Tertian Malaria (<i>Plasmodium vivax</i>and<i>Plasmodium ovale</i>) in Two Travelers Despite Atovaquone–Proguanil Prophylaxis

Jiménez, Beatriz C.; Navarro, Miriam; Huerga, Helena; López-Román, Eva María; Mendoza, A. Hermoso de; López‐Vélez, Rogelio

doi:10.1111/j.1708-8305.2006.00073.x

Cited by 16 publications

(13 citation statements)

References 10 publications

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“…There have been case reports of returned travellers receiving appropriate prophylaxis who nevertheless present with P. ovale malaria [15,16]. This has also been reported for P. vivax , another Plasmodium species with a hypnozoite phase [17,18].…”

Section: Discussionmentioning

confidence: 94%

Mixed-species Plasmodium falciparum and Plasmodium ovale malaria in a paediatric returned traveller

Senn

Alattas

Boggild

et al. 2014

Malar J

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Malaria is a common and potentially fatal cause of febrile illness in returned travellers. Endemic areas for different malaria parasites overlap, but mixed species infections are rare. An adolescent male returned from a trip to Ghana in late summer 2013. He subsequently presented with blood smears positive for two species of malaria parasite, Plasmodium falciparum and Plasmodium ovale, on two isolated hospital visits within a six-week period. The epidemiology of mixed infections, likely pathophysiology of his presentation, and the implications for malaria testing and treatment in returned travellers are discussed.

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Section: Discussionmentioning

confidence: 94%

Mixed-species Plasmodium falciparum and Plasmodium ovale malaria in a paediatric returned traveller

Senn

Alattas

Boggild

et al. 2014

Malar J

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“…Pyrimethamine (an inhibitor of dihydrofolate reductase), atovaquone (an inhibitor of the mitochondrial cytochrome c) and primaquine (putatively a mitochondrial inhibitor), have all been demonstrated to fully inhibit normal hepatic stage parasites in vivo and in vitro [10], [21], [22], [23], [24], [25]. Only primaquine however, is able additionally to eliminate hypnozoites [5], [6].…”

Section: Resultsmentioning

confidence: 99%

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

et al. 2011

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BackgroundAmongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. Novel compounds are thus urgently needed to replace primaquine. Discovery of compounds active against hypnozoites is restricted to the in vivo P. cynomolgi-rhesus monkey model. Slow growing hepatic parasites reminiscent of hypnozoites had been noted in cultured P. vivax-infected hepatoma cells, but similar forms are also observed in vitro by other species including P. falciparum that do not produce hypnozoites.Methodology P. falciparum or P. cynomolgi sporozoites were used to infect human or Macaca fascicularis primary hepatocytes, respectively. The susceptibility of the slow and normally growing hepatic forms obtained in vitro to three antimalarial drugs, one active against hepatic forms including hypnozoites and two only against the growing forms, was measured.ResultsThe non-dividing slow growing P. cynomolgi hepatic forms, observed in vitro in primary hepatocytes from the natural host Macaca fascicularis, can be distinguished from similar forms seen in P. falciparum-infected human primary hepatocytes by the differential action of selected anti-malarial drugs. Whereas atovaquone and pyrimethamine are active on all the dividing hepatic forms observed, the P. cynomolgi slow growing forms are highly resistant to treatment by these drugs, but remain susceptible to primaquine.ConclusionResistance of the non-dividing P. cynomolgi forms to atovaquone and pyrimethamine, which do not prevent relapses, strongly suggests that these slow growing forms are hypnozoites. This represents a first step towards the development of a practical medium-throughput in vitro screening assay for novel hypnozoiticidal drugs.

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“…In 1969, Shute and Maryon retrospectively conceded the occurrence of one possible relapse among 200 infected persons: "In 200 cases of general paresis infected with P. ovale by mosquito bites at this hospital the disease disappeared spontaneously and there was only one relapse" (Shute and Maryon 1969). The follow-up of further 17 naturally acquired and 22 artificially P. ovaleinfected subjects who did not receive primaquine again did not reveal any relapse (Mühlens 1934;de Meillon and Gear 1940;Jiménez et al 2006;Coldren et al 2007): Coldren et al described a case of a P. ovale infection in a woman, where primaquine was deferred for more than 1 year because of pregnancy and lactation. The primary infection promptly responded to chloroquine.…”

Section: Non-occurrence Of Relapses Despite Absent Anti-hypnozoite Mementioning

confidence: 92%

“…Trophozoite transmitted experimental infections are not mentioned because hypnozoites are not expected to be transmitted via this way. Publications on primary malarial attacks after a long latency are not listed here, since these are not necessarily related to hypnozoites and are also described for malaria due to plasmodia not thought to display hypnozoites, such as P. malariae and P. falciparum (Dixit 1958;Trager and Most 1963;Miller et al 1965;Gleason et al 1970;Charmot et al 1979;Coulaud et al 1979;Gentilini et al 1981;Le Marty et al 1987;Van den Ende et al 1991;Jiménez et al 2006;Gallien et al 2008;Grobusch et al 2004;Müller-Stöver et al 2008;Greenwood et al 2008;Szmitko et al 2009;Theunissen et al 2009;Focà et al 2009). …”

Section: Recrudescencementioning

confidence: 95%

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What is the evidence for the existence of Plasmodium ovale hypnozoites?

et al. 2010

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Relapsing human malaria is regarded to be caused by Plasmodium vivax and Plasmodium ovale. P. vivax relapses originate from dormant liver stages: "hypnozoites". Also, P. ovale, a species considered as closely related to P. vivax, is in analogy assumed to display hypnozoites. A close biologic relationship is, however, not supported by molecular genetic studies. Therefore, original literature published since the description of P. ovale in 1922 was systematically screened for the demonstration of hypnozoites or circumstantial evidence for their existence, i.e. the occurrence of true relapses. In P. ovale infection, hypnozoites have never been demonstrated by biological experiments, and the few reports published on relapses have conflicting results.

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Tertian Malaria (Plasmodium vivaxandPlasmodium ovale) in Two Travelers Despite Atovaquone–Proguanil Prophylaxis

Abstract: There is limited data regarding the efficacy of prophylaxis with atovaquone/proguanil (A/P) against non-falciparum malaria in travelers. Two cases, one Plasmodium vivax infection and another Plasmodium ovale infection, in travelers despite A/P prophylaxis are presented.

Cited by 16 publications

References 10 publications

Mixed-species Plasmodium falciparum and Plasmodium ovale malaria in a paediatric returned traveller

Mixed-species Plasmodium falciparum and Plasmodium ovale malaria in a paediatric returned traveller

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

What is the evidence for the existence of Plasmodium ovale hypnozoites?

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