Bubonic plague - natural strategies for resistant strains

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The recent revelations of the reappearance of the bubonic plague on mainland China, and the fact that the causative agent of the plague is steadily building resistance to our arsenal of antibiotics suggests that we take action now to prepare ourselves for any possible spread of resistant plague organisms worldwide. Once again, the complex chemistry of plant medicines and insights gained from their traditional usage can help when modern systems fail.

Bubonic plague is a disease caused by Yersinia pestis, a gram-negative, non-motile, rod-shaped coccobacillus bacterium that is transmitted to humans most often through the bite of the Oriental rat flea, Xenopsylla cheopis. The bacteria produce a biofilm within the flea largely composed of a homopolymer of N-acetyl-d-glucosamine, common within bacterial biofilm matrices, which blocks the oesophagus of the flea, causing it to bite continuously in the vain attempt to feed. Blood is repelled by the biofilm, returning to the host animal accompanied by bacteria, and so infection begins. Two to seven days after infection (exposure), flu-like symptoms such as headache, fever and vomiting start to develop. The buboes characteristic of bubonic plague (swollen and painful lymph nodes) appear initially closest to the area of the bite, or other bacterial entry site, and these may split open. The lymph nodes may be painful for some days before swelling appears. As the infection progresses further symptoms are: high fever (> 39° C/102.2° F), chills, muscle cramps, seizures, laboured breathing, vomiting blood, fatigue, digestive problems, gangrene of the extremities, and pain from decaying flesh. Bubonic plague may spread to the blood or to the lungs, where it then becomes classified as septicaemic and pneumonic plague respectively.

Alarmingly, the plague organism has historically been used in biological warfare, from the Mongols catapulting plague-infected bodies into the city of Caffa in 1346, through Russian (1710) and Tunisian (1785) use, to Japanese shelling of Ningbo in occupied Manchuria with ceramic shells containing infected fleas in 1940, killing as many as 400,000 people. Both US and Russian militaries have developed viable techniques for aerial disbursement of Yersinia pestis without the need for an intermediate host, and we are best to assume that these involve the resistant organisms. Biological infectious agents can and do escape from supposedly secure facilities, intentional release in a warfare, espionage or other setting must always be considered a possibility, as must sale to of theft by extremist political organisations. Human nature being what it is, and history being what it is, we would be wise to prepare for the release, accidental or otherwise, of any number of resistant pathogenic organisms. When any organisms is given a high media profile, it would perhaps be prudent to consider that organism a potential imminent threat.

The death rate of the plague before modern advances in sanitation and antibiotic therapy has been estimated at between 40 – 70%, with modern rates ranging from 8 – 15% mortality with treatment, with the highest survival being in those treated within 24 hours of symptoms appearing. The problem of antimicrobial resistance (AMR), however, is known within Yersinia pestis. Genes coding for the development of both antimicrobial production and resistance developed in bacteria billions of years ago, so we are talking about processes that were refined and genetically set before complex life even evolved on earth. The genes are most usually carried on a plasmid, a small packet of DNA that can replicate independently of the chromosomes, and which can be passed between bacteria of the same or other species, a concept called horizontal gene transfer. The development of AMR in Yersinia pestis is believed to be horizontal gene transfer within the midgut of the flea host. Resistance to eight separate antibiotics has been demonstrated, and there is no reason not to think total resistance to all antibiotics will be the eventual end state for Yersinia pestis. This is the time when it may be prudent to look for other ways to prevent or combat the plague.

Serum therapy was first trialed in the late 19th century by Alexandre Yersin (who discovered the causative agent of the plague in 1894). A serum derived from horses was administered, the control group having 64% mortality, and the serum group 13% mortality. Side effects of serum therapy included serum sickness and anaphylactic shock, and subsequent attempts proved less than successful. Phage therapy is another technique which had an initial success (d’Herelle 1925). Bacteriophages are a group of viruses made of proteins encapsulating either a RNA or DNA genome that infect and ‘eat’ bacteria. A highly virulent anti-plague phage isolated from rat faeces was used to successfully treat 4 plague victims, but the results could not be replicated in either animal models or further trials. Bacteriocins are antimicrobial agents produced by bacteria, and some of these were trialed in vitro with some success in 1970 against Yersinia pestis  and Y. enterocolitica. The development of antimicrobial resistance in Yersinia pestis  has renewed interest in all three of the above methods, but there are other methods that have been in use for hundreds of years, methods that have now been corroborated by scientific studies. I am talking of course about herbal and traditional medicines.

 



 

Chinese rhubarb (Rheum officinale, syn. R. palmatum)

In a study testing inhibition of Yersinia pestis  by traditional Chinese medicines, Chinese rhubarb showed the strongest inhibition of both strains tested (201 and EV76). In further testing looking at the effects of Chinese rhubarb on gene expression in Y. pestis, major changes to genes encoding cell envelope and transport/binding proteins was observed, as was a strong down-regulation of genes encoding proteins involved in ribosome protein synthesis. These genetic changes compromise the ability of the Y. pestis to invade cells, as well as compromising both the intra and extra-cellular survivability of the organism. A typical doseage for Rhuem officinale is a 1:5 tincture of 50% alcohol and 10% glycerine, 15 to 30 drops up to 4 x per day. Contraindications are not during pregnancy or lactation, not in children under 12, where any IBD exists, and people taking cardiac glycosides, antiarrhythmic medicinal products, medicinal products inducing QT-prolongation, diuretics, adrenocorticosteroids or liquorice root, should consult a doctor before taking Chinese rhubarb.
 
Coptis chinensis and other berberine plants

Renowned herbalist Stephen Buhner considers most berberine containing plants (and certainly all the commonly used ones) to be interchangeable in effect and usage. Anyone concerned about emerging resistant bacterial and viral pathogens should be in possession of Buhner’s books on the matter (see references). Berberine plants include goldenseal (Hydrastis canadensis), Mahonia genus (e.g. Oregon grape), Berberis  genus (e.g. barberry), Coptis genus (preferred, as highest in berberine), and to a lesser extent, plants in the genera Tinospora, Phellodendron (not Philodendron), and Corydalis. Alkaloids in berberine-bearing plants are hardly water soluble, so a tincture is the only effective way to use them. A suitable doseage may be 1:5 tincture, 70 or 50% alcohol, 30 – 60 drops up to 3 x per day. Contraindicated during pregnancy and lactation.

Coptis chinensis, (Huang lian), has long been used to treat plague in traditional Chinese medicine, apparently with much success. A major study on the effects of C. chinensis on the genetics of Yersinia pestis sheds some light on why this is so. A total of 360 genes in Y. pestis were differentially expressed in response to berberine. These genes included those that encode proteins involved in metabolism, genes encoding cellular envelope and transport/binding functions, genes related to iron uptake, and a number of genes of unknown encoding or unassigned functions.

Usnea sp. (old man’s beard)

Usnea species and other lichens are known to be potent natural antibacterial agents, even against resistant organisms. Usnea has been shown to inhibit Yersinia pestis. A suitasble doseage may be a tincture 1:5, 50% alcohol, 30 – 60 drops up to 4 x per day, but not during pregnancy.

 



Mullein (Verbascum Thapsus)

Mullein has been found to have substantial antibacterial action against Yersinia pestis. A suitable dosage might be a tincture, ¼ tsp 3 to 4 times per day.

Red Root (Ceanothus sp.)

Red root is a genus native to Central and North America, most species within it are considered medicinally and identically active. First and foremost, red root is a lymph system stimulant and tonic. It is anti-inflammatory for the spleen and liver, a mucous membrane tonic, astringent, alterative, antiseptic, antispasmodic, a powerful blood coagulant, and an immune system strengthener. Red root is contraindicated during pregnancy, and should not be used in conjunction with coagulant or anticoagulant medications. Standard dosages of red root are tincture: 1:5 in 50% alcohol, 30 drops, up to 4 x per day. Capsules: 10 – 30 ‘00’ capsules per day.

Bidens pilosa

Bidens has never been tested against against Yersinia pestis to my knowledge, but it is such a powerful, systemic natural antibacterial agent with effects on both resistant organisms, and organisms structurally and functionally similar to Y. pestis that I would be remiss not to include it here. A 1:2 tincture of 95% alcohol, 50 drops in water 4 x a day, or for an acute, serious infections, anywhere from 1 tsp to 1 tbsp in water up to 6 x daily. Bidens may potentiate tetracycline, and use with caution and monitoring in diabetics as Bidens can alter blood glucose and insulin levels. The fresh leaves of Bidens may also be brewed several times a day, and taken as tea.

Ayurveda

In Ayurvedic medicine, the leaves of Syzygium caryophyllatum (Chota jambal) are used to relieve symptoms. The leaves increase absorption of vitamin E, and are also antibacterial. Ayurveda also recommendeds elderflower for its antibacterial, antiviral, antiseptic, and anti-inflammatory actions. As a diuretic, elderflower will help swollen lymph nodes internally, and also externally as a wash on the swollen nodes (buboes). Take elderflower as a tincture, 30 drops in water twice a day, or as a strong decoction, 2 tbsp twice a day. Camphor essential oil (Kaphur ka tel) from the camphor laurel tree (Cinnamomum camphora) vaporised in the environment will help, or keep a tin of camphor wood shavings and leaves on a stove for the same effect. Lastly, gum from Commiphora wightii (Guggul), a kind of myrrh. Take 3 to 4 g of the resin and place on a dried cow pat. Burn the cow pat to purify the environment (and to ensure social distancing no doubt!).

Vitamin B12

Yersinia pestis upon initial entry to the body is engulfed by both neutrophils and macrophages. It is most often destroyed within the neutrophils, but most often survives within the macrophages. In the second stage, Y. pestis survives in both neutrophils and macrophages, and in the third stage it will survive anywhere within the body. Though no hard data exists to confirm this, many naturopaths and dieticians tout adequate vitamin B12 as an essential for neutrophil manufacture. Neutrophils have a very short half life in the body, so must be continuously manufactured. Vitamin B12 is essential to maintain adequate DNA for neutrophil turnover.

In closing

A good diet and a strong immune system will always be your first line of defence against any pathogen. Herbs good for optimal immune system function include ashwagandha, astragulus, boneset, red root, reishi, rhodiola and Siberian ginseng, and good multi-function adaptogenic herbs such as tulsi will help. Organic Italian garlic is also useful, 3 cloves crushed, let sit for 10 minutes, then chewed and swallowed 3 x a day would be part of my regimen for any suspected infection. Antiinflammatory foods/herbs that are also multi-functional food are also advisable, things like ginger and turmeric.

There is however, one thing that will surely compromise your immune system, and that is fear. Try to cultivate a good, healthy bodily system, and a good, healthy mind. Use both to be proactive about your health, including exercise for body and mind. A good exercise for the mind is to research those things which may through lack of knowing cause you to fear.

References

Bai Q, Jia Y, Dai X, et al. (2009) Study of molecular mechanism of Rheum officinale against Yersinia pestis. Zhongguo Zhong Yao Za Zhi 34(1):92-95.

Buhner, Stephen Harrod (2012) Herbal Antibiotics: natural alternatives for treating drug resistant bacteria (2nd ed.). Storey Publishing, MASS.

Buhner, Stephen Harrod (2013) Herbal Antivirals: natural remedies for emerging and resistant viral infections. Storey Publishing, MASS.

Darby C. (2008) Uniquely insidious: Yersinia pestis biofilms. Trends Microbiol. 16(4):158-164.

Ditchburn J-L, Hodgkins R (2019) Yersinia pestis, a problem of the past and a re-emerging threat. Biosafety and Health 1(2):65-70.

Eggers CT, Murray IA, Delmar VA et al. (2004) The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase. Biochem. J. 379:107-118.

Filippov AA, Sergueev KV, He Y et al. (2011) Bacteriophage-resistant mutants in Yersinia pestis: identification of phage receptors and attenuation for mice. PLoS ONE 6:9 doi.org/10.1371/journal.pone.0025486

Galimand M, Carniel E, Courvalin P (2006) Resistance of Yersinia pestis to antimicrobial agents. Antimicrobial Agents and Chemotherapy 50(10):3233-36.

Hinnebusch BJ, Russo M-L, Schwan TG, Carniel E (2002) High-frequency conjugative transfer of antibiotic resistance genes to Yersinia pestis in the flea midgut. Molecular Microbiology 46(2):349-354.

Jian-jiang XUE, Li-hhong LI, Hai-xia QIAO et al. (2008) Antibacteral effect of six Chinese traditional medicines on Yersinia pestis. Chinese Journal of Endemiology 27(2):152-153.

Ke Y, Chen Z, Yang R (2013) Yersinia pestis: mechanisms of entry into and resistance to the host cell. Front. Cell. Infect. Microbiol. 3(106):1-9.

Kortright KE, Chan BK, Koff JL, Turner PE (2019) Phage therapy: a renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe 25:219-232

Prakash V, Rana S, Sagar A (2016) Studies on antibacterial activity of Verbascum thapsus. Journal of Medicinal Plants Studies 4(3): 101-103.

Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 484–488.

Şi̇ri̇n N, Dülger B (2015) Ramalina farinacea (L.) Ach. ve Usnea intermedia (A.Massal.) Jatta Likenlerinin Antimikrobiyal Aktiviteleri Üzerine Araştırmalar. Düzce Üniversitesi Bilim ve Teknoloji Dergisi 3(2): 340-349.


Summers WC (1993) Cholera and plague in India: the bacteriophage inquiry of 1927–1936 J. Hist. Med. Allied Sci. 48:275-301.

Zajtchuk R, Bellamy RF, eds. (1997) Medical Aspects of Chemical and Biological Warfare. Washington, DC: Borden Inst.721 pp.

Zhang J, Zuo G, Bai Q, Wang Y, Yang R, Qiu J (2009) Microarray expression profiling of Yersinia pestis in response to berberine. Planta Med. 75(4):396-398.

 

 

 

 

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

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