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  • Reply to: Breaking news from clinical trials with Artemisia plants   2 days 1 hour ago

    Pascale Gisenya, Pierre Lutgen

    In 2014, the blog « Artequick programmed for failure » on www.malariaworld.org had started a heated debate.

    Indeed several mass drug administration trials have  failed, the largest one performed in the Comoros by a Chinese company. This does not prevent other people to use Africans as guinea pigs for further mass drug administration trials with the same ACTs.

    Okebe, J., Dabira, E., Jaiteh, F. et al. Reactive, self-administered malaria treatment against asymptomatic malaria infection: results of a cluster randomized controlled trial in The Gambia. Malar J 20, 253 (2021). https://doi.org/10.1186/s12936-021-03761-8

    Quote. "Systematically treating all residents of compounds where clinical malaria cases occur would clear these infections and reduce transmission. This was tested in a cluster randomized trial carried out in 50 villages in Central Gambia. In the intervention arm, dihydroartemisinin-piperaquine was administered to all residents of compounds with a clinical malaria case. At the end of the intervention, malaria prevalence was not significantly lower in the intervention than in the control arm".

    Meanwhile several clinical trials in African countries with Artemisia afra, a local plant which is completely legal,  have demonstrated strong prophylactic properties. Eradication also becomes a possibility because Artemisia kills all residual gametocytes liable to transmit the disease.

    None of the current antimalarial drugs has prophylactic properties. None completely eliminates gametocytes, except primaquine which has no therapeutic effect on Plasmodium falciparum at the asexual stage, but acts at the sexual stage (with strong side-effects for G6PD patients)

  • Reply to: Breaking news: Artemisia afra cures tuberculosis   4 days 4 hours ago

     

    In April we published the attached paper

           Daddy B, Lutgen P, Gisenya P. Breakthrough against tuberculosis: high efficacy of Artemisia afra infusions. Pharm Pharmacol Int J. 2021;9(2):58‒62.

    Independently of these 15 case studies a patient, who was also cured from his TB infection after drinking  Artemisia afra infusion for a few weeks, wanted to have this confirmed by XRay examination.

    The medical report confirmed the dispappearance of the tuberculosis infection

    (medical report and pictures available on request)

  • Reply to: NOT Open Access | High proportion of genome-wide homology and increased pre-treatment pvcrt levels in Plasmodium vivax late recurrences: a chloroquine therapeutic efficacy study   2 weeks 4 hours ago
    Further to Rovira-Vallbona et al.’s important findings, which have implications in relation to the non-circulating, non-hypnozoite parasite origin of Plasmodium vivax malarial recurrences, also see this illuminating and highly topical blog: https://malariaworld.org/blog/plasmodium-vivax-malarial-recurrence-theory-vindicated
  • Reply to: Breaking news: Artemisia afra cures tuberculosis   2 weeks 14 hours ago

    Already 30 years ago it was known that human monocytes which have ingested hemozoin are unable to neutralize pathogenic bacteria, fungi, and tumor cells, and that macrophage responses decline during the course of human and animal malaria. Hemozoin (Hz) is a biocrystal synthesized by Plasmodium and other blood-feeding parasites to avoid the toxicity of free heme derived from the digestion of hemoglobin during invasion of the erythrocytes.

    Schwarzer E, Turrini F, Ulliers D, Giribaldi G, Ginsburg H, Arese P. Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment. J Exp Med. 1992 Oct 1;176(4):1033-41
    Amodu OK, Adeyemo AA, Olumese PE, Ketiku O, Gbadegesin RA. Intraleucocyte malaria pigment in asymptomatic and uncomplicated malaria. East Afr Med J. 1997 Nov;74(11):714-6. PMID: 9557443.
    Turrini F, Schwarzer E, Arese P. The involvement of hemozoin toxicity in depression of cellular immunity. Parasitol Today. 1993 Aug;9(8):297-300. doi: 10.1016/0169-4758(93)90129-4. PMID: 15463787.

    Hemozoin (malaria pigment) is found in many tissues during malaria infections. In mice that have self-cured from Plasmodium yoelii and Plasmodium chabaudi infections, liver hemozoin concentration and total content decreased for 6-9 months after parasite clearance. However, both spleen hemozoin concentration and total hemozoin content increased dramatically during this time period. Thus, hemozoin or hemozoin-laden macrophages continue to accumulate in murine spleens for at least several months after malaria parasitemia becomes undetectable.

    Levesque MA, Sullivan AD, Meshnick SR. Splenic and hepatic hemozoin in mice after malaria parasite clearance. J Parasitol. 1999 Jun ;85(3) :570-3. PMID: 10386458.

    This is well described in a recent paper. Plasmodium infection impairs host immunity to diverse bacteria, including S. pneumoniae, through multiple effects on innate immunity, and that a parasite-specific factor (Hz+bound bioactive molecules) directly contributes to Plasmodium-induced suppression of antibacterial innate immunity biomolecules. Due to the highly amphiphilic nature of hemozoin these biomolecules easily adsorb to hemozoin crystals.
    There remain important knowledge gaps that impede treatment of bacteria co-infections during malaria. Few studies have looked directly at the interactions between innate immune cells and Hz in the context of in vivo bacterial infection. Malaria and tuberculosis (TB) endemic regions overlap considerably, especially in sub-Saharan Africa. Although it is very likely that co-infections occur in these regions, not much is known about malaria-TB co-infections in humans, and how the interplay between these two infections might affect the prognosis of co-infected individuals.
    Hemozoin isolated from Plasmodium infected mice containing naturally associated bioactive molecules, such as host and parasite-derived proteins and lipids significantly impaired the ability of splenic phagocytes to control growth of intracellular bacteria.
    Following erythrocyte rupture, Hz is released into circulation and engulfed by phagocytic cells resulting in deposition in tissues and organs such as spleen, liver, brain, lungs, and bone marrow.
    In their study with Plasmodium yoelii infected mice, they found a decreased survival of infected mice following Salmonella pneumonia infection. Bacterial burdens trended higher in the lungs and were significantly higher in both the blood and spleen. These data demonstrate that Plasmodium infection also impairs control of bacteremia, and that the Plasmodium-driven susceptibility is prevalent beyond clearance of infected RBCs from peripheral circulation. This impaired antimicrobial functions of innate immune cells from African children with uncomplicated malaria was found to last up to 8 weeks after antimalarial treatment.
    Production of reactive oxygen species (ROS) is an important antibacterial effector mechanism used by phagocytic cells that is necessary for immunity to a multitude of bacterial pathogens. The results of this study clearly identify impairment of ROS production in neutrophils as a potential mechanism by which Plasmodium suppresses antibacterial innate immunity during systemic bacterial infections. An association between pulmonary pathology (SARS) and the levels of Hz deposition was also found.
    The impairment of ROS is not surprising, because during the parasite’s erythrocytic life cycle stages, it produces hemozoin to avoid oxidative stress

    Harding CL, Villarino NF, Valente E, Schwarzer E, Schmidt NW. Plasmodium Impairs Antibacterial Innate Immunity to Systemic Infections in Part Through Hemozoin-Bound Bioactive Molecules. Front Cell Infect Microbiol. 2020 Jun 30; 10:328. doi: 10.3389/fcimb.2020.00328. PMID: 32714882

    A study in Portugal confirmed that repeated malarial episodes will lead to increased Hz deposition in host organs with potential detrimental effects. If Hz impairs cellular functions, such as phagocytosis and oxidative burst, the ability to kill intracellular bacteria might be impaired. It was also observed that hemozoin-containing macrophages participated in granuloma formation in response to tuberculosis infection. This might prove relevant in the context of a tuberculosis infection by the virulent strain M. tuberculosis, in which tighter control by immune cells is necessary to prevent tuberculosis dissemination.
    They found that during incubation of synthetic hemozoin (sHz) with whole blood monocytes and granulocytes readily absorb hemozoin

    PMBC cells loaded with hemozoin have a lower phagocytic capacity

    The Portuguese study also confirms the reduction of ROS production. The mechanism by which hemozoin ingestion leads to impairment of phagocytosis is not known. However, inhibition of ROS production by hemozoin ingestion seems to be associated to production of lipid peroxidation derivatives, which promote oxidation and damage of essential components of the oxidative response.
    They were also impressed by the long residence time of hemozoin in the body. Considering that the average life span of a mouse is around 850 days, it is impressive that hemozoin could still be detected in mouse organs 280 and 140 days. This represents approximately a quarter of the life span of a mouse. Assuming that the same happens in humans and considering that in malaria endemic regions, such as sub-Saharan Africa, the same individual is likely to get infected several times throughout life, then it is likely that the amount of hemozoin accumulated in organs is enormous. If intracellular hemozoin in these organs consistently contributes to impairment of functions of these cells, then affected individuals will potentially have a proportion of immune cells that respond to other pathogens at suboptimal levels.

    Frita, Rosangela, Malaria and tuberculosis co-infection: role for hemozoin immunosuppression. Teses de Doutoramento. Universidade de Lisboa, Faculdade de Medicina 2014, http://hdl.handle.net/10451/11435

    The causal relationship between hemozoin and lung inflammation was investigated and confirmed by injecting P. falciparum-derived hemozoin intravenously into malaria-free mice.

    Deroost K, Tyberghein A, Lays N, Noppen. Hemozoin induces lung inflammation and correlates with malaria-associated acute respiratory distress syndrome. Am J Respir Cell Mol Biol. 2013 May;48(5):589-600. doi: 10.1165/rcmb.2012-0450OC

    The extensive work done by the University of Al-Quds in Palestine on beta-hematin inhibition by Artemisia and other plants may open a large array of possibilities to reduce the hemozoin load in the human body.

    Akkawi M, Jaber S, Abu-Remeleh Q, Engeu OP, Lutgen P (2014)
    Investigations of Artemisia Annua and Artemisia Sieberi Water Extracts Inhibitory
    Effects on Β-Hematin Formation. Med Aromat Plants 3 : 150. doi : 10.4172/2167-
    0412.1000150

  • Reply to: NOT Open Access | High proportion of genome-wide homology and increased pre-treatment pvcrt levels in Plasmodium vivax late recurrences: a chloroquine therapeutic efficacy study   2 weeks 4 days ago
    This excellent paper by Rovira-Vallbona et al. in Antimicrobial Agents and Chemotherapy contains hard genetic evidence that apparently supports Markus’s Plasmodium vivax malarial recurrence hypothesis, which he explains here: http://dx.doi.org/10.1016/j.pt.2017.03.002 In a nutshell, the hypothesis is that hypnozoites are not the only non-circulating parasite source of P. vivax malarial recurrences (hypnozoite-mediated recurrences being relapses), but also non-circulating merozoites (which give rise to recrudescences). Rovira-Vallbona et al. consider, on the basis of their data together with the timing of some recurrences they encountered, that relapses and such recrudescences will seemingly both occur in the particular time frame with which they were concerned.