Infectious Reservoir of Plasmodium Vivax and Plasmodium Falciparum Malaria in an Endemic Region of Sri Lanka

Gamage-Mendis, Asoka C.; Rajakaruna, Jagath; Carter, Richard; Mendis, Kamini

doi:10.4269/ajtmh.1991.45.479

Cited by 56 publications

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“…In Sri Lanka, an area of epidemic P. falciparum malaria, gametocyte prevalence decreases with age, while infectivity measures show no clear trends. 27 Githeko and others 28 supported Muirhead-Thomson's 29 conclusions that in endemic regions of Africa gametocyte prevalence decreases with age and older gametocyte carriers are typically less infectious; however, Githeko and others added the crucial observation that the ratio of circulating sexual-to-asexual-form densities increases with host age. In a P. falciparum endemic region of India, gametocyte densities are lower but conversion rates are higher among adults.…”

mentioning

confidence: 82%

A target for intervention in Plasmodium falciparum infections.

McKenzie¹,

Bossert²

1998

The American Journal of Tropical Medicine and Hygiene

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We present a set of simple mathematical models to investigate interactions between malaria parasites and the human immune system and the differentiation of parasites from asexual, pathogenic into sexual, transmissible blood stages. Each model represents a different combination of empirically based hypotheses, and salient behaviors of each fit criteria developed from clinical data. In all models, however, higher gametocyte conversion rates result in lower peak asexual-form densities. Therefore, to the extent that asexual-form densities are associated with disease symptoms, interventions that stimulate gametocytogenesis should produce unexpected clinical benefits.In many infectious diseases the severity of clinical symptoms appears to vary directly with pathogen density. Though Plasmodium falciparum infections exhibit remarkably wide variation across individuals, populations and particular symptoms, in general terms worse prognoses are associated with higher asexual parasitemias. 1-12 Most antimalarial drugs aim to kill asexual blood-stage parasites precisely because pathogenesis is associated solely with merogony.No disease symptoms are associated with gametocytes, the sexual, transmissible forms that may develop from asexual blood-stage parasites, and it is widely accepted that the few host immune responses provoked by gametocytes act only against the life-cycle stages that may subsequently develop within a vector mosquito. 13-15 , but see 16 The factors that trigger and regulate the production of gametocytes remain largely mysterious. 17, 18 The once-common view that conversion is related to some element(s) of host immunity has faded considerably following the demonstration of gametocytogenesis in long-term culture; 19 emphasis has shifted toward genetic or more direct environmental mechanisms. 20-21 , but see 22 As with the relationship between asexual-form density and clinical severity, higher gametocyte densities are generally but loosely associated with greater infectivities to mosquitoes. 13,[23][24][25] At the human population level, Schuffner's 26 study of malaria in epidemic and endemic regions of Sumatra showed that in both regions P. falciparum gametocyte prevalence roughly tracks asexual-form prevalence, remaining high and relatively constant across age groups during an epidemic but decreasing with age at an endemic site. In Sri Lanka, an area of epidemic P. falciparum malaria, gametocyte prevalence decreases with age, while infectivity measures show no clear trends. 27 Githeko and others 28 supported Muirhead-Thomson's 29 conclusions that in endemic regions of Africa gametocyte prevalence decreases with age and older gametocyte carriers are typically less infectious; however, Githeko and others added the crucial observation that the ratio of circulating sexual-to-asexual-form densities increases with host age. In a P. falciparum endemic region of India, gametocyte densities are lower but conversion rates are higher among adults. 30Epidemiologic surveys invariably report much lower prevalence...

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mentioning

confidence: 82%

A target for intervention in Plasmodium falciparum infections.

McKenzie¹,

Bossert²

1998

The American Journal of Tropical Medicine and Hygiene

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“…In one study, P. vivax infected patients were infectious to mosquitoes immediately after the appearance of asexual parasites detected by microscopy, but significantly before the emergence of gametocytes (Jeffery 1952). Similarly, several reports of infectivity at undetectable P. vivax gametocytemia have been published (Gamage-Mendis et al 1991;Sattabongkot et al 1991;McKenzie et al 2002;Coleman et al 2004;Pethleart et al 2004;Bharti et al 2006). Comparative studies of P. falciparum and P. vivax indicate that malaria transmission by P. vivax parasites is likely to be highly efficient, with lower gametocyte densities typically resulting in mosquito infection (Pukrittayakamee et al 2008).…”

Section: Relationship Between Gametocyte Density and Infectiousness Tmentioning

confidence: 99%

“…This heterogeneity in mosquito infection may result in part from sampling bias: Samples are generally collected via venipuncture but there may be a specified localization or clustering of gametocytes in the human vasculature during a blood meal (Pichon et al 2000). Similarly, in P. vivax infections, the relationship between gametocyte density and mosquito infection is poorly defined which is attributed to limited sensitivity of microscopy to detect and differentiate gametocyte stages (Gamage-Mendis et al 1991;Bharti et al 2006). In one study, P. vivax infected patients were infectious to mosquitoes immediately after the appearance of asexual parasites detected by microscopy, but significantly before the emergence of gametocytes (Jeffery 1952).…”

Section: Relationship Between Gametocyte Density and Infectiousness Tmentioning

confidence: 99%

“…Although there is a positive correlation between gametocyte density and mosquito infection rate (Schneider et al 2007;Ouédraogo et al 2009), the association is highly variable and complex at low gametocyte densities (van der Kolk et al 2005). High gametocyte densities do not necessarily result in mosquito infection (Graves et al 1988;Gamage-Mendis et al 1991;Schneider et al 2007), whereas individuals with low densities that carry no observable gametocytes have been found to be infectious (Jeffery and Eyles 1955;Muirhead-Thomson 1998;Coleman et al 2004;Schneider et al 2007). This heterogeneity in mosquito infection may result in part from sampling bias: Samples are generally collected via venipuncture but there may be a specified localization or clustering of gametocytes in the human vasculature during a blood meal (Pichon et al 2000).…”

Section: Relationship Between Gametocyte Density and Infectiousness Tmentioning

confidence: 99%

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Biology of Malaria Transmission

Meibalan

Marti

2016

Cold Spring Harb Perspect Med

141

137

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Understanding transmission biology at an individual level is a key component of intervention strategies that target the spread of malaria parasites from human to mosquito. Gametocytes are specialized sexual stages of the malaria parasite life cycle developed during evolution to achieve crucial steps in transmission. As sexual differentiation and transmission are tightly linked, a deeper understanding of molecular and cellular events defining this relationship is essential to combat malaria. Recent advances in the field are gradually revealing mechanisms underlying sexual commitment, gametocyte sequestration, and dynamics of transmissible stages; however, key questions on fundamental gametocyte biology still remain. Moreover, species-specific variation between Plasmodium falciparum and Plasmodium vivax transmission dynamics pose another significant challenge for worldwide malaria elimination efforts. Here, we review the biology of transmission stages, highlighting numerous factors influencing development and dynamics of gametocytes within the host and determinants of human infectiousness. C urrent measures for malaria elimination have been inspired by the Global Malaria Eradication Program (GMEP), which operated under the World Health Organization (WHO) between 1955 and 1969. The strategy of GMEP was largely based on dichlorodiphenyltrichloroethane (DDT)-based indoor residual spraying (DDT-IRS) complemented with mass drug administration (Pampana 1969). Although GMEP was able to eliminate malaria from many regions of the world, it was eventually abandoned because of technical challenges, increasing spread of both insecticide resistance and drug-resistant parasite strains, and lack of continuous political support (Najera et al. 2011 ual parasites and early transmission stages, whereas mature infectious transmission stages are unaffected. To block transmission, ACT is often combined with the only transmissionblocking drug on the market, Primaquine. However, recent emergence of artemisinin resistance in Southeast Asia asks for urgent evaluation of alternative treatment strategies (Noedl et al. 2008;Dondorp et al. 2009;Mbengue et al. 2015;Straimer et al. 2015).Of the five Plasmodium species known to cause malaria in humans, Plasmodium falciparum is lethal and responsible for severe disease pathology and the majority of deaths due to malaria, especially in sub-Saharan Africa. Plasmodium vivax typically causes milder infections than P. falciparum but has a much greater geographical distribution (Gething et al. 2012). The clinical symptoms of malaria are largely a result of the replication of asexual stages in human blood, but transmission to mosquitoes is only achieved through the development of sexual stages, termed gametocytes. To abrogate transmission of P. falciparum, we must be able to clear asexual and sexual stages from the human host, eventually rendering an individual noninfectious to mosquitoes. However, in the case of P. vivax, elimination is highly challenging because of the relapse of dormant liver-stage h...

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“…As with most of its congeners, P. vivax gametocyte sex ratios are typically female-biased (Carter and Graves, 1988;Read et al, 1995), with macrogametocyte densities typically about twice those of microgametocytes (Boyd, 1942a). As with P. malariae (McKenzie et al, 2001), the infectivity of P. vivax may vary widely (Boyd et al, 1935;Boyd, 1942a): it seems at most loosely coupled to gametocyte density, and, as one would expect, gametocyte density seems more closely related to mean oocyst density per mosquito than to the proportion of mosquitoes infected (Knowles and Basu, 1944;Gamage-Mendis et al, 1991;Sattabongkot et al, 1991).The present paper takes advantage of a unique opportunity to address several unresolved questions about relationships between P. vivax parasitemia, fever, gametocytemia, and infectivity by examining the preintervention dynamics of trophozoite-and sporozoite-induced infections in malaria-naive U.S. neurosyphilis patients infected with a well-characterized strain of the parasite. …”

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confidence: 99%

Plasmodium vivax Blood-Stage Dynamics

McKenzie¹,

Jeffery²,

Collins³

2002

The Journal of Parasitology

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We examine the dynamics of parasitemia and gametocytemia reflected in the preintervention charts of 221 malaria-naive U.S. neurosyphilis patients infected with the St. Elizabeth strain of Plasmodium vivax, for malariatherapy, focusing on the 109 charts for which 15 or more days of patency preceded intervention and daily records encompassed an average 98% of the duration of each infection. Our approximations of merogony cycles (via "local peaks" in parasitemia) seldom fit patterns that correspond to "textbook" tertian brood structures. Peak parasitemia was higher in trophozoiteinduced infections than in sporozoite-induced ones. Relative densities of male and female gametocytes appeared to alternate, though without a discernably regular period. Successful transmission to mosquitoes did not depend on detectable gametocytemia or on absence of fever. When gametocytes were detected, transmission success depended on densities of only male gametocytes. Successful feeds occurred on average 4.7 days later in an infection than did failures. Parasitemia was lower in homologous reinfection, gametocytemia lower or absent.Plasmodium vivax asexual blood-stage cycles are authoritatively cited as displaying a period of 48 hr (Cox, 1993;Reisberg, 1997). Hence, a single-brood P. vivax infection would be expected to produce peaks of asexual parasitemia (in the form of merozoites) and corresponding fevers on alternate days and a 2-brood infection to produce daily (quotidian) peaks of parasitemia and fever. Whorton et al. (1947) attributed their observations of irregular or steady fevers to irregular parasite segmentation. Kitchen (1949) agreed, noting that the earliest phases of patent P. vivax infections might be marked by "continuous fever caused by more or less constant sporulation," but argued that "the great majority of the vivax plasmodia are segregated into two pyrogenic broods … whose corresponding developmental stages are separated by approximately twenty-four hours." Coatney et al. (1971) found P. vivax as often tertian as quotidian and remarked that "if the infection is allowed to run, it is not unusual for multiple broods to get-in-step resulting in a tertian fever pattern; likewise, tertian patterns, sometimes, become quotidian for a time, only to revert to tertian again." Garnham (1966) reported that "the process of schizogony in P. vivax is never of clockwork regularity." According to Shute (1958), "the true explanation is that the cycle depends on the patient and not on the parasite," meaning, in particular, that quotidian behavior marks the initial infection in a malaria-naive patient, whereas tertian behavior typifies relapses and subsequent infections.A companion paper on trophozoite-induced P. malariae infections addressed some of these phenomena (McKenzie et al., 2001). With the P. vivax charts, they can be addressed in the context of sporozoite-as well as trophozoite-induced infections. Inoculation modes may influence subsequent events: sporozoite-induced infections will show longer prepatency and incuba...

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Infectious Reservoir of Plasmodium Vivax and Plasmodium Falciparum Malaria in an Endemic Region of Sri Lanka

Cited by 56 publications

References 0 publications

A target for intervention in Plasmodium falciparum infections.

A target for intervention in Plasmodium falciparum infections.

Biology of Malaria Transmission

Plasmodium vivax Blood-Stage Dynamics

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