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Viruses, Malaria, Platelets and Artemisia

May 23, 2020 - 10:12 -- Pierre Lutgen

 

In my previous comments on www.malariaworld.org I alerted to the possibility that the widespread malaria infections in sub-Saharan Africa might provide a protection against the Covid virus. Trying to find an explanation for this observation might be important.

Platelets are small non-nucleated cells and play a crucial role in regulating hemostasis. Recent findings show that beyond the hemostatic function platelets also play a main role in fighting against pathogens including viruses. With their receptors, platelet interacts with viral pathogens and this interaction between platelets and viral pathogens result in activation of platelets. Activated platelets release different molecules that have antiviral activity. In addition, activated platelet has antiviral role by different mechanism including phagocytosis of viral pathogen, produce reactive oxygen species and interact with and activate other immune cells.

      Masresha Seyoum; Bamlaku Enawgaw. Human blood platelets and viruses: defense mechanism and role in the removal of viral pathogens. Thrombosis J. 2018, 16:16

Activation of platelets appears to be a critical parameter. And this activation is well known for malaria infections. Activated platelets in malaria-infected patients are hypersensitive and enhance haemostatic responses.

       Asare, R., Opoku-Okrah, C., Danquah, K.O. et al. Assessment of platelet indices and platelet activation markers in children with Plasmodium falciparum malaria. Malar J 19, 143 (2020).

      Inyang AL, Sodeinde O, Okpako DT, Essien EM. Platelet reactions after interaction with cultured Plasmodium falciparum infected erythrocytes. Br J Haematol. 1987; 66:375–8.

It would be important also to understand how Artemisia infusions interfer. Artemisia plant extracts increase and stabilize the platelet count in malaria infections and increase survival.

      Shahriyary L, Yazdanparast R. Inhibition of blood platelet adhesion, aggregation and secretion by Artemisia dracunculus leaves extracts. J Ethnopharmacol. 2007 Nov 1;114(2):194-8

      Bamunuarachchi, Daya Ratnasooriya,  Platelet and WBC Increasing Effect of Artemisia vulgaris Ethanolic Leaf Extract in a Rat Model. Young Scientists Forum (YSF) Symposium (2012), Vol 2. Sri Lanka Vol 2

Artemisia infusions are also very efficient against diabetes as shown in a recent paper by Jerome Munyangi and Pierre Lutgen. Diabetes and obesity heavily contribute to the death toll related to the coronavirus. Maybe a similar lead should be investigated more in depth.

 

     J. Munyangi, P. Lutgen. Five case reports on treatment of diabetes by Artemisia annua and Artemisia afra herbal tea.: Pharm Pharmacol Int J 2020 8(2): 79-85

But this is not the case for artemisinin derivatives, which are strong pro-oxidants. Artesunate was shown to decrease hemoglobulin, erythrocyte and platelet count. Artemether caused significant reduction of the hematological profile of the animals in a dose dependent manner. This can probably aggravate anemia when artemether is administered to malaria patients

       Papiya Bigoniya, Taranginee Sahua. Hematological and biochemical effects of sub-chronic artesunate exposure in rats. Toxicology reports, 2015, 2, 280-28

       IO Osonuga, OA Osonuga.  Effect of artemether on hematological parameters of healthy and uninfected adult Wistar rats Asian Pac J Trop Biomed. 2012 Jun; 2(6): 493–495.

 

Covid, malaria, immunoglobulins and Artemisia

 

Congratulations for Jerome Munyangi who with other Africans run the successful large scale double blind clinical trials in RDC against malaria and bilharzia, confirming previous smaller clinical trials run in other countries by African medical teams.

Everybody wants to find Artemisia now for infusions against Covid and Malaria. Several of our partners in Africa are confronted with a stockout.

Several newspapers or blogs confirm that malaria endemic regions are virtually Covid free. They relate this to malaria drugs. We rather are of the opinion that it is due to acquired immunity, immunoglobulins and their enhancement by Artemisia infusions (not artemisinin or ACTs).

Mosquito-borne diseases are associated with major global health burdens. In a recent paper: J Munyangi, P Ogwang, P Gisenya, P Lutgen. An unexpected, revolutionary property of Artemisia infusions. Pharm Pharmacol Int J. 2020;8(1):46‒62. the authors describe how the saliva of mosquitoes during parasite or virus infection may affect transmission. For their blood meal mosquitoes inject saliva. Reactions to mosquito bites, lead to immunological reactions, to swelling, wheal and flare of the skin. Mosquito saliva contains many biological materials, anticlotting and antiplatelet factors and vasodilators which presumably increase the speed at which blood from the host is imbibed. But also, immunomodulators, allergens which bind to IgE and induce histamine and iNOS release. Allergens are present in the saliva of most of the mosquitoes, even in those which are not infected. A study has shown in a murine model that bites from uninfected mosquitoes prior to Plasmodium yoelii infection influence the local and systemic immune responses and limit parasite development within the host.  And it may explain why people living in countries with dense Anopheles populations are immunized by these bites.

A similar phenomenon has been noticed for other diseases: repeated infestation with Ixodes scapularis ticks induces resistance to Borrelia burgdorferi transmission. And multiple exposure to bites from uninfected sand flies prior to infection confer resistance to Leishmania major.

Aedes spp. and Culex spp. are primarily responsible for the transmission of the most medically important viruses, including dengue virus, West Nile virus and Zika virus. Despite the burden of these pathogens on human populations, the interactions between viruses and their hosts remain enigmatic, especially during the transmission phase from mosquito to human host. Some authors find that the saliva of the bite increases virus replication, others that it is inhibited :

        Tonnerre P, Melgaço JG. Evolution of the innate and adaptive immune response in women with acute Zika virus infection. Nat Microbiol. 2020 Jan;5(1):76-83

        Garcia M, Alout H. Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva. Front Cell Infect Microbiol. 2018 Nov 2; 8:387

         Vogt MB, Lahon A, Arya RP. (2018) Mosquito saliva alone has profound effects on the human immune system and increases the frequency of CD4+CD8+ double positive T cells and natural killer T cells. PLoS Negl Trop Dis 2018,  12(5): e0006439

A few decades ago, the almost complete absence of infectious HIV in saliva was noticed. Inhibition of HIV may be partly due to several inhibitors of viruses that are present in the saliva. Inhibitory factors to human immunodeficiency virus type 1 (HIV-1) in saliva may be responsible for the infrequent isolation of virus from saliva and also may account for the marked infrequency of salivary and/or oral transmission of HIV-1. Incubation of HIV-1 with  human saliva followed by addition of the mixture to susceptible cells leads to partial or complete suppression of viral replication in vitro.

       Malamud D, Abrams WR, Barber CA. Antiviral Activities in Human Saliva. Adv Dent Res. 2011 Apr; 23(1): 34–37.

         DW Archibald, GA Cole  In vitro inhibition of HIV-1 infectivity by human salivasAIDS Res Hum Retroviruses, 1990:6, 1425-32

        Philip C. Fox, Saliva inhibits HIV-1 infectivity. J Am Dental Assoc, 1988 Volume 116, 6,635–637

        Fultz PN Components of saliva inactivate human immunodeficiency virus.  Lancet. 1986; 2:1215

 

It is possible that people living in malaria endemic areas are immunized against Covid-19,

  • either by the saliva injected in frequent mosquito bites; some of its constituents remain for days or weeks in the skin and in the body
  • or by the development of specific immunoglobulins.
  • or by platelet activation

Comments

Submitted by Anonymized User (not verified) on

I read that Madagascar plans mass drug administration of IV artesunate, with the approval of WHO. Apparently this highly  hemotoxic product is already available in African pharmacies. Thousands of innocent people risk to be killed.

 

Submitted by Pierre Lutgen on

In the recent confrontations of  WHO with African governments on the use of Artemisia annua and its infusions as remedies against coronavirus and malaria, Artemisia afra was somewhat neglected in the discussions. Artemisia afra is a local plant growing from the Cape to Ethiopia. It has been used for generations against malaria and other tropical diseases like bilharzia, tinea capitis, Buruli ulcer, tuberculosis, trypanosoma. Many clinical trials made by Africans have confirmed this extraordinary efficacy. This entails that the plant if perfectly legal in African countries in accordance with the WHO prescriptions.

WHO/EDM/TRM/2000.1      Traditional use refers to documentary evidence that a substance has been used over three or more generations of recorded use for a specific health related or medicinal purpose.

In this case WHO maintains its position that there is no requirement for pre-clinical toxicity testing.

Pre-clinical toxicity testing is only required for new medicinal herbal products which contain herbs of no traditional history of use.

The plant does not contain artemisinin, the molecule used by Bigparma in ACTs. The risk that it may lead to artemisinin resistance is thus absent.