, England, Thursday June 25, 2020. (John Cairns, University said that as a child in Northamptonshire’s of Oxford via AP)

NIRT Library News Bulletin 5 Many people are fascinated with Dr Gilbert’s The big question: Will there be a coronavirus success in balancing the extra demands that vaccine this year? women with a career in science face. According to UNESCO, women make up less than 30 per cent of the world’s researchers. In science, Dr Gilbert is cautiously hopeful. In an interview to technology, engineering and mathematics, the BBC, she said, “Nobody can be absolutely sure women also “publish less, are paid less for their that it is possible. That’s why we have to do trials. I research and do not progress as far as men in their think the prospects are very good but it is not careers”. completely certain.”

On the website of the Nuffeld Department of Medicine (of which Jenner Institute, where she works, is a part), Dr Gilbert has been quoted as saying: “Work life balance is very difficult, and impossible to manage unless you have good Key affected AIDS populations protest support. Because I had triplets in 1998, nursery fees apathy from govt, multilateral would have cost more than my entire income as a post-doctoral scientist, so my partner has had to agencies in providing emergency sacrifice his own career in order to look after our Covid care children.” A total of 10,483 people from 236 Indian and international organisations have publicly petitioned She described how 18 weeks of paid maternity The Global Fund to Fight AIDS, Tuberculosis and leave with three premature babies to care for and Malaria (GFATM), demanding allocation to meet work to be completed, was tough: “If there is a their basic survival needs of food, shelter, and three-year grant and a woman wants a year-long emergency medical care. maternity leave, it can disrupt the progress of the July 21, 2020 project. The situation becomes worse if more than one person is away simultaneously.”

Dr Gilbert’s advice to women: “One of the good things about being a scientist is that the hours are not fixed, so there is a fair amount of flexibility for working mothers. Having said that, there are also times when things (such as overseas conferences and important meetings) are fixed and you have to make sacrifices. It is exceptionally hard work. It’s important to plan ahead, and make sure you A statement issueed by Kiran Deshmukh, president, National Network of Sex Workers; Ashok Row Kavi, Convener, India Network have people who are willing to cover for you at for Sexual Minorities, and others have raised concerns over key home while you work. That might be your partner populations affected by HIV losing jobs and not receiving or relatives, or you may be able to buy in help.” government welfare measures. (Representational/File)

As the 23rd International AIDS Conference drew to Her own children “seem to have survived a close, key populations affected by HIV/AIDS — unscathed, but none of them wants to be sex workers, transpeople, gay and bisexual men, scientists”, she said. drug users, and people living with HIV/AIDS —

have protested being ignored by governments and multilateral agencies in Covid-related emergency relief efforts. NIRT Library News Bulletin 6 A total of 10,483 people from 236 Indian and international organisations have publicly petitioned The Global Fund to Fight AIDS,

Tuberculosis and Malaria (GFATM), demanding allocation to meet their basic survival needs of food, shelter, and emergency medical care.

A statement issueed by Kiran Deshmukh, president, National Network of Sex Workers; Ashok Row Kavi, Convener, India Network for Sexual Structure of SARS-CoV-2, including the spike protein. (Source: Minorities, and others have raised concerns over Wikipedia) key populations affected by HIV losing jobs and not receiving government welfare measures. This The spike protein of SARS-CoV-2 — the ‘corona’ in section of the community continued to be the coronavirus that causes Covid-19 disease — discriminated against and even had difficulty in has just revealed new secrets. Researchers have obtaining ration cards, said Meena Seshu from found that the spike protein changes its form after Sangram NGO. it attaches itself to a human cell, folding in on itself and assuming a rigid hairpin shape. The In the petition, GFATM is being asked to issue researchers have published their findings in the notification to governments to repurpose funds to journal Science, and believe the knowledge can ensure direct support for food, shelter, and help in vaccine development. emergency medical care for populations affected by HIV/AIDS, Seshu said. What is the spike protein? It is a protein that protrudes from the surface of a As many as 236 organisations are signatories to the coronavirus, like the spikes of a crown or corona petition, which has strongly protested the apathy — hence the name ‘coronavirus’. In the SARS- of multilateral agencies and even United Nations CoV-2 coronavirus, it is the spike protein that organisations, stating: “In fact not one of those initiates the process of infection in a human cell. It who signed on to that promise has allocated any attaches itself to a human enzyme, called the resource to ensure access to emergency ration, ACE2 receptor, before going on to enter the cell shelter, and medical care, which are critical to and make multiple copies of itself. help us survive through this period.” What has the new research found? Using the technique of cryogenic electron microscopy (cryo-EM), Dr Bing Chen and colleagues at Boston Children’s Hospital have

freeze-framed the spike protein in both its shapes Explained: How ‘corona’ of the virus — before and after fusion with the cell. changes into a hairpin shape — and The images show a dramatic change to the why hairpin shape after the spike protein binds with the Freeze frames of SARS-CoV-2 spike protein show ACE2 receptor. In fact, the researchers found that dramatic change of shape after it fuses with a human the “after” shape can also show itself before fusion cell. Scientists suggest it may help distract our — without the virus binding to a cell at all. The immune system; findings may matter in vaccine spike can go into its alternative form prematurely. development July 25, 2020 | Kabir Firaque

NIRT Library News Bulletin 7 Do the two forms share any similarities? Yes, both the “before” and “after” forms have sugar molecules, called glycans, at evenly spaced locations on their surface. Glycans are another feature that helps the virus avoid immune detection.

How is the knowledge about the alternative shape Cryo-EM images of SARS-CoV-2 before and after fusion with the useful? human cell. Postfusion shape is like a rigid hairpin. (Source: Provided by Dr Bing, Chen, Boston Children’s Hospital) The researchers believe the findings have implications for vaccine development. Many What does that signify? vaccines that are currently in development use Dr Chen suggests that assuming the alternative the spike protein to stimulate the immune system. shape may help keep SARS-CoV-2 from breaking But these may have varying mixes of the prefusion down. Studies have shown that the virus remains and postfusion forms, Chen said. And that may viable on various surfaces for various periods of limit their protective efficacy. time. Chen suggests that the rigid shape may explain this. Chen stressed the need for stabilising the spike protein in its prefusion structure in order to block More significantly, the researchers speculate that the conformational changes that lead to the the postfusion form may also protect SARS-CoV-2 postfusion state. If the protein is not stable, from our immune system. antibodies may be induced but they will be less effective in terms of blocking the virus, he said. In what way can it protect the virus from the immune system? “Using our prefusion structure as a guide, we The postfusion shape could induce antibodies should be able to do better (introducing stabilizing that do not neutralise the virus. In effect, the spikes mutations) to mimic the prefusion state, which in this form may act as decoys that distract the could be more effective in eliciting neutralizing immune system. antibody responses,” Chen told The Indian Express. “We are in the process of doing this in case the first “Antibodies specifically targeting the postfusion round of vaccines are not as effective as we all state would not be able to block membrane hope.” fusion (viral entry) since it would be too late in the process. This is well established in the field of other viruses, such as HIV,” Chen told The Indian Express, by email.

In principle, if both conformations shared Covid antibodies fade rapidly, raising neutralising epitopes (the part of the virus targeted by antibodies), then the postfusion form risk of lost immunity too could induce neutralising antibodies, Chen The researchers found that antibody levels fell said. “But because the two structures are often quickly, with a half-life of about 73 days between the very different, in particular, in case of SARS-CoV-2 two time frames. The loss of antibodies occurred and HIV, I think it is not very likely that the more quickly than with SARS, an earlier type of postfusion form would be useful as an coronavirus infection. immunogen,” he explained. July 22, 2020 | Bloomberg

NIRT Library News Bulletin 8 Further studies will be needed “to define a quantitative protection threshold and rate of decline of antiviral antibodies beyond 90 days,” according to the researchers led by F. Javier

Ibarrondo, from the David Geffen School of

Medicine at the University of California Los Angeles.

While the protective role of antibodies against infection isn’t fully understood, they are generally The antibody response is being closely studied by scientists worldwide for indications of how long-lasting immunity may be. considered a good representation of some (Bloomberg) protection against infection in general, according to the report. Recovering from Covid-19 may not offer much lasting protection from future infections for those A recent study from King’s College London with only mild cases, according to a report that showed that the level of antibodies may drop to a suggests caution regarding so-called herd degree that makes them undetectable as soon as immunity as well as the durability of vaccines. three months after infection. However, the body also mounts other forms of immunity responses, The correspondence in the New England Journal including from so-called T-cells, which appear to of Medicine outlined research on antibodies play a role in protecting against reinfection with taken from the blood of 34 patients who had Covid-19. recovered after suffering mainly mild symptoms that didn’t require intensive care. Just two needed In Sweden, the nation’s top health authority said supplemental oxygen and received an HIV on Tuesday that people who have had the virus medication, and none were on a ventilator or are likely to be immune for at least six months after getting Gilead Sciences Inc.’s remdesivir. being infected, whether they’ve developed antibodies or not. In new guidance, the Swedish The first analysis was done on antibodies taken an Public Health Agency said it’s now considered average of 37 days after symptoms began, with a safe for individuals who’ve been infected to come second after about 86 days, or less than three into contact with people in high-risk groups. months. The researchers found that antibody levels fell quickly, with a half-life of about 73 days between the two time frames. The loss of antibodies occurred more quickly than with SARS, an earlier type of coronavirus infection. Pandemic hits TB screening, testing The antibody response is being closely studied by across Meghalaya scientists worldwide for indications of how long- Jul 23, 2020 lasting immunity may be. While there’s little evidence to suggest reinfections are broadly SHILLONG: Screening and testing for tuberculosis occurring, health experts have yet to pin down (TB) in Meghalaya has dropped drastically, specifics. The latest findings raise concern that courtesy the coronavirus pandemic. People are protection from reinfection may not last long in afraid to get tested for TB in such times, even those with mild symptoms, which accounts for the though the disease has killed many more than majority of cases. Covid-19.

NIRT Library News Bulletin 9 “In response to the Covid pandemic, patient attendance in general OPD has reduced almost to less than half of regular days due to different Brazil set to test Chinese coronavirus government advisories, protocols, lockdown and fear of contracting the virus. These factors have, vaccine despite laboratories remaining fully operational, Jul 21, 2020 reduced sputum examination and TB case SAO PAULO: Brazil will begin advanced clinical notification,” commissioner and secretary of the testing of a Chinese-made vaccine against the health and family welfare department Sampath new coronavirus Tuesday, issuing the first doses to Kumar said, urging health authorities to augment around 900 volunteers, officials said. the process of screening for TB.

The coronavirus vaccine, developed by private The health commissioner added, “Field activities Chinese pharmaceutical firm Sinovac, is the third of health workers have also significantly gone in the world to enter Phase 3 trials, or large-scale down or completely halted leading to reduction testing on humans -- the last step before in referral of presumptive TB cases from field staff.” regulatory approval.

“The matter should be considered on priority basis It will be administered to doctors and other health and effective measures to be taken by the workers who volunteer for the program across six Medical Officers of PHC, CHC and District Hospital states in Brazil, one of the countries hit hardest by to take the opportunity of the influenza like illness the pandemic. (ILI) and severe acute respiratory infections (SARI)

Clinics for screening of tuberculosis as well, "Trials of CoronaVac, one of the vaccines that has because the clients of these clinics have similar advanced furthest in testing in the world, will begin respiratory symptoms like that of pulmonary TB. at the Clinical Hospital of Sao Paulo," the state's Screening for TB patients should be also done governor, Joao Doria, told a news conference. during house hold visits. Emphasize on contact tracing of TB patients,” the order read. He said initial results were expected within 90 days.

It added, “LabTech will use simple hand gloves, Sinovac is partnering with a Brazilian public health N95 mask, face shield and plastic apron for research center, the Butantan Institute, on the examination of samples from non-Covid patients. trials. Due to safety reasons, sputum sample will not be collected from Covid-positive patients and If the vaccine proves safe and effective, the people with history of high risk exposure till institute will have the right to produce 120 million molecular test result is negative for the novel doses under the deal, according to officials. coronavirus.”

"In Brazil, we could have the first vaccine to be put The health commissioner urged all deputy to widespread use, which is very, very promising," commissioners and district medical officers to said the head of the Butantan Institute, Dimas supervise the activities mentioned in the official Covas. order.

Brazil is the second-hardest-hit country in the

coronavirus pandemic, after the United States.

Its death toll surpassed 80,000 on Monday, and it

has registered 2.1 million infections. NIRT Library News Bulletin 10 Those grim figures make it an ideal testing ground persons suffering from tuberculosis has fallen to for potential vaccines, since the virus is still half during the latest survey to 38 per 1,00,000 spreading quickly. persons from the earlier level of 76 per 1,00,000.

Brazil is also helping carry out Phase 3 testing of The Intensified Mission Indradhanush, launched by another experimental vaccine, developed by PM Modi in 2017, aims to reach each and every Oxford University in Britain and pharmaceutical child under two years of age and all pregnant firm AstraZeneca. women who have been left uncovered under the routine immunisation programme. Another vaccine, developed by state-owned Chinese company Sinopharm, also entered Phase The survey shows majority of the children received 3 trials this month in the United Arab Emirates. vaccination from government hospitals or clinics.

They are the three most advanced of the dozens About 95% of children in rural India and 86% of of projects worldwide by scientists racing to children in urban India had received some develop and test a vaccine against the new virus. vaccination from government hospitals including primary and community health centres or even A fourth, existing vaccine against tuberculosis is Anganwadi centres. Private sector catered to also in Phase 3 trials in Australia as a potential about 5% of children in rural India, though the coronavirus immunization. percentage was slightly higher at 14% of children in urban India who received any vaccination.

The government had set a target to achieve 90% immunisation coverage this year. However, the programme has suffered a big blow due to the 60% of kids under five years fully pandemic, experts said. immunised: Survey Jul 21, 2020

NEW DELHI: Around 60% of children under five years of age were fully immunised, a survey conducted by National Statistical Office (NSO) PM to launch three labs today to help during July 2017-June 2018 shows. This includes ramp up testing about 59% of boys and 60% of girls across the These centres will be able to test over 10,000 samples country who had been fully immunised with all in a day, and reduce turnaround time and exposure eight prescribed vaccinations — BCG, OPV- 1, 2,3, of lab personnel to infectious clinical materials. DPT- 1,2,3 and measles. Jul 27, 2020

In rural India, about 58% (57% boys and 60% girls) Prime Minister Narendra Modi will launch high children under five years, and about 62% (62% throughput Covid-19 testing facilities in Noida, boys and 61% girls) children in urban India had Mumbai and Kolkata on Monday to ramp up been fully immunised. testing capacity and help strengthen early detection and treatment, the Prime Minister’s The report also shows a decline in estimated Office said. anaemia cases during the 75th round of the survey with cases dropping to 5,96,200 from High throughput faculties allow experiments or 8,80,700 during the 71st round. Proportion of screening that large scale or on higher volume. NIRT Library News Bulletin 11 These centres will be able to test over 10,000 only a mild case, according to a report that samples in a day, and reduce turnaround time suggests caution regarding so-called herd and exposure of lab personnel to infectious immunity as well as vaccine durability. clinical materials.

“The three high throughput testing facilities have been set up strategically at ICMR institutions -- National Institute of Cancer Prevention and Research in Noida, National Institute for Research in Reproductive Health in Mumbai and National Institute of Cholera and Enteric Diseases in Kolkata,” the PMO said in the statement.

The virtual launch of these centres will be Cells that produce antibodies against the coronavirus disease attended by union health minister Harsh Vardhan (Covid-19) are seen through a microscope, in a university lab in and Maharashtra CM, Uddhav Thackeray, West Athens, Greece. (REUTERS)

Bengal CM , Mamata Banerjee and Uttar Pradesh Recovering from Covid-19 may not offer much CM,Yogi Adityanath. protection from future infections for those with

only a mild case, according to a report that “The labs are enabled to test diseases other than suggests caution regarding so-called herd COVID-19 as well, and post the pandemic, will be immunity as well as vaccine durability. able to test for Hepatitis B and C, HIV, mycobacterium tuberculosis, cytomegalovirus, The correspondence in the New England Journal chlamydia, neisseria and dengue,” the statement of Medicine outlined a analysis of antibodies said. taken from the blood of 34 patients who had

recovered after suffering mainly mild symptoms On Sunday, the PM in his radio broadcast Mann KI that didn’t require intensive care. Just two needed Baat cautioned against letting the guard down supplemental oxygen and received an HIV and said people should refrain from taking off the medication, and none were on a ventilator or masks during interaction. getting Gilead Sciences Inc.’s remdesivir.

The first analysis was done on antibodies taken an average of 37 days after symptoms began, with a second after about 86 days, or less than three months. The researchers found that antibody Covid-19 antibodies fade rapidly, levels fell quickly, with a half-life of about 73 days raising risk of lost immunity between the two time frames. The loss of The correspondence in the New England Journal of antibodies occurred more quickly than with SARS, Medicine outlined a analysis of antibodies taken an earlier type of coronavirus infection. from the blood of 34 patients who had recovered after suffering mainly mild symptoms that didn’t The antibody response is being closely studied by require intensive care. scientists worldwide for indications of how long- Jul 23, 2020 | lasting immunity may be. While there’s little Bloomberg | Posted by: Shankhyaneel Sarkar evidence to suggest reinfections are broadly occurring, health experts have yet to pin down Recovering from Covid-19 may not offer much specifics. The latest findings raise concern that protection from future infections for those with protection from reinfection may not last long in

NIRT Library News Bulletin 12 those with mild symptoms, which accounts for the majority of cases.

Further studies will be needed “to define a Covid-19 antibodies fade rapidly, quantitative protection threshold and rate of raising risk of lost immunity decline of antiviral antibodies beyond 90 days,” While the protective role of antibodies against according to the researchers led by F. Javier infection isn’t fully understood, they are generally Ibarrondo, from the David Geffen School of considered a good representation of some Medicine at the University of California Los protection against infection in general, according to Angeles. The brief report was in the form of a the report. correspondence published in the journal. Jul 22, 2020 | Bloomberg | Posted by Prashasti Singh While the protective role of antibodies against infection isn’t fully understood, they are generally Recovering from Covid-19 may not offer much considered a good representation of some protection from future infections for those with protection against infection in general, according only a mild case, according to a report that to the report. suggests caution regarding so-called herd immunity as well as vaccine durability. A recent study from King’s College London showed that the level of antibodies may drop to a The correspondence in the New England Journal degree that makes them undetectable as soon as of Medicine outlined an analysis of antibodies three months after infection. However, the body taken from the blood of 34 patients who had also mounts other forms of immunity responses, recovered after suffering mainly mild symptoms including from so-called T-cells, which appear to that didn’t require intensive care. Just two needed play a role in protecting against reinfection with supplemental oxygen and received an HIV Covid-19. medication, and none were on a ventilator or getting Gilead Sciences Inc.’s remdesivir. In Sweden, the nation’s top health authority said on Tuesday that people who have had the virus The first analysis was done on antibodies taken an are likely to be immune for at least six months after average of 37 days after symptoms began, with a being infected, whether they’ve developed second after about 86 days, or less than three antibodies or not. In new guidance, the Swedish months. The researchers found that antibody Public Health Agency said it’s now considered levels fell quickly, with a half-life of about 73 days safe for individuals who’ve been infected to come between the two time frames. The loss of into contact with people in high-risk groups. antibodies occurred more quickly than with SARS, an earlier type of coronavirus infection. For more articles like this, please visit us at bloomberg.com The antibody response is being closely studied by ©2020 Bloomberg L.P. scientists worldwide for indications of how long- lasting immunity may be. While there’s little evidence to suggest reinfections are broadly occurring, health experts have yet to pin down

specifics. The latest findings raise concern that protection from reinfection may not last long in those with mild symptoms, which accounts for the

majority of cases.

NIRT Library News Bulletin 13 Further studies will be needed “to define a quantitative protection threshold and rate of decline of antiviral antibodies beyond 90 days,” according to the researchers led by F. Javier

Ibarrondo, from the David Geffen School of

Medicine at the University of California Los

Angeles. The brief report was in the form of a correspondence published in the journal.

While the protective role of antibodies against infection isn’t fully understood, they are generally Clinical staff wear personal protective equipment (PPE) while considered a good representation of some caring for a patient in the Bronchoscopy unit at the Royal protection against infection in general, according Papworth Hospital, operated by the Royal Papworth Hospital NHS to the report. Foundation Trust, in Cambridge, UK.(Bloomberg)

One of the great mysteries of the coronavirus is A recent study from King’s College London how quickly it rocketed around the world. showed that the level of antibodies may drop to a degree that makes them undetectable as soon as It first flared in central China and, within three three months after infection. However, the body months, was on every continent but Antarctica, also mounts other forms of immunity responses, shutting down daily life for millions. Behind the including from so-called T-cells, which appear to rapid spread was something that initially caught play a role in protecting against reinfection with scientists off guard, baffled health authorities and Covid-19. undermined early containment efforts — the virus

could be spread by seemingly healthy people. In Sweden, the nation’s top health authority said on Tuesday that people who have had the virus As workers return to offices, children prepare to are likely to be immune for at least six months after return to schools and those desperate for being infected, whether they’ve developed normalcy again visit malls and restaurants, the antibodies or not. In new guidance, the Swedish emerging science points to a menacing reality: If Public Health Agency said it’s now considered people who appear healthy can transmit the safe for individuals who’ve been infected to come illness, it may be impossible to contain. into contact with people in high-risk groups.

“It can be a killer and then 40 percent of people

don’t even know they have it,” said Dr. Eric Topol, head of Scripps Research Translational Institute.

Researchers have exposed the frightening Silent spread of Covid-19 keeps likelihood of silent spread of the virus by scientists grasping for clues asymptomatic and presymptomatic carriers. But Covid-19 first flared in central China and, within three how major a role seemingly healthy people play months, was on every continent but Antarctica, in swelling the ranks of those infected remains shutting down daily life for millions. Behind the rapid unanswered — and at the top of the scientific spread was something that initially caught scientists agenda. off guard, baffled health authorities and undermined early containment efforts — the virus could be The small but mighty coronavirus can unlock a spread by seemingly healthy people. human cell, set up shop and mass produce tens Jul 22, 2020 | Posted by Shivani Kumar of thousands of copies of itself in a single day. Virus

NIRT Library News Bulletin 14 levels skyrocket before the first cough, if one ever transmission during the incubation period,” said arrives. And astonishing to scientists, an estimated Lauren Ancel Meyers, a disease modeler at the 4 in 10 infected people don’t ever have University of Texas at Austin. symptoms. Behind the scenes, scientists like Meyers were The slyness of the virus remains on the minds of sharing their alarming finding with health officials. many scientists as they watch societies reopen, By scouring the websites of Chinese health wondering what happens if silent spreaders aren’t departments, Meyers and her team found more detected until it’s too late. than 50 cases between Jan. 21 and Feb. 8 where the person who brought the virus home didn’t Travelers with no coughs can slip past airport develop symptoms until after infecting a family screens. Workers without fevers won’t be caught member. by temperature checks. People who don’t feel tired and achy will attend business meetings. “When we looked at the data, we said, ‘Oh no, And outbreaks could begin anew. this can’t be true,’” Meyers said. “It was shocking.”

The first hints Clues on a cruise ship As early as January, there were signs people could Rebecca Frasure, who contracted the virus while harbor the virus without showing symptoms. A 10- aboard the Diamond Princess cruise, sat in bed in year-old boy in China who traveled to Wuhan had Japan in late February, frustrated to be kept no symptoms but tested positive, along with six hospitalized even though she didn’t have any others in his family who had coughs and fevers. symptoms. More troubling was a report out of Germany: A business traveler from China spread the virus to “I’m perfectly healthy except having this virus in colleagues in Munich, even though she appeared my body,” Frasure said. healthy. Without widespread and frequent testing, it’s Still, many scientists remained unconvinced. impossible to know how many people without symptoms might carry it. The Diamond Princess, The concept of people unwittingly spreading which idled in the Port of Yokohama, while the disease has never been an easy one to grasp, virus exploded onboard, enticed researchers. from the polio epidemic of mid-century America to the spread of HIV decades later. After an ill passenger tested positive, only those with symptoms initially got tests. At the turn of the 20th century, a seemingly healthy New York cook named Mary Mallon left a Rein Houben, a disease tracker at the London deadly trail of typhoid infections that captivated School of Hygiene and Tropical Medicine, set out the public and led to her being forced into to build a mathematical model to estimate how quarantine on an East River island. “Typhoid Mary” many infected people without symptoms were remains a haunting symbol of silent spread. being missed. After four weeks, it indicated a startling three-quarters of infected people on the As Covid-19 emerged, health officials believed it Princess were asymptomatic. would be like other coronaviruses and that people were most infectious when showing symptoms like At first, the researchers worried they had done cough and fever, with transmission rare otherwise. something wrong. But they hadn’t, and they had “We were thinking this thing is going to look like their answer: Asymptomatic carriers “may SARS: a long incubation period and no contribute substantially to transmission.”

NIRT Library News Bulletin 15 In Washington state, similar clues emerged for Dr. Days later, Chinese researchers published a paper Jeff Duchin as a team of investigators examined saying patients are most infectious two to three the Life Care nursing home — where the first major days before developing symptoms. Evidence U.S. cluster of coronavirus cases broke out —and continues to accumulate, and the CDC now found health care workers were spreading the estimates 40% of transmission is occurring before virus to other elder care facilities. They believed at people feel sick. least some of them were working while infected but before feeling symptoms. Still, doubt remains among scientists, most notably among the World Health Organization, which has In March, more than half the residents at another discounted the importance of asymptomatic nursing home who tested positive didn’t have infection, though it recently began to symptoms, though most would go on to develop acknowledge that possibility and advised people them. to wear masks.

That underscored the need to shift gears and U.S. health officials blame China for delays in acknowledge the virus couldn’t be totally sharing information on silent spread. But Topol stopped. contends the U.S. could have mounted its own testing program with viral genome sequencing. “This disease is going to be extremely hard to That’s no small matter: Gaining scientific clarity control,” Duchin recalled thinking. earlier would have saved lives.

Unanswered questions “We’ve been slow on everything in the United The nose and mouth are convenient entryways for States,” Topol said. “And I have to say it’s the coronavirus. Once inside, the virus shameful.” commandeers the cell’s machinery to copy itself, while fending off the body’s immune defenses.

Virus levels skyrocket in the upper airway, all without symptoms early on. Many scientists believe that, during these days, people can spread virus just by talking, breathing or touching surfaces.

In the truly asymptomatic, the immune system wins the battle before they ever feel sick. That may Imaging and machine learning have been what happened with Jessie Cornwell. system created to discover After an outbreak at her Seattle assisted living facility, Cornwell tested positive for coronavirus, tuberculosis drugs although she never had symptoms. She may have Researchers have developed MorphEUS, a infected the Rev. Jane Pauw, who drove Cornwell technology to identify new drugs that combat M. to a Bible study meeting and later ran a high fever tuberculosis by revealing how compounds destroy the bacteria. and tested positive. 24 July 2020 | Victoria Rees (Drug Target Review)

As it became clearer that healthy people could A new technology that combines high throughput spread the virus, U.S. health authorities opted not imaging and machine learning has been to wait for scientific certainty. In early April, the developed, which the researchers say could Centers for Disease Control and Prevention speed up the discovery of drugs to recommended people wear masks. fight tuberculosis (TB).

NIRT Library News Bulletin 16 first author on the paper and a postdoctoral researcher in the Aldridge laboratory.

The researchers explained that MorphEUS

harnesses this variation by incorporating measurements of heterogeneity itself into morphological profiles and combining this enhanced feature set with machine learning and other complex analytical tools. Network webs and matrices visualise the data analysis. For example, much of the heterogeneity in staining patterns in M. tuberculosis is due to its thick, complex cell

wall. There is increased staining and less variation Conducted at Tufts University, US, the study unveils in staining patterns when M. tuberculosis is treated the new technology named Morphological with cell-wall targeting antibiotics compared with Evaluation and Understanding of drug Stress other classes of antibiotics. (MorphEUS). According to the researchers,

MorphEUS provides a rapid, efficient and cost- “With MorphEUS, we used the distribution of effective way to determine how specific staining across a large number of bacilli to learn compounds act to destroy Mycobcterium how each drug acts on M. tuberculosis,” said tuberculosis, the bacterium that causes Aldridge. “Similarly, we looked at staining intensity tuberculosis. and the spread of that brightness across

thousands of cells to identify more subtle patterns.” “We urgently need shorter, more effective TB MorphEUS, like all cytological profiling techniques, therapies and MorphEUS enables us to screen is data-driven and based on classification among through drug candidates, see how they actually a pool of other profiles. It requires multiple affect the cell and learn which drugs have unique representative profiles from M. ways to kill the M. tuberculosis,” said Bree tuberculosis treated with compounds known to Aldridge, associate professor of molecular biology target the same broad cellular target. As the drug and microbiology at Tufts University School of set expands, the accuracy and resolution of Medicine and senior author of the paper. MorphEUS will improve, the researchers say. Aldridge and colleagues applied MorphEUS to 34 MorphEUS can also determine if drugs have off- currently available antibiotics for which modes of target or secondary effects that are otherwise action were already established and three non- hard to identify. Such complex mechanisms of commercial compounds. They found that drug action can be key in designing multidrug MorphEUS categorised the drugs correctly 94 therapies. percent of the time. In the remaining instances, MorphEUS identified previously unknown target “We expect that the success of MorphEUS in pathways. profiling drug action in an organism like M. tuberculosis with significant inherent “We found that conventional morphological heterogeneity and subtle cytological profiling approaches did not work with M. responsiveness will make it useful in other tuberculosis, because the bacterium’s inherent pathogens and cell types,” said Aldridge. response to treatment was extremely variable and changes in morphology were much less obvious However, the researchers highlight that MorphEUS than in bacteria like E. coli,” said Trever Smith, co- is limited in its ability to identify target pathways of

NIRT Library News Bulletin 17 compounds with novel mechanisms of action that therapies, and MorphEUS enables us to screen are unlike the other profiled drugs in the reference through drug candidates, see how they actually set. affect the cell, and learn which drugs have unique ways to kill the M. tb," said Bree Aldridge, associate The results can be found in Proceedings of the professor of molecular biology and microbiology National Academies of Sciences. at Tufts University School of Medicine and senior author on the associated paper about the new Source: platform published online in the Proceedings of https://www.drugtargetreview.com/news/65702/im the National Academies of Sciences (PNAS) on aging-and-machine-learning-system-created-to- July 17. discover-tuberculosis-drugs/ Aldridge and her colleagues applied MorphEUS to 34 currently available antibiotics for which modes of action were already established and three non- commercial compounds. MorphEUS categorized the drugs correctly 94 percent of the time. In the remaining instances, MorphEUS identified Cell Profiling Method Set To previously unknown target pathways.

Accelerate Discovery of Drugs for The search for new TB treatments has been Tuberculosis stymied by difficulties in identifying the biological Jul 24, 2020 | Original story from Tufts University activity of compounds early in the drug discovery process and the need to clarify the mechanism of A new technology that combines high throughput action of existing therapies. Antibacterials kill imaging and machine learning could speed pathogens via specific molecular actions, for discovery of drugs to fight tuberculosis, which for example, by destroying the microbe's cell wall or generations has killed more people worldwide inhibiting protein synthesis. The drugs leave clues than any other disease caused by a single agent- to their particular modus operandi: characteristic -4,000 people every day. physical unraveling of the bacterial cells, which may affect length, width, shape of structures like Current treatment requires multiple drugs for at the chromosome, staining ability, and other least six months and sometimes years, and properties. Morphological profiling to categorize antibiotic resistance is growing, increasing drugs by these changes is well-established with urgency for finding new treatments. pathogens such as E. coli, but Aldridge's team was the first to test it with M. tb. However, drug discovery typically requires production of hundreds of derivatives of an "We found that conventional morphological original compound in order to find the most profiling approaches didn't work with M. tb, effective version. The new technology--dubbed because the bacterium's inherent response to MorphEUS (Morphological Evaluation and treatment was extremely variable, and changes Understanding of drug Stress)--provides a rapid, in morphology were much less obvious than in efficient, cost-effective way to determine how bacteria like E. coli," said Trever C. Smith II, co-first specific compounds act to destroy Mycobcterium author on the paper and a postdoctoral tuberculosis (M. tb), the bacterium that causes researcher in the Aldridge laboratory. tuberculosis. MorphEUS harnesses this variation by "We urgently need shorter, more effective TB incorporating measurements of heterogeneity

NIRT Library News Bulletin 18 itself into morphological profiles and combining Reference: Smith, et al. (2020). Morphological this enhanced feature set with machine learning profiling of tubercle bacilli identifies drug and other complex analytical tools. Network webs pathways of and matrices visualize the data analysis. For action. PNAS DOI: https://doi.org/10.1073/pnas.2 example, much of the heterogeneity in staining 002738117 patterns in M. tb is due to its thick, complex cell wall. There is increased staining and less variation This article has been republished from the in staining patterns when M. tb is treated with cell- following materials. Note: material may have wall targeting antibiotics compared with other been edited for length and content. For further classes of antibiotics. "With MorphEUS, we used the information, please contact the cited source. distribution of staining across a large number of bacilli to learn how each drug acts on M. tb," said Source: Aldridge. "Similarly, we looked at staining intensity https://www.technologynetworks.com/drug- and the spread of that brightness across discovery/news/cell-profiling-method-set-to- thousands of cells to identify more subtle patterns." accelerate-discovery-of-drugs-for-tuberculosis- 337843 MorphEUS can also determine if drugs have off- target or secondary effects that are otherwise hard to identify. Such complex mechanisms of drug action can be key in designing multidrug therapies.

"We expect that the success of MorphEUS in Continued from page no.1 profiling drug action in an organism like M. tb with significant inherent heterogeneity and subtle cytological responsiveness will make it useful in COVID-19 affects HIV and other pathogens and cell types," said Aldridge, who is also a core faculty member of Tufts Center tuberculosis care for Integrated Management of Antimicrobial

Resistance, member of the immunology and …Shortly after instituting coronavirus disease 2019 molecular microbiology program faculties at Tufts (COVID-19) mitigation measures, such as banning Graduate School of Biomedical Sciences, and an air travel and closing schools, the South African adjunct associate professor at Tufts government implemented a national lockdown University's School of Engineering. on 27 March 2020 when there were 402 cases and

the number of cases was doubling every 2 days MorphEUS, like all cytological profiling techniques, (1). This drastic step, which set out to curb viral is data-driven and based on classification among transmission by restricting the movement of a pool of other profiles. It requires multiple people and their interactions, has had several representative profiles from M. tb treated with unintended consequences for the provision of compounds known to target the same broad health care services for other prevalent conditions, cellular target. As the drug set expands, the in particular the prevention and treatment of accuracy and resolution of MorphEUS will improve. tuberculosis (TB) and HIV. Key resources that had MorphEUS is also limited in its ability to identify been extensively built up over decades for the target pathways of compounds with novel control of HIV and TB are now being redirected to mechanisms of action that are unlike the other control COVID-19 in various countries in Africa, profiled drugs in the reference set. particularly South Africa. These include diagnostic

platforms, community outreach programs,

NIRT Library News Bulletin 19 medical care access, and research infrastructure. patients attending these facilities. Delayed HIV However, the COVID-19 response also provides and TB testing impedes initiation of appropriate potential opportunities to enhance HIV and TB treatment, which increases the risk of new control. infections and drug resistance.

In Africa, the COVID-19 epidemic is unfolding Both TB and HIV diagnostic platforms are against a backdrop of the longstanding TB and important contributors to COVID-19 testing. The HIV epidemics. South Africa ranks among the GeneXpert point-of-care testing platform, which is worst-affected countries in the world for both widely used in South Africa to diagnose TB, with diseases. Despite having just 0.7% of the world's more than 2 million individuals tested annually, is population, South Africa is home to ∼20% (7.7 to also being used to diagnose COVID-19. Until now, 7.9 million people) of the global burden of HIV the limited availability of the GeneXpert COVID-19 infection and ranks among the worst affected cartridges has meant that spare capacity is mostly countries in the world for TB, with the fourth highest being used with little, if any, displacement of TB rate of HIV-TB co-infection (59%). South Africa has testing. Because there was also a decline in CD4+ made steady progress since 2010 in controlling assays (to test for immune status in HIV patients), it both diseases. Increased access to antiretroviral indicates decreased demand rather than drugs for treatment and for prevention of mother- displacement because this assay is not used for to-child transmission of HIV has resulted in a 33% COVID-19. This may change as the demand for reduction in AIDS-related deaths between 2010 COVID-19 point-of-care testing rises and and 2018. Similarly, the death rate among TB cases GeneXpert cartridges for COVID-19 become has declined from 224 per 100,000 population in more readily available. 2010 to 110 per 100,000 population in 2018 . Have the strategies implemented for COVID-19 South African clinical laboratories have substantial mitigation, particularly the lockdown, capacity to perform high-throughput PCR assays inadvertently threatened these gains in HIV and for HIV viral load (more than 50,000 tests per day). TB? However, the lack of COVID-19 test kits in South Africa, stemming from the global shortage, has HIV and TB polymerase chain reaction (PCR) tests meant that the available spare capacity on these are key to treatment initiation and monitoring to platforms has sufficed for COVID-19 testing. The full achieve the United Nations goals for the control of potential of this PCR capacity is likely to be called HIV and TB. Disturbingly, these diagnostic tests upon when the country needs to expand COVID- declined during the lockdown. The 59% drop in 19 PCR testing for the expected surge in cases, the median number of daily GeneXpert TB tests— estimated to exceed 1 million at peak. Laboratory a cartridge-based PCR test capable of capacity for PCR testing developed for HIV and TB diagnosing TB within 2 hours while simultaneously is now an essential resource for COVID-19 testing. testing for drug resistance—was accompanied by The use of this capacity for COVID-19 needs to be a 33% reduction in new TB diagnoses. The monitored to identify and address any potential restriction of people's movement and curtailment displacement of HIV and TB testing. of public transport has led to substantial declines in patient attendance at health care facilities. A South Africa's experience in dealing with survey of 339 individuals in South Africa revealed substantial HIV and TB epidemics has laid the that 57% were apprehensive about visiting a clinic foundations for the country's rapid, early or hospital during the lockdown, in part because community-based response. Both TB and COVID- of concerns that they may be exposed to 19 are respiratory infections and can present with infection by severe acute respiratory syndrome similar symptoms. They therefore present coronavirus 2 (SARS-CoV-2) from COVID-19 substantial infection control challenges, requiring

NIRT Library News Bulletin 20 timely and rapid diagnosis. Both diseases can only COVID-19 transmission but also that of TB and spread more easily in conditions associated with other respiratory infections. After the COVID-19 poverty where social distancing is difficult to surge, integrated services could potentially implement. Well-established community outreach provide an important approach to balancing capabilities for contact tracing, established for TB, ongoing vigilance for COVID-19 with early were deployed to undertake contact tracing and community-based detection of individuals with quarantine monitoring for COVID-19. HIV and/or TB.

With the highest HIV burden in the world, South Access to medical care for non–COVID-19 Africa has a highly developed network of health conditions was limited during the lockdown, with care providers that includes tens of thousands of health facilities experiencing declines in the community health care workers who are trained number of TB and HIV patients collecting their to interact safely with infectious individuals and medication on schedule. The World Health have experience in undertaking door-to-door Organization estimates that a 6-month disruption visits in South Africa's most socially vulnerable of antiretroviral therapy could lead to more than communities. About 28,000 HIV community health 500,000 additional deaths from AIDS-related illness care workers were deployed for COVID-19 in 2021 and a reversal of gains made in the symptom screening and testing referral (HIV prevention of mother-to-child transmission. In outreach was put on hold) in 993 vulnerable, high- South Africa, 1090 TB patients and 10,950 HIV density communities, many lacking running water, patients in one province have not collected their to identify cases and thus reduce time to diagnosis medications on schedule since the start of the and hence limit transmission. As clinical cases national lockdown. A national survey of 19,330 increased, there were insufficient tests for individuals in South Africa found that 13.2% community-based screening, creating testing indicated that their medication for chronic backlogs that delayed hospital patient results and disease was inaccessible during the lockdown. led to curtailment of the community program with Furthermore, hospital admissions for HIV and TB proposed adjustment to screening and declined as a result of hospitals reducing quarantine without testing. nonurgent admissions in preparation for a surge of COVID-19 cases and owing to closures to reduce The established community engagement and exposure to COVID-19 patients. The potential outreach for HIV, TB, and noncommunicable negative impact on the continuity of care for HIV diseases (such as hypertension and diabetes) and TB patients could have substantial provide an opportunity for integrating screening repercussions for both treatment and control, and testing in the long-term COVID-19 response. including development of drug resistance. This approach will play an important role in reaching at-risk populations who do not readily The biological and epidemiological interaction of make use of health services to establish a broader COVID-19, HIV, and TB is not well understood. program of health promotion, prevention, and Patients immunocompromised by HIV or with TB early detection. Such integration can be lung disease could be more susceptible to severe facilitated by the expansion of mobile onsite rapid COVID-19. However, preliminary results from a testing approaches, using newly developed study of 12,987 COVID-19 patients in South Africa COVID-19 tests and existing tests for HIV and other indicate that HIV and TB have a modest effect on conditions on readily accessible samples such as COVID-19 mortality, with 12% and 2% of COVID-19 saliva and blood from finger pricks. Combining deaths attributable to HIV and TB, respectively, health promotion programs for these diseases will compared to 52% of COVID-19 deaths reduce duplication and provide synergistic attributable to diabetes. The small contribution of messaging because social distancing affects not HIV and TB to COVID-19 mortality is mainly due to

NIRT Library News Bulletin 21 these deaths occurring in older people, in whom http://www.sciencemag.org/about/science- HIV and active TB are not common. Integrated licenses-journal-article-reuse medical care for these three conditions is This is an article distributed under the terms of important as COVID-19 patients coinfected with the Science Journals Default License. HIV or TB start attending health care services in So: larger numbers. https://science.sciencemag.org/content/369/6502/366.full

South Africa's COVID-19 response, especially the lockdown, has led to substantial economic hardship, particularly among the poor and vulnerable. This has had a disproportionate impact on women, many of whom are self- employed or day laborers without a safety net. This may have a longer-term effect on increasing diseases associated with poverty (such as TB) and with gender, such as HIV, for which young women Number of tuberculosis bear a disproportionate burden. The social cases in India halved in last determinants of HIV and TB will need to be carefully monitored to assess the impact of five years: survey Cost of treatment, hospitalisation have has gone COVID-19. The effect of the lockdown on the up economy, including declining taxes, is also likely to negatively affect funding for HIV and TB programs, By Pratul Sharma July 21, 2020 18:54 IST among many others.

New and ongoing research on HIV and TB prevention and treatment have been severely affected by the COVID-19 epidemic. At the initiation of the lockdown in South Africa, the National Health Research Ethics Committee suspended all medical research, including clinical trials. Research progress on these two conditions has also slowed because several of the country's AIDS and TB researchers are redirecting their efforts to COVID-19. However, COVID-19 research efforts have increased collaboration and created new approaches to speed up therapeutic and In 2018, on an average, a person in the rural India vaccine development and testing, which will likely spent about Rs 16,676, and his urban counterpart have long-term benefits for medical research spent Rs 26,475 on medical expenditure for beyond COVID-19. Several countries in Africa hospitalisation, predictably most of it in private have well-developed HIV and TB clinical trial hospitals. Ninety-five per cent of people trusted infrastructure that could contribute to COVID-19 the allopathic medicines to get well, while the vaccine trials. Past investments in infectious percentage of people using alternative disease training and research have generated medicines was minuscule. The cost of treatment handsome returns to the COVID-19 response, has increased in the last five years—in 2014 a highlighting the importance of maintaining these person, on average, spent around Rs 2,000 less on investments in the future. hospitalisation.

NIRT Library News Bulletin 22 These are the findings of the latest survey on As the survey was conducted before the launch household social consumption related to health, of Ayushman Bharat scheme, it found that only 14 conducted by the National Statistical Office per cent of the rural population and 19 per cent during the period from July 2017 to June 2018, as of the urban population had health expenditure a part of 75th round of National Sample Survey coverage. (NSS). The previous consumption survey was The survey noted that in rural India, percentage conducted in 2013-14. people receiving free medicines, and facilities like These government surveys are important as they X-ray, ECG’, and other diagnostic tests have gone offer a peek into the changing consumption levels up by over two per cent, when compared to the in the country, and how the citizenry was findings in the previous survey. changing. The report, Health in India, released this For funding their hospital finances, the rural and week, is based on information collected from urban households mostly dipped into their 1,13,823 households (64,552 in rural areas and personal savings (around 80 per cent) and on 49,271 in urban areas), covering 5,55,115 persons borrowings (13 per cent). Dependence of the (3,25,883 in rural areas and 2,29,232 in urban urban households on their ‘income/savings’ was areas). more (84 per cent) for financing expenditure on What has changed between the last survey in hospitalisation, than on ‘borrowings’ (about 9 per 2014, and the latest survey is the number of TB cent). cases, which halved in five years. According to The survey also recorded childbirth and maternity the report, the proportion of persons suffering from care services and found that among women in tuberculosis saw a drastic decline—38 per 1,00,000 the age-group 15-49 years, about 7.4 per cent in persons from 76 per 1,00,000 persons. It also rural areas and 5.3 per cent in urban areas were recorded a decline in estimated number of cases reported as pregnant during the 365 days of anaemia—from 8,80,700 cases to 5,96,200 preceding the date of survey. “In rural areas, cases. about 90 per cent childbirths were institutional (in “Average out-of-pocket medical expenditure per government and private hospitals) and in urban hospitalisation case (excluding childbirth) was areas it was about 96 per cent. Among about Rs 15,937 in rural India, and Rs 22,031 in institutional childbirths, in rural areas, about 69 per urban India. In government/public hospitals, on cent cases were in government hospitals and an average Rs 4,072 in rural and Rs 4,408 in urban about 21 per cent in private hospitals and, in areas, and in private hospitals about Rs 26,157 in urban areas, about 48 per cent cases each were rural and Rs 32,047 in urban areas were spent,” the in government hospitals and private hospitals.” report said. In terms of expenditure on pre-natal and post- Given the affordable healthcare in the natal care, among women in the age-group 15- government hospitals, in terms of the 'in-patient 49 years, about 97 per cent of women took pre- hospitalisation' (excluding childbirth), about 42 per natal care and about 88 per cent took post-natal cent (46 per cent in rural areas, 35 per cent in care. “On an average, about Rs 2,786 (Rs 2,271 in urban areas) of population availed treatment in rural areas and Rs 4,405 in urban areas) was spent public hospitals, 55 per cent (52 per cent in rural on pre-natal care and about Rs 1,306 (Rs1,137 in areas, 61 per cent in urban areas) of population rural areas and Rs 1,832 in urban areas) was spent availed treatment in private hospitals and 2.7 per on post-natal care.” cent (2.4 per cent in rural areas, 3.3 per cent in The survey found out that surgery was done in urban areas) of population availed treatment in about 28 per cent of hospital childbirths in India (in charitable trust/NGO-run hospitals. rural India about 24 per cent, and in urban India about 41 per cent). In government hospitals only NIRT Library News Bulletin 23 about 17 per cent of childbirths were surgery cases (in rural India about 14 per cent and in urban India about 26 per cent) and, in private hospitals about 55 per cent of childbirths required surgery (in rural India about 54 per cent and in urban India about 56 per cent).

Average expenditure per hospital childbirth was recorded at about Rs 2,404 in rural India and Rs 3,106 in urban India at government hospitals, and about Rs 20,788 in rural and Rs 29,105 in urban were spent for childbirth at private hospitals. “For a normal delivery: average expenditure per childbirth in a government hospital was about Rs. 2,084 in rural India and Rs 2,459 in urban India and average,” the report said. Indians have not been untouched by the epidemics and pandemics the world has seen In rural India, about 97 per cent of both boys and over the past 30 years. India is better placed girls had received any vaccination and in urban today to tackle and counter pandemics such as India, about 98 per cent of boys and 97 per cent Covid-19. We had our share of failures and of girls had received vaccination. learning over decades while managing About 59 per cent of boys and 60 per cent of girls pandemics like cholera, plague, influenza, polio, at all-India level had been fully immunised SARS, Japanese Encephalitis, Chikungunya, H1N1 (received all 8 prescribed vaccinations). About 58 and Nipah. per cent (57 per cent boys and 60 per cent girls) children in rural India and about 62 per cent (62 In all these decades, more than 30 new infectious per cent boys and 61 per cent girls) children in agents or pathogens have been detected urban India had been fully immunised, the survey worldwide. Around 60% of these were found to said. have zoonotic origin. Covid-19 has resulted in an so: unimaginable situation with lockdowns and https://www.theweek.in/news/health/2020/07/21/number movement restrictions restrictions being imposed -of-tuberculosis-cases-in-india-halved-in-last-five-years- in many countries. Apart from this threat at hand, survey.html there are many other infectious diseases that continue to claim lives in India, such as malaria and tuberculosis, which have a high mortality rate associated with them. As per WHO, in 2018 India accounted for 27% of TB population across the world. A majority amongst this number is the adult population but a significant portion of children also suffer from pulmonary TB. Tuberculosis is a multi-faceted challenge. Can we learn to fight The current government has set a deadline of tuberculosis from 2025 to eradicate TB from India. Far-fetched but coronavirus? this deadline has led to multiple innovations that can help us overcome challenges associated with Dr. Vedam Ramprasad, JUL 23 2020, 00:16 ISTUPDATED: JUL 23 2020, 02:27 IST TB. Not only is the country home to the largest TB

NIRT Library News Bulletin 24 population and associated deaths, but also faces as a next-gen diagnostics arena which is boosting significant challenges panning from developing drug and vaccine development basis a relatively an accurate base of TB patients, keeping the new-found scientific basis. In TB specifically, the affected population on the medication regime, country saw two big advances last year that affordability, as well as accessibility. could augment the way drugs are developed for the Indian population. One was SPIT-SEQ that sequences the entire genomic make-up of the A targeted approach to identify the population Mycobacterium Tuberculosis (Mtb) which affected from TB remains the biggest hurdle. The provides intelligence as to which drug will work on aspect demands to methodically identify the bacteria and the second is Genexpert individuals who are at risk for new infection as well machine that establishes in a couple of hours as individuals at increased risk for reactivation due whether the patient has resistance to a select list to associated high-risk conditions. The Indian of drugs. When SPIT SEQ was originally launched in population is not proactively surfacing for a Aug-2019, it was a research use only (RUO) test check-up due to resources, stigma, consequential with validation studies underway. As a result of treatment cost et al which needs a successful validation results, the study was comprehensive approach altogether. Identifying published in the International Journal of this missing TB population through a well-framed Tuberculosis and hence the test is now available testing infrastructure is half battle won! The steps to be used in a clinical set-up. taken to overcome initial stigma and inertia in case of Covid-19 through large mass The Covid-19 environment saw multiple schools of communication channels can be replicated to thoughts-- one spoke of advantages of BCG apply for TB. vaccine, the other of using anti-malaria drug or even anti-arthritis drug. It will be smart to leverage The public health ecosystem has taken into the scaled-up learnings from this outbreak to account infrastructural, economical and socio- manage other public health issues the country political approaches developed by the world’s needs to defeat. leading forces assigned to overcome the (The writer is the CEO, MedGenome Labs) challenge. One model that India can use from Covid-19 pandemic is to tackle the eminent problem of of deploying a fine TB testing mechanism and infrastructure to progress and address TB testing roadblocks in India. Despite hurdles, key pieces of the necessary data infrastructure for mass TB surveillance and management can be extracted from Covid-19 model and utilised for collecting data at scale, albeit with gaps, through labs, public and local health agencies. CORONAVIRUS CRISIS

Once this is deployed, the other giant problem is better and effective drugs that can help people How to break coronavirus living with MDR and XDR TB. In all these years, stigma at the workplace: USFDA has approved only three drugs that can help in managing TB well including Bedaquiline, Notes from two TB survivors Jul 21, 2020 · 03:30 pm Linezolid and now Pretomanid which is yet to be launched in the country. Genomics has emerged Diptendu Bhattacharya & Himanshu Patel

NIRT Library News Bulletin 25 difficult for them to seek care or complete their treatment. Alongside the financial burden, there is emotional and mental distress as well as loss of self-confidence. It makes you feel incapable, frightened, anxious and often incomplete. Some worry if they will ever be hired again.

However, there are some positive experiences too. The other one of us, Himanshu, received constructive support from his employers and MDR TB survivors Diptendu Bhattacharya (left) and Himanshu Patel. | Diptendu Bhattacharya/Himanshu Patel colleagues while struggling with TB. His employer asked the right questions and involved other India is home to the highest number of tuberculosis stakeholders within the organisation to create a cases, and currently is also the fourth-worst Covid- supportive environment. He was granted a three- 19 hit country. Despite this, awareness about these month paid sabbatical. When Himanshu diseases remains poor, and fear and stigma presented a doctor’s certificate when he widespread. The rise of Covid-19 has been became non-infectious, he was asked to come accompanied with stigma against patients, back to work. He had flexibility in terms of working families and health personnel. Such trends are hours and was allowed emergency leave. similar and extreme in TB cases. Thus, he was able to work and finance his Misinformation leads to discrimination within treatment. Besides, his colleagues were supportive communities, workplaces and educational too. Each of his team members worked a few institutions, further leading to social isolation and extra hours so that he could go home on time and neglect. With workplaces now having opened up his workload was shared. They took him out for post the lockdown, how do we address stigma dinners and he never faced any stigma. All this around Covid-19-affected individuals? Can we and continuing work gave him the strength that learn from TB? was needed to fight the disease.

One of us, Diptendu, was diagnosed with multiple Stigma is not self-protection – it’s a choice, and a drug-resistant or MDR TB while studying at the bad one. So, what can we do? In such cases, Indian Institute of Technology-Kharagpur. After awareness and sensitisation at the workplace can returning from a medical leave, he found that his go a long way. Companies must also institute supervisor, a scientist, was reluctant to work with workplace policies to deal with such stigma, by him because he was under treatment – even recognising that diseases such as TB and Covid-19 though it was for non-infectious TB. Facing are and will remain widespread for a while. discrimination from a mentor discouraged and Addressing this calls for stricter HR policies that destabilised him completely. This, coupled with his penalise such discrimination. financial inability to continue his higher education, forced Diptendu to give up on his dream of a PhD But this is not enough. Every educational institution and he eventually withdrew. In the blink of an eye, and workplace must necessarily conduct trainings all that he had worked for stood erased. sessions to build better understanding of the diseases and the impact of stigma on patients. We don’t realise it, but stigma aids the spread of These policies also need to make provisions for infectious diseases such as TB and Covid-19. Many counselling patients on dealing with these patients can lose their jobs, which often makes it

NIRT Library News Bulletin 26 challenges, and ensure a redressal mechanism so 4. Modeling drug-resistant tuberculosis patients can register complaints. amplification rates and intervention strategies in Bangladesh Moreover, such policies need to have legal MA Kuddus, MT Meehan, LJ White, ES McBryde… - PloS one, 2020 backing and be supported by broader, anti- discrimination legislations – along the lines of the 5. Endeavors towards transformation of M. legislation for HIV. India needs to do its bit in the tuberculosis thymidylate kinase (MtbTMPK) fight stigma and make workplaces safe and inhibitors into potential antimycobacterial inclusive for those fighting infectious diseases like agents TB and Covid-19. We need society to understand Y Jian, R Merceron, S De Munck, HE that no one chooses to get sick, but we can Forbes, F Hulpia… - European Journal choose whether we stigmatise them or not. of …, 2020

Diptendu Bhattacharya is an MDR-TB Survivor, 6. Graphene Oxide-Linezolid Combination educationist and Fellow associated with Survivors as Potential New Anti-Tuberculosis Against TB, a collective of survivors, advocates Treatment and experts working on TB and related F De Maio, V Palmieri, G Santarelli, G comorbidities. Perini, A Salustri… - Nanomaterials, 2020

Himanshu Patel is an MDR-TB Survivor, operations 7. COVID-19 affects HIV and tuberculosis analyst and is a Survivors Against TB Fellow. care QA Karim, SSA Karim - Science, 2020 So: https://scroll.in/article/966011/how-to-break- coronavirus-stigma-at-the-workplace-notes-from-two-tb- 8. Impacts of hepatitis B and hepatitis C co- survivors infection with tuberculosis, a prospective cohort study BE Feleke, TE Feleke, WG Adane, A Girma - Virology Journal, 2020 ONLINE FIRST | ARTICLES ON TB 9. Factors of Multidrug Resistance Tuberculosis 1. Vitamin D Supplements for Prevention of V Kumar, VV Raje - Journal of Cardiovascular Disease Research, 2020 Tuberculosis Infection and Disease

D Ganmaa, B Uyanga, X Zhou, G Gantsetseg… - New England Journal of …, 10. Is interleukin-2 an optimal marker for 2020 diagnosing tuberculosis infection? A systematic review and meta-analysis 2. Host Sirtuin 2 as an immunotherapeutic X Qiu, H Wang, Y Tang, X Su, L Ge, Y Qu, D target against tuberculosis Mu - Annals of Medicine, 2020 A Bhaskar, S Kumar, MZ Khan, A Singh, VP Dwivedi… - eLife, 2020 11. Interferon-γ release assays or tuberculin skin test for latent tuberculosis infection 3. No antimicrobial resistance research Harriet Mayanja-Kizza, Achilles Katamba agenda without tuberculosis Published:July 13, 2020 GM Knight, MC Raviglione, RG White - The DOI:https://doi.org/10.1016/S1473- Lancet Global Health, 2020 3099(20)30363-7

12. Interferon-γ release assays or tuberculin skin test for detection and management

NIRT Library News Bulletin 27 of latent tuberculosis infection: a systematic review and meta-analysis Guozhong Zhou, PhD et al. Published: July 13, 2020 DOI:https://doi.org/10.1016/S1473- 3099(20)30276-0

13. Diagnostic accuracy of IP-10 mRNA release assay for tuberculosis Thomas Blauenfeldt et.al. DOI: 10.1128/JCM.00848-20

NIRT Library News Bulletin 28