In the spotlight: NTD Network research highlighted in new RSC Medicinal Chemistry themed collection

This May saw the launch of a new themed collection of articles from the Royal Society of Chemistry’s journal, RSC Medicinal Chemistry, bringing together scientific breakthroughs and incisive insights from global experts seeking new routes to therapeutic solutions for neglected tropical diseases (NTDs).  This themed collection, entitled “Neglected Tropical Diseases” and edited by NTD Network members Dr Charles Mowbray (DNDi), Professor Nahid Ali (IICB Kolkata) and Dr Steven Cobb (Durham University), currently includes 15 articles. Read their editorial introduction to this collection here.
Three of these papers are co-authored by our own Network researchers, although all of them highlight, by example, our vital need for cross-disciplinary, multi-institutional approaches and long-term collaborations in order to make new progress against the old challenge of NTDs, which together threaten the lives of over a billion people worldwide.  First of the reserch papers is a review co-authored by one of our NTD Network Fellows, Dr. Kalesh Karunakaran (Durham University, UK).

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Reconnecting: Launch of the NTD Network online research seminars series

Our huge thanks to Professor Ariel Silber, from the University of Sao Paulo, Brazil, and the head of our South American HUB, who opened our online research seminar series today, introduced by Network Fellow Dr. Brian Mantilla and also to the 65 attendees who joined us!  This is the first of a series of talks providing our NTD Network partners with a route to share findings and discuss ideas, in the absence of face-to-face research updates at our AGM this year.  The seminars will take place on the first and third Wednesdays of each month, and are open to our NTD Network partners, their teams, and our international advisory panel members.

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“Love in a time of [coronavirus]”: COVID-19 in context

“All that was needed was shrewd questioning… to conclude once again that the symptoms of love were the same as those of cholera.”
This quote is from the novel ‘Love in a time of Cholera’ by Gabriel Garcia Marquez (‘Gabo’ to our South American colleagues), set during the sixth cholera pandemic of 1899-1923.  I began reading it in January, alongside the emerging research literature on COVID-19, whilst representing our Network and the Durham Centre for Global infectious Diseases though over 30 interviews to UK local, national and international radio and TV, discussing the biology and disease epidemiology of coronaviruses.  This juxtaposition has caused me to think a lot about pandemics and has brought to my awareness some surprising similarities between cholera and COVID-19.  Let me explain.

 

1. Cholera and COVID19 both infect the gut, and are difficult to diagnose
The first clinical cases of SARS-CoV-2 (causing COVID-19), in Wuhan, China, were identified when patients with severe disease were admitted to hospital with acute respiratory distress.1  The virus is genetically similar to SARS-CoV (Severe Acute Respiratory Syndrome), spreading via airborne droplets.2  In practice, the disease is difficult to identify and diagnose with many patients showing no or only mild respiratory symptoms.3  The virus also infects the small intestine,4 causing nausea and diarrhoea, and can spread via a faecal-oral transmission route;5-7 some patients present only enteric (gut-based) symptoms.  Since the live virus persists in faeces for some time after patient recovery, some clinicians are now calling for routine stool sample testing for SARS-CoV-2alongside throat swabs.8.9
Cholera is also an enteric disease, spread by contaminated food or water.10.11  As with COVID-19, cholera is difficult to diagnose because most cases show mild or moderate symptoms, which are similar to those caused by a range of other infections.10
2. Cholera, COVID-19 and coronavirus diseases can pass between humans and animals
Coronaviruses are familiar to veterinarians as enteric diseases of livestock, and can spread from animals to humans – and vice versa.  Although we do not yet know the animal source of the now human disease SARS-CoV-2, a few cases of human to animal transmission have been reported so far, including a domestic dog12 and a tiger in captivity.13
Cholera is considered primarily a human disease. However, cholera can infect humans from an animal source,14 and human-derived cholera outbreaks have been reported in bison, cattle and domestic dogs.10,15

Tree pangolin (Phataginus tricuspis). Pangolins are a suspected route of transmission for SARS-CoV-2 from animals to humans.  Image: Wikimedia Commons

3. Cholera and COVID-19 disproportionately impact populations living in poverty
Risks from cholera (and other major pandemic diseases – HIV, TB, malaria and neglected tropical diseases, NTDs) are exacerbated by conditions of overcrowding and poor sanitation,10 which are frequently associated with poverty.  Likewise, close contact and poor hygiene are known to increase rates of COVID-19 transmission.
The economic impact of COVID-19 is anticipated to increase poverty in lower and middle income countries in 2020 and 2021, effectively erasing the progress made since 2017 towards alleviating poverty via the sustainable development goals.16  Many of India’s poorest people were literally starving after only a short time in lockdown, without paid work.17  This shows that economic factors also impact health risks for members of our poorest communities.
4. We are currently amidst global pandemics of both cholera and COVID-19

The last cholera pandemic began in 1961, and has not yet ended, with epidemics currently in Algeria, Angola, Bangladesh, Burundi, Chad, the Democratic Republic of the Congo, Djibouti, Ethiopia, Kenya, Saudi Arabia, Haiti, India, Malawi, Mozambique, Nigeria, Niger, Somalia, Sudan, South Sudan, United Republic of Tanzania, Uganda, Yemen, Zambia, and Zimbabwe.11,18  This ‘forgotten pandemic’ highlights cholera’s neglect, alongside the ‘officially’ neglected diseases and is similarly prioritised with World Health Organization (WHO) ‘roadmap’ goals for 2030.19
The COVID-19 outbreak, which began in late 2019, has elicited intense global attention and a rapid international response.  Yet this is the third coronavirus epidemic to threaten global health in last two decades; the earlier SARS-CoV and MERS-CoV outbreaks, in 2003 and 2018 respectively, show that risks from this virus family have also been overlooked.20
 
So what about cholera, COVID-19 and…love?
“There are only two emotions: love and fear”
Elizabeth Kubler Ross
In ‘Love in a time of cholera’, Marquez uses the cholera pandemic as a metaphor for love and death, both of which challenge us to change.
The COVID-19 pandemic is our current challenge, obliging us to face death, grief, and our own vulnerabilities.  The discomfort from physical distancing measures reveals just how closely connected we are with each other, which I feel shows how our connections with each other are based on love.
Distancing to reduce our risk of encountering or transmitting the virus, also shows how our choices as individuals do make a difference.  As we navigate the coming emergence from lockdown, we have the chance to consciously choose ‘love’, and implement radical changes that will, in time, transform our world.
Be well.  Take care.  Stay safe.

 

Mags Leighton

 

References

  1. Huang C, et al. Lancet 2020; 395: 497–506.
  2. World Health Organization. Coronavirus. Available at https://www.who.int/health-topics/coronavirus#tab=tab_1 (accessed May 2020).
  3. Arons MM, et al. N Eng J Med 2020; 382(22): 2081-2090.
  4. Ziegler et al., 2020, Cell 181, 1–20.
  5. Xiao F, et al. Gastroenterol 2020; 158: 1831-1833.
  6. Ng SC, Tilg H. Gut 2020; 69(6): 973-974.
  7. Gu J, et al. Gastroenterol 2020;158:1518–1519
  8. Cipriano M, et al. Cureus 12(3): e7422.
  9. Xiao F, et al. Gastroenterol 2020; 158: 1831-1833.
  10. Mayo Clinic. Cholera: Symptoms and causes. Available at https://www.mayoclinic.org/diseases-conditions/cholera/symptoms-causes/syc-20355287 (Accessed May 2020).
  11. World Health Organization. Cholera: The forgotten pandemic. October 2018.  Available at https://www.who.int/cholera/the-forgotten-pandemic/en/ (accessed May 2020).
  12. Lanese N. “First dog with confirmed coronavirus infection has died – but we don’t know if it was because of the virus”. Livescience.com. March 18, 2020. Available at https://www.livescience.com/coronavirus-first-case-human-to-dog-transmission.html (accessed May 2020).
  13. BBC News. “Coronavirus: Tiger at Bronx zoo tests positive for COVID-19”. April, 2020. Available at https://www.bbc.co.uk/news/world-us-canada-52177586 (accessed May 2020).
  14. Almagro-Morena S and Taylor RK. Microbiol Spectr 2013; 1(2): doi:10.1128/microbiolspec.OH-0003-2012
  15. Center for Food Security and Public Health, Iowa State University. Cholera: Fast Facts. June 2006.  Available at http://www.cfsph.iastate.edu/FastFacts/pdfs/cholera_F.pdf (accessed May 2020).
  16. Kharas H and Hamel K. Turning back the poverty clock: how will COVID-19 impact the world’s poorest people? 6th May 2020. Available at https://www.brookings.edu/blog/future-development/2020/05/06/turning-back-the-poverty-clock-how-will-covid-19-impact-the-worlds-poorest-people/ (accessed May 2020).
  17. Guardian News. How India’s coronavirus lockdown is affecting its poorest citizens. April 2nd 2020. Available at https://www.theguardian.com/world/video/2020/apr/02/how-indias-coronavirus-lockdown-is-affecting-its-poorest-citizens-video (accessed May 2020).
  18. Pritchard, H. Cholera Pandemic has a single Global Source. 25th August, 2011.  Available at https://www.bbc.co.uk/news/health-14664450 (accessed May 2020).
  19. World Health Organization Global Task Force on Cholera Control. Ending Cholera: A global Roadmap to 2030. Available at https://www.who.int/cholera/publications/global-roadmap.pdf?ua=1 (accessed May 2020).
  20. Contini C, et al. J Infect Dev Ctries 2020; 14(3):254-264.

A warm Dales welcome for the NTD Network UK HUB meeting

On a quiet day before the start of the UK University term, the UK-based members of the Global Network for Neglected Tropical Diseases (NTDs) left their desks in York and Durham Universities, for the wilds of North Yorkshire. The cosy hospitality of the locally renowned Charles Bathurst Inn (Arkengarthdale) was a warm contrast to the wild weather that swept down the valley during our meeting!  This event provided a perfectly timed opportunity to review the year and think ahead, sharing ideas and insights.
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Prize-worthy research by NTD Network PhD student in Chandigarh

Our congratulations go to Mr Naushad Akhtar, from India’s Council for Science and Industrial Research Institute of Microbial Technology (CSIR-IMTECH), for his prize-winning work!
On 17th November 2019, Naushad received the Young Researcher award for his excellent poster, submitted to the 2nd National Biomedical Research Competition, hosted at the Postgraduate Institute of Medical Education and Research, Chandigarh, India.  Naushad is studying for a PhD with NTD Network member Dr Pradip Sen, Principal Scientist at CSIR-IMTECH in Chandigarh.  Pradip’s research team are investigating how dendritic cells, a vital component of our immune system, responds to infection by Leishmania donovani, the parasite causing the lethal neglected tropical disease (NTD) visceral leishmaniasis, known in India as kala-azar.
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Gaining skills for drug discovery and beyond: Medicinal Chemistry training in Mendoza

“This training provided me with input which I didn’t know I needed, but has changed everything!” 
“These four days have been a real turning point!”
These remarks, from Jaime Isern and Victor De Sousa-Agostino, were the first responses I heard from our two PhD students from Durham University, upon their return from the NTD Network’s medicinal chemistry training workshop, held in Medoza city, Argentina, 2nd-4th November 2019.

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Winning insights: Prize awarded to young researchers investigating a new potential drug target for Chagas disease

Our huge congratulations go to Dr Daniele Chame (above), post-doctoral research associate from the Federal University of Minas Gerais (UFMG), Brazil, and Carlos Estevez, a masters’ student at UFMG, co-recipients of the 2019 Zigman Brener award at the XXXV Annual Meeting of the Brazilian Society for Protozoology (SBPz).
Daniele and Carlos are early career researchers from Professor Santuza Teixeira‘s team at UFMG, Belo Horizonte; they presented their findings as a poster in the Translational Biology session during the meeting, held in Caxambu, Brazil, 4th-6th November 2019.  Daniele had to accept the prize alone, as Carlos was busy elsewhere, at our “Workshop in Drug Discovery” training and industry symposium, held in Mendoza, Argentina, 2nd-4th November.  
This success marks the second year running that the NTD Network has won this award!  Last year’s winner was Mr Douglas Escrivani from the Federal University of Rio de Janeiro.
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Connecting with the challenge of leishmaniasis

This November, our student training workshop “New anti-leishmanial leads from natural sources”, hosted at the International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, brought together an international team of staff and 30 early career researchers from south Asia and across the Middle East.
For Dr Paul Denny and myself, the visit included a meeting with Dr Bahram Khoso and his clinical team at Jinnah hospital, Karachi; here, the human reasons behind our pre-clinical research became clear, and very real.  Before us stood four children, siblings; each face disfigured by cutaneous leishmaniasis.

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Early career researcher skills training in Karachi, Pakistan

The latest NTD Network training workshop, ‘New Anti-leishmanial leads from Natural Sources: Concepts and Approaches’, went live today!
This workshop provides practical training for PhD students, post-docs and faculty members in basic concepts and modern applications to find new anti-leishmanials using natural sources, and is held at the International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan.

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Industrial partners commit to join the medicinal chemistry training team in Mendoza, Argentina

Pharmaceuticals industry representatives, NTD Network members and associated colleagues are now on their way to Mendoza, Argentina, to deliver an early career researcher (ECR) training workshop in medicinal chemistry skills, held 2nd-4th November, 2019.  This three-day training, “Workshop in techniques and technologies in drug discovery”, will provide ECRs from neglected disease-endemic countries throughout South America with skills in medicinal chemistry and the drug discovery process. The final session of the workshop is an open symposium of drug discovery case studies, delivered by representatives from Novartis, GSK and DNDi.  This symposium is free to attend: industry symposium flyer.   

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