Experimental, therapeutic and natural transmission of Plasmodium vivax tertian malaria: scientific and anecdotal data on the history of Dutch malaria studies

Abstract

When Plasmodium vivax tertian malaria was prevalent in The Netherlands, the use of therapeutic malaria for the treatment of neurosyphilis patients presented an opportunity for biological studies of the parasite’s behaviour, in healthy volunteers. One unexplained phenomenon was the long latency between natural exposure to a single infected mosquito and the appearance of clinical signs (average 8 months). Dutch studies with volunteers and syphilis patients, suggested that hundreds of sporozoites transmitted by several mosquito bites were enough to provoke an early attack, known from tropical vivax-malaria. Sporozoites appeared to be programmed either to delay their pre-erythrocytic development or to proceed to an early attack within three weeks. The number of infectious bites also determined the relapse rate and the number of relapses after a primary attack. Analyses of primary cases and relapses from the previous year were used to predict the incidence for the next year. These historic findings fit well with recent studies on genotyping of blood stages during primary attacks and relapses. External factors (i.e. the milieu inside the human host) may trigger hypnozoites to reactivate, but predetermined periods of latency should also be considered.

Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico

“…These criteria are similar to those proposed by Adak based on several P. vivax relapse studies in India [32]. The relatively long-term relapses detected here are consistent with relapses observed in other temperate zones [5,6,52]. During 2004–2005, malaria transmission in southern Mexico declined precipitately, with only a few malaria cases reported.…”

“…A person inoculated with P. vivax sporozoites has from 5 to 80% probability of producing latent hypnozoites after the primary attack [4]. These latent parasites are activated at variable latency periods by as yet unknown factors [5,6]. The relapse pattern comprises the latency period and number of relapse episodes; it may be influenced by parasite strain, transmission dynamics, sporozoite inoculation rate for different vector species, and host factors [5-8].…”

A second chance to tackle African malaria vector mosquitoes that avoid houses and don't take drugs

“…Unlike Plasmodium vivax, which can survive for years hidden cryptically as hypnozoites within the liver of its human hosts, 51 P. falciparum must primarily survive seasonal and periodic minima of transmission as blood stages that are vulnerable to treatment with curative drugs. However, asexual blood stages, and the infectious sexual-stage gametocytes they give rise to, enable temporary escape from the human body as sporogonic stages living in the bodies of mosquitoes that may survive for up to 14 feeding cycles, equivalent to at approximately one and a half months.…”

A Second Chance to Tackle African Malaria Vector Mosquitoes that Avoid Houses and Don't Take Drugs

“…Unlike Plasmodium vivax , which can survive for years hidden cryptically as hypnozoites within the liver of its human hosts,51 P. falciparum must primarily survive seasonal and periodic minima of transmission as blood stages that are vulnerable to treatment with curative drugs. However, asexual blood stages, and the infectious sexual-stage gametocytes they give rise to, enable temporary escape from the human body as sporogonic stages living in the bodies of mosquitoes that may survive for up to 14 feeding cycles, equivalent to at approximately one and a half months 52.…”