Cryptic Plasmodium chronic infections: was Maurizio Ascoli right?
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Malaria Journal Open Access
REVIEW
Cryptic Plasmodium chronic infections: was Maurizio Ascoli right? Wuelton Monteiro1,2*, José Diego Brito‑Sousa1,2, Aleix Elizalde‑Torrent3,4,5, Camila Bôtto‑Menezes1,2, Gisely Cardoso Melo1,2, Carmen Fernandez‑Becerra3,4, Marcus Lacerda1,6 and Hernando A. del Portillo3,4,7*
Abstract Cryptic Plasmodium niches outside the liver possibly represent a major source of hypnozoite-unrelated recrudes‑ cences in malaria. Maurizio Ascoli, an Italian physician and scientist, suggested that infection was maintained as a result of the persistence of endoerythrocytic parasites in the circulatory bed of some internal organs, mainly the spleen. This would explain a proportion of the recurrences in patients, regardless of the Plasmodium species. Ascoli proposed a method that included the co-administration of adrenaline, in order to induce splenic contraction, and quinine to clear expelled forms in major vessels. Driven by controversy regarding safety and effectiveness, along with the introduction of new drugs, the Ascoli method was abandoned and mostly forgotten by the malaria research com‑ munity. To date, however, the existence of cryptic parasites outside the liver is gaining supportive data. This work is a historical retrospective of cryptic malaria infections and the Ascoli method, highlighting key knowledge gaps regard‑ ing these possible parasite reservoirs. Keywords: Ascoli‘s method, Cryptic infection, Plasmodium, Parasite recurrence, Spleen Hypnozoites, the prototype of cryptic chronic infections The possible existence of malaria parasites outside red blood cells (RBCs) has been considered since the very beginning of malariology [1–3]. It is related to the approximate ten-day period in which parasites disappear from blood after infections. The discovery of the exoerythrocytic forms of the malaria parasites in the liver of experimentally infected nonhuman primates and later in human livers established that malaria parasites could invade cells other than RBCs. Yet, it took years to unveil the mystery of the long-term prepatent periods observed in temperate strains of Plasmodium vivax. In fact, the discovery of a dormant exoerythrocytic stage, *Correspondence: [email protected]; hernandoa.delportillo@isglobal. org 1 Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil 3 ISGlobal, Hospital Clínic—Universitat de Barcelona, Barcelona, Spain Full list of author information is available at the end of the article
the hypnozoite (from the Greek words hypnos—sleep— and zoon—animal), a term coined in relation to studies on other non-plasmodial apicomplexan parasites [4], was made only in 1982. This happened as a result of a collaboration between Krotoski in the USA and Garnham in the UK. They attributed the phenomenon of extended prepatent periods and periodic reappearance of microscopically detectable P. vivax parasites in the bloodstream to an activation of quiescent hepatic hypnozoites [5]. Malaria relapses occur at variable times after infection and repr
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