Selenium, Malaria and Ebola

Selenium is an essential trace element in human health and disease. It is currently a subject of intense interest and appears to play a key role in malaria. Selenium has important health effects related to the immune response. It appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. In the context of health effects, low selenium status in some parts of the world, notably in Africa, is giving cause for concern.
Selenium and immunity
Selenium enters the food chain through plants, which take it up from the soil. Deficiency has been identified in parts of the world notable for their low soil selenium content. The lowest plasma levels are reported in some areas of China and they are associated with the Keshan disease leading to cardiomyopathy and arthritis. Investigations to date, based on animal and human models, have delivered increasing evidence of Se involvement in the functioning of the immune system. It is a component of selenoproteins such as antioxidant glutathione peroxidases and its role in the endothelial immune system is known since many years (J Spallholz, Antioxidant Nutrients and Immune Function, Plenum Press, NY, 1990). When selenium is deficient, we can assume that glutathione levels will be dramatically lower. A linear correlation between selenium levels and glutathione peroxidase has been demonstrated (A Koçyigit et al., Tr J of Medical Sciences, 1999, 29, 291-295).
Selenium supplementation up-regulates IL-2 leading to the proliferation of NK-cells and. Glutathione boosts the white blood cell production to fight infection, particularly the T-cells, which are called lymphocytes. Selenium supplementation may down-regulate abnormally high levels of IL-8 associated with inflammation (MK Baum et al., J Infect Diseases, 2000, 182, S69-73). Selenium is normally found in significant amounts in immune tissues such as liver, speen and lymph nods. Selenium is also important for preventing blood coagulation reactions leading to hemorrhaging.
Reduced CD4+ cellcounts are a marker for immunodeficiency. Retroviruses like HIV depress selenium levels in their hosts and reduce the glutathione level. This entails a reduction in CD4+ cellcounts. Mice fed selenium diets for 8 weeks saw an increase in CD4+ Tcells proportional to the dose in the diet (KF Hoffmann et al., J of Nutrit. 2010, 1155-1161).
The geographical link between selenium deficient regions viral infections like HIV, Ebola or Hantavirus.
The Ebola virus takes its name from a river near Kikwit in RDCongo where a first outbreak of this haemorrhagic fever was noticed in 1995. The soil of this area is extremily poor in selenium
A very recent paper finds that selenite could be an ultimate inhibitor of Ebola (B Lipinski et al., Bri J Med and Medical Res. 2015, 6-3, 319-24). But it should be supplemented in the form tetravalent selenite and not hexavalent selenate.
Along similar lines, it is of considerable interest that high rates of endemic Kaposi’s sarcoma are noticed in African subsistence farmers and geographic regions in Africa where the soils are of volcanic origin.These include regions surrounding the entire East African Rift Valley and the Nigeria-Cameroon border. It is widely documented that low Se levels in plants and Se deficiency syndromes of livestock are common in areas with soils of volcanic origin: the Rift Valley is a typical example. Furthermore, Se deficiency in humans has been specifically documented in northern Zaire.
In China the hemorrhagic Hantavirus is associated with selenium deficiency. Selenium supplementation leads to decreased viral replication (Li-Qun Fang et al., Viruses, 2015, 7, 333-351).
Selenium also increases the pathology of a influenza virus infection, mainly by increasing pulmonary inflammation ( M Beck et al., FASEB, 2011, 10, 1481-85).
Recently, the importance of selenium in the progression of some viral diseases (e.g. AIDS) has been revealed (P Zagrodzki, Post Hig Med Dosw 2004, 58 , 140-149). HIV figures from Harvard University (ISIS Report 20/07/04) put infection rates as follows : Zimbabwe 25.84%, Botswana 25.10%, Zambia 19.07%, South Africa 12.91%, Ivory Coast 10.06%, Tanzania 9.42%, Ethiopia 9.31% and Congo 4.31%.
But Senegal in West Africa has the lowest numbers of AIDS prevalence at 1.77 % in the general population along with the highest levels of selenium in soils. The soil is of Cretaceous origin and contains the selenium rich phosphorite.
A study in Zambia (Dr Alida Melse-Boonstra, Lusaka, May 2007) found that in this country soil data were at an average of 0.10 ppm for selenium, which is below the reported range of worlwide values for this element of 0.5 -1.27 ppm. In Malawi a widespread selenium deficiency was noticed (R Hurst et al., 2013, Scientific Reports, nature.com, , 3, 1425). In Djibouti the daily intake is 27 microgr and in Ghana 264 microgr.
Selenium in plants
Selenate ions are rapidly absorbed and transported into the plant. Selenite absorption on the other hand is slower but is more rapidly metabolized to organoselenium. Plants will tolerate more selenium on high-sulfate soils.
Some plants such as alfalfa and white clover are very sensitive and will show signs of damage at low soil selenium concentrations. Others can accumulate >100 microg Se/kg without damage. Selenium uptake will generally be in the order : Cruciferae > grass> legumes >cereal grains. This if of importance for regions where the soil is poor in selenium and nutrition could be selenium deficient.
Selenium also acts as „systemic insecticide“. In 1936 it was discovered that wheat growing in soil containing sodium selenate was not attacked by aphids or spider mites. The term « systemic insecticide » is given to any compound that is readily absorbed by a growing plant and trans-located in the sap stream of the plant in an amount sufficient to render the plant toxic to insects that feed on it.

The easiest way for people living in countries with low selenium in soils to raise their plasma selenium level is regular consumption of staple foods rich in selenium like peanuts, chickpeas, lentils, white beans. A large study in Romania showed that selenium content is higher in stems and leaves than in flowers: 60 versus 35 microg/kg (D Antal et al., Analele Universitatii din Oradea, 2010, XVII, 23-28). Plants from the Artemisia family also accumulate many minerals, including selenium, 10 times more than fruits and vegetables (U.S. Geological Survey Bulletin 2117). The same accumulator effect has been shown in China for Artemisia argyi (Ping Liu Xin et al., Adv Mat Res 2013, 1, 634-638) and the US for Artemisia ludoviciana (A Mehdawi et al., Current Biology, 2011, 21, 1440-48). The metal is present in the form of selenium polysaccharide. A study from Iran comparing the selenium uptake by garden herbs and vegetables: garden cress, leek, basil mint, onion, radish and tarragon (Artemisia dracunculus). Tarragon had the highest uptake (M Shariatpanahi et al, Biol Trace Elem Res, 1986, 11, 177-83).
This may explain why several of our partners in Congo, Uganda, Tanzania and India have found that the regular consumption of Artemisia annua or Artemisia afra infusion increases the CD4+ count.
Selenium, malaria and other tropical diseases.
Several papers have shown that serum selenium concentration is decreasing in patients with malaria (A Seyrek et al., Biol Trace Elem Res. 2005, 106, 107-110). In another paper more precisely from 49.1 in healthy control subjects to 41,7 in Plasmodium falciparum infected persons (S Baloch et al., Indo American J Pharmaceut Res, 2014 ISSN 2231-6876). The most drastic decrease has been noticed in a paper from Nigeria, from 3.76 microg/dl in healthy subjects to 0.15. But Se supplementation was able to increase it again to 7.8 microg/dl (OI Irighoghe et al., J Med and Med Res, 2013, Vol 1, 1-8).
Similar decreasing selenium levels were noticed in patients with cutaneous leishmaniasis (A Koçyigit et al, Tr J Med Sc. 1999, 29, 291-95). Selenium supplementation shows dose-dependant anti-leishmanial activities (Saled Soflaei et al., Comp Clin Path 2014, 23, 15-20.
For the Chagas disease selenium supplementation is an adjuvant therapy for cardiac alterations established by Trypanosoma cruzi infection (A Souza et al., Memo Inst Oswaldo Cruz, 2010, 105, 746-751).

Other benefits of dietary selenium
A Belgian study has shown that deficiency of selenium might be an underestimated factor for the development of high blood pressure (TS Nawrot et al., Eur Heart J. 2007, 28, 628-633). In patients with acute and chronic coronary artery disease selenium levels are significantly lower, levels of Cu and Zn not (M Hassanzadeh et al., Iran J Immunol, 3, 2006, 142-5).
In Uganda endemic goiter persistance is related to low serum selenium. In the US cancer mortality rates (lung, rectum, bladder, breast…) had a consistent inverse correlation with soil selenium content in different counties (LC Clark et al., Arch Environ Health 1991, 46, 37-42).
The Female Center for Scientific and Medical Colles in Saudi Arabia has shown that selenium is lethal to Giardia lamblia in an in vivo assay on mice and that it was equivalent to metronidazole (Magda Saned et al., Res J Biol Sc 2011, 6, 263-271). Diet with selenium was shown to be beneficial in the the treatment of parasitoses, like Trichinelel spiralis (M Gabrashanska et al., Parasitol Res, 2010 106, 561-70).
Clays are often used in wound healing. Clays are rich in selenium. Buruli ulcer has been healed with clays. A study confirmed (G Shor-Posner et al., J Acquir Immun Defic Syndr 2002, 29, 169-173) that selenium levels are very low in people infected by Mycobacterium ulcerans et tuberculosis. In Malawi lower plasma levels of selenium were found in smear-positive tuberculosis patients (A Arntsen et al., Ethiopian J Health Dev2011, 25 230-232). This was confirmed by another study: low selenium concentrations, high HIV load and high IL-6 concentrations are associated with anemia in adults with pulmonary tuberculosis (M van Lettow et al., Eur J Clin Nutri, 2005, 59, 526-532).

Selenium levels in human tissues are lower (1,15 mg/kg) for people affected by a gastrointestinal sarcoma than for healthy people (1,45 mg/kg). (P Kenneth et al., Jn Nutrit Org. Jan 1975).
Asthmatic and allergic persons often have a lower plasma selenium content.
Selenium is inversely associated with IL-6 as shown by a Taiwanese paper (CK Tseng et al., J Nutr Health Aging, 2013, 17, 280-4).
Small selenium dietary supplements are adviseable but attention must be paid that selenium has a very narrow hormetic curve and that overdose may cause toxicity. The safe upper limit is estimated to be 400 microgr per day. But this depends evidently on the health status of the person and medical advise is recommended.
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Pierre Lutgen
21 Feb 2015

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