Hypnozoite depletion in successive Plasmodium vivax relapses

Noviyanti, Rintis; Carey-Ewend, Kelly; Trianty, Leily; Parobek, Christian M.; Puspitasari, Agatha M.; Balasubramanian, Sujata; Zackary, Park,; Hathaway, Nicholas J.; Utami, Retno A. S.; Soebianto, Saraswati; Jeny, Jeny; Yudhaputri, Frilasita A.; Perkasa, Aditya; Coutrier, Farah N.; Tirta, Yusrifar K.; Ekawati, Lenny L.; Tjahyono, Bagus; Sutanto, Inge; Nelwan, Erni Juwita; Sudoyo, Herawati; Baird, J. Kevin; Lin, Jessica T.

doi:10.1371/journal.pntd.0010648

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…In addition to population heterogeneity, we found evidence that risk of relapse varies with time. This again is consistent with and follows from observations of temporal factors that have been observed to be associated with relapse risk, such as febrile illness [10] and even time since last infectious bite, since the reservoir of hypnozoites may deplete with each relapse [6,40]. Moreover, strain-specific immunity may also influence the pattern of observed recurrences, e.g.…”

Section: Discussionsupporting

confidence: 89%

Population heterogeneity in Plasmodium vivax relapse risk

et al. 2022

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A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to ‘temporal heterogeneity’ in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to ‘population heterogeneity’ in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.

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Section: Discussionsupporting

confidence: 89%

Population heterogeneity in Plasmodium vivax relapse risk

et al. 2022

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“…As it was not an outbreak investigation, we did not enquire about participants’ travel histories or distinguish whether an active infection resulted from a recent inoculation by an infected Anopheles vector or a relapse from activation of latent hypnozoites. In endemic countries, a substantial proportion of P. vivax cases is reportedly caused by the activation of hypnozoites with genotypes distinct from those that caused the initial infections 53 . Detecting potential relapses from heterologous hypnozoites among the P. vivax infections in the 2002 Aneityum samples could have complicated the utilisation of genotyping or DNA sequencing to determine the source of the parasites responsible for the outbreak.…”

Section: Discussionmentioning

confidence: 99%

Tracing the origins of Plasmodium vivax resurgence after malaria elimination on Aneityum Island in Vanuatu

Sekine,

Chan,

Kalkoa

et al. 2024

Commun Med

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Background Five years after successful malaria elimination, Aneityum Island in Vanuatu experienced an outbreak of Plasmodium vivax of unknown origin in 2002. Epidemiological investigations revealed several potential sources of P. vivax. We aimed to identify the genetic origin of P. vivax responsible for the resurgence. Methods Five P. vivax microsatellite markers were genotyped using DNA extracted from archived blood samples. A total of 69 samples from four P. vivax populations was included: 29 from the outbreak in 2002, seven from Aneityum in 1999 and 2000, 18 from visitors to Aneityum in 2000, and 15 from nearby Tanna Island in 2002. A neighbour-joining phylogenetic tree was constructed to elucidate the relationships among P. vivax isolates. STRUCTURE and principal component analysis were used to assess patterns of genetic structure. Results Here we show distinct genetic origins of P. vivax during the outbreak on Aneityum. While the origin of most P. vivax lineages found during the outbreak remains unidentified, limited genetic diversity among these lineages is consistent with a rapid expansion from a recent common ancestor. Contemporaneous P. vivax from neighboring Tanna and potential relapse of P. vivax acquired from other islands in 1999 and 2000 are also identified as minor contributors to the outbreak. Conclusions Multiple reintroductions of P. vivax after elimination highlight the high receptivity and vulnerability to malaria resurgence in island settings of Vanuatu, despite robust surveillance and high community compliance to control measures.

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“…Despite the general acceptance of the assertion that most non-reinfection episodes of recurrent P. vivax malaria are relapses, it is nevertheless unclear to me why hypnozoites should be the origin, in many human communities, of such a large number of non-reinfection recurrences. It does seem feasible, however [ 25 , 27 , 28 , 29 ]. Alternatively, non-circulating blood-stage merozoites (i.e., merozoites not detectable in peripheral blood) might be the source of more recrudescences (as opposed to relapses) than is readily apparent [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria

Markus

2023

TropicalMed

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Enhanced therapeutic efficacy achieved in treating Plasmodium vivax 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 P. vivax 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.

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Hypnozoite depletion in successive Plasmodium vivax relapses

Cited by 4 publications

References 17 publications

Population heterogeneity in Plasmodium vivax relapse risk

Population heterogeneity in Plasmodium vivax relapse risk

Tracing the origins of Plasmodium vivax resurgence after malaria elimination on Aneityum Island in Vanuatu

Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria

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