Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria.

Enhanced therapeutic efficacy achieved in treating malaria with an 8-aminoquinoline (8-AQ) drug such as primaquine (PQ) together with a partner drug such as chloroquine (CQ) is usually explained as CQ inhibiting asexual parasites in the bloodstream and PQ acting against liver stages. However, PQ's contribution, if any, to inactivating non-circulating, extra-hepatic asexual forms, which make up the bulk of the parasite biomass in chronic infections, remains unclear. In this opinion article, I suggest that, considering its newly described mode of action, PQ might be doing something of which we are currently unaware.

How does primaquine prevent Plasmodium vivax malarial recurrences?

Flannery et al. and Luiza-Batista et al. recently reported on liver and blood stages of Plasmodium vivax in humanized mice.

Theoretical origin of genetically homologous malarial recurrences.

Malaria caused by 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 of infection recurrences (which can be reinfections, recrudescences or relapses) is important epidemiologically for malaria elimination in Africa.

Safety and Efficacy of Tafenoquine for Malaria Prophylaxis and Radical Cure: Overview and Perspectives.

This article is inter alia a brief, first-stop guide to possible adverse events (AEs) associated with tafenoquine (TQ) intake. Safety and efficacy findings for TQ in malaria prophylaxis and radical cure are summarized and some of the latest TQ-related studies (published in 2020 and 2021) are highlighted. In addition, little-known biological and other matters concerning malaria parasites and 8-aminoquinoline (8-AQ) drug action are discussed and some correct terminology pertinent to malaria is explained.

Transition from Plasmodial Hypnozoite to Schizont Demonstrated.

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 relapse in malaria.

Killing of Plasmodium vivax by Primaquine and Tafenoquine.

Primaquine administration results in HO 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 hypnozoites only.

New Evidence for Hypnozoite-Independent Plasmodium vivax Malarial Recurrences.

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 merozoites in bone marrow.

Biological concepts in recurrent Plasmodium vivax malaria.

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 homologous, non-reinfection, relapse-like Plasmodium vivax recurrences that researchers ascribe to hypnozoite activation are probably hypnozoite-independent.

Malaria Eradication and the Hidden Parasite Reservoir.

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.

Mouse-Based Research on Quiescent Primate Malaria Parasites.

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 can be looked for.

Do hypnozoites cause relapse in malaria?

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 discuss it fully.

Dormancy in mammalian malaria.

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 relapsing malarial parasites will prove to be directly sporozoite-derived rather than merozoite-derived.

The hypnozoite concept, with particular reference to malaria.

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 decades old, the analysis remains valid today.

Malaria: origin of the term "hypnozoite".

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 P. vivax.

Helminthiasis, bystander diseases and vaccines: analysis of interaction.

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.

Ascaris, co-infection and allergy: the importance of analysis based on immunological variables rather than egg excretion.

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.

Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses.

Background: 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 impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly.

Paradoxical helminthiasis and giardiasis in Cape Town, South Africa: epidemiology and control.

Background: 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 areas without effective sanitation, more than 90% of children can be infected by STHs.