Miles B Markus

University of the Witwatersrand | wits · School of Animal, Plant and Environmental Sciences (also Wits Research Institute for Malaria)

Written in relation to two recent publications, this paper reflects mainly on radical cure-associated aspects of Plasmodium vivax malaria. It questions some prevailing dogma.

Helminthiasis, which is characterized inter alia by eosinophilia, is highly prevalent in Africa. What are the implications hereof for susceptibility to COVID-19, progression of the disease and vaccine efficacy? Eosinophilia and eosinopenia are discussed in this context.

Globally, approximately 2.5 billion people are at risk of acquiring Plasmodium vivax infection. Malaria caused by P. vivax is being diagnosed with increasing frequency in Africa. Some southern countries where it has been detected are Angola, Botswana, Mozambique, Namibia, Zambia and Zimbabwe. Knowing the parasite origin (mosquito or human tissue) o...

The link for easy cutting-and-pasting in order to access this blog is in the attached file. Alternatively, type (if this cannot be clicked on): https://malariaworld.org/blog/concealed-erythrocytic-parasites-and-elimination-plasmodium-vivax

Download the file to access the website for cutting-and-pasting into your browser. The website is: https://malariaworld.org/blog/can-p-vivax-sporozoites-having-same-genotype-be-both-tachysporozoites-and-bradysporozoites

Download the file provided to get the link to cut-and-paste into your browser in order to read the blog. But in case the link can be clicked on directly here, it is: https://malariaworld.org/blog/new-plasmodium-vivax-biology

Download the file provided to get the link to cut-and-paste into your browser in order to read the blog. But in case the link can be clicked on directly here, it is: https://malariaworld.org/blog/plasmodium-vivax-relapses-or-recrudescences

Miles B Markus1,2 1School of Animal, Plant and Environmental Sciences, Faculty of Science, University of the Witwatersrand, Johannesburg, South Africa; 2Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCorrespondence: Miles B MarkusWits Research Institut...

In 2021, evidence was published which inter alia, shows that Plasmodium vivax malaria is primarily a tissue (not a bloodstream) infection. This has various implications. Download the file containing the website link (if the link is not clickable here) to a blog on aspects of the subject, mainly matters concerning the spleen. The link can be cut-and...

This blog explains that there is now strong evidence that the non-circulating parasite origin of Plasmodium vivax malarial recurrences is merozoites as well as hypnozoites (not hypnozoites only). Download the file containing the blog’s website link (if the link is not clickable here). It can be cut-and-pasted into your browser. This is the link tha...

Blog in the MalariaWorld Newsletter. Download the file here to access the link to the blog.

Blog in the MalariaWorld Newsletter. The website link to the blog can be copied and pasted (into browser) from the file provided here.

Mistakes to avoid when writing papers on malaria. Download the file herewith for the link to the website concerned.

The progression to schizont formation of individual activated hypnozoites has been observed in vitro for the first time by Voorberg-van der Wel et al. Green-fluorescent-protein-positive hypnozoites turned red-fluorescent (mCherry) upon activation. Thus, we now have empirical parasitological proof that supports the 40-year-old hypnozoite theory of r...

BOTH FLASH TALK AND POSTER ABSTRACT: After I introduced the term “hypnozoite” four decades ago, the hypnozoite hypothesis became transmogrified into a “fact”. Although the evidence for a hypnozoite origin of Plasmodium vivax malarial recurrences is compelling (despite being parasitologically unproven in humans), there is no reason why it should nec...

Hypnozoites in the primate liver appear to be derived from dormant sporozoites. Can the equivalent stage of Plasmodium also persist elsewhere in the body, such as dermally or in the lymphatic system, and be a source of recurrent malaria? Plasmodium has certainly been seen in these particular sites in the early phase of infection (references will be...

At present, it is thought that most Plasmodium vivax malarial episodes are relapses, i.e. a consequence of hypnozoite activation. This is a theory (invariably stated as a fact) that is based mainly on the results of treatment of patients with an 8-aminoquinoline compound in combination with a blood schizontocide. The conclusion has been that hypnoz...

INTRODUCTION: The use of sensitive diagnostic techniques is leading to Plasmodium vivax being identified with increasing frequency in Africa, including Botswana, Mozambique, Namibia, Zambia and Zimbabwe. Since 1980, malariologists have considered the source of malarial relapse to be hypnozoites in the liver (the term "hypnozoite" having been coined...

Primaquine administration results in H2O2 accumulation in bone marrow, where gametocytes and asexual parasites are therefore killed. This finding, by Camarda et al., supports the theory that the nonperipheral blood origin of recurrent Plasmodium vivax malaria is both hypnozoites (relapse source) and merozoites (recrudescence source), not hypnozoite...

Parasite of the Month (Mini Review)

Before 1948, the main theory regarding the source of Plasmodium vivax malarial relapses was that they originated from the reticulo-endothelial system, a hypothetical source of P. vivax parasites in recurrence that has not been disproven. From 1948, however, P. vivax relapses were explained instead on the basis of (the presumed occurrence of) contin...

Important new information concerning the treatment of malaria is starting to emerge. This is relevant to the concept of eradicating plasmodial parasites. The article can be viewed at: http://theconversation.com/why-does-malaria-recur-how-pieces-if-the-puzzle-are-slowly-being-filled-in-108833

See uploaded poster and the 3 references cited.

Information provided in recent, related papers has wide-ranging implications concerning, inter alia, the transmission of malaria, drug treatment, and eradication of the disease. Additionally, the research results represent support for the idea that recurrences of Plasmodium vivax malaria can arise from both liver hypnozoites and extravascular meroz...

This talk will be about both human behaviour (amongst scientists) and malaria. What textbooks say concerning the origins of recrudescences and relapses in malaria should be taken with a pinch of salt. The textbooks are wrong (in part). That aside, Miles Markus's contributions on the subject of malarial recurrences include coining of the term "hypno...

When introducing the term "hypnozoite" in the late 1970s, I (like others at the time) theorized that hypnozoites trigger malarial relapses. This concept has since become transmogrified into a "fact", albeit unproven in humans. Nevertheless, the indirect evidence for the validity of the hypothesis is compelling, and it is almost certainly correct, a...

A curious aspect of the evolution of the hypnozoite theory of malarial relapse is its transmogrification from theory into ‘fact’, this being of historical, linguistic, scientific and sociological interest. As far as it goes, the hypnozoite explanation for relapse is almost certainly correct. I contend, however, that many of the genotypically homolo...

The hypnozoite hypothesis of malarial relapse does not adequately explain the fact that genetically homologous, relapse-like Plasmodium vivax recurrences are so commonly encountered. It is feasible, theoretically, that hypnozoites can be responsible for such recurrences, despite there being no in vivo parasitological proof hereof in humans. However...

This presentation is compatible with the theme of the 2017 BSP Autumn Symposium in that it is concerned with a host-parasite association as well as a control matter involving a vector. Accumulation of erythrocytic stages of P. vivax in bone marrow/spleen has been reported by various authors. Earlier this year, the bone marrow was, in fact, describe...

Accumulation of erythrocytic parasites in bone marrow and the spleen has been reported in cases of Plasmodium vivax malaria. If this occurs commonly, these stages represent a possible source of early, relapse-like homologous recurrences. Moreover, they might hinder the elimination of malaria from human populations. Pertinent research suggestions ha...

FREE PAPER: http://bo.adu.org.za/content.php?id=307

See uploaded file.

Since the 1980s, it has conventionally been stated that hypnozoites (a term coined by me 40 years ago) are found in the life-cycles of Plasmodium vivax and P. ovale but not in those of P. falciparum, P. knowlesi or P. malariae; and that hypnozoites are therefore the source of relapse-type recurrent malaria in P. vivax and P. ovale infections only....

Mice engrafted with primate tissue make two important plasmodial dormancy-related questions researchable. The first is concerned with whether latent merozoites in the lymphatic system can give rise to relapse-like, recurrent malaria in primates. The second is that genetic evidence of hypnozoite activation as the source of relapsing primate malaria...

Testimonials from PCC Garnham, FRS and FC Eloff, reflecting historical research background.

After Heinz Mehlhorn and I had discovered the apicomplexan "hypnozoite" in the mid-1970s, the term was introduced for Plasmodium by me at both at the Spring Meeting of the British Society for Parasitology, University of Kent, Canterbury, UK (5–7 April 1978) and the 4th International Congress of Parasitology, Warsaw, Poland (19–26 August 1978). This...

Ornithological Observations accepts papers containing faunistic information about birds. This includes descriptions of distri breeding, foraging, food, movement, measurements, habitat and plumage. It will also consider for publication a v relevant ornithological material: reports of projects and conferences, annotated checklists for a site or regio...

[See PDF of poster.]

The concept that hypnozoites give rise to relapses in Plasmodium vivax and Plasmodium ovale malaria has become dogma. However, it is evident from particular contemporary research findings that hypnozoites are not necessarily the origin of all relapse-like recurrences of malaria caused by these parasites. This is the core opinion presented, and I di...

Malaria, which is caused by Plasmodium spp., starts with an asymptomatic phase, during which sporozoites, the parasite form that is injected into the skin by a mosquito, develop into merozoites, the form that infects erythrocytes. This pre-erythrocytic phase is still the most enigmatic in the parasite life cycle, but has long been recognized as an...

To the Editor‐in‐Chief: Menner and colleagues reported on an interesting case of the development of symptomatic Plasmodium falciparum malaria following treatment for Plasmodium ovale malaria. 1 Another instance of sequential disease, in which clinical Plasmodium malariae infection followed acute P falciparum malaria, has also been published recent...

This analysis principally concerns biological aspects of dormancy in mammalian malaria, with particular reference to the hypnozoite. Research is needed to reveal what happens to sporozoites of Plasmodium cynomolgi between the time of inoculation and when hypnozoites are first seen in the liver 36-40 h later. It is likely that hypnozoites of relapsi...

The term "hypnozoite" is derived from the Greek words hypnos (sleep) and zoon (animal). Hypnozoites are dormant forms in the life cycles of certain parasitic protozoa that belong to the Phylum Apicomplexa (Sporozoa) and are best known for their probable association with latency and relapse in human malarial infections caused by Plasmodium ovale and...

What is a Hypnozoite? Miles B. Markus Imperial College London, London, United Kingdom In 1980, Krotoski and his colleagues reported their important discovery of a uninucleate, apparently dormant stage in the life cycle of Plasmodium. Two years earlier, the suggested use of the term “hypnozoite” had been set out by me in a key paper (reprints of...

In 1978, the nature of the hypnozoite was discussed in an article that appeared in a relatively obscure journal, which is also where the term was adopted for Plasmodium (a little-known fact). As a result, that commentary on the use of the word "hypnozoite" has been almost completely overlooked. Although the publication is now more than three decade...

CARRION CROWS ATTACKING LIVE BLACKBIRDS, by H. G. Cherry

Male Pin-tailed Whydahs Vidua macroura copulate infrequently and terminate most courtship displays, even when females are highly receptive. Female sexual interference is aimed at preventing other females from copulating, and is nearly always successful.

Helminthiasis has assumed a new medical and veterinary significance following the recognition of its immunomodulatory consequences for the severity of bystander conditions and the efficacy of immunization against non-helminthic diseases of humans and livestock. Recent papers by Jackson et al. and Turner et al. have an important bearing on research...

The ratio of Ascaris seropositivity to the presence of eggs in the faeces was 2.44 in children residing near Cape Town, South Africa. Similar and larger ratios have previously been described for children and women living in the city. The new finding strengthens the concept that when helminthic infections occur together with non-helminthic diseases,...

Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and i...

South Africa has endorsed a World Health Assembly (WHA) resolution calling for control of soil-transmitted helminths (STHs). In Cape Town, services and housing that exist in old-established suburbs should minimise the prevalence of intestinal parasitic infections, even when residents are poor. Where families live in shacks in densely-populated area...

SOUTH AFRICA IS A SIGNATORY TO WORLD Health Assembly (WHA) resolution 54.19 (May 2001), which calls for regular, synchronized treatment of helminthiasis in developing countries, particularly where the prevalence of worm infestation exceeds 50%. Helminthic infection is usually a hallmark of poverty and reasons why it should be controlled in disadvan...

To test the efficacy of albendazole against the whipworm Trichuris trichiura for school-based deworming in the south-western Cape, South Africa. Children infected with Trichuris were randomised to 3 doses of albendazole (400, 800 or 1200 mg), each repeated 4 times. The boy/girl ratio was 1. A group not infected with worms was treated with placebo,...

In May 2001, the World Health Assembly (WHA) estimated that two billion people were infected by soil-transmitted helminths (S-THs) and schistosomiasis, worldwide. The WHA urged member states to recognise that there can be synergy between public health control programmes for S-THs, schistosomiasis and other diseases. This is particularly relevant to...

This work was intended to test the classification of Acanthamoeba into genotypes based on nuclear ribosomal RNA gene (18S rDNA, Rns) sequences. Nearly all Acanthamoeba keratitis (AK) isolates are genotype RnsT4. This marked phylogenetic localization is presumably either due to an innate potential for pathogenicity or to a peculiarity of the gene se...

Eosinophil counts in venous blood were monitored during a randomized controlled deworming trial (n = 155 children) that lasted for a year, and in a whole-school deworming programme (range 174-256 children) of 2 years' duration. Mean eosinophil counts (x109/I) decreased from 0.70 in the randomized trial, and 0.61 in the whole-school study, to well w...

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