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Geophagia, Artemisia afra and Tuberculosis

April 16, 2015 - 14:57 -- Pierre Lutgen

Three diseases at least are caused by mycobacteria : leprosy, tuberculosis and Buruli ulcer. Iron is a prerequisite for the growth of mycobacteria. It is a cofactor for numerous enzymes encoded in the mycobacterium genome. It is required for the cytochromes involved in electron transport. It has been estimated that 7 to 64 g Fe per kg of mycobacterial cell mass is required to support growth. Iron limitation in vitro to levels below these results in growth restriction in many species of mycobacteria, such as M.tuberculosis.

Microorganisms have evolved many strategies for acquiring sufficient soluble iron for aerobic growth. An important component of the mammalian host defense involves restricting access of such organisms to iron. Mycobacterial acquisition of iron is mediated by siderophores. These substances are secreted by the bacteria to compete with other iron binding molecules in the human organism for the small amount of available iron. Siderophores are transient reservoirs of iron which bind to ferric iron during transport into the cell cytoplasm.

Clinical studies in Africa have also established a strong correlation between dietary iron overload and enhanced risk of death from tuberculosis (VR Gordeuk et al., Blood, 1996, 8, 3470-76). In a tragic attempt to rectify what was perceived as a debilitating iron deficiency in patients in Somalia, iron supplementation was actually found to promote the development of active tuberculosis (MJ Murray et al., Br Med J. 1978, 2, 1113-15). This is deplorable as already in 1926 Strachan (MD thesis, Glasgow) had established that the odds of death from tuberculosis in South Africa were 16.9 times higher in people with a splenic iron overload.

There is no good explanation for the widespread persistence of iron deficiency in the world, irrespective of race, culture, or ethnic background. There is convincing evidence that this deficiency protects against many infectious diseases such as malaria, plague, and tuberculosis as shown by diverse medical, historical, and anthropologic studies. Epidemic infections exerted a selection pressure under which the iron deficiency phenotype survived better.

Geophagia is the practice of eating earth or soil-like substrates such as clay or chalk. It occurs in non-human animals and also in humans, most often in rural or preindustrial societies among children and pregnant women. Geophagia is nearly universal around the world in tribal and traditional rural societies. In the ancient world, several writers noted the use of geophagia. Bloodletting which was common until recntly might have had a similar purpose. Geophagia may be an evolutionary adaptation acquired over millenia of interaction with bacteria.Mycobacteria appear to be a large group present in soil. Most cause no apparent disease, except a few virulent strains (notably tuberculosis, leprosy). 

It was conventionally assumed that clays which are rich in minerals, particularly iron, might help supplement these nutrients. This assumption was also based on the fact that these were potentially available for absorption in the body. An English team PS Hooda et al., Envir Chem and Health, 2002, 24, 305-319) has tested this assumption with five geophasic materials collected from Uganda, Tanzania, Turkey and India. The results showed that all five materials, regardless of their composition, absorbed large amounts of Fe and Zn across a range of dietary intake scenarios. However significant amounts od Ca were rendered bioavailable from calcareous soil samples.

Clays' are known for their rapid uptake of iron impairing bacterial metabolism. Zeolites are known for their immobilisation of metals. Bentonite clay is available worldwide as a digestive aid; kaolin is also widely used as as the base for some medicines. Beringite, is an artificial zeolite which is formed by the reaction of fly ash in NaOH solutions at 100 °C for several hours or days. The cation exchange capacity is increased from 100 to 3000 mmolc/kg.

French green clay is well known for its wound healing properties. This property is used in Africa for treating and healing the Buruli ulcer, in the Centre Anti-Ulcère de Buruli, Côte-d’Ivoire, for example.

The expanding bacterial resistance to antibiotics has become a growing concern worldwide. Mycobacterium tuberculosis which infects one third of the world population has seen the emergence of multidrug resistant strains that have made most of the front line drugs ineffective. This bacterial resistance is prompting the resurgence in research on herbs against resistant strains.

A study from India (SK Naik et al., Complement Alternat Med 2014, 14-87) finds that among some 10 medicinal herbs there are only two with antimycobacterial effect, Artemisia nilagirica-vulgaris and Murraya koeningii. Others like Azadirachta indica, Moringa oleifera have no effect. The ethanolic extract of A nilagirica was found to kill intracellular mycobacteria. In the artemisia family the anti-TB properties of Artemisia afra are described in several papers (S Ntulela et ., Tuberculosis, 2009 Dec, 33-40 ; IO Lawal et al., Evidence Based Compl Altern Med, 2014, ID 735423 ; M van de Venter, Planta Med 2014, 80-P1L29).

Artemisia abyssinica showed in vitro anti-mycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis strains. (A Gemechu et al., BMC Complement Altern Med. 2013 Oct 29;13:291).

There are no papers on similar properties documented for Artemisia annua. The antimalarial agent, artemisinin itself is not active against tuberculosis. (M Miller et al., J Am Chem Soc, 2011, 133, 2076-29). Antagonism between antimalarial drugs and tuberculosis treatment has been documented (M Lamorde et al., AIDS, 2013, 27, 961-5). Rifampicin intake simultaneously with Coartem lowers the AUC of artemether by 83% and lumefantrine by 84%. Similar antagonisms have been noticed for Efavirenz and Neviparine which are often used indiscriminitaly agains HIV and utberculosis. Pauline Byakik at Makerere University found that co-administration of Coartem (AL) with Efavirenz resulted in reduction in artemether, DHA, lumefantrine exposure. (J Antimicrob Chemother 2012, 67, 2213-2221).

The mechanism for the action of Artemisia afra gagainst mycobacterium is not fully understood. It is likely that the flavone luteolin plays a key role ( R Araujo et al., BMC, Complementary and Alternat Med. 2014, 14 :209) by inhibiting the Fenton reaction. Scopoletin also acts as iron chelator.

All this is in line with previous documents published on www. malariaworld.org. On Jan 23. 2015 « Gallium, key element in the excellent Bamileke artemisia ». The tea from Cameroon is very rich in the elements gallium and aluminium which interfer with iron homeostasis. On Mar 30 2015 „Vitamin C and malaria: beware!“ . Vitamin C favors the absorption of iron and boosts the malaria parasite.

Lucile Cornet-Vernet

Jérôme Munyangi

Pierre Lutgen

Comments

Submitted by Marc Vanacker (not verified) on

The document posted by Pierre Lutgen opens an interesting door. Because the use of plants against tuberculosis and leprosy is documented in the literature.

Already in 1923 the Transactions of the Royal Society of Tropical Medicine and Hygiene (M Hamzah, vol 17, 6-7, 386-391) described the results of treating leprosy with thymol: Disappearance of the irritating feeling on the face as well as the shooting pains in the muscles after a few injections. Drying up of the secretions of the ulcers after a few injections followed by complete healing of the ulcers. Flattening and general disappearance of the leprotic nodules which in the beginning were erythematous. In a few patients marked pigment spots took the places of the scars, but these were slowly resorbed and the skin regained its normal colour.

But phytomedicine confronted by pharmaceutical monotherapies declined for 100 year.

It is reviving, mostly under the pressure of research done in Southern countries. In 1992 Khadija Rhayour dedicated her Thesis at the University of Fès to the bactericidal action of essential oils of Thyme, Rosemary and Artemisia and found that all three were active against Mycobacteria. The monoterpenes thymol, carvacrol and eugenol were the strongest. Eugenol is well present in Syzygium aromaticum (clove).

A Pakistanese team studied two Origanum species and found that Origanum vulgaris had the best antibacterial properties. It contained thymol and carvacrol absent in Origanum majorana (A Hussain et al., Revista Brasileira de Pharmacognosis, 2011, 21, 943-952).
The Gauhaty University of India also made a survey of medicinal plants used against leprosy (SJ Deka et al., Plant Archives 2007, 7, 653-655).
A research team in Nigeria (O.I Faleyimu et al., AJOL, 8, 2009) examined the use of medicinal plants in the treatment of tuberculosis,. Eighty randomly selected questionnaires were administered to traditional healers, herbs traders, farmers and civil servants in the Local Government and were interviewed on the use of forest plants in the treatment of tuberculosis.

This study has proved that local people have a wealth of knowledge that needs to be the focal point in pharmaceutical research.

Submitted by Irene Teis on

Buruli, leprosy and tuberculosis are among the major killers in Africa. And endless suffering. Because chemical drugs sold by pharmaceutical companies from the North have failed or the resistance of mycobacterium to these drugs is becoming overwhelming.

It is very encouraging to find on internet the following project in Ghana

IN-VITRO SUSCEPTIBILITY OF MYCOBACTERIUM ULCERANS TO HERBAL PREPARATIONS
www.who.int/buruli/events/16.Addo_ENG.pdf

For several of the herbs involved in this project the inhibition of mycobacteria is equivalent or better than for Pefloxacin and/or Miconazole.

But the most encouraging are the conclusions of this WHO sponsored project :
A single herb is never a single compound but a group of compounds which potentiate each other or create synergy. The use of an herb or herbal cocktail would simulate combination therapy, which may prevent, or at least delay the development of microbial resistance.