One of our earlier blog’s ‘FMR’S WORK TOWARDS UNDERSTANDING THE ANTIDIARRHOEAL ACTIVITY OF GUAVA LEAVES’ mentioned the potential of guava leaf as a promising anti-diarrhoeal herbal remedy. The diarrhoea causing bacteria used for these studies were simple laboratory strains that could be killed by commonly used antibiotics. Hence, as an extension of this work, we further checked if the decoction prepared from guava leaves could also be effective against bacteria from diarrhoeal patients where in recommended antibiotics had failed to work.

Shigella is a germ that causes blood-associated diarrhoeal episodes. Infection due to this pathogen can, at times, be life-threatening and treatment with antibiotics is thus necessary. However, as is the case with several other disease causing bacteria, antibiotic resistance amongst Shigella species is increasing at an alarming rate. This bacterium was thus an obvious choice for our experiments.

The study with 43 multidrug-resistant clinical isolates of Shigella obtained from St. John’s Research Institute, Bengaluru and Hinduja Hospital, Mumbai showed that guava leaves could affect over 75% of the resistant Shigella isolates. Amongst these, it was noted that Shigella flexneri, the most common species of this bacterium, was more sensitive to the decoction.

The results highlight the ability of guava decoction to treat diarrhoea caused by antibiotic resistant Shigella species. Additionally, unlike antibiotics, a plant decoction has multiple chemical compounds that synergistically act together on the germs, chances of the bacteria developing resistance to it are minimal. The development of resistance in plant based treatment of diarrhoeal diseases is therefore very unlikely.

The findings are encouraging as alternatives are urgently required due to the fading ‘golden era’ of antibiotics.

The study was funded by Zoetis Pharmaceuticals Research Private Limited, India.

Diarrhoea not responding to antibiotics? Guava leaves to your rescue! was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

Over a decade, studies at the Foundation have demonstrated guava leaf extract to be a promising antidiarrhoeal plant remedy. Extensive laboratory assays, studies in a mouse model and a subsequent clinical trial undertaken supported the traditional use of guava leaves for gastrointestinal ailments. Realizing that standardization of plant extracts is an important aspect, using the antidiarrhoeal activity of this plant as an example, NMR based metabolomics was employed to explore the utility of this upcoming tool as a method of standardization.

The study funded by Zoetis Pharmaceuticals Research Private Ltd., involved correlating NMR spectra of 90 guava trees collected from different regions of Maharashtra state over different seasons with results of seven laboratory bioassays. The NMR spectral data was successfully correlated with results of the bioassays and key peaks in the spectra were identified that could be responsible for the antidiarrhoeal activity of guava leaf. It was also observed that multiple signals could be linked with individual bioactivity suggesting that multiple compounds contribute to the efficacy of guava leaf extract.

The study could be considered important since it highlights the holistic approach of fingerprint analysis. Unfortunately, though fingerprint analysis has been accepted by reputed organizations such as World Health Organization (WHO), Food and drug administration (FDA), limited reports indicate its use for assessing biological efficacy of plant extracts.

The study is useful for standardization of plant extracts and advances the process of modernization of traditional medicine.

Nuclear Magnetic resonance (NMR) based spectroscopy studies with guava leaf extract — A step… was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

The genome sequences of SARS-CoV-2 strains are important for designing/evaluating diagnostic tests, for tracking/tracing the ongoing COVID-19 outbreak and for identifying potential intervention options. It has been over a year since the first novel SARS-CoV-2 genome sequence was made publicly available and since then, it has resulted in unmatched growth in field of genomics, vaccine and diagnostic testing across the field of infection biology the world has ever seen. Currently, the GISAID database has over 350,000 SARS-CoV-2 genomes freely available to anyone interested in conducting genomic analysis. Whole genome sequencing within a matter of hours to days to determine the genomic characteristics of the virus has provided beneficial insights to what humans can do at the uncertain times of pandemic.

Unfortunately, there is currently a dearth of information on the viral strain types in India in the global database (with only over 4,300 strains from India, <0.05% cases sequenced), leading to lack of understanding and control over the viral strains in the country. In contrast, a country like UK
has sequenced over 5% of its cases (https://science.thewire.in/the-sciences/india-sars-cov-2-genome-sequencing-roadblocks-resources-b117-n440k-variants).

At the Foundation for Medical Research (FMR) we isolated the viral genomic RNA from 5 strains of SARS-CoV-2 collected from 5 COVID-19 patients between Aug-Sep 2020 (4 from nasopharyngeal swabs and 1 from membrane-lined N-95 mask) from Kasturba hospital. The sequence data obtained was analyzed to determine and understand the genomic structure and to find mutations (changes in the genome) in the 5 SARS-CoV-2 strains in comparison to the original Wuhan strain (Dec 2019) over time.

Mutations/changes (ranging from 8 to 22 mutations per genome) were observed in the genome of the 5 viral strains. All 5 SARS-CoV-2 strains were found to have the (D614G) mutation/change in the spike protein — a protein that is present on the surface of the virus and is required for the attachment of the virus to the host cell. This mutation/change leads to increased affinity of the virus to bind to the surface of the host cell and results in increase in efficiency of the virus to enter the host cell. Efficient entry of the virus into the host cells lead to increase in the intracellular viral load in patients having a viral strain with this genomic mutation/change. This predominant mutation/change has evolved in the viral strains since mid-Feb 2020 and is now found in almost all the SARS-CoV-2 strains globally. Another genomic mutation/change (c14408t in ORF1ab gene) was found in all 5 strains. This mutation/change is in the protein that produces new viral RNA in the host cell (it is part of the RNA dependent RNA polymerase) and has the potential to increase the rate of evolution of the virus leading to development of more virulent/infectious viral strains in future. All the strains belonged to the parent lineage B which is the pre-dominant lineage in the Indian population. The genome sequences of all the 5 strains have been uploaded on the GISAID database and are freely available for research use.

With the continuous evolution of the SARS-CoV-2 strains and concerns over the UK and South African variant strains that are notorious for their high transmission rates (70% more contagious) and increased immune evasion, respectively, it has become even more important to sequence as many viral strains as possible. In light of the new variant strains of SARS-CoV-2, prospective surveillance based on whole genome sequencing of 5% of the positive cases is being conducted by the National Task Force (NTF) in India through the Indian SARS-CoV-2 Genomics Consortium (INSACOG) labs — a group of 10 government labs. Considering the urgent sequencing need, FMR has also extended its support to the NTF for prospective surveillance by conducting genome sequencing of the SARS-CoV-2 strains from Mumbai (and Maharashtra) using Nanopore sequencing.

In near future, FMR plans to undertake additional studies on the genomics of SARS-CoV 2 not only for strain detection and surveillance but also to understand its activity through the integrity of the genome. This will allow us to understand what a positive RT-PCR test really means.

Dear Reader,
We are looking for financial support to undertake the study areas outline. If you wish to seek further details and contribute, please get in touch with us at fmr@fmrindia.org.

Thank you.

Decoding the Terror Code: Genome Sequencing of SARS-CoV- Strains from Mumbai was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

Detect Tuberculosis In Kids: Study

In an interesting finding that could pave the way for simpler and non-invasive ways of detecting tuberculosis (TB) in children, a city-based research organisation has found that the bacteria can be detected from the respiratory aerosols collected on masks. Through mask sampling, experts from the Foundation for Medical Research (FMR) could pick up tuberculosis bacilli in nine of the ten studied samples.

The study, presented at the virtually held 51st Union World Conference on Thursday, garnered much interest as sampling remains one of the major challenges in detecting paediatric tuberculosis. Obtaining sputum samples from children is often difficult due to which doctors have to rely on more invasive ways like collecting gastric lavage or bronchoalveolar lavage, which involves inserting a tube to collect contents from the stomach and lungs respectively.

The pilot study by FMR was carried out on 10 children who were made to wear N-95 masks containing a gelatin membrane (used to capture airborne microbes) for 10 minutes during which they were asked to read, recite, talk, cough and take tidal breaths 20 times to collect exhaled aerosols in the mask. The researchers then took out the membrane attached to the mask and processed it for isolation of TB RNA and looked for TB specific genes through the quantitative polymerase chain reaction (QT-PCR) test. Children who already had a microbiologically confirmed diagnosis of TB were selected for the study.

“Through mask sampling, we could pick up TB in nine out of 10 samples, hence showing that it could be developed as a reliable approach,” said Kalpana Sriraman, researcher from FMR. Children account for 10% of TB burden, but less than 7% are notified. “There is a huge detection gap owing to limitations in diagnosis,” she added.

Infectious disease expert Dr Tanu Singhal, who treats paediatric tuberculosis cases, said that there was a need for simpler, reliable tests for children that will work in real world settings. “Among newer techniques, stool detection is coming up, but the sensitivity is not as good as gastric lavage or nasopharyngeal. Many centres also rely on induced sputum tests but that needs a negative pressure room,” Dr Singhal said.

However, FMR researchers also found that the Genexpert test that is widely used for TB detection didn’t have much success in picking up the bacteria from mask samples. It could only detect one of the 10 cases, whereas RT-PCR could find TB in nine samples. “But RT-PCR is resource intensive and has scalability issues unlike Genexpert,” said Dr Nerges Mistry, director of FMR, adding that the institute will now work towards making mask sampling more viable for TB detection.

Source: Sumitra Debroy | Times of India | October 26, 2020

Mask Sampling Can Help Detect Tuberculosis In Kids: Study was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

This stage of disease is unknown to most people. Whist rehabilitation centres have been created by the government, they are largely dysfunctional, poorly located and do not offer comprehensive services to such patients.

BEYOND CURE is a film that testifies to the sufferings of these patients and suggests measures both community and public health based that can relieve their suffering.

Click on the link to watch the film: https://urldefense.proofpoint.com/v2/url?u=https-3A__drive.google.com_file_d_1-2DbXA3-5FlcvJE6dGJtGB5i8ACnnHjLmd-2DF_view-3Fusp-3Dsharing-5Feil-26ts-3D5edf7bc0&d=DwMFaQ&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5-BlNEf9p68RbIw5puyzM5GSzob-SXLLjDap63Lm66k&m=R6k5g9dQ6FlQfNI2bhkGe4Wd2nsKho8G3nzyfTxUVKA&s=vTlv2wms1tO478ki6VyTCLnykOzwCmSZ7WT1dEQfKec&e=

Beyond Cure In Leprosy was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

Diagnosis of SARS COVID-2 virus through nasal and throat swab is a ticklish business for the patient and a danger zone for the sampler. Sneezing/coughing during sampling through swab irritation can release millions of viral particles that can infect the sampler. Which is why samplers take often poor quality swabs from a distance to protect themselves. This leads to a false negative test result allowing an infectious patient several opportunities to infect others. Scientific reports reveal that undetected infectious patient can infect up to 400 people. This becomes more dangerous since over 70–80% of infected cases in India are reported to be asymptomatic and resilient to suspicion and diagnosis.

FMR a renowned medical and public health research organisation working in infectious disease since 1974, is developing a gelatin lined mask based method to capture aerosols from COVID 19 suspects with a period of 5–7 minutes comfortably with the patient talking coughing/surging. The gelatin is peeled off and processed for detection in the lab. This way far more viruses are captured for detection with utmost safety of the sampler and no discomfort to the patient. The BMC feels that the method would greatly enhance the COVID control measures in Mumbai through strengthening of diagnosis and would like us to generate scientific evidence for this at the earliest.

The Foundation a Public Trust, has invested Rs.1 million of its own funds to purchase chemicals and protective clothing for its researchers and requires an additional Rs. 8,00,000 to complete rigorous testing of at least 30 confirmed COVID patients and 30 normal healthy individuals. Given the interest and urgency expressed by the Municipal Corporation, we have initiated the study at Kasturba Hospital. Your support urgently needed at this juncture, would be timely and helpful in achieving correct and early diagnosis saving lives of both health workers and patients, and more effective control of COVID.

If successful, we would propose to introduce this mask widely for testing through mass production which would make the test much cheaper and therefore more affordable. Efforts are also being made to make this a Point of Care testing method through application of a more cutting edge technology CRISPR. Eventually such a test can be applicable not only to Covid but several other respiratory infections which could exist together in a patient without being detected.

Your contribution therefore would have far more than just direct impact for COVID-19.

Donations can be sent to The Foundation for Medical Research (Email : fmr@fmrindia.org) to our bank as per the details given below:

Name : The Foundation for Medical Research

Account №004910100032505

Bank — Bank of India

Branch — Worli Naka

IFSC Code BKID0000049

Donations are exempt u/s 35 (1) (ii) of the Income Tax Act.

A MASK FOR ALL SEASONS was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

COVID-19 caused by the novel corona virus (SARS-CoV-2) is perhaps the biggest threat the humanity is facing currently. Although it has been over five months since the outbreak, no medication or vaccine is yet available to combat the deadly virus.

In this scenario, lets take a glimpse at traditional system of medicine in India for a possible solution. Medicinal plants demonstrated for their beneficial effect in respiratory viral infections can be useful in treating Covid-19 too. These include common plants like tulsi, ginger & turmeric and other plants such as Echiniacae purpurea (purple coneflower), Andrographis paniculata (kalmegh), Sambucus nigra (Elderberry). Studies have shown that these plants have different bioactive constituents that have multiple targets to control viral attack. Besides plants are known to strengthen/boost immunity which in turn can play an important role in eliminating virus. Tinospora cordifloria (guduchi), Withania somnifera (ashwaganda), Emblica officinalis (amla), Terminalia chebula (harde), Alpinia galanga (Thai galanga) are few examples of immunomodulatory plants which could be useful. These plants could perhaps be included as adjuvants to conventional medications given to Covid-19 patients for faster recovery.

In the wake of the pandemic, experts have recommended several prophylactic measures – medicated water using spices like fennel and ginger, gargles with turmeric and neem water, nasal applications with medicated oils/ghee. Use of Rasayanas like ashwaganda and Yoga too have been suggested.

The Ministry of AYUSH, Government of India whilst promoting traditional medicines has suggested the AYUSH ‘Kwath’ as a herbal drink comprising of tulsi, dalchini, sunthi and kalimirchi, for improving one’s immunity. These ingredients as well as other common kitchen spices (cloves, garlic, ajwain, etc) should be used on regular basis.

With no ‘modern’ cure in sight, at least in the near future, it’s timely to look at alternative systems of medicine including Ayurveda — the ancient science of life, which emphasizes on a holistic approach towards good health.

Source:https://www.facebook.com/MyGovVolunteers/posts/567709727198070

Can Traditional Medicine Combat Covid – 19?? was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

Dr. Nerges Mistry, The Foundation for Medical Research, Mumbai. E-mail: fmr@fmrindia.org

Willy nilly the ICMR has transitioned from dismissing community transmission into accepting that it may be a reality. A big gap in our knowledge of COVID19 is the variety of immune responses that it may engender in different individuals and the possibility of the presence of viral carriers.

As reported by researchers from Columbia University asymptomatic infections were first seen in China and then subsequently from Germany and Italy. Measured to be only 55% contagious than those with symptoms, they were shown to contribute to 79% of infections. Prevalence of such transmitters were estimated to range from 1 asymptomatic to 5–10 symptomatics.

Given their importance in tracking of transmission of COVID19, the restricted sampling strategy in SARIs admitted in hospitals, begs questioning especially since temporal details such as duration of illness with respect to initiation of testing in various locales is obscure. In line with the recommendation of Dr.Ashish Jha from Harvard University, an epidemiology based random sampling of asymptomatic individuals in circumscribed areas of COVID19 clusters may yield a better picture of extent of community transmission and yield insights into the immune features of the Indian epidemic.

If we institute insightful surveillance, we will expect to see individuals with no overt or extremely mild symptoms reflecting in all probability a carrier or quasi carrier state. It would be logical to hypothesize that these would be younger people, healthy enough not to fall prey to the cytokine storm set off by the virus, but not capable of preventing viral spread. What would be their predominant age group, their health profile and the repertoire of their innate immunity. Could we not pick up correlates of protective immunity from these individuals which would help in the evaluation of a vaccine (apart from a robust IgG response).

A second angle of this issue would be a deep study of viral genomics from viral isolates from such individuals. Are these isolates any different from those that infect individuals who have increased severity of symptoms normalized for age and health profile.

The recovering Chinese population in Wuhan many of whom whose retrospective data would have been recorded would be an excellent source for the study of the abovementioned issues strengthened with the creation of a strategically selected viral repository. Have our national agencies, ICMR and DBT had the foresight to create such a viral repository complete with valuable metadata.

Whilst we fight the epidemic with conventional measures, the search for helpful knowledge that illuminates how our species and other protected species reacts to COVID19 over a period of time should not be belittled nor postponed. The ICMR (as its very name suggests) could have instituted a dedicated cell for basic research to understand the features of the COVID 19 epidemic in India, e.g. rapid genomics to understand the virus make-up and its evolution, the significance of antibody responses in COVID infection and the protective corelate of human response to COVID 19.

This knowledge will contribute significantly to our survival in the next pandemic when it comes. Its not a question of “if”.

The potential of the asymptomatics and the mild COVID19 cases was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading infectious diseases with more than 10 million active cases worldwide and approximately 25% of the world population being latently infected (WHO global tuberculosis report, 2018). TB is a disease with largest number of antibiotics used for treatment at one time. However post treatment the cure rate is around 85% for drug sensitive cases and 65% for drug resistant and 5% chances of relapse (Naidoo et al., 2019). While risk factors, improper adherence to treatment and development of resistance can explain some cases of treatment failures, the determinants for others remains unknown. Though traditionally TB studies have been focused on its single causative agent, emerging evidence suggests that multiple interactions between host, the TB germ and the organisms in our gut and lung (the microbiome) may play a major role in the disease process and outcomes and enable the shift between susceptibility and infection.

The collective total of microbial communities (bacterial, fungal, viral) inhabiting our body along with their genetic component sums up the human microbiome. The advances in the next generation sequencing and reducing costs have made it possible to study the various microbial communities that reside in specific sites in the human body. Studies have shown that the microbiome through the three axes (Gut-Brain, Gut-Liver and Gut-Lung), production of various metabolites,and involvement in nutrition, pathogenesis and immunology of the host plays an important role in health and disease. Throughout the lifetime of an individual many factors like dietary changes, infection followed by treatment, can bring about changes in the microbiome composition and function, thus establishing a state of disturbance. These disturbances can lead to reduced population of beneficial microbes and increase in the number of disease causing organisms. The few overlapping studies in the field of TB disease and microbiome have reported that the infection and its subsequent treatment causes similar and prolonged disturbance in the bacterial population in the gut. (Wipperman et al, 2017). However there is very little knowledge about the effect of TB infection on the organisms that are residents of the lung.

We are interested in understanding the effect of TB infection and early treatment with first line drugs on the bacteria that reside in the lungs (respiratory microbiome). The first line anti TB drugs consists of three narrow spectrums (mycobacterial specific) drugs — isoniazid, pyrazinamide and ethambutol — and one broad spectrum drug Rifampicin. The preliminary results from our studies, presented at TB Science 2019 in Hyderabad, showed that TB infection and treatment (up to two weeks) causes changes in the microbial and functional structure of respiratory microbiome. We observed that three days of anti-TB treatment suppressed the growth of beneficial organisms of Lactobacilli and Bifidobacterium species, while promoting the growth of harmful organisms (anaerobes) and increased expression of certain resistance factors. Though the consequences of changes in microbial structure are still being investigated we can speculate that disturbances in microbial community may have an effect on the immune system.

An improved understanding of the microbiomes association with tuberculosis will provide further insight into the disease especially in cases of treatment failures and relapse The microbiome tuberculosis crosstalk may also open up avenues to study interactions between microbiome and drug metabolism and or adverse effects.

References: -

· WHO global Tuberculosis report 2018

· Naidoo et al, Lancet Respir Med. 2019 Oct;7(10):892–906

· Wipperman et al, Sci Rep. 2017 Sep 7;7(1):10767

Do you know there is more in you than just the TB germ? was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.

The Foundation for Medical Research (FMR) is a 44 years old Government of India (GOI) recognized research institute that conducts research on major infectious diseases like leprosy and tuberculosis, modernization of traditional medicine and climate change. FMR was established with a vision of providing innovative and appropriate approaches for tackling the major infectious diseases of India.

At FMR, we have been working in the TB area for more than 15 years now and have contributed significantly to disease understanding that is relevant for TB control efforts. Our work in TB is recognized internationally, as can be seen from the:

• Wide spectrum of project funding received from several international and national organizations amounting to about Rs. 14.2 crores from the year 1991 onwards
• Over 45 publications in international journals in the field of TB
• Recognition as a Scientific and Industrial Research Organization (SIRO) by the Department of Science and Technology, GOI and Virtual Centre for Excellence in TB research by the Department of Biotechnology, GOI

Our key contributions towards the fight against TB are:

• Warning of high levels of drug-resistant TB in Mumbai and defined mechanisms of rapid acquisition of drug resistance
• Provided insights into patient pathways to care in collaboration with PATH’s public-private interface agency and Bill and Melinda Gates Foundation (BMGF), USA
• Working on rapid diagnostics of TB that will help individualized treatment for drug-resistant patients in collaboration with University of Oxford, UK and funded by Wellcome Trust, UK and BMGF, USA
• Working with GOI and national TB programme for national laboratory strengthening through onsite training and ECHO model.
• With the support from Tata Trusts through India Health Fund, we are also working on unravelling mechanisms behind TB transmission and its relevance to TB spread at the household level.

The Foundation is expanding its work towards more translational, preventive and public health aspects of diseases using a combination of cutting edge technologies, field-based research, and environmental monitoring.

To keep up with the expanding technological advancements in research and comply with the recently changed GOI laboratory regulations for ever-increasing hazardous microorganisms like drug-resistant tuberculosis and leprosy, FMR is planning to upgrade and build an advanced biosafety level 3 (BSL-3) laboratory in the third floor of its premises. This requirement has been accelerated due to the requirement of gene editing experiments that mandate higher laboratory safety for the protection of researchers undertaking such work.

A competent vendor who has built similar laboratories in higher-level referral labs in the public sector has been appointed to build the facility. The lab including ancillary equipment will cost Rs.80 lakhs. We have already raised Rs. 20 lakhs and are looking for additional donations to fill up the gap.

In case you would like to contribute to our infrastructure development and support us in our endeavours, please send in your amount by cheque or demand draft in the name of “The Foundation for Medical Research”. Donations made to the Foundation are exempt u/s 35 (1) (ii) of the Income-Tax Act 1961.

You may feel free to contact us for more details on +91 22 2493 4989 /8601 or by email on fmr@fmrindia.org.

We would be extremely grateful for any donation we receive to bridge the funding gap.

Thanking you

Yours sincerely,

Nerges Mistry, Ph.D.

Director

LETTER OF APPEAL was originally published in Foundation for Medical Research on Medium, where people are continuing the conversation by highlighting and responding to this story.