The Myth of Immune-Boosters

 The Myth of Immune-Boosters

 Artificial immune boosting may not be the right strategy to fight against COVID-19. Staying calm, maintaining social distancing and hygiene and using protective gear will help us in the long run.

The human immune system (inherited from gazillions of its preceding species in evolution) consists of a rather well-endowed immune response network. A network composed of cells (neutrophils, eosinophils, T cells, B cells, macrophages, and other cells) and non-cellular molecules (cytokines, leukotrienes, enzymes, etc.) form a formidable resistance, which intensely and strategically defend the wonderful bulwark that the human body is. This network however is useful and wonderful so long as it starts and ends on cue and does not overstay its welcome or overdo what is expected of it. In other words, balance is the key. “Immune boosting” would therefore mean artificially getting it all excited and ready to fight. Fight it must but only when it is necessary against a defined adversary, as much and as long as it requires to reinstate a desired state of health. 

        Not The Myth of Immune-Boosters Artificial immune boosting may not be the right strategy to fight against COVID-19. Staying calm, maintaining social distancing and hygiene and using protective gear will help us in the long run. more. Not less. This well-orchestrated response by a disciplined battalion of the immune army requires a band of welltrained scouts, elite strategists, and some seriously effective mobilisation of foot soldiers (granulocytes), mounted soldiers (antibody-dependant cell cytotoxicity), archers (inflammatory mediators and their receptors), powerful cannons (histamine, bradykinin), missiles (IL-6, IL-1, TNF-α, IFN-γ, chemokines), and target-locked nukes (antibodies). This arsenal in the immune repertoire (as is apparent from the analogies) must be kept under check. If not, tremendous and uncontrolled bombardment by its own defence system shall devastate the body’s ramparts (auto-immune response). We do not want that to happen under any circumstances because that will be disastrous! Now, to define "boosting" we revisit the original task, that of keeping the body in a state of preparedness but not draw first blood. Thus, (i) a "well-oiled" group of scouts (cells that are part of the first line of defence in our innate immune network and generally shoot from the hips but do manage to come back with useful information about a novel enemy) must be maintained such that even if an insidious attack is able to breach the body’s security system, it will not be allowed to penetrate too deep; (ii) the level of co-ordination among this network of immune players (innate and acquired immunity, long-term and short-term immunity, memory-directed immune stratification and new game plan against an unforeseen intruder) must be clear and specific such that no confusion (usually created by an intruder to set off false alarms) maybe unduly provoked. Thus, no immunosuppressant, no immunedepletion to red herring signals staged by sneaky pathogenic microbes maybe unduly evoked; and (iii) when the time comes, action is swift and lethal and cleanly eliminates the intruder. At last we come to the main point of this long prologue—SARS-CoV-2 and its pet scourge COVID-19. SARS-CoV-2 enters the human cell via a membranebound enzyme angiotensin converting enzyme 2 (ACE-2) and a transmembrane serene protease 2 that its spike protein combines efficiently with to initiate a smooth endocytosis reaction and the viral payload gains unobstructed entry into the cell. The receptor-binding spike making up its corona is the key to the host cell’s aforementioned lock. The dropletborne virus enters through the lung and quickly infiltrates circulation via its chosen portal and spreads systemically. ACE-2 being a blood pressure regulator, for the host humans, COVID-19 that may start with all the hallmarks of pneumonia, quickly and silently takes over multiple organs entering their cells via the endothelial lining of blood vessels, all of which express its chosen receptor protein. And all hell breaks loose! A severe “cytokine storm” starting with low levels of IFN-γand high levels of IL-6, TNF-α, IL-1β, CCL2, CCL3, CCL5 in huge amounts like a tsunami of powerful missiles by the body’s own defence

system completely overwhelms the immune system. This is what kills us—a total failure of our espionage system (scout cells), all the trained commandos, the diplomats, the strategists, and the entire security is breached and arson of the main weapon’s manufacturing units of the body leads to mayhem. Complete immune depletion due to foolish and explosive squandering of precious defensive resources turns into our own nemesis. And a final fatal blow jeopardises the thing called life from the poor human host. Thus, immune boosting, I feel, maybe accomplished simply by leading a balanced life—good nutrition (building, repairing and maintaining all the important faculties of the body and not just the immune system since it is not an isolated one), optimum and enjoyable activities (moderate exercise such as walking, swimming, yoga, pranayam and intellectually or creatively stimulating tasks that generate the happy 'hormones') and sufficient and quality sleep (that recharges, replenishes and regenerates the expenditure in the aforementioned enterprises). Ayurvedic knowledge (curcumin in turmeric, fisetin in apple and strawberry, piperine in black pepper, etc.), local and seasonal food (raw fruits and coloured vegetables high in flavonoids, phenolic compounds rich in anti-oxidants), clean lifestyle sans the redundant practices (avoiding nothing but excess), and effective armament (of offensive attack against the infectious agents) supplemented by western medicine (antiviral drugs such as avifavir, ritonavir, remdesivir, and others like hydroxychloroquine and azithromycine combination therapy, convalescent plasma therapy, intravenous immunoglobulin (IVIG) by recombinant DNA technology and support from ventilator, extracorporeal membrane oxygenation (ECMO) and excellent supportive care) may yet save us even if that wicked and troublesome rogue virus the SARS-CoV-2 manages to gain entry. A vaccine (such as Moderna’s mRNA1273 or Oxford University’s ChAdOx1, which are in various stages of clinical trial) may take long to come and offer a shield against COVID-19. And while we are at it, may I warn against frivolous advertisements claiming immune boosting because there is nothing to gain from a “boosted” immunity other than expediting and intensifying a pro-inflammatory disease like COVID-19. We do not want our immunity to be unnecessarily boosted. We want it to stay calm and in a state of preparedness so that it will not be fooled and respond to provocation and spend itself unnecessarily. We want the casualties of war (immune maintenance and immune surveillance circuits) to be efficiently replenished, replaced and regenerated and rejuvenated to remain healthy and balanced. We want capacity to generate and maintain a diverse immune weaponry, not necessarily in a state of preparedness but skilled and fit and there in case they are called into action. And most importantly, we want the regulatory mechanisms to remain alert and effective such that even if we need to go into a well-thought-out war (innate and acquired immunity including but not limited to inflammation and T and B cell-mediated cytotoxicity or humoral response, the designated cells with very specific and specialised immune functions, signalling peptides, receptors that regulate intercellular cross-talk, etc.) they are efficiently regulated and brought down to normal levels when it is over. Thus, balance is the key to a healthy ability to mount anti-viral immunity, rather than “boosting” it. I’d say, stay calm, stay safe, and stay alert, but most importantly, stay clean (social distancing, protective gear, hygiene) and “immune boosting” or not, we shall be able to keep the COVID-19 at bay. Dr Ena Ray Banerjee is Professor, Dept of Zoology, University of Calcutta, Immunology and Regenerative Medicine Research Unit, Translational Outcomes Research. Email: erb@caluniv.ac.in

COVAXIN

 With the announcement of COVAXIN by Bharat Biotech and ZyCov-D Vaccine by Zydus Cadila the proverbial silver line in the dark clouds of COVID-19 appears at the horizon. The nod given by the Drug Controller General of India CDSCO (The Central Drugs Standard Control Organisation) for the conduct of the human trial for the vaccines marks the beginning of the end. More than 140 candidate vaccines are under various stages of development. One of the leading candidates is AZD1222 developed by Jenner Institute of University of Oxford and licensed to AstraZeneca BritishSwedish multinational pharmaceutical and biopharmaceutical company headquartered in Cambridge, England. Parallelly, Indian institutions have also engaged in R&D for the development of vaccines in India. With the primary scientific inputs coming from ICMR’s Pune-based institution National Institute of Virology and Hyderabadbased CSIR institution Centre for Cellular and Molecular Biology, six Indian companies are working on a vaccine for COVID-19. IIT Mandi develops 98% efficient face masks from waste plastic bottles at nearly one tenth the cost . Researchers at Indian Institute of Technology (IIT) Mandi developed high-efficiency face masks out of waste plastic bottles. The PET bottles were successfully converted into a nanofibre membrane. This membrane can be layered with nylon on both sides to create the mask. Research scholars Ashish Kakoria and Sheshang Singh Chandel produced the mask under the guidance of Prof Sumit Sinha Ray. The nanofibre membrane is 250 times thinner than a human hair and can remove minute particles with 98% efficiency. 

SUB HEALTH CENTRES

INFRASTRUCTURE OF A HEALTH SUB CENTRE

1. Waiting room 

2, Labour room with one labour table and NBC , 

3.1 room with 2-4 beds ,

 4.room for store 

 5 1 room for clinic/office 

 6 Toilet facility in labour room, ward room 

7 Residential facility for one ANM  

8 Residential facility {2 staff (E) and 3 staff (D)}

EQUIPMENT IN SUB HEALTH CENTRE

1. Basin 825 ml.: 1 + 1 (D)  

2 Basin deep (capacity 6 litre):  

3 Tray instrument/Dressing with cover  

4 Flashlight/Torch Box-type pre-focused 

5 Torch (ordinary)2  

6 Dressing Drum with cover 0.945 liters ss: 1  

7 Hemoglobin meter – set Sahli type complete1  

8 Weighing Scale, Adult 125 kg/280  

9 Weighing Scale, Infant (10 Kg) 1  

10 Weighing Scale, (baby) hanging type, 5 kg:1  

11 Sterilizer 1  

12 Surgical Scissors straight: 1  

13 Sphygmomanometer Aneroid 300 mm with cuff: 1+ 2(D)  

14 Kelly’s hemostat Forceps straight : 1  

15 Vulsellum Uterine Forceps curved: 1  

16 Cusco’s/Graves Speculum vaginal bi-valve medium: 1  

17 Sims retractor/depressor: 1  

18 Sims speculum vaginal double ended ISS Medium: 1

19 Uterine sound graduated: 1  

20 Cheatle’s forcep: 1  

21 Vaccine carrier: 2 

22 Ice pack box: 8 

23 Sponge holder: 2 + 2 (D) 

24 Plain Forceps: 5 

25 Tooth Forceps: 2  

26 Needle Holder: 2  

27 Suture needle straight: 10  

28 Suture needle curved: 10 

29 Kidney tray: 4 

30 Artery Forceps, straight: 5 + 5 (D) 

31 Dressing Forceps (spring type): 1  

32 Cord cutting Scissors, Blunt, curved on flat: 1  

33 Clinical Thermometer oral and rectal: 1 

34 Talquist Hb scale 1 

35 Stethoscope: 1  

36 Foetoscope: 1  

37 Hub cutter and Needle destroyer: 1  

38 Ambu Bag (Pediatric size) with Baby mask: 1  

39 Suction Machine: 1D  

40 Oxygen Administration Equipment:1 

41 Tracking bag and tickler box (Immunization): 1D 

42 Measuring tape: 1  

43 I/V Stand:1 

Source: Field survey

C. Physical Performance vis-à-vis Equipments

The data on physical performance of Sub Centres in Mahendergarh with respect to equipments have been presented in table-3. A glance at the table shows that none of the Sub Centres in district Mahendergarh had a 6 litre capacity deep Basin, Kelly’s hemostat, straight Forceps, Suture straight needles, Suture curved needles, Oxygen Administration Equipment and a I/V Stand. The sub centres at Deroli Ahir, Majra Kalan, Jatwas, Duloth Ahir, Atali and Beri did not have equipments mentioned at sr. no. 16, 19, 11, 11, 18 and 21 respectively out of a total of 43 equipments required in a Sub Centre as per IPHS guidelines.

             The data on physical performance of Sub Centres in Sirsa with respect to equipments have been presented in table 4. A glance at the table shows that availability / non availability of equipments shows almost a uniform pattern across various Sub Centres. None of the SCs in district Sirsa had a 6 litre capacity deep Basin, Kelly’s hemostat straight Forceps, a Sterilizer, Surgical Scissors straight, Sims speculum vaginal double ended ISS Medium, Suture straight needles, Suture curved needles, Oxygen Administration Equipment, Talquist Hb scale, Foetoscope and a Suction Machine. The sub centres at Pohrka, Khari Surera, Jivan Nagar, Nuhian wali, Chormar and Kalanwali Village did not have 12 equipments each out of a total of 43 equipments required in a Sub Centre as per IPHS guidelines.

Conclusion

The findings of the paper shows that the sub-centres of district Mahendergarh are good in term of human resources but they are in poor condition in the terms of building and equipments as per the IPHS. The sub-centres of District Sirsa are in poor condition in all terms i.e. human resources, building infrastructure and equipments. Sub-Health Centre (Sub-centre) is the most peripheral and first point of contact between the primary health care system and the community providing all the primary health care services. The success of NHM would depend largely on the proper functioning of Sub-centres providing services of acceptable standard to the people. So, the government should ensure the human resources, building infrastructure and equipment facilities at the grass root level for the better implementation of health policies.

Cuba offers UK salutary lesson in ‘shoe-leather’ epidemiology:

 COVID-19: Cuba offers UK salutary lesson in ‘shoe-leather’ epidemiology:

Cuba’s successful containment of COVID-19 through door-to-door screening of every home in the country, shows how ‘shoe-leather’ epidemiology could have averted the dramatic failure of the UK’s response to the pandemic. In Cuba there have been 2,173 confirmed cases and 83 deaths, with no reported deaths throughout the first week in June.

The term ‘shoe leather’ epidemiology, where much of the work is carried out on foot in the community, was first demonstrated during the Soho cholera epidemic in 1854.

Writing in the Journal of the Royal Society of Medicine, Professor John Ashton describes how, when China first reported the emerging epidemic in Wuhan in January 2020, Cuba promptly drew up a cross-government contingency plan. When the first cases of the virus were confirmed in the country among three tourists from Italy on 11 March, the plan was immediately put into action.

Screening was carried out in Cuba by tens of thousands of family doctors, nurses and medical students on foot, with testing, tracing and quarantining of suspected cases in state-run isolation centres for 14 days.

Prof Ashton said: “Cuba has long been renowned for its ability to turn in world beating health statistics while continuing to struggle economically. With a health system grounded in public health and primary care, the country invests heavily in producing health workers who are primarily trained to work in the community. Their efforts with COVID-19 have been outstanding.”

He added: “Cuba was one of the first countries to send health workers to support the control of the epidemic in Wuhan, back in January, just one example of its unrivalled commitment to international solidarity in humanitarian disasters.”

Shoe leather epidemiology in the age of COVID: lessons from Cuba (DOI: 10.1177/0141076820938582) by John Ashton is published the Journal of the Royal Society of Medicine

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The failure of the UK government to follow the advice of the World Health Organization to ‘Test, Test, Test’ for COVID-19 has cost the country dear. Having been slow to treat the pandemic with due urgency once the initial Public Health Emergency of International Concern had been called at the end of January, the country of John Snow and the Broad Street pump was left playing an embarrassing and fatal game of catch-up as the disease spread.

For those trained in the proud tradition of UK public health, this disaster has proved all the more galling in its neglect of the basic lessons of 1854 and the Soho cholera epidemic, when shoe leather epidemiology first demonstrated its worth. It was from walking the streets from house to house and business to business that Snow was able to demonstrate the concentration of cases among those drinking water from the street pump and persuaded the select vestry to remove the pump handle.

This very practical and local approach to public health provided the leit motif for its effective practice for generations until the disastrous reorganisation of the National Health Service, and with it public health, in England in 2013. The creation of a flawed agency, Public Health England, with its unremitting centralisation and undermining of local and regional public health, paved the way for the dramatic failure of response to COVID-19 in 2020. The inability to undertake large-scale testing for the coronavirus and to follow through with contact tracing, triaging, isolation and treatment followed as light follows day. Local capacity of the skilled workforce and local knowledge was run down and along with it the ability to mobilise the rich network of laboratory assets. Over-dependence on prominent London figures, institutions and laboratories, together with fly-by-night private sector contractors operating from anonymous call centres, were no substitute for hands-on experience with local knowledge and established networks of collaboration. The result was chaos and incompetence.

Comparison with one country that has performed exceptionally in response to the emergency illustrates what might have been possible had we not seemed hellbent on destroying a functioning public health system and had instead played to national strengths in primary care. Cuba has long been renowned for its ability to turn in world beating health statistics while continuing to struggle economically. With a health system grounded in public health and primary care, the country invests heavily in producing health workers who are primarily trained to work in the community, with only a small proportion going on to specialise in hospital medicine. Their efforts with COVID-19 have been outstanding.

When China first reported that a new coronavirus had been identified as the cause of the emerging epidemic in Wuhan in January 2020, Cuba promptly drew up a cross-government contingency plan and was ready to act. The first cases were confirmed among three tourists from the high disease incidence area of Lombardy in Italy on 11 March, the same day that World Health Organization declared that COVID-19 qualified as a pandemic, the patients were immediately hospitalised and the plan put into action. Tens of thousands of family doctors, nurses and medical students screened all homes in the country for cases on foot, with testing, tracing and quarantining suspected cases in state-run isolation centres for 14 days. The epidemic was soon contained after a total of 2173 confirmed cases and 83 deaths with no reported deaths throughout the first week in June. In addition, Cuba had been one of the first countries to send health workers to support the control of the epidemic in Wuhan, back in January, just one example of its unrivalled commitment to international solidarity in humanitarian disasters.

As the pandemic in the UK enters a new phase and we wait to see whether there will be a second and third wave, as happened in the Spanish flu of 1918–1920, or whether it just disappears as happened with its close relative SARS in 2003, the time for reflection has already begun. Let us hope that we can put to one side the Little England mentality that has been so much in evidence in the handling of COVID-19 and be willing to learn from others who still understand and value the ‘shoe leather epidemiology’ that was invented in Broad Street 170 years ago!